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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 4301. Отображено 100.
02-02-2012 дата публикации

Animal ectoparasite-controlling agent

Номер: US20120029038A1
Автор: Kaori Ikari
Принадлежит: Sumitomo Chemical Co Ltd

The present invention provides an animal ectoparasite-controlling agent containing as an active ingredient a hydrazide compound represented by the formula (1) wherein R 3 represents a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group or a hydrogen atom, R 5 and R 6 are the same or different each other and each represents a methyl group or a hydrogen atom, R 4 represents a C1-C6 haloalkyl group, which shows excellent controlling effects on animal ectoparasites.

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Номер записи: 1
02-02-2012 дата публикации

Synthesis of enone intermediate

Номер: US20120029199A1
Автор: Andrew G. Myers, Jason D. Brubaker
Принадлежит: Harvard College

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate.

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Номер записи: 2
01-03-2012 дата публикации

5-aryl isoxazolines for controlling invertebrate pests

Номер: US20120053051A9
Автор: Benjamin Kenneth Smith, George Philip Lahm, Kanu Maganbhai Patel, Thomas Francis Pahutski, Jr.
Принадлежит: EI Du Pont de Nemours and Co

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein A 1 , A 2 and A 3 are independently selected from the group consisting of CR 3 and N; B 1 B 2 and B 3 are independently selected from the group consisting of CR 2 and N; Q is a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —CN, —NO 2 , —N(R 4 )R 5 , —C(W)N(R4)R 5 , —C(O)OR 5 and R 8 ; or —S(O) 2 N(R 21 )R 22 , —S(O) p R 25 or —S(O)(═NR 28 )R 29 ; and R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 21 , R 22 , R 25 , R 28 , R 29 ; p and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition' of the invention.

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Номер записи: 3
20-09-2012 дата публикации

Iodine radiolabelling method

Номер: US20120237444A1
Автор: Michelle Avory
Принадлежит: Individual

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are novel radioiodinated BTMs prepared using the method, as well as radiopharmaceutical compositions comprising such radioiodinated BTMs. The invention also provides radioiodinated intermediates useful in the method, as well as in vivo imaging methods using the radioiodinated BTMs.

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Номер записи: 4
13-12-2012 дата публикации

Isoxazoline derivatives as insecticides

Номер: US20120316124A1
Автор: Jérôme Yves CASSAYRE, Myriem El Qacemi, Peter Renold, Thomas Pitterna, Vladimir Bobosik
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A 1 , A 2 , A 3 , A 4 , G 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 17 , R 18 , R 19 and R 20 are as defined in claim 1 ; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.

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Номер записи: 5
10-01-2013 дата публикации

Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same

Номер: US20130011788A1
Автор: Pushkara R. Varanasi, Sen Liu
Принадлежит: International Business Machines Corp

The present invention relates to a fluorine-free photoacid generator (PAG) and a photoresist composition containing the same. The PAG is characterized by the presence of an onium cationic component and a fluorine-free fused ring heteroaromatic sulfonate anionic component containing one or more electron withdrawing substituents. The onium cationic component of the PAG is preferably a sulfonium or an iodonium cation. The photoresist composition further contains an acid sensitive imaging polymer. The photoresist composition is especially useful for forming material patterns on a semiconductor substrate using 193 nm (ArF) lithography.

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Номер записи: 6
10-01-2013 дата публикации

Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same

Номер: US20130011793A1
Автор: Pushkara R. Varanasi, Sen Liu
Принадлежит: International Business Machines Corp

The present invention relates to a fluorine-free photoacid generator (PAG) and a photoresist composition containing the same. The PAG is characterized by the presence of an onium cationic component and a fluorine-free fused ring heteroaromatic sulfonate anionic component containing one or more electron withdrawing substituents. The onium cationic component of the PAG is preferably a sulfonium or an iodonium cation. The photoresist composition further contains an acid sensitive imaging polymer. The photoresist composition is especially useful for forming material patterns on a semiconductor substrate using 193 nm (ArF) lithography.

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Номер записи: 7
21-03-2013 дата публикации

LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS

Номер: US20130072449A1
Автор: Buckman Brad O., Emayan Kumaraswamy, Nicholas John B., Seiwert Scott D.
Принадлежит: INTERMUNE, INC.

Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided. 5. The compound or pharmaceutically acceptable salt of claim 2 , wherein m=1 claim 2 , and wherein Ris hydrogen and Ris selected from the group consisting of optionally substituted phenyl claim 2 , imidazole claim 2 , pyridine claim 2 , thiazole claim 2 , and oxazole.6. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein m=1 claim 2 , and wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 2 , an optionally substituted oxetane claim 2 , an optionally substituted beta-lactam claim 2 , an optionally substituted tetrahydropyran claim 2 , an optionally substituted cyclopropyl claim 2 , an optionally substituted cyclobutyl claim 2 , an optionally substituted cyclopentyl claim 2 , or an optionally substituted cyclohexyl.711.-. (canceled)13. (canceled)15. (canceled)18. (canceled)20. (canceled)21. (canceled)22. (canceled)24. The compound or salt thereof of claim 1 , selected from compounds of Table 1 claim 1 , and pharmaceutically acceptable salts thereof.25. The compound or salt thereof of claim 1 , selected from compounds of Table 2 claim 1 , and pharmaceutically acceptable salts thereof.26. The compound or salt thereof of claim 1 , selected from compounds of Table 3 claim 1 , and pharmaceutically acceptable salts thereof.28. The compound or pharmaceutically acceptable salt thereof of claim 27 , wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 27 , an optionally substituted oxetane claim 27 , an optionally substituted beta-lactam claim 27 , an optionally substituted tetrahydropyran claim 27 , an optionally ...

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Номер записи: 8
28-03-2013 дата публикации

Benzisoxazoles and Azabenzisoxazoles as MGLUR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction

Номер: US20130079366A1
Автор: Conn P. Jeffrey, Engers Darren W., Hopkins Corey R., Lindsley Craig W., Niswender Colleen M.
Принадлежит: VANDERBILT UNIVERSITY

Benzisoxazole and azabenzisoxazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction. 2. The method of claim 1 , wherein the mammal is a human.3. The method of claim 1 , wherein the dysfunction is Parkinson's disease.4. The method of claim 1 , wherein the dysfunction is schizophrenia claim 1 , psychosis claim 1 , “schizophrenia-spectrum” disorder claim 1 , depression claim 1 , bipolar disorder claim 1 , cognitive disorder claim 1 , delirium claim 1 , amnestic disorder claim 1 , anxiety disorder claim 1 , attention disorder claim 1 , obesity claim 1 , eating disorder claim 1 , or NMDA receptor-related disorder.5. The method of claim 1 , wherein the dysfunction is Parkinson's disease; anxiety; motor effects after alcohol consumption; neurogenic fate commitment and neuronal survival; epilepsy; or certain cancers claim 1 , for example claim 1 , medulloblastoma claim 1 , inflammation (for example claim 1 , multiple sclerosis) and metabolic disorders (for example claim 1 , diabetes) and taste enhancing associated with glutamatergic dysfunction and diseases in which mGluR4 receptor is involved.6. The method of claim 1 , wherein the mammal has been diagnosed with the dysfunction prior to the administering step.7. The method of claim 1 , further comprising the step of identifying a mammal having a need for treatment of the dysfunction.8. The method of claim 1 , wherein the endogenous ligand for mGluR4 potentiation is glutamate claim 1 , L-SOP claim 1 , or a neurotransmitter.925-. (canceled)28. The compound of claim 26 , wherein one X is CRwith Rbeing H claim 26 , and the other X is N.29. The compound of claim 26 , wherein Y is O ...

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Номер записи: 9
18-04-2013 дата публикации

Substituted carbamoylmethylamino acetic acid derivatives as novel NEP inhibitors

Номер: US20130096168A1
Автор: IWAKI Yuki, KAWANAMI Toshio, KSANDER Gary Michael, MOGI Muneto
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I; 119-. (canceled)22. The compound according to wherein s is 0; or a pharmaceutically acceptable salt thereof.23. The compounds according to wherein{'sup': '2', 'Xis Cl, or a pharmaceutically acceptable salt thereof.'}24. The compound according to selected from:(S)-2-[(S)-2-(3′-chloro-biphenyl-4-yl)-1-(1H-tetrazol-5-ylcarbamoyl)-ethylamino]-propionic acid ethyl ester;(S)-2-[(S)-2-(3′-chloro-biphenyl-4-yl)-1-(1H-tetrazol-5-ylcarbamoyl)-ethylamino]-propionic acid; and(S)-2-[(S)-2-(3′-Chloro-biphenyl-4-yl)-1-(3-hydroxy-isoxazol-5-ylcarbamoyl)-ethylamino]-propionic acid; or a pharmaceutically acceptable salt thereof.25. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.26. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.27. A combination comprising: a compound according to claim 20 , or a pharmaceutically acceptable salt thereof and one or more therapeutically active agents selected from HMG-Co-A reductase inhibitor claim 20 , an anigiotensin receptor blocker claim 20 , angiotensin converting enzyme Inhibitor claim 20 , a calcium channel blocker claim 20 , an endothelin antagonist claim 20 , a renin inhibitor claim 20 , a diuretic claim 20 , an ApoA-I mimic claim 20 , an anti-diabetic agent claim 20 , an obesity-reducing agent claim 20 , an aldosterone receptor blocker claim 20 , an endothelin receptor blocker claim 20 , an aldosterone synthase inhibitors claim 20 , a CETP inhibitor and a phophodiesterase type 5 (PDE5) inhibitor.28. A combination comprising: a compound according to or a pharmaceutically acceptable salt thereof and one or more therapeutically active agents selected from HMG-Co-A reductase inhibitor claim 24 , an anigiotensin receptor blocker claim 24 , angiotensin converting ...

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Номер записи: 10
25-04-2013 дата публикации

Process for Producing Imine Compounds for Combating Invertebrate Pests

Номер: US20130102462A1
Автор: Bandur Nina Gertrud, Deshmukh Prashant, Dickhaut Joachim, Kaiser Florian, Koerber Karsten, LANGEWALD Juergen, Narine Arun, REIN Christian, Schmidt-Leithoff Joachim, VON DEYN Wolfgang
Принадлежит: BASF SE

The present invention relates to a process for producing aromatic carbonyl compounds of formula I and aromatic imine compounds of formula III 145-. (canceled)48. The process as claimed in claim 46 , where Z is Br claim 46 , I or —OSO—R.49. The process as claimed in claim 48 , where Z is Br claim 48 , I or —OSO—R claim 48 , where Ris selected from the group consisting of CH claim 48 , CFand 4-methylphenyl claim 48 , and is preferably Br.50. The process as claimed in claim 46 , where carbon monoxide and hydrogen are used in a molar ratio of from 20:1 to 1:10.51. The process as claimed in claim 50 , where carbon monoxide and hydrogen are used in a molar ratio of from 2:1 to 1:2 and are preferably used in the form of synthesis gas.52. The process as claimed in claim 46 , where the catalyst is a group VIII metal complex.53. The process as claimed in claim 52 , where the metal is selected from the group consisting of Pd claim 52 , Pt claim 52 , Ni claim 52 , Rh claim 52 , Ir and Ru and is preferably Pd.54. The process as claimed in claim 46 , where the catalyst contains a monodentate and/or bidentate ligand.55. The process as claimed in claim 46 , where the catalyst contains a phosphorus-containing ligand.56. The process as claimed in claim 55 , where the phosphorus-containing ligand is a monodentate ligand selected from the group consisting of phosphorus compounds of formula PRRR claim 55 , where{'sup': a', 'b', 'c', 'd', 'e, 'sub': 3', '12', '3', '12', '3', '10', '3', '10', '5', '18', '5', '18, 'claim-text': or', {'sup': a', 'b', 'e, 'sub': 3', '10, 'Rand Rtogether with the phosphorus atom to which they are bound form a 5-, 6-, 7- or 8-membered heterocyclic ring which may be additionally fused to one, two or three C-C-cycloalkyl, heterocyclyl, aryl or hetaryl groups, where the heterocyclic ring and, if present, the fused-on groups may each independently carry one, two, three or four substituents R;'}, {'sup': d', '1', '2', '1', '2', '3+', '−, 'sub': 3', '10', '3', '10', ...

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Номер записи: 11
23-05-2013 дата публикации

PEST CONTROL COMPOSITION

Номер: US20130131115A1
Автор: Ikari Kaori
Принадлежит: Sumitomo Chemical Company, Limited

A pest control composition comprising a hydrazide compound shown by formula (1) below (in the formula, G, M, Q, Q, Q, Q, R, R, R, Rand m have the same meanings described in the specification) and etofenprox and a method for controlling pests whereby an effective dose of the hydrazide compound represented by formula (1) and etofenprox is applied to a pest or a pest habitat. 2. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , G is a group shown by G-1 claim 1 , Yis an oxygen atom claim 1 , Ris a trifluoromethyl group claim 1 , each of Q claim 1 , Q claim 1 , and Qis a CH group claim 1 , Qis a CRgroup claim 1 , Ris the group defined above claim 1 , (R)is a substituent at 3- and 5-positions claim 1 , m is 2 claim 1 , and Ris a chlorine atom.3. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a hydrogen atom.4. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a hydrogen atom or a methyl group.5. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a halogen atom.6. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a chlorine atom.7. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a C2 to C6 alkyl group claim 1 , a C1 to C6 haloalkyl group claim 1 , a C3 to C6 cycloalkyl group claim 1 , or a (C1 to C6 alkoxy) C1 to C6 alkyl group.8. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a C2 to C6 alkyl group.9. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a C1 to C6 haloalkyl group.10. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a C3 to C6 cycloalkyl group.11. The pest control composition according to claim 1 , wherein in the formula (1) claim 1 , Ris a (C1 to C6 alkoxy) C1 to C6 alkyl ...

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Номер записи: 12
30-05-2013 дата публикации

CRYSTALLINE FORM OF 4- [5 - [3 -CHLORO-5 - (TRIFLUOROMETHYL) PHENYL] -4, 5 - DIHYDRO - 5 - (TRIFLUOROMETHYL) -3 - ISOXAZOLYL] -N- [2-0X0-2- [ ( 2, 2, 2 - TRIFLUOROETHYL) AMINO] ETHYL] -1- NAPH-THALENECARBOXAMIDE

Номер: US20130137735A1
Автор: Currie Martin James
Принадлежит: E.I. Du Pont De Nemours and Company

Disclosed is a solid form of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide (Compound 1). Also disclosed are compositions containing a solid form of Compound 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a solid form of Compound 1 or a composition containing a solid form of Compound 1. 2. A composition comprising the polymorph Form B of and at least one additional component selected from the group consisting of surfactants claim 1 , solid diluents and liquid diluents claim 1 , said composition optionally further comprising at least one additional biologically active compound or agent.3. A composition for protecting an animal from an invertebrate parasitic pest comprising a parasiticidally effective amount of the polymorph Form B of and at least one carrier.4. The composition of in a dosage form for oral administration.5. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of the polymorph Form B of .6. The method of wherein the environment is a plant.7. The method of wherein the environment is an animal. This invention relates to a solid form of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide.The solid state of chemical compounds can be amorphous (i.e. no long-range order in the positions of atoms) or crystalline (i.e. atoms arranged in an orderly repeating pattern). While only one crystal form is known for the solid state of many compounds, polymorphs have been discovered for some compounds. The term “polymorph” refers to a particular crystal form (i.e. structure of crystal lattice) of a chemical compound that can exist in more than one crystal ...

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Номер записи: 13
30-05-2013 дата публикации

Nitrogen-containing heterocyclic compound and pest control agent

Номер: US20130137876A1
Автор: Jyun Iwata, Masahiro Kawaguchi
Принадлежит: Nippon Soda Co Ltd

The present invention offers compounds or their salts expressed by formula (I) (in the formula, X indicates an alkyl group, or the like; Y indicates an alkyl group; Z indicates a respectively independent nitro group, or the like; n indicates any integer from 0 to 3; A indicates carbon atom, or the like, and hydrogen atom is bonded thereto in the case where the carbon atom is not substituted with Z; D indicates oxygen atom, or the like; W indicates hydrogen atom, or the like; R 1 and R 2 indicate respectively independent hydrogen atoms, or the like; R 1 and R 2 may be bonded, and may form a heterocycle together with the nitrogen atom between R 1 and R 2 ).

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Номер записи: 14
06-06-2013 дата публикации

PRODUCTION METHOD OF ISOXAZOLINE-SUBSTITUTED BENZOIC ACID AMIDE COMPOUND

Номер: US20130144066A1
Автор: FUKUYA Shunsuke, KOUSAKA Hiroyuki, MIZUKOSHI Takashi, MORIYAMA Yuji, YAOSAKA Manabu
Принадлежит: NISSAN CHEMICAL INDUSTRIES, LTD.

A production method of an isoxazoline-substituted benzoic acid amide compound of Formula (1) where X is a halogen atom, Chaloalkyl, etc., Y is a halogen atom, Calkyl, etc., Ris a Chaloalkyl, etc., Rand Rindependently of each other are a hydrogen atom, Calkyl, etc., Ris Calkyl, Chaloalkyl, etc., Ris a hydrogen atom, Calkyl, etc., m is an integer of 0 to 5, n is an integer of 0 to 4, including: reacting an isoxazoline-substituted benzene compound of Formula (3) where X, Y, R, m, and n are the same as defined above, L is a chlorine atom, a bromine atom, —C(O)OH, —C(O)J, etc., J is a halogen atom, with a 2-aminoacetic acid amide compound of Formula (2) where R, R, R, and Rare the same as defined above, or a salt thereof; crystal forms and the production method thereof. 2. The crystal of claim 1 , wherein the crystal is a I-form crystal in which a diffraction angle (2θ) in a powder X-ray diffraction spectrum has peaks at 4.4° claim 1 , 8.7° claim 1 , 11.1° claim 1 , 13.1° claim 1 , 14.4° claim 1 , 17.7° claim 1 , 18.1° claim 1 , 18.8° claim 1 , 19.4° claim 1 , 21.2° claim 1 , 21.9° claim 1 , 22.3° claim 1 , 23.0° claim 1 , 23.9° claim 1 , 26.3° claim 1 , and 27.3°.3. The crystal of claim 2 , further comprising peaks at 14.8° claim 2 , 16.3° claim 2 , 16.9° claim 2 , 17.4° claim 2 , 24.5° claim 2 , and 25.0°.4. The crystal of claim 1 , wherein the crystal is a II-form crystal in which a diffraction angle (2θ) in a powder X-ray diffraction spectrum has peaks at 10.2° claim 1 , 12.3° claim 1 , 14.7° claim 1 , 15.9° claim 1 , 18.4° claim 1 , 20.1° claim 1 , 21.2° claim 1 , 22.0° claim 1 , 22.8° claim 1 , 24.6° claim 1 , and 26.6°.5. The crystal of claim 1 , wherein the crystal is a III-form crystal in which a diffraction angle (2θ) in a powder X-ray diffraction spectrum has peaks at 4.3° claim 1 , 8.7° claim 1 , 11.1° claim 1 , 14.4° claim 1 , 17.7° claim 1 , 18.7° claim 1 , 19.4° claim 1 , 19.9° claim 1 , 21.2° claim 1 , 21.8° claim 1 , 22.3° claim 1 , 23.8° claim 1 , and ...

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Номер записи: 15
27-06-2013 дата публикации

Insecticidal compounds

Номер: US20130165490A1
Автор: Jérôme Yves CASSAYRE, Myriem El Qacemi, Peter Renold, Thomas Pitterna
Принадлежит: SYNGENTA CROP PROTECTION LLC

A compound of formula (I): wherein A 1 , A 2 , A 3 , A 4 , G 1 , G 2 , R 1 , R 2 , R 3 and R 4 are as defined in claim 1 ; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode and mollusc pests.

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Номер записи: 16
04-07-2013 дата публикации

NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS

Номер: US20130172363A1
Автор: Chambon Sandrine, CHANTALAT Laurent, Clary Laurence, Pascal Jean-Claude, ROSIGNOLI Carine, ROYE Olivier, Schuppli Marlene
Принадлежит: GALDERMA RESEARCH & DEVELOPMENT

Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions. 1. A compound having the name (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide.2. A composition comprising the compound as claimed in claim 1 , and an acceptable carrier.3. A pharmaceutical composition comprising the compound claim 1 , as claimed in and a pharmaceutically acceptable carrier.5. The compound as claimed in claim 4 , in which{'sub': '4', 'Ris an alkyl radical containing 1 to 4 carbon atoms; and'}{'sub': '3', 'Ris a polycyclic aromatic heterocylic radical containing the heteroatom N;'}and salts thereof, and enantiomers thereof.6. The compound as claimed in claim 4 , wherein the compound is (S)—N-hydroxy-3-[4-(2-methylquinolin-4-ylmethoxy)benzenesulfonylamino]-2-[4-(propane-2-sulfonyl)piperazin-1-yl]propionamide claim 4 , and salts thereof claim 4 , and enantiomers thereof.7. A composition comprising the compound as claimed in claim 4 , or a salt thereof claim 4 , or an enantiomer thereof claim 4 , and an acceptable carrier.8. A pharmaceutical composition comprising the compound as claimed in claim 4 , a salt thereof claim 4 , or an enantiomer thereof claim 4 , and a pharmaceutically acceptable carrier.9. A method of treating an inflammatory skin disease claim 3 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 3 , to a subject in need thereof.10. The method of claim 9 , wherein the inflammatory skin disease is psoriasis or atopic dermatitis.11. A method of treating an inflammatory skin disease claim 8 , wherein the method comprises administering the pharmaceutical composition as claimed in claim 8 , to a subject in need thereof.12. The method of claim 11 , wherein the inflammatory skin ...

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Номер записи: 17
04-07-2013 дата публикации

CHIRAL SYNTHESIS OF ISOXAZOLINES, ISOXAZOLINE COMPOUNDS, AND USES THEREOF

Номер: US20130172553A1
Автор: Pruitt James, Sielecki-Dzurdz Thais
Принадлежит: CPSI STOCKHOLDER TRUST

Processes for the chiral syntheses of isoxazolines and intermediates are described. Compounds prepared thereby, and methods of using the compounds are also described. 6. The process of claim 5 , wherein the separating is carried out by a process comprising recrystallization claim 5 , chromatography claim 5 , or a combination thereof.9. The process of claim 8 , wherein the separating is carried out by a process comprising recrystallization claim 8 , chromatography claim 8 , or a combination thereof.11. The process of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently hydrogen claim 1 , an alkyl group claim 1 , a cycloalkyl group claim 1 , an alkenyl group claim 1 , an alkynyl group claim 1 , an oxo group claim 1 , an aryl group claim 1 , a heterocyclic group claim 1 , a heteroaryl group claim 1 , an aralkyl group claim 1 , a heteroaralkyl group claim 1 , an amino group claim 1 , an alkylamino group claim 1 , a dialkylamino group claim 1 , an amidine group claim 1 , an amide group claim 1 , an alkylcarbonyl group claim 1 , an alkoxycarbonyl group claim 1 , an alkylaminocarbonyl group claim 1 , a dialkylamino carbonyl group claim 1 , an arylcarbonyl group claim 1 , an aryloxycarbonyl group claim 1 , an alkylsulfonyl group claim 1 , an arylsulfonyl group claim 1 , perhaloalkyl group claim 1 , a perhalocycloalkyl group claim 1 , a perhaloalkenyl group claim 1 , a perhaloalkynyl group claim 1 , a perhaloaryl group claim 1 , or a perhaloaralkyl group; wherein Rand Rmay be taken together to form a cyclic group; wherein Rand Rmay be taken together to form a cyclic group; wherein each group may be optionally and independently straight or branched; wherein each group may be optionally and independently substituted by one or more independent substituents; and wherein one or more than one atom in each group may be optionally and independently replaced with one or more independent heteroatoms.12. The process of claim 1 , wherein R claim ...

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Номер записи: 18
11-07-2013 дата публикации

ISOXAZOLE TREATMENTS FOR DIABETES

Номер: US20130178506A1
Автор: AGUILAR Hector, COBB Melanie, DIOUM Elhadji, FRANTZ Doug, Schneider Jay
Принадлежит: The Board of Regents of the University of Texas System

The present invention relates to compounds and methods for inducing synthesis and secretion of insulin from pancreatic beta cells. The methods may take place in vitro, ex vivo such as in isolates from adult mammalian tissue, or in vivo. Compounds and methods described herein may find use in the treatment of diabetes. 2. The method of claim 1 , wherein Ris a substituent of formula (A).3. The method of claim 2 , wherein G is S.4. The method of claim 3 , wherein R claim 3 , Ror Ris hydrogen.5. The method of claim 4 , wherein R claim 4 , Rand Rare each hydrogen.6. The method according to claim 1 , wherein Ris hydrogen.7. The method according to claim 1 , wherein Ris —NRR.8. The method of claim 7 , wherein Ror Ris cyclopropyl claim 7 , cyclobutyl claim 7 , cyclopentyl or cyclohexyl.9. The method of claim 8 , wherein Ror Ris cyclopropyl.11. The method of claim 10 , wherein G is S.12. The method of claim 11 , wherein R claim 11 , Ror Ris hydrogen.13. The method of claim 12 , wherein R claim 12 , Rand Rare each hydrogen.14. The method according to claim 1 , wherein Ris hydrogen.15. The method according to claim 1 , wherein Ris cyclopropyl or an aliphaticalcohol or an aliphaticpolyol.17. The method according to claim 1 , wherein said cell is located in an animal subject.18. The method according to claim 1 , wherein said cell is contacted ex vivo.2036-. (canceled)3852-. (canceled)5470-. (canceled)72. (canceled) This application claims benefit of priority to U.S. Provisional Application Ser. Nos. 61/563,419, filed Nov. 23, 2011, and 61/566,056, filed Dec. 2, 2011, the entire contents of both applications being incorporated by reference herein.The invention was made with government support under NIH P60 DK079626, R37 DK34128 and R01 DK55310 awarded by the National Institutes of Health. The government has certain rights in the invention.1. Field of the InventionThe present invention relates generally to the fields of cell biology, developmental biology and medicine. More ...

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Номер записи: 19
18-07-2013 дата публикации

N-((3-BENZYL)-2,2-(BIS-PHENYL)-PROPAN-1-AMINE DERIVATIVES AS CETP INHIBITORS FOR THE TREATMENT OF ATHEROSCLEROSIS AND CARDIOVASCULAR DISEASES

Номер: US20130184279A1
Автор: Johnson James A., Salvati Mark E., Xu Ningning
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

Compounds of formula Ia and Ib 2. The compound of claim 1 , wherein A is:{'sub': 1', '6', '40', '46', '1', '6', '29', '30', '40', '40', '40', '40', '40', '40', '1', '6, "(a) phenyl, which is substituted with one or more substituents selected from the group consisting of: 1) halo, 2) (C-C)-alkyl, which may be optionally substituted with one or more R's, 3) —OR, 4) (C-C)-alkylthio, 5) cyano, 6) nitro, 7) —NRR, 8) aryl, which may be optionally substituted with one or more R's, 9) arylalkyl, which may be optionally substituted with one or more R's, 10) heteroaryl, which may be optionally substituted with one or more R's, 11) heteroarylalkyl, which may be optionally substituted with one or more R's, 12) heterocyclyl, which may be optionally substituted with one or more R's, 13) heterocyclylalkyl, which may be optionally substituted with one or more R's, 14) halo(C-C)alkyl,"}{'sub': 46', 'p', '46', '2', '46', '46, '15) —COR, 16) ═O, 17) —S(O)R, 18) —SONHR, 19) —COOR,'}{'sub': 46', '46', '46', '2', '6', '40', '2', '6', '40', '46', '46', '46', '46', '40, "20) —NHC(CN)NHR, 21) —CONRR, 22) (C-C)-alkynyl, which may be optionally substituted with one or more R's, 23) (C-C)-alkenyl, which may be optionally substituted with one or more R's, 24) —OCOR, 25) —OCOOR, or 26) —OCONRR; or any two adjacent substituents may join together to form a 4- to 8-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S and be optionally substituted with one or more R's;"}{'sub': 1', '6', '40', '46', '1', '6', '29', '30', '40', '40', '40', '40', '40', '40', '1', '6, "(b) heteroaryl, which is substituted with one or more substituents selected from the group consisting of: 1) halo, 2) (C-C)-alkyl, which may be optionally substituted with one or more R's, 3) —OR, 4) (C-C)-alkylthio, 5) cyano, 6) nitro, 7) —NRR, 8) aryl, which may be optionally substituted with one or more R's, 9) arylalkyl, which may be optionally substituted with one or more R's, 10) heteroaryl, which ...

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Номер записи: 20
25-07-2013 дата публикации

MODIFIED MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS

Номер: US20130190369A1
Автор: Al-Abed Yousef
Принадлежит: The Feinstein Institute For Medical Research

Provided are various compounds of Formula I (I). Also provided are various compounds of Formula II (II). Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor. 136-. (canceled)38. The compound of claim 37 , wherein R2 is F.41. A pharmaceutical composition comprising the compound of in a pharmaceutically acceptable excipient. This application claims the benefit of U.S. Provisional Application No. 60/785,898, filed Mar. 24, 2006.(1) Field of the InventionThe present invention relates to cytokine inhibitors. More specifically, the present invention identifies and characterizes several inhibitors of macrophage migration inhibitory factor.(2) Description of the Related ArtMacrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, critically involved in the pathogenesis of inflammatory disorders (Calandra and Roger, 2003; Riedemann et al., 2003). Recent studies have clearly defined MN as a critical factor in the pathophysiology of sepsis (Al-Abed et al., 2005). Abolition of MIF activity during sepsis by antibodies or ISO-1 improves cardio-circulatory efficiency and prevents the lethality associated with sepsis (Al-Abed et al., 2005; Lin et al., 2005). The specific inhibitor ISO-1, an isoxazoline, was designed to fit into the hydrophobic active site of MIF, an interaction confirmed by the crystal structure of the MIF complex with ISO-1 () (Lubetsky et al., 2002). Administration of ISO-1 in a clinically relevant model of sepsis confers moderate protection (80% versus 40% control). These results identify ISO-1 as the first small ...

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Номер записи: 21
08-08-2013 дата публикации

PARASITICIDAL ORAL VETERINARY COMPOSITIONS COMPRISING SYSTEMICALLY-ACTING ACTIVE AGENTS, METHODS AND USES THEREOF

Номер: US20130203692A1
Автор: Cady Susan Mancini, Cheifetz Peter, Galeska Izabela, Larsen Diane, Soll Mark David
Принадлежит: MERIAL LIMITED

This invention relates to oral veterinary compositions for combating ectoparasites and endoparasites in animals, comprising at least one systemically-acting active agent in combination with a pharmaceutically acceptable carrier. This invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the compositions of the invention to the animal in need thereof. 2. The soft chewable veterinary composition of claim 1 , wherein:W is O;{'sup': '4', 'sub': 1', '6, 'Ris H or C-Calkyl;'}{'sup': '5', 'sub': 2', '2', '3, 'Ris —CHC(O)NHCHCF;'}{'sup': 1', '2', '3', '4', '5', '6, 'each of A, A, A, A, Aand Ais CH;'}{'sup': 1', '6, 'sub': 1', '6, 'Ris C-Calkyl each optionally substituted with one or more substituents independently selected from R;'}{'sup': '6', 'sub': 1', '6, 'Ris halogen or C-Calkyl; and'}{'sup': 1', '2', '3, 'sub': 1', '6', '1', '6', '1', '6, 'B, B, and Bare independently CH, C-halogen, C—C-Calkyl, C—C-Chaloalkyl, or C—C-Calkoxy.'}3. The soft chewable veterinary composition of claim 1 , wherein:W is O;{'sup': '1', 'sub': '3', 'Ris CF;'}{'sup': '2', 'Bis CH;'}{'sup': '1', 'Bis C—Cl;'}{'sup': '3', 'sub': '3', 'Bis C—CF;'}{'sup': 1', '2', '3', '4', '5', '6, 'each of A, A, A, A, Aand Ais CH;'}{'sup': '4', 'Ris H; and'}{'sup': '5', 'sub': 2', '2', '3, 'Ris —CHC(O)NHCHCF.'}4. The soft chewable veterinary composition of claim 1 , wherein the carrier comprises one or more fillers claim 1 , at least one flavoring agent claim 1 , at least one binder claim 1 , one or more solvents claim 1 , one or more surfactants claim 1 , at least one humectant claim 1 , optionally an antioxidant claim 1 , and optionally a preservative.5. The soft chewable veterinary composition of claim 4 , wherein the one or more fillers is soy protein fines claim 4 , corn starch claim 4 , or a mixture thereof.6. The soft chewable veterinary composition of claim 4 , wherein the binder is ...

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Номер записи: 22
08-08-2013 дата публикации

ACYLSULFONAMIDES AND PROCESSES FOR PRODUCING THE SAME

Номер: US20130203709A1
Автор: Doi Kenichiro, du Boulay Courtney, GUIDA WAYNE, Iyamu Iredia D., Kulkarni Sameer, Manetsch Roman, Santiago Daniel, Wang Hong-Gang
Принадлежит:

The present disclosure relates to acylsulfonamides and processes for their preparation. The processes involve a target-guided synthesis approach, whereby a thioacid and a sulfonyl azide are reacted in the presence of a biological target protein, a Bcl-2 family protein, to form the acylsulfonamide. 2. The compound of wherein the Bcl-2 family protein is Mcl-1.3. A composition comprising a Bcl-2 claim 1 , Bcl-XL claim 1 , and/or Bcl-w inhibitor; and an Mcl-1 and/or A1/Bfl-1 inhibitor claim 1 , wherein at least one inhibitor is the compound of .4. A method of treating or preventing cancer claim 1 , the method comprising administering the compound of .5. A compound comprising a first fragment selected from SZ1 to SZ31 and a second fragment selected from TA1 to TA15.6. The compound of having the formula selected from SZ31TA2 claim 5 , SZ15TA2 claim 5 , and SZ17TA2.7. A method of screening for an inhibitor claim 5 , as described herein.8. The method of comprising contacting a fragment library with a Bcl-2 family protein.9. The method of wherein the Bcl-2 family protein is selected from one or more of Bcl-2 claim 8 , Bcl-XL claim 8 , Bcl-w claim 8 , Mcl-1 claim 8 , and A1/Bfl-1.10. The method of wherein the Bcl-2 family protein is Mcl-1.11. The compound of claim 1 , wherein Zis aryl claim 1 , substituted aryl claim 1 , or heteroaryl.13. The compound of claim 1 , wherein Z claim 1 , Z claim 1 , Z claim 1 , Z claim 1 , and Zare independently hydrogen claim 1 , hydrocarbyl claim 1 , substituted hydrocarbyl claim 1 , amino claim 1 , alkoxy claim 1 , nitro claim 1 , or trihalomethoxy.15. The compound of claim 1 , wherein Zis substituted or unsubstituted furyl claim 1 , thienyl claim 1 , pyridyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , imidazolyl claim 1 , pyridyl claim 1 , pyrimidyl claim 1 , purinyl claim 1 , triazolyl claim 1 , or thiazolyl.16. The compound of claim 1 , wherein Zis substituted or unsubstituted morpholino claim 1 , pyran claim 1 , tetrahydropyran claim ...

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Номер записи: 23
22-08-2013 дата публикации

Naphthalene Isoxazoline Invertebrate Pest Control Agents

Номер: US20130217736A1
Автор: Lahm George Philip, Long Jeffrey Keith, Xu Ming
Принадлежит:

Disclosed are compounds of Formula 1, 2. A compound of wherein{'sup': '4', 'Ris H; and'}{'sup': '5', 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '2', '7', '2', '7, 'Ris C-Calkyl substituted with one substituent independently selected from C-Calkylthio, C-Calkylsulfinyl, C-Calkylsulfonyl, C-Calkylaminocarbonyl and C-Chaloalkylaminocarbonyl.'}3. A compound of wherein{'sup': '1', 'sub': '3', 'Ris Cl, Br or CF;'}{'sup': '2', 'Ris H; and'}{'sup': '3', 'sub': '3', 'Ris H, F, Cl, Br or CF.'}4. A compound of wherein{'sup': '1', 'sub': '3', 'Ris CF.'}5. A compound of wherein{'sup': '3', 'sub': '3', 'Ris Cl, Br or CF.'}6. A compound of wherein{'sup': '5', 'sub': 1', '6', '2', '7', '3', '7, 'Ris C-Calkyl substituted with one C-Calkylaminocarbonyl or C-Chaloalkylaminocarbonyl.'}7. A compound of that is selected from the group consisting of4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylamino)-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(ethylamino)-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-[(1-methylethyl)amino]-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide,4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylamino)-2-oxoethyl]-1- ...

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Номер записи: 24
22-08-2013 дата публикации

SYNTHESIS OF ENONE INTERMEDIATE

Номер: US20130217886A1
Автор: Brubaker Jason D., Myers Andrew G.
Принадлежит: President and Fellows of Harvard College

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate. 1102-. (canceled)104. The method of claim 103 , wherein Ris hydrogen.105. The method of claim 103 , wherein Rand Rare hydrogen.106. The method of claim 103 , wherein Ris —N(R).107. The method of claim 106 , wherein Ris —N(CH).108. The method of claim 103 , wherein n is not 0 claim 103 , and at least one instance of Ris halogen.109. The method of claim 103 , wherein n is not 0 claim 103 , and at least one instance of Ris —NHC(O)R.110. The method of claim 103 , wherein n is not 0 claim 103 , and at least one instance of Ris —OR.111. The method of claim 103 , wherein n is not 0 claim 103 , and at least one instance of Ris cyclic or acyclic claim 103 , substituted or unsubstituted claim 103 , branched or unbranched heteroaliphatic.112. The method of claim 103 , wherein deprotecting the enolate of the ketone (VII) under suitable conditions comprises use of BBror BCl.114. The method of claim 113 , wherein the lipase is Amano Lipase AK.115. The method of claim 113 , wherein the suitable conditions comprise the presence of vinyl acetate.117. The method of claim 116 , wherein the vinyl reagent is a metal vinyl reagent. The present application is a continuation of and claims priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 13/043,742, filed Mar. 9, 2011, which is a continuation of and claims priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 12/833,628, filed Jul. ...

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Номер записи: 25
29-08-2013 дата публикации

COMPOUNDS, COMPOSITIONS, PROCESSES OF MAKING, AND METHODS OF USE RELATED TO INHIBITING MACROPHAGE MIGRATION INHIBITORY FACTOR

Номер: US20130225586A1
Автор: De La Cruz Vidal F., Sielecki-Dzurdz Thais
Принадлежит: CPSI STOCKHOLDER TRUST

The present invention provides a compound having Formula I or II: 2. The compound of claim 1 , which is a compound having Formula I claim 1 , a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable prodrug thereof.3. The compound of claim 1 , which is a compound having Formula II claim 1 , a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable prodrug thereof.7. The compound of claim 1 , wherein B is oxygen.8. The compound of claim 1 , wherein R and Rare each independently selected from the group consisting of hydrogen claim 1 , (C-C)cycloalkyl claim 1 , (C-C)alkoxy claim 1 , (C-C)alkyl claim 1 , phenyl claim 1 , (C-C)heteroaryl claim 1 , (C-C)heterocyclic and (C-C)cycloalkyl; wherein each of the aforesaid (C-C)alkyl claim 1 , phenyl claim 1 , (C-C)heteroaryl claim 1 , (C-C)heterocyclic and (C-C)cycloalkyl substituents may optionally be substituted by one to four moieties independently selected from the group consisting of halo claim 1 , (C-C)alkyl claim 1 , (C-C)alkenyl claim 1 , (C-C)alkynyl claim 1 , perhalo(C-C)alkyl claim 1 , phenyl claim 1 , (C-C)heteroaryl claim 1 , (C-C)heterocyclic claim 1 , (C-C)cycloalkyl claim 1 , hydroxy claim 1 , (C-C)alkoxy claim 1 , perhalo(C-C)alkoxy claim 1 , phenoxy claim 1 , (C-C)heteroaryl-O— claim 1 , (C-C)heterocyclic-O— claim 1 , (C-C)cycloalkyl-O— claim 1 , (C-C)alkyl-S—; wherein two independently chosen Ralkyl-containing groups may be taken together with any nitrogen atom to which they are attached to form a three to forty membered claim 1 , cyclic heterocyclic or heteroaryl ring.9. The compound of claim 1 , wherein R and Rare each independently selected from the group consisting of hydrogen claim 1 , (C-C)cycloalkyl claim 1 , (C-C)alkoxy claim 1 , (C-C)alkyl claim 1 , phenyl claim 1 , (C-C)heteroaryl claim 1 , (C-C)heterocyclic and (C-C)cycloalkyl; wherein each of the aforesaid (C-C)alkyl claim 1 , phenyl claim 1 , (C-C)heteroaryl claim 1 , (C-C)heterocyclic and (C-C)cycloalkyl ...

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Номер записи: 26
29-08-2013 дата публикации

Method for preparing substituted isoxazoline compounds and their precursors 4-chloro, 4-bromo- or 4-iodobenzaldehyde oximes

Номер: US20130225826A1
Автор: Kaiser Florian, Koerber Karsten, Kordes Markus, Rack Michael, VON DEYN Wolfgang
Принадлежит: BASF SE

The present invention relates to a method for preparing 4-chloro-, 4-bromo- or 4-iodobenzaldehyde oximes and phenyl-substituted isoxazoline compounds prepared from these oximes. 129-. (canceled)32. The method as claimed in claim 30 , where step (ii) is carried out at a pH of at least 5.1.33. The method as claimed in claim 32 , where step (ii) is carried out at a pH of 5.1 to 14.34. The method as claimed in claim 30 , where step (ii) is carried out in the presence of a Cu(I) salt.35. The method as claimed in claim 34 , where the Cu(I) salt is generated in situ by carrying out step (ii) in the presence of a Cu(II) salt and a reduction agent.36. The method as claimed in claim 35 , where the reduction agent is selected from the group consisting of sulfite salts claim 35 , dithionite salts claim 35 , thiosulfate salts claim 35 , meta-bisulfite salts claim 35 , hydroxymethanesulfinate salts claim 35 , SnCl claim 35 , Zn and hydrazine.37. The method as claimed in claim 30 , where in step (ii) the diazonium salt is added to a solution containing the formoxime claim 30 , a copper salt and claim 30 , if the copper salt is a Cu(II) salt claim 30 , also a reduction agent.38. The method as claimed in claim 37 , where the diazonium salt is cooled to -10 to +15° C. before being added to the solution containing the formoxime claim 37 , a copper salt and claim 37 , if the copper salt is a Cu(II) salt claim 37 , also a reduction agent.39. The method as claimed in claim 37 , where the solution containing the formoxime claim 37 , a copper salt and claim 37 , if the copper salt is a Cu(II) salt claim 37 , also a reduction agent claim 37 , is adjusted to a pH of >5 claim 37 , before the diazonium salt is added.40. The method as claimed in claim 30 , where in the course of the reaction of step (ii) the pH is controlled continuously or periodically and if necessary adjusted to a pH of >5.41. The method as claimed in claim 30 , where the adjustment of the pH is performed by using a system ...

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Номер записи: 27
05-09-2013 дата публикации

NOVEL ORGANOMETALLIC COMPLEXES WHICH EMIT IN THE RED TO GREEN SPECTRAL REGION AND THEIR USE IN OLEDS

Номер: US20130231489A1
Автор: Boerner Herbert Friedrich, LOEBL Hans-Peter, POPOVA Elena, Salbeck Josef
Принадлежит: BASF SE

Organometallic complexes which bear at least one ligand which has a unit having a triplet energy of at least 22 000 cm, a process for preparing the organometallic complexes, a mixture comprising at least one inventive organometallic complex, the use of the organometallic complexes or of the mixture in organic light-emitting diodes, the organometallic complexes preferably being used as emitter materials, and specific nitrogen- or phosphorus-substituted triphenylene derivatives and a process for their preparation. 216-. (canceled) The present invention relates to organometallic complexes which bear at least one ligand which has a unit having a triplet energy of at least 22 000 cm, to a process for preparing the organometallic complexes, to a mixture comprising at least one inventive organometallic complex, to the use of the organometallic complexes or of the mixture in organic light-emitting diodes, the organometallic complexes preferably being used as emitter materials, and to specific nitrogen- or phosphorus-substituted triphenylene derivatives and to a process for their preparation.Organic light-emitting diodes (OLEDs) exploit the property of materials to emit light when they are excited by electrical current. OLEDs are of particular interest as an alternative to cathode ray tubes and liquid-crystal displays for the production of flat visual display units and as a particularly efficient light source. Owing to the very compact design and the intrinsically low power consumption, devices comprising OLEDs are suitable especially for mobile applications, for example for applications in cellphones, laptops, digital cameras, etc.The basic principles of the way in which OLEDs function and suitable constructions (layers) of OLEDs are known to those skilled in the art and are specified, for example, in WO 2005/113704 and the literature cited therein. The light-emitting materials (emitters) used may, as well as fluorescent materials (fluorescence emitters), be phosphorescent ...

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Номер записи: 28
12-09-2013 дата публикации

COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

Номер: US20130237531A1
Автор: Ibrahim Prabha N., Shi Songyuan, Spevak Wayne, Tsai James, Wu Guoxian, Zhang Chao, Zhang Jiazhong
Принадлежит:

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of claim 2 , wherein Ris halogen.4. The compound of claim 2 , wherein Ris optionally substituted phenyl.5. The compound of claim 2 , wherein Ris phenyl optionally substituted with one or more halogen substituents.6. The compound of claim 1 , wherein Ris phenyl optionally substituted with one or more fluoro substituents.7. The compound of claim 6 , wherein Ris phenyl substituted with two fluoro substituents.8. The compound of claim 1 , wherein each Ris independently optionally substituted lower alkyl or optionally substituted heteroaryl.9. The compound of claim 8 , wherein one Ris lower alkyl and the other Ris heteroaryl substituted with one or more NHgroups.10. The compound of claim 8 , wherein one Ris lower alkyl and the other Ris pyrimidinyl substituted with one or more NHgroups.11. The compound of claim 10 , wherein one Ris t-butyl and the other Ris pyrimidinyl substituted with NH.13. The compound of claim 12 , wherein Ar is thiazolyl.14. The compound of claim 12 , wherein Ar is 4-thiazolyl.16. A pharmaceutical composition comprising: a compound of and a pharmaceutically acceptable carrier or excipient.17. A pharmaceutical composition comprising: a compound of and a pharmaceutically acceptable carrier or excipient.18. A pharmaceutical composition comprising a compound of and another therapeutic agent.19. A method for treating a subject suffering from melanoma claim 15 , thyroid cancer or colorectal cancer claim 15 , said method comprising: administering to the subject an effective amount of a compound of .20. The method of claim 19 , wherein the melanoma is melanoma having a mutation encoding a V600E amino acid substitution. This application is a continuation application of U.S. application Ser. No. 12/669,450, filed Jan ...

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Номер записи: 29
12-09-2013 дата публикации

AGONISTS OF GPR40

Номер: US20130237571A1
Автор: Angupillai Sathesh Kumar, Ansari Mohd Mudabbir, Arul George Fernanda, Arumugam Nagarajan, Bommegowda, D Shivanageshwara, George Jenson, Gudla Chandrasekhas, Jidugu Pradeep, Kottamalai Ramamoorthy, Pachiyappan Shanmugam, Ramalingam Manivannan, Ranganath Rao Jagannath Madanahalli, Rao, Y Kenchegowda
Принадлежит: Conexios Life Sciences PVT. LTD.

The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are therefore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity. 2. The compound according to claim 1 , wherein L is selected from the group consisting of —COH claim 1 , —SOH claim 1 , —PO3H claim 1 , —SONH claim 1 , —CONHSOCH claim 1 , and tetrazol-5-yl.3. The compound according to claim 1 , wherein L is —COH.442-. (canceled)43. The compound according to claim 1 , wherein Rand Rare each H.44. The compound according to claim 1 , wherein Z is CRR.45. The compound according to claim 44 , where 1 of Ror Rwhen taken together with one of Rand Rand the atoms to which they are attached forms a cyclic moiety.46. The compound according to claim 45 , wherein the cyclic moiety is a cyclopropyl group.47. The compound according to claim 43 , wherein Ris H.48. The compound according to claim 45 , wherein Ris selected from the group consisting of H claim 45 , cyano and isoxazol-3-yl.49. The compound according to claim 47 , wherein Ris selected from the group consisting of H claim 47 , cyano and isoxazol-3-yl.53. The compound according to claim 1 , wherein Y is selected from the group consisting of:(a) a bond(b) —O—(c) —S—(d) —S(═O)—{'sub': '2', '(e) —S(═O)—'}{'sup': '10', '(f) —N(R)—,'}{'sup': '10', 'sub': '2', '(g) —C(R)—,'}{'sup': '10', 'sub': '2', '(h)—C(R)O—'}{'sup': 10', '10, 'sub': '2', '(i) —C(R)N(R)—'}{'sup': '11', '(j) —C(═R)'}{'sub': '1-5', '(k) —OCalkyl-,'}{'sub': '1-5', '(l) —CalkylO—,'}{'sub': 1-5', '1-5, '(m) —CalkylOCalkyl,'}{'sup': '10', 'sub': '1-5', '(n) —N(R)Calkyl-,'}{'sub': '1-5', 'sup': '10', '(o) —CalkylN(R)—;'}{'sub': 1-5', '1-5, 'sup': '10', '(p) —CalkylN(R)Calkyl-,'}{'sup': '10', '(q) —N(R)CO—,'}{'sup': '10', 'sub': '1-5', ...

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Номер записи: 30
19-09-2013 дата публикации

INDAZOLE, BENZISOXAZOLE, AND BENZISOTHIAZOLE KINASE INHIBITORS

Номер: US20130245015A1
Автор: Dai Yujia, Davidsen Steven K., Ericsson Anna M., Hartandi Kresna, Ji Zhiqin, Michaelides Michael R.
Принадлежит:

Compounds having the formula 3. The compound of wherein X is O.4. The compound of wherein X is NR.5. The compound of wherein L is CHC(O)NR.6. The compound of wherein L is (CH)N(R)C(O)N(R)(CH).7. The compound of wherein X is O and L is (CH)N(R)C(O)N(R)(CH).8. The compound of selected from the group consisting ofN-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-methylphenyl)urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-methylphenyl)urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-[3-(trifluoromethyl)phenyl]urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(3-chlorophenyl)urea;N-[4-(3-amino-7-methoxy-1,2-benzisoxazol-4-yl)phenyl]-N′-(2-fluoro-5-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-[3-(trifluoromethyl)phenyl]urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-chlorophenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(2-fluoro-5-methylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3,5-dimethylphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-phenoxyphenyl)urea;N-{4-[3-amino-7-(4-morpholinylmethyl)-1,2-benzisoxazol-4-yl]phenyl}-N′-(3-bromophenyl)urea;N-(4-{3-amino-7-[2-(4-morpholinyl)ethoxy]-1,2-benzisoxazol-4-yl}phenyl)-N′-[3-( ...

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Номер записи: 31
26-09-2013 дата публикации

NOVEL FLUORINATED SULFAMIDES EXHIBITING NEUROPROTECTIVE ACTION AND THEIR METHOD OF USE

Номер: US20130253022A1
Автор: Brenneman Douglas E., Du Yanming, Reitz Allen B., SMITH GARRY ROBERT, Zhang Yan
Принадлежит:

Pharmaceutical compositions of the invention include fluorinated sulfamide derivatives having a disease-modifying action in the treatment of diseases associated with excitotoxicity and accompanying oxidative stress that include epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease, heavy metal toxicity and any neurodegenerative disease involving glutamate toxicity. 2. The compound according to wherein R is phenyl claim 1 , 2-fluorophenyl claim 1 , 3-fluorophenyl claim 1 , 4-fluorophenyl claim 1 , 2 claim 1 ,4-difluorophenyl claim 1 , 2 claim 1 ,5-difluorophenyl claim 1 , 2 claim 1 ,6-difluorophenyl claim 1 , 2-chlorophenyl claim 1 , 2-bromophenyl claim 1 , 2-trifluoromethylphenyl claim 1 , 3-trifluoromethylphenyl claim 1 , 2 claim 1 ,6-dichlorophenyl claim 1 , 2 claim 1 ,4-dichlorophenyl claim 1 , 2-methylphenyl claim 1 , 2-ethylphenyl claim 1 , 2-methoxyphenyl claim 1 , 2-chloro-6-fluorophenyl claim 1 , 2-chloro-4-fluorophenyl claim 1 , 2-fluoro-6-methoxyphenyl claim 1 , 4-fluoro-2-methoxyphenyl claim 1 , 2-chloro-6-methoxyphenyl claim 1 , benzo[b]thiophen-3-yl claim 1 , or benzo[d]isoxazol-3-yl.3. The compound according to wherein Ris methyl or hydrogen.4. The compound according to wherein Ris fluorine.5. The compound according to that is:2,2-Difluoro-2-phenyl-ethyl-1-sulfamide;2,2-Difluoro-2-(2-fluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(3-fluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(4-fluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2,6-difluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2,4-difluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2,5-difluorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2-chlorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2-trifluoromethylphenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(3-trifluoromethylphenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2,6-dichlorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2,4-dichlorophenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2-methylphenyl)ethyl-1-sulfamide;2,2-Difluoro-2-(2-methoxyphenyl)ethyl-1-sulfamide;2,2- ...

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Номер записи: 32
26-09-2013 дата публикации

POLYCYCLIC LPA1 ANTAGONIST AND USES THEREOF

Номер: US20130253023A1
Автор: Brittain Jason Edward, King Christopher David, Rosso Victor W., Seiders Thomas Jon
Принадлежит:

Described herein is the LPA1 antagonist 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-bi-phenyl-4-yl}-cyclopropanecarboxylic acid (Compound 1), or pharmaceutically acceptable salts thereof. Also described are methods of preparing the LPA1 antagonist, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions suitable for administration to a mammal that include the LPA1 antagonist, or pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating LPA-dependent or LPA-mediated diseases or conditions. 1. A crystalline form of 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid , 1-{4′-[3-methyl-4-((S)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid , or 1-{4′-[3-methyl-4-(1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid , or a pharmaceutically acceptable salt , or solvate thereof.2. The crystalline form of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt claim 1 , calcium salt claim 1 , potassium salt claim 1 , ammonium salt claim 1 , L-arginine salt claim 1 , L-lysine salt claim 1 , or N-methyl-D-glucamine salt claim 1 , or solvate thereof.3. The crystalline form of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt claim 1 , or solvate thereof.4. The crystalline form of that is 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid claim 1 , or a pharmaceutically acceptable salt claim 1 , or solvate thereof.5. The crystalline form of that is a pharmaceutically acceptable salt of 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid claim 1 , or solvate thereof.6. The crystalline form of claim 1 , wherein the crystalline form is a hydrate.7. The crystalline form of that is 1-{4′-[3- ...

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Номер записи: 33
03-10-2013 дата публикации

CRYSTALLINE FORMS OF (R)-3-[N-(3'-CHLOROBIPHENYL-4-YLMETHYL)-N'-(3-HYDROXYISOXAZOLE-5-CARBONYL)HYDRAZINO]-2-HYDROXYPROPIONIC ACID ISOPROPYL ESTER

Номер: US20130259897A1
Автор: Nzerem Jerry, Rapta Miroslav, Thalladi Venkat R.
Принадлежит:

The invention provides crystalline forms of (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester. This invention also provides pharmaceutical compositions comprising the crystalline compound, processes and intermediates for preparing the crystalline compound, and methods of using the crystalline compound to treat diseases. 1. A crystalline (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester , selected from:a neutral monohydrate Form 1 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.26±0.20, 14.68±0.20, 15.64±0.20, 16.36±0.20, 18.52±0.20, 20.40±0.20, 21.08±0.20, 21.48±0.20, 21.68±0.20, 23.18±0.20, 24.50±0.20, 24.80±0.20, 25.34±0.20, and 26.56±0.20;a neutral Form 2 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.48±0.20, 8.02±0.20, 9.38±0.20, 12.24±0.20, 14.86±0.20, 18.72±0.20, 20.94±0.20, 21.34±0.20, 22.32±0.20, and 24.68±0.20;a neutral solvated Form 2′ characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.26±0.20, 8.05±0.20, 12.20±0.20, 14.48±0.20, 15.84±0.20, 16.22±0.20, 18.78±0.20, 20.60±0.20, 21.29±0.20, 21.74±0.20, 23.10±0.20, 24.16±0.20, and 24.44±0.20;a neutral anhydrous Form 3 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.12±0.20, 8.86±0.20, 11.92±0.20, 13.68±0.20, 16.10±0.20, 18.12±0.20, 18.46±0.20, 19.06±0.20, 19.48±0.20, 20.60±0.20, 21.28±0.20, 24.46±0.20, 25.94±0.20, and 26.40±0.20;a neutral anhydrous Form 4 characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 8.70±0.20, 13.00±0.20, 16.00±0.20, 16.94±0.20, 17.36±0.20, 18.72±0.20, 19.00±0.20, 19.78±0.20, 20.24±0.20, 21.70±0.20, 23.68±0.20, and 27.94±0.20;a tromethamine salt characterized by a powder x-ray diffraction pattern ...

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Номер записи: 34
03-10-2013 дата публикации

Therapeutic Compounds for Protozoal and Microbial Infections and Cancer

Номер: US20130261133A1
Автор: Bolstad David Brian, Hoody John Howard
Принадлежит: The University of Montana

The compounds of the invention exhibit antiprotozoal, antimicrobial, and anticancer properties that are useful for the treatment or prevention of infections or cancer in a patient (e.g., a human). For example, the compounds and methods described herein can be used for the treatment or prevention of protozoal infections such as leishmaniasis, malaria, and infections, bacterial infections such as and , and cancers such as breast, colon, lung, or prostate cancer. The invention further provides methods of synthesizing such compounds as well as kits useful for administering the compounds. 2. The compound of claim 1 , wherein said compound is selected from the group consisting of (3S claim 1 ,8R)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxyheptadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxyhexadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxypentadeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8S)-8-hydroxytetradeca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8R)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3S claim 1 ,8S)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 ,8R)-8-hydroxytrideca-1-en-4 claim 1 ,6-diyn-3-yl acetate; (3R claim 1 , ...

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Номер записи: 35
10-10-2013 дата публикации

Modulators of Aldehyde Dehydrogenase and Methods of Use Thereof

Номер: US20130267501A1
Автор: Chen Che-Hong, Mochly-Rosen Daria, Yang Wenjin
Принадлежит: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

The present disclosure provides compounds that function as modulators of aldehyde dehydrogenase (ALDH) enzymatic activity, as well as compositions and formulations comprising the compounds. The present disclosure provides therapeutic methods involving administering a subject compound, or a subject pharmaceutical composition. 176.-. (canceled)78. The compound of claim 77 , wherein Xand Xare both O.79. The compound of claim 77 , wherein z is 1.80. The compound of claim 77 , wherein Ar is a substituted phenyl.81. The compound of claim 80 , wherein the phenyl is substituted with a methyl group.82. The compound of claim 81 , wherein the phenyl is further substituted with an isoxazoly group.83. The compound of claim 82 , wherein the isoxazolyl group is substituted with one or more methyl groups.84. The compound of claim 77 , wherein Ar is a substituted thiophenyl group85. The compound of claim 84 , wherein the thiophenyl group is substituted with C(O)NH.87. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00077', 'claim 77'}, 'a) a compound of ; and'}b) a pharmaceutically acceptable excipient.88. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00086', 'claim 86'}, 'a) a compound of ; and'}b) a pharmaceutically acceptable excipient.89. A method of reducing a level of aldehyde present at a toxic level in an individual to below the toxic level comprising administering to an individual an effective amount of a compound of .90. The method of claim 89 , wherein the individual has alcohol intolerance claim 89 , alcohol addiction claim 89 , or an alcohol abuse disorder.91. A method of treating a disease or disorder selected from alcohol intolerance claim 77 , alcohol addiction claim 77 , alcohol abuse disorder claim 77 , methanol poisoning claim 77 , ethylene glycol monomethyl ether poisoning claim 77 , and poisoning due to other xenogenic or biogenic aldehyde compounds claim 77 , comprising administering to an individual an effective ...

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Номер записи: 36
17-10-2013 дата публикации

(2-UREIDOACETAMIDO)ALKYL DERIVATIVES AS FORMYL PEPTIDE RECEPTOR 2 MODULATORS

Номер: US20130274230A1
Автор: Beard Richard L., Donello John E., Duong Tien, Garst Michael E., Viswanath Veena
Принадлежит: ALLERGAN, INC.

The present invention relates to (2-ureidoacetamido)alkyl derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor 2. 2. A compound according to claim 1 , wherein:{'sup': 3', '11', '16, 'sub': 1-8', '3', '2, 'Ris substituted or unsubstituted Calkyl, halogen, —SR, —CFor —S(O)R.'}4. A compound according to claim 1 , wherein:{'sup': 6', '19, 'sub': 1-8', '2, 'Ris substituted or unsubstituted Calkyl, or —CHR.'}5. A compound according to claim 1 , wherein:{'sup': '26', 'Ris hydrogen;'}{'sup': '27', 'Ris hydrogen;'}{'sup': '28', 'Ris hydrogen; and'}{'sup': '29', 'Ris hydrogen;'}8. A compound according to claim 1 , selected from:Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}methyl)phosphonate;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-4-methyl-N-(1H-tetrazol-5-ylmethyl)pentanamide;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-4-methyl-N-[2-(1H-tetrazol-5-yl)ethyl]pentanamide;(2S)-2-({[(4-Bromophenyl)amino]carbonyl}amino)-N-[(3-hydroxyisoxazol-5-yl)methyl]-4-methylpentanamide;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}methyl)phosphonate;Diethyl({[(2S,3S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methylpentanoyl]amino}methyl)phosphonate;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)pentanoyl]amino}methyl)phosphonate;Diethyl({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-phenylpropanoyl]amino}methyl)phosphonate;Diethyl(2-{[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methylpentanoyl]amino}ethyl)phosphonate;Ethyl hydrogen ({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-4-methyl pentanoyl]amino}methyl)phosphonate;Ethyl hydrogen ({[(2S,3S)-2-({[(4-bromophenyl)amino]carbonyl}amino)-3-methyl pentanoyl]amino}methyl)phosphonate;Ethyl hydrogen ({[(2S)-2-({[(4-bromophenyl)amino]carbonyl}amino)pentanoyl]amino}methyl)phosphonate;({[(2S)-4-Methyl-2-({[4-(trifluoromethyl)phenyl] ...

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Номер записи: 37
17-10-2013 дата публикации

NOVEL INHIBITORS OF BACTERIAL BIOFILMS AND RELATED METHODS

Номер: US20130274256A1
Автор: Buckle Ronald Neil, Edward John, Eldridge Gary, Ellis Michael, Huang Zhongping
Принадлежит: SEQUOIA SCIENCES, INC.

Certain multi-cyclic compounds and compositions thereof are useful for reducing or inhibiting the growth of bacterial biofilms and for controlling bacterial biofilm infections. Such compounds and compositions are also useful in methods for reducing or inhibiting the growth of biofilms and for controlling bacterial biofilm infections involving biofilms. 162-. (canceled)65. A compound according to wherein Ris selected from the group consisting of methyl claim 63 , halide claim 63 , lower haloalkyl claim 63 , nitrile claim 63 , lower alkyl nitrile claim 63 , lower alkyl claim 63 , substituted lower alkyl claim 63 , lower alkenyl claim 63 , substituted lower alkenyl claim 63 , lower alkynyl claim 63 , substituted lower alkynyl claim 63 , lower cycloalkyl claim 63 , lower cycloalkenyl claim 63 , aryl claim 63 , substituted aryl claim 63 , heteroaryl claim 63 , and substituted heteroaryl claim 63 , preferably Ris selected from the group consisting of pyrrolyl claim 63 , pyrazolyl claim 63 , imidazolyl claim 63 , oxazolyl claim 63 , isoxazolyl claim 63 , oxadiazolyl claim 63 , thiazolyl claim 63 , isothiazolyl claim 63 , thienyl claim 63 , furanyl claim 63 , furazanyl claim 63 , pyridinyl claim 63 , pyrimidinyl claim 63 , pyridazinyl claim 63 , indolyl claim 63 , 3H-indolyl claim 63 , isoindolyl claim 63 , indolinyl claim 63 , indolizinyl claim 63 , indazolyl claim 63 , dihydroindolyl claim 63 , tetrahydroindolyl claim 63 , purinyl claim 63 , pyrazinyl claim 63 , quinolinyl claim 63 , isoquinolinyl claim 63 , tetrahydroisoquinolinyl claim 63 , quinoxalinyl claim 63 , quinazolinyl claim 63 , cinnolinyl claim 63 , pteridinyl claim 63 , benzimidazolyl claim 63 , benzopyranyl claim 63 , benzoxazolyl claim 63 , benzisoxazolyl claim 63 , benzofuranyl claim 63 , isobenzofuranyl claim 63 , benzothiazolyl claim 63 , benzisothiazolyl claim 63 , benzothienyl claim 63 , furopyridinyl claim 63 , phthalazinyl claim 63 , napthyridinyl claim 63 , pyrazolopyridyl claim 63 , ...

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Номер записи: 38
31-10-2013 дата публикации

Isoxazole Compounds As Inhibitors Of Heat Shock Proteins

Номер: US20130289026A1
Автор: Cheung Kwai Ming, Drysdale Martin James, Dymock Brian William, Finch Harry, James Karen Elizabeth, Matthews Thomas Peter, McDonald Edward, Webb Paul
Принадлежит:

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: 327-. (canceled)30. (canceled)31. The method as claimed in wherein the compound is selected from:5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-piperidin-1-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide4-(4-Diethylaminomethyl-phenyl)-5-(2,4-dihydroxy-5-isopropyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-ethylaminomethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-[4-(isopropylamino-methyl)-phenyl]-isoxazole-3-carboxylic acid ethylamide4-(4-Cyclohexylaminomethyl-phenyl)-5-(2,4-dihydroxy-5-isopropyl-phenyl)-isoxazole-3-carboxylic acid ethylamide4-[4-(tert-Butylamino-methyl)-phenyl]-5-(2,4-dihydroxy-5-isopropyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-{4-[(2-methoxy-ethylamino)-methyl]-phenyl}-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid isopropylamide5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-isoxazole-3-carboxylic acid isopropylamide5-(5-tert-Butyl-2,4-dihydroxy-phenyl)-4-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-isoxazole-3-carboxylic acid ethylamide5-(5-tert-Butyl-2,4-dihydroxy-phenyl)-4-(4-piperidin-1-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isobutyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(2,4-Dihydroxy-5-isobutyl-phenyl)-4-(4-piperidin-1-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide5-(5-tert-Butyl-2,4-dihydroxy-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic ...

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Номер записи: 39
07-11-2013 дата публикации

ISOXAZOLINE-SUBSTITUTED BENZAMIDE COMPOUND AND PESTICIDE

Номер: US20130296559A1
Автор: Kikuchi Takamase, KOMODA Mitsuaki, MITA Takeshi, MIZUKOSHI Takashi, YAOSAKA Manabu
Принадлежит:

A substituted alkenylbenzene compound of formula (4): 2. The substituted alkenylbenzene compound of formula (4) according to claim 1 , wherein:{'sup': '1', 'sub': 5', '1', '6', '1', '6', '1', '6, 'Xis selected from the group consisting of a halogen atom, —SF, C-Chaloalkyl, C-Chaloalkoxy and C-Chaloalkylthio;'}{'sup': '3', 'sub': 1', '6', '1', '6', '1', '6, 'Xis selected from the group consisting of a hydrogen atom, halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl and C-Calkoxy;'}{'sup': '4', 'Xis a hydrogen atom or halogen atom;'}{'sup': 3a', '3b, 'Rand Rare each a fluorine atom;'}{'sup': 3c', '2', '3', '4', '1', '3', '4', '1', '3', '4', '3c, 'Ris selected from the group consisting of a hydrogen atom, fluorine atom, chlorine atom, bromine atom and trifluoromethyl, with a proviso that in case where Xis a fluorine atom, chlorine atom or trifluoromethyl and both Xand Xare a hydrogen atom, in case where both Xand Xare a fluorine atom and Xis a hydrogen atom, and in case where both Xand Xare trifluoromethyl and Xis a hydrogen atom, Ris a hydrogen atom, chlorine atom, bromine atom or trifluoromethyl.'} This is a Divisional Application of application Ser. No. 13/166,294, filed Jun. 22, 2011, which is a Divisional Application of application Ser. No. 12/509,859, filed on Jul. 27, 2009, which is a Divisional Application of application Ser. No. 11/514,921, filed Sep. 5, 2006, which in turn is a Continuation-in-part of International Application No. PCT/JP05/04268, filed Mar. 4, 2005, which claims priority to Japanese Patent Applications Nos. 2004-200119, filed Jul. 7, 2004, and 2004-061749, filed Mar. 5, 2004. The disclosures of the prior applications are hereby incorporated by reference herein in their entirety.The present invention relates to a novel isoxazoline-substituted benzamide compound and the salt thereof, and a pesticide characterized by containing the compound as an active ingredient. The pesticide in the present invention means a pest controlling agent applied ...

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Номер записи: 40
21-11-2013 дата публикации

Methods including latent 1,3-dipole-functional compounds and materials prepared thereby

Номер: US20130310570A1
Автор: Frederic Friscourt, Geert-Jan Boons, Ngalle Eric Mbua, Petr A. Ledin
Принадлежит: University of Georgia Research Foundation Inc UGARF

Methods that include latent 1,3-dipole-functional compounds are disclosed herein. The latent 1,3-dipole-functional compound (e.g., an oxime) can be used to form an active 1,3-dipole-functional compound (e.g., a nitrile oxide) that can be used to react with a cyclic alkyne in a dipolar cycloaddition reaction.

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Номер записи: 41
28-11-2013 дата публикации

Chiral3-(benzylsulfinyl)-5,5-dimethyl-4,5-dihydroisoxazole derivatives and 5,5-dimethyl-3-[(1h-pyrazol-4-ylmethyl)sulfinyl]-4,5-dihyddroisoxazole derivatives, method for the production thereof, and use of same as herbicides and plant growth regulators

Номер: US20130316904A1
Автор: Dietrich Hansjoerg, DITTGEN JAN, Feucht Dieter, MARTELLETTI Arianna, ROSINGER CHRISTOPHER HUGH
Принадлежит: Bayer CropScience AG

The invention relates to 3-(benzylsulfinyl)-5,5-dimethyl-4,5-dihydroisoxazole derivatives and 5,5-dimethyl-3-[(1H-pyrazol-4-ylmethyl)sulfinyl]-4,5-dihydroisoxazole derivatives of the formula (I) and their salts 2. The compound of the formula (I) as claimed in wherein{'sup': 1', '5', '9', '10', '9', '10', '9', '10, 'sub': 1', '4', '3', '6', '1', '4', '1', '4', '1', '4', '1', '4', '1', '2', '1', '3', '1', '3', '1', '4', '3', '6', '3', '6', '1', '2', '3', '6', '1', '4', '1', '2', '3', '4', '3', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '3', '4', '2', '4', '6', '1', '4', '6', '1', '4', '2', '4', '2', '4', '1', '6', '3', '6', '1', '6', '1', '6', '1', '6, 'the substituents Rto Rare independently of one another selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, nitro, amino, C(O)OH, (C-C)-alkyl, (C-C)-cycloalkyl, (C-C)-haloalkyl, (C-C)-alkoxy, (C-C)-haloalkoxy, (C-C)-alkoxy-(C-C)-alkyl, (C-C)-alkylcarbonyl, (C-C)-alkylcarbonyloxy, (C-C)-alkoxycarbonyl, (C-C)-cycloalkoxycarbonyl, (C-C)-cycloalkyl-(C-C)-alkoxy, (C-C)-cycloalkoxy, (C-C)-alkoxycarbonyl-(C—O)-alkoxy, (C-C)-alkenyloxy, (C-C)-alkynyloxy, (C-C)-alkylthio, (C-C)-haloalkylthio, (C-C)-alkylsulfinyl, (C-C)-haloalkylsulfinyl, (C-C)-alkylsulfonyl, (C-C)-haloalkylsulfonyl, (C-C)-alkylsulfonyloxy, di-(C-C)-alkylamino, (C-C)-alkenyloxycarbonyl, (C-C)-alkynyloxycarbonyl, C-aryl-(C-C)-alkoxycarbonyl, C-aryl-(C-C)-alkoxy, formyl, (C-C)-alkenyl, (C-C)-alkynyl, phenyl, —C(O)NRR, where Rand Rindependently of one another are selected from the group consisting of hydrogen, (C-C)-alkyl, (C-C)-cycloalkyl, (C-C)-haloalkyl, or where Rand Rtogether form a (C-C)-alkylene group which may contain one oxygen or sulfur atom or one or two amino or (C-C)-alkylamino groups;'} {'sub': 1', '6', '1', '6, 'two substituents ortho to one another together form a (C-C)-alkylene group which may contain one or more oxygen and/or sulfur atoms, where the (C-C)-alkylene group may be mono- or ...

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Номер записи: 42
28-11-2013 дата публикации

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

Номер: US20130317007A1
Автор: Anderson Eric, Jiang Xin, Visnick Melean
Принадлежит: REATA PHARMACEUTICALS, INC.

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 34-. (canceled)710-. (canceled)11. The compound of claim 5 , wherein either Xor Xis OR claim 5 , wherein Ris absent.12. The compound of claim 6 , wherein Xis ORand Ris absent.13. The compound of claim 5 , wherein Xis hydrogen.14. (canceled)15. The compound of claim 6 , wherein Y is NRR.1617-. (canceled)18. The compound of claim 6 , wherein Ror Rcomprises a fluoro group.19. The compound of claim 18 , wherein one of Ror Rcomprises a trifluoromethyl group.20. The compound of claim 6 , wherein Rand Rare each independently hydrogen claim 6 , alkyl claim 6 , aryl claim 6 , aralkyl claim 6 , heteroaryl claim 6 , heteroaralkyl claim 6 , or a substituted version of any of these groups.2123-. (canceled)24. The compound of claim 6 , wherein Ris alkylsulfonyl claim 6 , arylsulfonyl claim 6 , aralkylsulfonyl claim 6 , heteroarylsulfonyl claim 6 , heteroaralkylsulfonyl claim 6 , or a substituted version of any of these groups.2529-. (canceled)30. The compound of claim 6 , wherein Ris acyl.31. The compound of claim 6 , wherein Ris substituted acyl.32. (canceled)33. The compound of claim 6 , wherein R′ is cyano.34. (canceled)35. The compound of claim 2 , wherein Ris absent.3637-. (canceled)38. The compound of claim 6 , wherein Rand Rare each methyl.39. The compound of claim 5 , wherein Rand Rare each hydrogen.40. The compound of claim 2 , wherein the bond joining carbon 1 and carbon 2 is a double bond.41. The compound of claim 6 , wherein the bond joining carbon 9 and carbon 11 is a double bond.42. The compound of claim 6 , wherein the bond joining carbon 9 and carbon 11 is a single bond.43. The compound of claim 5 , wherein the bond joining carbon 12 and carbon 13 is a single bond.44. The compound of claim 5 , wherein the bond joining carbon 13 and carbon 18 is a single bond.45. (canceled)47. (canceled)49. (canceled)51. (canceled)53. (canceled)55. (canceled)57. (canceled)59. ( ...

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Номер записи: 43
28-11-2013 дата публикации

METHODS OF PEST CONTROL IN SOYBEAN

Номер: US20130317073A1
Автор: Cassayre Jerome Yves, El Qacemi Myriem, Vock Christoph
Принадлежит:

The present invention provides methods comprising applying to a crop of soybean plants, the locus thereof, or propagation material thereof, a compound a compound of formula III wherein A, A, A and A are independently C—H, or nitrogen and wherein #1 indicates the bond to X and #2 indicates the bond to cycle B; cycle B is selected from B1 to B6 wherein #1 indicates the bond to cycle A, #2 indicates the bond to Rand #3 indicates the bond to cycle C; cycle C is phenyl; Ris chloro, bromo, CFor methyl; Ris chlorodifluoromethyl or trifluoromethyl; each Ris independently bromo, chloro, fluoro or trifluoromethyl; p is 2 or 3; and wherein X is defined in the claims. The methods are preferably for the control of stinkbugs, in particular . 2. (canceled)6. A method according to claim 5 , wherein the method is for controlling and/or preventing infestation of the soybean crop by stinkbugs.7. (canceled)8. A method according to claim 5 , wherein X is P4 claim 5 , P5 or P6.9. A method according to claim 4 , wherein cycle B is cycle B1.11Nezara viridula, PiezodorusAcrosternumEuchistus heros.. A method according to claim 4 , wherein stinkbug is spp. claim 4 , spp claim 4 ,12Euschistus.. A method according to claim 4 , wherein stinkbug is13EuschistusEuschistus heros.. A method according to claim 1 , wherein is14. A method or use according to claim 1 , wherein the compound of formula I or formula II is applied in combination with one or more additional active ingredients selected from neonicotinoids claim 1 , pyrethroids claim 1 , strobilurins claim 1 , triazoles and carboxamides.15. A method according to claim 1 , wherein the compound is applied to the crop by foliar application.16. A method according to claim 1 , wherein the compound of formula I or formula II is applied in combination with an attractant selected from glucose claim 1 , saccharose claim 1 , salt claim 1 , glutamate claim 1 , citric acid claim 1 , soybean oil claim 1 , peanut oil and soybean milk. The present invention ...

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Номер записи: 44
05-12-2013 дата публикации

NITRIC OXIDE DONOR NEPRILYSIN INHIBITORS

Номер: US20130323271A1
Автор: Hughes Adam D., Mammen Mathai
Принадлежит:

In one aspect, the invention relates to compounds having the formula: 2. The compound of claim 1 , where Ris —Calkyl substituted with 1 or 2 —ONOgroups.3. The compound of claim 2 , where Ris —(CH)(ONO).6. The compound of claim 1 , where Ris —OH and Ris H.7. The compound of claim 1 , where Ris —CHOH and Ris —CH.8. The compound of claim 1 , where X is selected from —COOR claim 1 , pyrazole claim 1 , imidazole claim 1 , triazole claim 1 , benzotriazole claim 1 , furan claim 1 , pyrrole claim 1 , tetrazole claim 1 , pyrazine claim 1 , thiophene claim 1 , oxazole claim 1 , isoxazole claim 1 , thiazole claim 1 , isothiazole claim 1 , oxadiazole claim 1 , thiadiazole claim 1 , pyridazine claim 1 , pyridine claim 1 , pyrimidine claim 1 , pyran claim 1 , benzimidazole claim 1 , benzoxazole claim 1 , benzothiazole claim 1 , pyridylimidazole claim 1 , and pyridyltriazole.10. The compound of claim 8 , where X is —COOR claim 8 , and Ris H.12. The compound of claim 1 , where Ris absent or is selected from H claim 1 , —Calkylene-OH claim 1 , —Calkylene-O—Calkyl claim 1 , —C(O)—Calkyl claim 1 , ═O claim 1 , and phenyl substituted with one halo.13. The compound of claim 1 , where Ris selected from H claim 1 , —OH claim 1 , —Calkyl claim 1 , pyridinyl claim 1 , and phenyl optionally substituted with one halo.14. The compound of claim 1 , where b is 0 or b is 1 and Ris 3′-chloro.15. The compound of claim 1 , where c is 0 claim 1 , or c is 1 and Ris 3′-chloro claim 1 , or c is 0 and Ris 2′-fluoro claim 1 , 5′-chloro or 2′ claim 1 ,5′-dichloro.18. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.19. The pharmaceutical composition of claim 18 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 18 , α-adrenergic receptor antagonists claim 18 , β-adrenergic receptor antagonists claim 18 , β-adrenergic receptor agonists claim 18 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim ...

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Номер записи: 45
12-12-2013 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20130330366A1
Автор: Fleury Melissa, Hughes Adam D.
Принадлежит:

In one aspect, the invention relates to compounds having the formula XII: 3. The compound of claim 2 , where Ris H and Ris selected from H and —CHCH.5. The compound of claim 4 , where Ris H and Ris selected from H and —CHCH.13. The compound of claim 12 , where Ris H and Ris selected from H claim 12 , —CHOC(O)CH claim 12 , —CHOC(O)OCHCH claim 12 , —CHOC(O)OCH(CH) claim 12 , and —C(O)CH[CH(CH)]—NHC(O)OCH.15. The compound of claim 14 , where R is —CH claim 14 , Ris H claim 14 , and Ris selected from —CHOC(O)CH claim 14 , —CHOC(O)OCH(CH) claim 14 , —CHOC(O)OCHCH claim 14 , and —CHOC(O)CH[CH(CH)]—NHC(O)OCH.19. The compound of claim 18 , where Ris H and Ris selected from —CHOC(O)OCHCHand —CHOC(O)CH[CH(CH)]—NHC(O)OCH.21. The compound of claim 20 , where Ris H claim 20 , Ris —CHOP(O)(OH)or —CHOC(O)CH[CH(CH)]NH claim 20 , and Ris —CHCH; or Ris —C(O)CH[CH(CH)]NH claim 20 , Ris H claim 20 , and Ris —CHCH.23. The compound of claim 22 , where R claim 22 , R claim 22 , and Rare H; or Rand Rare H claim 22 , and Ris —CHOC(O)OCHCH.25. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .26. The pharmaceutical composition of claim 25 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 25 , α-adrenergic receptor antagonists claim 25 , β-adrenergic receptor antagonists claim 25 , β-adrenergic receptor agonists claim 25 , dual-acting β-adrenergic receptor antagonist/α-receptor antagonists claim 25 , advanced glycation end product breakers claim 25 , aldosterone antagonists claim 25 , aldosterone synthase inhibitors claim 25 , aminopeptidase N inhibitors claim 25 , androgens claim 25 , angiotensin-converting enzyme inhibitors and dual-acting angiotensin-converting enzyme/neprilysin inhibitors claim 25 , angiotensin-converting enzyme 2 activators and stimulators claim 25 , angiotensin-II vaccines claim 25 , anticoagulants claim 25 , anti-diabetic agents claim 25 , antidiarrheal agents claim 25 , anti- ...

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Номер записи: 46
19-12-2013 дата публикации

uPAR-uPA INTERACTION INHIBITORS AND METHODS FOR TREATING CANCER

Номер: US20130338144A1
Автор: Meroueh Samy
Принадлежит: INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

The invention described herein pertains to compounds, compositions and formulations comprising the compounds, and methods for use of the compounds, compositions and/or formulations in the treatment of diseases responsive to the inhibition of uPAR-uPA interactions, such as cancer. 3. The composition of wherein each Ris hydrogen.4. The composition of wherein Y is optionally substituted aryl or optionally substituted heteroaryl claim 1 , substituted with a carboxylic acid claim 1 , or derivative or analog thereof.5. The composition of wherein X is an optionally substituted nitrogen-containing heterocycle attached at nitrogen.6. The composition of further comprising one or more carriers claim 1 , diluents claim 1 , or excipients claim 1 , or a combination thereof.7. A unit dose or unit dosage form for treating cancer claim 1 , the unit dose or unit dosage form comprising a therapeutically effective amount of one or more compositions of for treating cancer.8. A method for treating cancer in a patient claim 1 , the method comprising the step of administering to the patient a therapeutically effective amount of one or more compositions of claim 1 , or one or more unit doses or unit dosage forms thereof claim 1 , or a combination thereof.9. The method of wherein the compound makes an energetically positive interaction with one or more of the residues selected from the group consisting of L150 claim 8 , L155 claim 8 , L168 claim 8 , and R53 on uPAR.10. The method of wherein the compound makes an energetically positive interaction with L168 uPAR.11. The method of wherein the compound makes an energetically positive interaction with R53 uPAR.12. The method of wherein the total of all interactions with uPAR is less than or equal to about −10 kcal/mol.1314-. (canceled)15. The method of wherein the interaction with L150 is less than about −2 kcal/mol.1617-. (canceled)18. The method of wherein the interaction with L168 is less than about −1 kcal/mol.19. The method of wherein the ...

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Номер записи: 47
26-12-2013 дата публикации

METHODS OF TREATING CANCER AND OTHER DISORDERS

Номер: US20130345270A1
Автор: Kridel Steven J., Lowther W. Todd, Odens Herman W., Schmitt Jeffrey D.
Принадлежит: Waake Forest University Health Sciences

Active compounds useful for inhibiting fatty acid synthase in a subject in need thereof are described. The active compounds are, in general, a 5-mercapto-1H-Indazole-4,7-dione or an analog thereof. The compounds are useful for treating subjects afflicted with, cancer, obesity, diabetes, a viral infection, a bacterial infection, a fungal infection, or a protozoal infection. 1. A method of reversibly or irreversibly inhibiting fatty acid synthase in a subject in need thereof , comprising administering to said subject an active compound as described herein in a treatment-effective amount; wherein said active compound is an 5-mercapto-1H-Indazole-4 ,7-dione or an analog thereof.2. The method of claim 1 , wherein said subject is afflicted with cancer.3. The method of claim 1 , wherein said subject is afflicted with obesity.4. The method of claim 1 , wherein said subject is afflicted with diabetes5. The method of claim 1 , wherein said subject is afflicted with a viral infection.6. The method of claim 1 , wherein said subject is afflicted with a bacterial infection.7. The method of claim 1 , wherein said subject is afflicted with a fungal infection.8. The method of claim 1 , wherein said subject is afflicted with a protozoal infection.11. (canceled) The present invention concerns methods of treatment, and compounds and compositions useful for carrying out such methods.A first aspect of the present invention is a method of inhibiting fatty acid synthase in a subject in need thereof, comprising administering to said subject an active compound as described herein in a treatment-effective amount. Examples of subjects in need thereof include, but are not limited to, subjects afflicted with cancer, obesity, diabetes, viral infection, bacterial infection, fungal infection or protozoal infection.A second aspect of the present invention is the use of an active compound as described herein for the preparation of a medicament for carrying out a method as described herein, such as ...

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Номер записи: 48
09-01-2014 дата публикации

ISOXAZOLINE DERIVATIVES AS ANTIPARASITIC AGENTS

Номер: US20140011758A1
Автор: Kyne Graham M., Menon Sanjay, Vaillancourt Valerie A., Wendt John A.
Принадлежит:

This invention recites isoxazoline substituted derivatives of Formula (1) stereoisomers thereof, geometric isomers thereof, veterinarily acceptable salts 5 thereof, compositions thereof, and their use as a parasiticide in animals. The variables A, W, R 1a, R 1b, R 1c, R 2, R 3, R 5, and n are as described herein. 10. A compound selected from the group consisting of3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (2,2,2-trifluoro-ethyl)-amide;3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid cyclopropylamide;3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid methylamide;3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid dimethylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid cyclopropylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid cyclopropylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (2,2,2-trifluoro-ethyl)-amide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid (2,2,2-trifluoro-ethyl)-amide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid methylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid methylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid dimethylamide;3-fluoro-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3 ...

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Номер записи: 49
16-01-2014 дата публикации

Sulfonamides as hib protease inhibitors

Номер: US20140018326A1
Автор: Daniel J. Mckay, Marie-Eve Lebrun, Oscar M. Moradei, Sheldon Crane, Vouy Linh Truong
Принадлежит: Merck Canada Inc

Compounds of Formula I are disclosed: wherein L, A, R 1 , R 2 , R 3A , R 3B , R 4A , R 4B , R 5 , R 6 and R 7 are defined herein. The compounds encompassed by Formula I include compounds which are HIV protease inhibitors and other compounds which can be metabolized in vivo to HIV protease inhibitors. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

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Номер записи: 50
23-01-2014 дата публикации

Isoxazole Derivatives Useful As Antibacterial Agents

Номер: US20140024690A1
Автор: Abramite Joseph Alan, Brown Matthew Frank, Chen Jinshan Michael, Melnick Michael Joseph, MONTGOMERY JUSTIN IAN, Reilly Usa
Принадлежит: PFIZER INC.

The present invention is directed to a new class of hydroxamic acid derivatives, their use as LpxC inhibitors and, more specifically, their use to treat bacterial infections. 2. The compound according to wherein{'sup': '1', 'sub': 1', '3, 'Ris (C-C)alkyl;'}{'sup': '2', 'sub': 1', '3, 'Ris (C-C)alkyl;'}{'sup': '3', 'Ris hydrogen;'}{'sub': 2', 'n', '2', 'n', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', 'p, 'sup': 4', '4', '4', '4, 'L is a bond, —(CH)—, —(CH)O(CH)—, —(CH)S(CH)—, —(CH)NR(CH)—, —(CH)SONR(CH)—, —(CH)CONR(CH)—, or —(CH)NRCO(CH)—;'}{'sup': 4', '5, 'sub': 1', '6', '3', '8, 'Rand Rare independently hydrogen, (C-C)alkyl, or (C-C)cycloalkyl;'}n is 0, 1, or 2;p is 0, 1, or 2;{'sup': 6', '4', '5, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '6', '12', '6', '12', '3', '8', '5', '12', '1', '10, 'Ris (C-C)alkoxy(C-C)alkyl, (C-C)alkoxycarbonyl, (C-C)alkylthiocarbonyl, (C-C)aryl, (C-C)aryloxy, (C-C)cycloalkyl, (C-C)heteroaryl, hydroxy(C-C)alkyl, or (NRR)carbonyl; and'}{'sup': '7', 'sub': 3', '13, 'Ris absent or (C-C)heterocycle.'}3. The compound according to wherein{'sup': '1', 'Ris methyl;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'Ris hydrogen;'}{'sub': 2', 'n', '2', 'n', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'p', '2', 'n', '2', 'p', '2', 'n', '2', 'p, 'sup': 4', '4', '4', '4, 'L is a bond, —(CH)—, —(CH)O(CH)—, —(CH)S(CH)—, —(CH)NR(CH)—, —(CH)SONR(CH)—, —(CH)CONR(CH)—, or —(CH)NRCO(CH)—;'}{'sup': '4', 'sub': 1', '6', '3', '8, 'Ris hydrogen, (C-C)alkyl, or (C-C)cycloalkyl;'}n is 0, 1, or 2;p is 0, 1, or 2;{'sup': '6', 'sub': 6', '12', '6', '12', '6', '12', '1', '6', '1', '6', '1', '6, 'Ris (C-C)aryl or (C-C)aryloxy, wherein the (C-C)aryl group for each is phenyl optionally substituted with 1, 2, or 3 substituents that are independently (C-C)alkoxy, (C-C)alkyl, halo(C-C)alkoxy, halogen, or methylenedioxy; and'}{'sup': '7', 'sub': 3', '13', '3', '13, 'Ris absent or (C-C) ...

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Номер записи: 51
30-01-2014 дата публикации

PHENYL-ISOXAZOL DERIVATIVES AND PREPARATION PROCESS THEREOF

Номер: US20140031364A1
Автор: Ahn Choong Am, Cho Dae Jin, Kim Dong Yeon, Kim Hong Youb, Kim Sung Moo, Lee Gong Yeal, Lee Hae Un, Woo Seok Hun, Yoon Seung Bin
Принадлежит: IL-YANG PHARM. CO., LTD.

Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient. 2. The compound of or its pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , prodrug claim 1 , or composite claim 1 , wherein when Ris the radical of Formula 2:{'sub': 1', '2', '3', '4', '5', '6', '7, 'two from among R, Rand Rare hydrogen, the remaining one is lower alkyl optionally substituted with halogen, lower alkoxy optionally substituted with halogen, or halogen, Ris methyl or amine, and from among R, Rand R, one or two each independently is hydrogen, lower alkyl optionally substituted with halogen, hydroxy, lower alkoxy, or halogen; or'}{'sub': 1', '2', '3', '4', '5', '6', '7, 'two from among R, Rand Rare hydrogen, the remaining one is trifluoromethyl, fluoro, or trifluoromethoxy, Ris methyl or amine, and from among R, Rand R, one or two each independently is hydrogen, methoxy, chlorine, fluoro, trifluoromethyl or hydroxy; or'}{'sub': 1', '4', '2', '3', '5', '7', '6, 'Ris halogen, preferably chlorine, Ris methyl or amine, R, R, R, and Reach is hydrogen, and Ris alkoxy.'}3. The compound of or its pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , prodrug claim 1 , or composite claim 1 , wherein when Ris the radical of Formula 2:{'sub': 1', '2', '3', '4', '5', '6', '7, 'Ris trifluoromethyl or trifluoromethoxy, Rand Rare hydrogen, Ris methyl or amine, and from among R, Rand R, one or two each independently is hydrogen, hydroxy, methoxy, or chlorine; or'}{'sub': 1', '4', '2', '3', '5', '7', '6, 'Ris chlorine, Ris methyl, R, R, Rand Reach is hydrogen, and Ris methoxy; or'}{'sub': 2', '1', '3', '4', '5', '6', '7, 'Ris fluoro, trifluoromethyl, or trifluoromethoxy, Rand Reach is ...

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Номер записи: 52
06-02-2014 дата публикации

ISOXAZOLINES FOR CONTROLLING INVERTEBRATE PESTS

Номер: US20140038821A1
Автор: Lahm George Philip, SHOOP Wesley Lawrence, Xu Ming
Принадлежит: E.I. Du Pont De Nemours and Company

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, 2. A compound of wherein{'sup': 1', '6, 'sub': 1', '3, 'Ris C-Calkyl optionally substituted with one or more substituents independently selected from R;'}{'sup': '2', 'sub': 1', '6', '1', '6, 'each Ris independently H, halogen, C-Chaloalkyl, C-Chaloalkoxy or —CN; and'}{'sup': '3', 'sub': 1', '6', '1', '6', '3', '6, 'each Ris independently H, halogen, C-Calkyl, C-Chaloalkyl, C-Ccycloalkyl,'}{'sub': 3', '6', '1', '6', '1', '6', '2, 'C-Chalocycloalkyl, C-Calkoxy, C-Chaloalkoxy, —CN or —NO.'}3. A compound of wherein{'sup': 1', '2', '3', '2, 'B, Band Bare independently CR;'}W is O;{'sup': '4', 'sub': 1', '6', '2', '7', '2', '7, 'Ris H, C-Calkyl, C-Calkylcarbonyl or C-Calkoxycarbonyl; and'}{'sup': 5', '11', '12', '1', '7, 'sub': 1', '4', '2', '4', '2', '4', '3', '4', '4', '7', '4', '7, 'Ris H, NRRor Q; or C-Calkyl, C-Calkenyl, C-Calkynyl, C-Ccycloalkyl, C-Calkylcycloalkyl or C-Ccycloalkylalkyl, each optionally substituted with one or more substituents independently selected from R.'}4. A compound of wherein{'sup': '1', 'sub': 1', '3, 'Ris C-Calkyl optionally substituted with halogen;'}{'sup': '2', 'sub': 3', '3, 'each Ris independently H, CF, OCF, halogen or —CN;'}{'sup': '3', 'sub': 1', '4', '1', '4', '3', '6', '1', '4, 'each Ris independently H, C-Calkyl, C-Chaloalkyl, C-Ccyclopropyl, C-Calkoxy or —CN; and'}{'sup': 7', '2, 'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '2', '4', '2', '4', '2', '5', '2', '5', '2', '5', '2', '5', '2', '2, 'each Ris independently halogen, C-Calkyl, C-Calkoxy, C-Calkylthio, C-Calkylsulfinyl, C-Calkylsulfonyl, C-Calkylcarbonyl, C-Calkoxycarbonyl, C-Calkylaminocarbonyl, C-Chaloalkylcarbonyl, C-Chaloalkoxycarbonyl, C-Chaloalkylaminocarbonyl, —NH, —CN or —NO; or Q.'}5. A compound of wherein{'sup': '4', 'Ris H;'}{'sup': 5', '7, 'sub': 1', '4, 'Ris C-Calkyl optionally substituted with one of more substituents independently ...

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Номер записи: 53
13-02-2014 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20140045906A1
Автор: Fleury Melissa, Hughes Adam D.
Принадлежит:

In one aspect, the invention relates to compounds having the formula: 6. The compound of claim 5 , where Ris selected from —CH claim 5 , —OCH claim 5 , and Cand Ris H; or Ris selected from H claim 5 , —CH claim 5 , Cl claim 5 , and F claim 5 , and Ris Cl; or Ris H and Ris selected from —CHand —CN; Ris selected from H claim 5 , —Calkyl claim 5 , and —(CH)ORwhere Ris H or —CH; and Ris H.10. The compound of claim 9 , where Ris F claim 9 , Ris Cl claim 9 , Ris H claim 9 , Ris —OCHor —OCHCH claim 9 , and Ris H.14. The compound of claim 13 , where Ris F claim 13 , Ris Cl claim 13 , Ris H claim 13 , and Ris H.17. The compound of claim 16 , where Rand Rare H; Ris selected from —Calkyl claim 16 , —(CH)OR claim 16 , and —(CH)NRR; Ris selected from —OH claim 16 , —OCH claim 16 , —OCHCH claim 16 , and —Calkyl; and Ris H.18. The compound of claim 17 , where Rand Rare H claim 17 , Ris —CH claim 17 , Ris —OH or —OCH claim 17 , and Ris H.20. The compound of claim 19 , where Ris H claim 19 , Ris Cl claim 19 , Ris H claim 19 , —CH claim 19 , —CHCHor —(CH)OH claim 19 , Ris —OH or —OCH claim 19 , and Ris H; or Ris F claim 19 , Ris Cl claim 19 , Ris H or —Calkyl claim 19 , Ris —OH claim 19 , —OCHor —Calkyl claim 19 , and Ris H.22. The compound of claim 21 , where Ris H or F; Ris Cl; Ris H or —Callyl; Ris —OCH claim 21 , —OCHCH claim 21 , or —Calkyl; R claim 21 , if present claim 21 , is H; and Ris H.24. The compound of claim 23 , where Ris F claim 23 , Ris Cl claim 23 , Ris H or —Calkyl claim 23 , R claim 23 , if present claim 23 , is H claim 23 , and Ris H.27. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .28. The pharmaceutical composition of claim 27 , further comprising a therapeutic agent selected from adenosine receptor antagonists claim 27 , α-adrenergic receptor antagonists claim 27 , β-adrenergic receptor antagonists claim 27 , β-adrenergic receptor agonists claim 27 , dual-acting β-adrenergic receptor antagonist/α-receptor ...

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Номер записи: 54
13-02-2014 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20140046053A1
Автор: Fleury Melissa, Gendron Roland, Hughes Adam D.
Принадлежит: THERAVANCE, INC.

In one aspect, the invention relates to compounds having the formula: 14-. (canceled)5. The compound of claim 22 , where Ris selected from —ORand —NRR claim 22 , Ris H claim 22 , Ris H or —OH claim 22 , and Ris H.8. The compound of claim 22 , where Ris —NRR claim 22 , where Ris H and Ris H.9. The compound of claim 22 , where Ris H.1015-. (canceled)16. The compound of claim 22 , where a is 0; or a is 1 and Ris 3-chloro.17. The compound of claim 22 , where b is 0; or b is 1 and Ris 3′-chloro claim 22 , 3′-methyl claim 22 , or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro claim 22 , 2′ claim 22 ,5′-dichloro claim 22 , 2′-methyl-5′-chloro claim 22 , or 3′-chloro-5′-hydroxy.18. The compound of claim 22 , where the methylene linker on the biphenyl is substituted with 2 methyl groups.20. The compound of claim 22 , where{'sup': 1', '7, 'Ris —OR;'}{'sup': '2', 'Ris H;'}{'sup': '5', 'a is 0; or a is 1 and Ris 3-chloro;'}{'sup': 6', '6, 'b is 0; or b is 1 and Ris 3′-chloro, 3′-methyl, or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro, 2′,5′-dichloro, 2′-methyl-5′-chloro, or 3′-chloro-5′-hydroxy;'}andthe methylene linker on the biphenyl is optionally substituted with 2 methyl groups.21. (canceled)2328-. (canceled) This application claims the benefit of U.S. Provisional Application No. 61/423,180, filed on Dec. 15, 2010; the entire disclosure of which is incorporated herein by reference.1. Field of the InventionThe present invention relates to novel compounds having neprilysin-inhibition activity. The invention also relates to pharmaceutical compositions comprising such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat diseases such as hypertension, heart failure, pulmonary hypertension, and renal disease.2. State of the ArtNeprilysin (neutral endopeptidase, EC 3.4.24.11) (NEP), is an endothelial membrane bound Zn+ metallopeptidase found in many organs and tissues, including the brain, kidneys, lungs, ...

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Номер записи: 55
20-02-2014 дата публикации

Histone Deacetylase Inhibitors

Номер: US20140051680A1
Автор: Jacques Vincent, Peet Norton P., Rusche James R., Singh Jasbir
Принадлежит: REPLIGEN CORPORATION

This invention relates to generally inhibiting histone deacetylase (HDAC) enzymes (e.g., HDAC1, HDAC2, and HDAC3). 2. The compound or salt of claim 1 , wherein n is 1.3. The compound or salt of claim 2 , wherein X is —Y—[C(R)]-A-[C(R)]-B-.4. The compound or salt of claim 3 , wherein A is a bond and/or B is a bond.5. The compound or salt of claim 3 , wherein each occurrence of Rand R(when present) is independently selected from H claim 3 , F claim 3 , OH claim 3 , C1-C6 alkyl claim 3 , C3-C6 cycloalkyl claim 3 , NH claim 3 , OCO—(C1-C6 alkyl) claim 3 , OCO—(C3-C6 cycloalkyl) claim 3 , C1-C6 alkoxy claim 3 , C1-C6 fluoroalkoxy claim 3 , and cyano.6. (canceled)7. The compound or salt of claim 5 , wherein each occurrence of Rand R(when present) is H.8. The compound or salt of claim 3 , wherein Y is CR═CR claim 3 , O claim 3 , or NR.934-. (canceled)35. The compound or salt of claim 1 , wherein each of R4 and R5 is H.3646-. (canceled)47. The compound or salt of claim 1 , wherein n is 0.48. The compound or salt of claim 47 , wherein Ar′/Het′ is:{'sup': 'p', '(i) phenyl, pyridyl, or pyrimidinyl, each of which is optionally substituted with from 1-3 R; provided that the point of connection on said phenyl, pyridyl, or pyrimidinyl to U (i.e., the connection U—Ar′/Het′ in formula I) and the point of connection on said phenyl, pyridyl, or pyrimidinyl to the amide carbonyl (i.e., the connection Ar′/Het′-C(═O) in formula I) do not result in 1,2-relation to one another on said phenyl, pyridyl, or pyrimidinyl (i.e., the points of connection to U and C(O) on said phenyl, pyridyl, or pyrimidinyl are not ortho with respect to one another).'}49. The compound or salt according to claim 47 , wherein Ar′/Het′ is:{'sup': 'p', '(i) phenyl, pyridyl, or pyrimidinyl, each of which is optionally substituted with from 1-3 R; wherein the point of connection on said phenyl, pyridyl, or pyrimidinyl to U (i.e., the connection U—Ar′/Het′ in formula I) and the point of connection on said phenyl, ...

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Номер записи: 56
20-03-2014 дата публикации

Fungicidal azocyclic amides

Номер: US20140081027A1
Автор: Mary Ann Hanagan, Rafael Shapiro, Robert James Pasteris
Принадлежит: EI Du Pont de Nemours and Co

Disclosed are compounds of Formulae 1, 1A, 1B and 1C including all geometric and stereoisomers, N-oxides, and salts thereof, wherein R 1 , R 2 , R 4a1 , R 4a2 , A, A a , G, M, W, Z 1 , Z 3 , X, J, J 1 and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

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Номер записи: 57
27-03-2014 дата публикации

Substituted carbamoylmethylamino acetic acid derivatives as novel NEP inhibitors

Номер: US20140088165A1
Автор: IWAKI Yuki, KAWANAMI Toshio, KSANDER Gary Michael, Moji Muneto
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I; 7. The method of wherein{'sup': '1', 'sub': '2', 'Ais a bond or CH; or a pharmaceutically acceptable salt thereof.'}8. The method of wherein{'sup': 1', '5', '4, 'Ris methyl or ethyl, Rand Rare H; or a pharmaceutically acceptable salt thereof.'}10. The method of wherein{'sup': '3', 'Ris tetrazole; or a pharmaceutically acceptable salt thereof.'}11. The method of wherein{'sup': '2', 'Xis Cl, or a pharmaceutically acceptable salt thereof.'}1219-. (canceled) Endogenous atrial natriuretic peptides (ANP), also called atrial natriuretic factors (ANF) have diuretic, natriuretic and vasorelaxant functions in mammals. The natural ANF peptides is metabolically inactivated, in particular by a degrading enzyme which has been recognized to correspond to the enzyme neutral endopeptidase (NEP) EC 3.4.24.11, also responsible for e.g. the metabolic inactivation of enkephalins.Neutral endopeptidase (EC 3.4.24.11; enkephalinase; atriopeptidase; NEP) is a zinc-containing metalloprotease that cleaves a variety of peptide substrates on the amino side of hydrophobic residues [see , Vol. 45, p. 87 (1993)]. Substrates for this enzyme include, but are not limited to, atrial natriuretic peptide (ANP, also known as ANF), brain natriuretic peptide (BNP), met- and leu-enkephalin, bradykinin, neurokinin A, endothelin-1 and substance P. ANP is a potent vasorelaxant and natriuretic agent [see , Vol. 19, p. 1923 (2001)]. Infusion of ANP in normal subjects resulted in a reproducible, marked enhancement of natriuresis and diuresis, including increases in fractional excretion of sodium, urinary flow rate and glomerular filtration rate [see , Vol. 27, p. 927 (1987)]. However, ANP has a short half-life in circulation, and NEP in kidney cortex membranes has been shown to be the major enzyme responsible for degrading this peptide [see , Vol. 9, p. 173 (1988)]. Thus, inhibitors of NEP (neutral endopeptidase inhibitors, NEPi) should increase plasma ...

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Номер записи: 58
04-01-2018 дата публикации

AZOLINE COMPOUNDS SUBSTITUTED BY A CARBOCYCLIC CONDENSED RING SYSTEM

Номер: US20180000079A1
Автор: BINDSCHAEDLER Pascal, BRAUN Franz-Josef, Datta Gopal Krishna, VON DEYN Wolfgang
Принадлежит: BASF SE

Compounds of formula (I) 2. The compounds as claimed in claim 1 , where Xis O.3. The compounds as claimed in claim 1 , where Xis CH.4. The compounds as claimed in claim 1 , wherein A is the group A claim 1 ,{'sup': '7a', 'Ris hydrogen;'}{'sup': '7b', 'sub': 3', '3, 'Ris selected from hydrogen, CH, CFand CN;'}{'sup': '51', 'sub': 1', '3, 'Ris selected from hydrogen and C-C-alkyl; and'}{'sup': 61', '81', '16, 'sub': 1', '6', '1', '6', '1', '4', '3', '6', '3', '6', '3', '6, 'claim-text': {'sup': 81', '16, 'sub': 3', '6', '3', '6', '3', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris selected from CN, C-C-cycloalkyl, C-C-cycloalkyl which carries one of a CN and a CFsubstituent, C-C-halocycloalkyl, C-C-alkoxy, C-C-haloalkoxy, C-C-alkylthio, C-C-haloalkylthio, C-C-alkylsulfinyl, C-C-haloalkylsulfinyl, C-C-alkylsulfonyl, C-C-haloalkylsulfonyl, phenyl, phenyl optionally substituted with up to 3 substituents R, and the heterocyclic ring selected from the rings of formulae E-1 to E-63;'}, 'Ris selected from C-C-alkyl, C-C-haloalkyl, C-C-alkyl substituted by one radical R, C-C-cycloalkyl, C-C-cycloalkyl which carries a CN substituent, C-C-halocycloalkyl, phenyl, phenyl which is substituted with up to 5 substituents R; and the heterocyclic ring selected from the rings of formulae E-1 to E-63;'} {'sup': '16', 'sub': 1', '4', '1-', '4', '1', '4', '1', '4, 'the Rin phenyl and in the rings of formulae E-1 to E-63 is selected from halogen, cyano, C-C-alkyl, CC-haloalkyl, C-C-alkoxy and C-C-haloalkoxy.'}, 'and'}5. The compounds as claimed in claim 4 ,wherein{'sup': 7a', '7b, 'Rand Rare hydrogen;'}{'sup': '51', 'Ris hydrogen; and'}{'sup': 61', '81, 'sub': 1', '6', '1', '6', '1', '4', '3', '6', '3', '6', '3', '6, 'claim-text': {'sup': '81', 'sub': 3', '6', '3', '6', '3', '3', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris selected from CN, C-C-cycloalkyl, C-C-cycloalkyl which carries one of a CN and ...

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Номер записи: 59
02-01-2020 дата публикации

ISOXAZOLINE-SUBSTITUTED BENZAMIDE COMPOUND AND PESTICIDE

Номер: US20200000777A1
Автор: KIKUCHI Takamasa, KOMODA Mitsuaki, MITA Takeshi, MIZUKOSHI Takashi, Takii Shinji, YAOSAKA Manabu
Принадлежит: NISSAN CHEMICAL CORPORATION

A substituted alkenylbenzene compound of formula (4): 2. The substituted alkenylbenzene compound of formula (4) according to claim 1 , wherein:{'sup': '1', 'sub': 5', '1', '6', '1', '6', '1', '6, 'Xis selected from the group consisting of a halogen atom, —SF, C-Chaloalkyl, C-Chaloalkoxy and C-Chaloalkylthio;'}{'sup': '3', 'sub': 1', '6', '1', '6', '1', '6, 'Xis selected from the group consisting of a hydrogen atom, halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl and C-Calkoxy;'}{'sup': '4', 'Xis a hydrogen atom or halogen atom;'}{'sup': 3a', '3b, 'Rand Rare each a fluorine atom;'}{'sup': 3c', '2', '3', '4', '1', '3', '4', '1', '3', '4', '3c, 'Ris selected from the group consisting of a hydrogen atom, fluorine atom, chlorine atom, bromine atom and trifluoromethyl, with a proviso that in case where Xis a fluorine atom, chlorine atom or trifluoromethyl and both Xand Xare a hydrogen atom, in case where both Xand Xare a fluorine atom and Xis a hydrogen atom, and in case where both Xand Xare trifluoromethyl and Xis a hydrogen atom, Ris a hydrogen atom, chlorine atom, bromine atom or trifluoromethyl.'} This application is a continuation of U.S. patent application Ser. No. 15/972,939, filed May 7, 2018, which is a continuation of U.S. patent application Ser. No. 15/097,002, filed Apr. 12, 2016, now U.S. Pat. No. 10,045,969, which is a continuation of U.S. patent application Ser. No. 14/568,964, filed Dec. 12, 2014, which is a continuation of U.S. patent application Ser. No. 13/850,067, filed Mar. 25, 2013, now U.S. Pat. No. 8,946,492, which is a divisional of U.S. patent application Ser. No. 13/350,297, filed Jan. 13, 2012, now U.S. Pat. No. 8,492,311, which is a divisional of U.S. patent application Ser. No. 13/166,294, filed Jun. 22, 2011, now U.S. Pat. No. 8,138,213, which is a divisional of U.S. patent application Ser. No. 12/509,859, filed Jul. 27, 2009, now U.S. Pat. No. 8,022,089, which is a divisional of U.S. patent application Ser. No. 11/514,921, filed Sep. 5, ...

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Номер записи: 60
07-01-2016 дата публикации

CRYSTALLINE FORMS OF TRYOSINE KINASE INHIBITORS AND THEIR SALTS

Номер: US20160002182A1
Автор: WANG Ling, Wu Jay Jie-Qiang
Принадлежит: VM PHARMA LLC

The invention relates to various polymorphic forms and amorphous form of sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzate, including the polymorphic form A, mixtures of the polymorphs, process for the preparation thereof and the use thereof in a pharmaceutical composition containing thereof. 2. A pharmaceutical composition claim 1 , comprising: the compound according to .3. A crystalline form of Compound I.4. The crystalline Compound I of claim 3 , which is crystalline polymorph Form A.5. The crystalline polymorph of claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 10.0±0.3 claim 4 , 20.1±0.3 claim 4 , and 23.6±0.3.65. The crystalline polymorph of any of - claims 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 14.5±0.3 and 18.1±0.3.76. The crystalline polymorph of any of - claims 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 9.7±0.3 and 21.2±0.3.87. The crystalline polymorph of any of - claims 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having three or more peak positions at degree two-theta selected from the group consisting of about: 7:160 claims 4 , 8.757 claims 4 , 9.820 claims 4 , 10:161 claims 4 , 12.459 claims 4 , 14.641 claims 4 , 15.219 claims 4 , 17:680 claims 4 , 18.240 claims 4 , 19.104 claims 4 , 20:220 claims 4 , 21.381 claims 4 , 22.579 claims 4 , 23.721 claims 4 , 24:898 claims 4 , 25.761 claims 4 , 25.522 claims 4 , 27.161 claims 4 , 28:321 claims 4 , 28.321 claims 4 , 29.481 claims 4 , 30.921 claims 4 , and 34:281.98. The crystalline polymorph of any of - claims 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having five or more peak positions at degree two-theta ...

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Номер записи: 61
07-01-2016 дата публикации

SYNTHESIS OF TETRACYCLINES AND INTERMEDIATES THERETO

Номер: US20160002183A1
Автор: Dion Amelie, Hecker Evan, Kummer David A., Li Derun, Myers Andrew G., Wright Peter M.
Принадлежит: President and Fellows of Harvard College

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides more efficient routes for preparing the enone intermediate and allows for substituents at positions 4a, 5, 5a, and 12a of the tetracycline ring system. 2. The compound of claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , —OR claim 1 , or Calkyl.3. The compound of claim 1 , wherein Ris hydrogen claim 1 , halogen claim 1 , —OR claim 1 , or Calkyl.4. The compound of claim 1 , wherein Ris —N(R)or —OR.5. The compound of claim 1 , wherein Ris —OR.6. The compound of claim 1 , wherein Ris Calkyl.7. The compound of claim 1 , wherein Ris —N(R).8. The compound of claim 1 , wherein Ris substituted or unsubstituted alkyl claim 1 , —OR claim 1 , or halogen.9. The compound of claim 1 , wherein Ris hydrogen or substituted or unsubstituted alkyl.10. The compound of claim 1 , wherein Ris —ORor —N(R). The present application is a continuation of and claims priority under 35 U.S.C. §120 to U.S. Application, U.S. Ser. No. 13/266,788, filed Jan. 11, 2012, which is a national stage filing under 35 U.S.C. §371 of international PCT application, PCT/US2010/001284, filed Apr. 30, 2010, which claims priority under 35 U.S.C. §119(e) to U.S. provisional patent applications, U.S. Ser. No. 61/174,185, filed Apr. 30, 2009, and U.S. Ser. No. 61/322,613, filed Apr. 9, 2010, each of which is incorporated herein by reference.This invention was made with U.S. Government support under grant R01 AI048825 and predoctoral fellowship GM007598-30 awarded by the National ...

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Номер записи: 62
05-01-2017 дата публикации

CRYSTALLINE FORMS OF TYROSINE KINASE INHIBITORS AND THEIR SALTS

Номер: US20170001969A9
Автор: WANG Ling, Wu Jay Jie-Qiang
Принадлежит: Purdue Pharma L.P.

The invention relates to various polymorphic forms and amorphous form of sodium 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzate, including the polymorphic form A, mixtures of the polymorphs, process for the preparation thereof and the use thereof in a pharmaceutical composition containing thereof. 2. A pharmaceutical composition claim 1 , comprising: the compound according to .3. A crystalline form of Compound I.4. The crystalline Compound I of claim 3 , which is crystalline polymorph Form A.5. The crystalline polymorph of claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 10.0±0.3 claim 4 , 20.1±0.3 claim 4 , and 23.6±0.3.6. The crystalline polymorph of any of - claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 14.5±0.3 and 18.1±0.3.7. The crystalline polymorph of any of - claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having peak positions at degree two-theta of about: 9.7±0.3 and 21.2±0.3.8. The crystalline polymorph of any of - claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having three or more peak positions at degree two-theta selected from the group consisting of about: 7.160 claim 4 , 8.757 claim 4 , 9.820 claim 4 , 10.161 claim 4 , 12.459 claim 4 , 14.641 claim 4 , 15.219 claim 4 , 17.680 claim 4 , 18.240 claim 4 , 19.104 claim 4 , 20.220 claim 4 , 21.381 claim 4 , 22.579 claim 4 , 23.721 claim 4 , 24.898 claim 4 , 25.761 claim 4 , 25.522 claim 4 , 27.161 claim 4 , 28.321 claim 4 , 28.321 claim 4 , 29.481 claim 4 , 30.921 claim 4 , and 34.281.9. The crystalline polymorph of any of - claim 4 , wherein the crystalline polymorph exhibits an x-ray powder diffraction pattern having five or more peak positions at degree two-theta selected from the group consisting ...

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Номер записи: 63
04-01-2018 дата публикации

ANTIOXIDANT INFLAMMATION MODULATORS: OLEANOLIC ACID DERIVATIVES WITH AMINO AND OTHER MODIFICATIONS AT C-17

Номер: US20180002277A1
Автор: Anderson Eric, Jiang Xin, Visnick Melean
Принадлежит: REATA PHARMACEUTICALS, INC.

This invention provides, but is not limited to, novel oleanolic acid derivatives having the formula: 1257-. (canceled)259264-. (canceled)266. The method of claim 265 , wherein Ris hydrogen.267. The method of claim 265 , wherein Ris alkylor substituted alkyl.268. The method of claim 265 , wherein Ris alkylsulfonyl claim 265 , arylsulfonyl claim 265 , aralkylsulfonyl claim 265 , heteroarylsulfonyl claim 265 , heteroaralkylsulfonyl claim 265 , or a substituted version of any of these groups.269. The method of claim 265 , wherein Ris acylor substituted acyl.270. The method of claim 269 , wherein Ris substituted acyl.272. The method of claim 271 , wherein Ris hydrogen.273. The method of claim 271 , wherein Ris alkylor substituted alkyl.274. The method of claim 271 , wherein Ris alkylsulfonyl claim 271 , arylsulfonyl claim 271 , aralkylsulfonyl claim 271 , heteroarylsulfonyl claim 271 , heteroaralkylsulfonyl claim 271 , or a substituted version of any of these groups.275. The method of claim 271 , wherein Ris acylor substituted acyl.276. The method of claim 271 , wherein Ris substituted acyl.278. The method of claim 277 , wherein the acylation agent is an acyl halide or an anhydride.279. The method of claim 277 , wherein the acylation agent is an acyl halide.280. The method of claim 277 , wherein the acylation agent is an acyl chloride.281. The method of claim 258 , wherein the modification is conducted in a medium comprising a solvent.282. The method of claim 281 , wherein the solvent is benzene or dichloromethane.283. The method of claim 258 , wherein the modification is conducted in the presence of a base.284. The method of claim 283 , wherein the base is NEt. The present application is a continuation of U.S. patent application Ser. No. 14/753,297, filed Jun. 29, 2015, now U.S. Pat. No. 9,670,147, which is a continuation of U.S. patent application Ser. No. 13/861,208, filed Apr. 11, 2013, now U.S. Pat. No. 9,102,681, which is a continuation of U.S. patent application ...

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Номер записи: 64
03-01-2019 дата публикации

CRYSTALLINE(2S,4R)-5-(5'-CHLORO-2'-FLUORO-[1,1'-BIPHENY]-4-YL)-2-(ETHOXYMETHYL)-4-(3-HYDROXYISOXAZOLE-5-CARBOXAMIDO)-2-METHYLPENTANOIC ACID AND USES THEREOF

Номер: US20190002416A1
Автор: Baldwin R. Michael, Bourdet David L., Fleury Melissa, Hughes Adam D., Rapta Miroslav, Thalladi Venkat R.
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

In one aspect, the invention relates to a crystalline form of the structure: 116-. (canceled)17. A method for treating hypertension , heart failure , or renal disease , the method comprising administering (2S ,4R)-5-(5′-chloro-2′-fluoro-[1 ,1′-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid (Compound I) or crystalline free acid form of (2S ,4R)-5-(5′-chloro-2′-fluoro-[1 ,1′-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3 -hydroxyi soxazole-5-carboxamido)-2-methylpentanoic acid (Compound to a patient once-daily.18. The method according to claim 17 , wherein hypertension is primary hypertension claim 17 , pulmonary arterial hypertension claim 17 , chronic thromboembolic pulmonary hypertension claim 17 , or hypertension with renal artery stenosis.19. The method according to claim 17 , wherein renal disease is diabetic nephropathy claim 17 , chronic kidney disease claim 17 , proteinuria claim 17 , acute kidney injury claim 17 , nephrotic syndrome claim 17 , focal segmental glomerulosclerosis or polycystic kidney disease.20. A method of treating hypertension claim 17 , heart failure claim 17 , or renal disease in a renally-impaired patient claim 17 , the method comprising administering a therapeutically effective amount of (2S claim 17 ,4R)-5-(5′-chloro-2′-fluoro-[1 claim 17 ,1′-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid Compound or crystalline free acid form of (2S claim 17 , 4R)-5-(5′-chloro-2′-fluoro-[1 claim 17 ,1′-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid (Compound I′) to the patient once-daily.21. The method according to claim 20 , wherein the renally-impaired patient has chronic kidney disease with an estimated glomerular filtration rate (eGFR) between 60 mL/min/1.73 mand 15 mL/min/1.73 m.22. A method of increasing atrial natriuretic peptide (ANP) or cyclic guanosine monophosphate (cGMP) levels in a human for at least 24 hours ...

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Номер записи: 65
07-01-2021 дата публикации

HETEROCYCLIC COMPOUNDS AS FUNGICIDES

Номер: US20210002232A1
Автор: ADHAV Nilesh Bharat, AUTKAR Santosh Shridhar, BHUJADE Paras Raybhan, Garg Ruchi, GUMME Sachin Nagnath, KLAUSENER Alexander G.M., NAIK Maruti N, Pawar Rajesh, Potlapally Rajender Kumar, VENKATESHA Hagalavadi M, YUVARAJ J.
Принадлежит: PI INDUSTRIES LTD.

The present invention relates to novel heterocyclic compound of Formula I, 2. The compound of claim 1 ,wherein,Het is Het-1, Het-2, Het-3, Het-4, Het-5, Het-6, Het-7 and Het-9;{'sup': '1', 'sub': 3', '2', '2', '2', '3', '2', '2', '3', '3', '2', '3, 'Ris selected from the group consisting of CF, CHF, CFCl, CFCFCHF, CHCF, CHClCFand CClCF;'}{'sup': '1', 'Lis direct bond;'}A is phenyl; and{'sup': 2', '2a', '2b', '2c', '2f', '2g, 'sub': '2', 'Lis S(═O), C(═O), L, L, L, Land L.'}3. The compound of claim 1 , is selected from the group consisting of:{'sup': 6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '6, 'N-((4-fluorophenyl)(methyl)(oxo)-λ-sulfaneylidene)-4-(5-(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzamide; N-(4-(5-(difluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-N-methoxybenzamide; N-(4-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)benzyl)pivalamide; 5-(difluoromethyl)-3-(4-(phenylsulfonyl)phenyl)-1,2,4-oxadiazole; N-((4-fluorophenyl)(methyl)(oxo)-λ-sulfaneylidene)-4-(5-(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzamide; N-((4-fluorophenyl)(methyl)(oxo)-λ-sulfaneylidene)-4-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)benzamide; N-(methyl(oxo)(phenyl)-λ-sulfaneylidene)-4-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)benzamide; 3-(4-(phenylsulfonyl)phenyl)-5-(trifluoromethyl)-1H-1,2,4-triazole; N-(methyl(oxo)(phenyl)-A-sulfaneylidene)-4-(5-(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzamide; N-methyl-N-(2-phenoxyethyl)-4-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)benzamide; 3-(4-(phenylsulfonyl)phenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazole; N-methyl-N-(2-phenoxyethyl)-4-(5-(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-3-yl)benzamide; (4-methoxyphenyl)(methyl)((4-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)phenyl)imino)-λ-sulfanone; (4-methoxyphenyl)(methyl)((4-(5-( ...

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Номер записи: 66
07-01-2021 дата публикации

A CRYSTAL OF A CASPASE INHIBITOR

Номер: US20210002235A1
Автор: He Haiying, Mou Jianfeng, Wu Songliang
Принадлежит:

Disclosed herein a crystal structure of a caspase inhibitor, and more specifically a crystal structure of an (S)-3-((S)-2-(5-(2-chlorophenyl)isoxazole-3-formylamide)proponamide)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)valeric acid, a preparation method therefor, a crystal polymer, a pharmaceutical composition and uses thereof. The compound A of formula (I) disclosed herein exhibits high crystal structure stability, low hygroscopicity, and advantageously shows physical properties, safety and metabolic stability while having relatively high pharmaceutical value. 232-. (canceled)33. The crystal according to claim 1 , wherein the crystal is crystal IV of the compound of formula I-A claim 1 , and wherein the X-ray powder diffraction spectrum represented by 2θ values has diffraction peaks at about 5.6° claim 1 , 11.2° claim 1 , 12.9° claim 1 , 15.1° claim 1 , 15.6° claim 1 , 16.7° claim 1 , 22.7° claim 1 , and 25.6°.34. The crystal according to claim 33 , wherein the X-ray powder diffraction spectrum represented by 2θ values has diffraction peaks at about 5.6° claim 33 , 7.6° claim 33 , 8.6° claim 33 , 9.1° claim 33 , 11.2° claim 33 , 12.0° claim 33 , 12.9° claim 33 , 14.0° claim 33 , 15.1° claim 33 , 15.6° claim 33 , 16.4° claim 33 , 16.7° claim 33 , 19.3° claim 33 , 22.7° claim 33 , 23.5° claim 33 , 25.1° claim 33 , 25.6° claim 33 , 27.2° claim 33 , 27.8° claim 33 , 29.1° claim 33 , 30.7° claim 33 , 31.5° claim 33 , 33.7° claim 33 , 34.7° claim 33 , 36.6° claim 33 , 37.0° claim 33 , and 38.2°.35. The crystal according to claim 1 , wherein the crystal is crystal IV of the compound of formula I-A claim 1 , and wherein in a differential scanning calorimetry (DSC) measurement pattern claim 1 , an onset of absorption peak is at about 167° C.36. The crystal according to claim 1 , wherein the crystal is crystal I of the compound of formula I-A claim 1 , and wherein the X-ray powder diffraction spectrum represented by 2θ values has diffraction peaks at about 9.6° claim 1 , 14.0° ...

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Номер записи: 67
01-01-2015 дата публикации

CRYSTALLINE POLYMORPHS OF ISOXAZOLINE COMPOUND AND PRODUCTION METHOD THEREOF

Номер: US20150005507A1
Автор: IMANAKA Hotaka, Kagami Takahiro, Kobayashi Masaki, MATOBA Kazutaka, MATSUBARA Kotatsu, MITA Takeshi, MIYACHI Rika, NAKAHIRA Kunimitsu, OHNO Masashi
Принадлежит:

A method for manufacturing a crystal and a crystal of (S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide and a method for manufacturing the crystal. It is elucidated that (S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]benzamide that has a crystalline polymorph. 1. A crystalline polymorph of (S)-4-[5-(3 ,5-dichlorophenyl)-5-(trifluoromethyl)-4 ,5-dihydroisoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2 ,2 ,2-trifluoroethylamino)ethyl]benzamide that has characteristic peaks at angles of diffraction 2θ=6.56 , 7.38 , 11.52 , 12.92 , 13.19 , 15.60 , 16.04 , 16.36 , 17.59 , 18.27 , 18.47 , 19.45 , 20.62 , 21.12 , 22.20 , 23.19 , 24.59 , 25.12 , 25.74 , and 26.48 in powder X-ray diffraction with a Cu—Kα ray.2. The crystalline polymorph according to claim 1 , whereincharacteristic peaks are at angles of diffraction 2θ=3.66, 5.73, 6.56, 7.38, 7.76, 9.18, 11.52, 12.24, 12.92, 13.19, 13.98, 14.81, 15.60, 16.04, 16.36, 16.98, 17.59, 18.02, 18.27, 18.47, 18.87, 19.45, 20.21, 20.48, 20.62, 21.12, 21.51, 21.92, 22.20, 22.66, 23.19, 23.58, 24.24, 24.59, 24.96, 25.12, 25.74, 26.08, 26.48, 27.52, 28.20, 29.18, 29.61, 30.06, 30.50, 30.88, 35.77, and 38.92 in powder X-ray diffraction with a Cu—Kα ray.3. A crystalline polymorph of (S)-4-[5-(3 claim 1 ,5-dichlorophenyl)-5-(trifluoromethyl)-4 claim 1 ,5-dihydroisoxazol-3-yl]-2-methyl-N-[2-oxo-2-(2 claim 1 ,2 claim 1 ,2-trifluoroethylamino)ethyl]benzamide that has characteristic peaks at angles of diffraction 2θ=6.56±0.2 claim 1 , 7.38±0.2 claim 1 , 11.52±0.2 claim 1 , 12.92±0.2 claim 1 , 13.19±0.2 claim 1 , 15.60±0.2 claim 1 , 16.04±0.2 claim 1 , 16.36±0.2 claim 1 , 17.59±0.2 claim 1 , 18.27±0.2 claim 1 , 18.47±0.2 claim 1 , 19.45±0.2 claim 1 , 20.62±0.2 claim 1 , 21.12±0.2 claim 1 , 22.20±0.2 claim 1 , 23.19±0.2 claim 1 , 24.59±0.2 claim 1 , 25.12±0.2 claim 1 , 25.74±0.2 claim 1 , ...

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Номер записи: 68
12-01-2017 дата публикации

PROCESS FOR PREPARING CLOMAZONE, NOVEL FORM AND USE OF THE SAME

Номер: US20170008860A1
Автор: BRISTOW James Timothy
Принадлежит: ROTAM AGROCHEM INTERNATIONAL COMPANY LIMITED

A process for preparing clomazone is provided, the process comprising reacting 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride in an aqueous medium in the presence of a base, in particular an alkali metal hydroxide. A method for preparing clomazone is also disclosed, the method comprising (a) crystallizing clomazone from solution in an organic solvent; and (b) isolating the resulting crystals. N-benzene is a particularly suitable solvent. Further, there is provided Form I crystalline 2-[(2-chlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone (clomazone), wherein the polymorph Form I is characterized by at least one of the following properties: 1. A process for preparing clomazone , the process comprising:reacting 4,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride in an aqueous medium in the presence of a first base.2. The process according to claim 1 , wherein the first base is selected from a hydroxide claim 1 , a carbonate claim 1 , a hydride or a mixture thereof.3. The process according to claim 1 , wherein the first base is a metal base.4. The process according to claim 3 , wherein the metal is an alkali or alkaline earth metal.5. The process according to claim 4 , wherein the metal is sodium or potassium.6. The process according to claim 1 , wherein the reaction mixture has a pH of the in the range of from 7.5 to 9.5.7. The process according to claim 6 , wherein the pH is in the range of from 8.5 to 9.5.8. The process according to claim 1 , wherein the reaction is conducted at an elevated temperature.9. The process according to claim 8 , wherein the reaction is conducted at a temperature in the range of from 50 to 95° C.10. The process according to claim 9 , wherein the reaction is conducted at a temperature in the range of from 60 to 90° C.11. The process according to claim 1 , wherein 4 claim 1 ,4-dimethyl-3-isoxazolidinone with 2-chlorobenzyl chloride is prepared by cyclizing 3-chloro-N-hydroxy-2 claim 1 ,2-dimethylpropanamide with a ...

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Номер записи: 69
14-01-2016 дата публикации

SUBSTITUTED BENZOXAZOLES AND METHODS OF USE THEREOF

Номер: US20160009667A1
Автор: Chen Chien-An, Chowdhury Sultan, DEHNHARDT Christoph Martin, Sun Shaoyi
Принадлежит:

The invention provides compounds having the general formula (I): and pharmaceutically acceptable salts thereof, wherein the variables RA, subscript n, ring A, X, L, subscript m, X, R, R, R, R, and Rhave the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions. 3. (canceled)4. The compound of wherein Ris F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , or Ccarbocycle.5. (canceled)6. The compound of wherein Ris Cl or Ccyclopropyl.7. The compound of wherein Ris Calkyl or Ccarbocycle claim 1 , wherein the aliphatic portions of Rare optionally substituted with from 1 to 5 Rsubstituents.8. (canceled)9. The compound of wherein Ris methyl claim 7 , cyclopropyl claim 7 , or 2-methoxyethyl.11. The compound of wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted group selected from the group consisting of Calkylene claim 1 , Calkenylene or Calkynylene.1217-. (canceled)18. The compound of wherein A is an optionally substituted ring selected from the group consisting of cyclopropane claim 1 , cyclobutane claim 1 , cyclopentane claim 1 , cyclohexane claim 1 , cycloheptane claim 1 , adamantane claim 1 , bicyclo[2.1.1]hexane claim 1 , bicyclo[2.2.2]octane claim 1 , bicyclo[2.2.1]heptane claim 1 , bicyclo[3.1.1]heptane claim 1 , bicyclo[3.2.1]octane claim 1 , bicyclo[4.1.1]octane claim 1 , bicyclo[3.3.1]nonane and 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-1 claim 1 ,4-methanonaphthalene claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroisoquinoline claim 1 , cubane claim 1 , spiro[2 claim 1 ,5]octane claim 1 , tetrahydronaphthalene and chroman.19. The compound of claim 18 , wherein ring A is an optionally substituted ring selected from the group consisting of cyclopropane claim 18 , cyclobutane claim 18 , cyclopentane claim 18 , cyclohexane claim 18 , adamantane claim 18 , cubane claim ...

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Номер записи: 70
09-01-2020 дата публикации

Compounds, compositions, and methods for increasing cftr activity

Номер: US20200010461A1
Автор: Benito Munoz, Cecilia M. Bastos, Daniel Parks, Matthew Cullen
Принадлежит: Proteostasis Therapeutics Inc

The present disclosure is directed to disclosed compounds that increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells.

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Номер записи: 71
03-02-2022 дата публикации

INSECTICIDAL COMPOUNDS

Номер: US20220033364A1
Автор: BIGOT Aurelien, El Qacemi Myriem, Jeanguenat Andre
Принадлежит: SYNGENTA CROP PROTECTION AG

The present invention relates to compounds of formula (I) wherein A, A, A, A, R, R, R, Rand n are as defined in claim ; or a tautomer, isomer, enantiomer, salt or N-oxide thereof; to intermediates for preparing compounds of formula (I), to compositions comprising them and to methods of using them to combat and control insect, acarine, nematode and mollusc pests. 2. The compound according to claim 1 , wherein{'sup': 1', '5', '2', '3', '4', '5, 'sub': 1', '8', '3', '8', '1', '8', '2', '8, 'Ais C—R; Ais C—H; Ais C—H; and Ais C—H, wherein Ris halogen, cyano, nitro, C-Calkyl, C-Ccycloalkyl, C-Chaloalkyl, or C-Calkenyl.'}3. The compound according to claim 1 , wherein Ris selected from —(C-Calkyl)-C(═O)—C-Ccycloalkyl and —(C-Calkyl)-O—C-Ccycloalkyl.4. The compound according to claim 1 , wherein Ris C-Chaloalkyl.5. The compound according to claim 1 , wherein Ris C-Chaloalkyl.6. The compound according to claim 1 , wherein Ris phenyl or phenyl substituted by one to three R; wherein Ris independently halogen claim 1 , cyano claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , or C-Chaloalkoxy.7. The compound according to claim 1 , wherein Ais CRand A claim 1 , Aand Aare each CH; Ris selected from —(C-Calkyl)-C(═O)—C-Ccycloalkyl and —(C-Calkyl)-O—C-Ccycloalkyl; Ris C-Chaloalkyl; Ris C-Chaloalkyl; Ris aryl or aryl substituted by one to three R; and n is 2; wherein Ris C-Calkyl; and Ris independently halogen claim 1 , cyano claim 1 , nitro claim 1 , C-Calkyl claim 1 , or C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , or C-Chaloalkoxy.10. A method of combating and/or controlling an invertebrate animal pest which comprises applying to the pest claim 1 , to a locus of the pest claim 1 , or to a plant susceptible to attack by the pest a pesticidally effective amount of a compound of formula (I) claim 1 , as defined in .11. A pesticidal composition claim 1 , which comprises at least one compound of formula (I) according to claim 1 , or where appropriate a tautomer ...

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Номер записи: 72
03-02-2022 дата публикации

INSECTICIDAL COMPOUNDS

Номер: US20220033389A1
Автор: BIGOT Aurelien, El Qacemi Myriem, Jeanguenat Andre
Принадлежит: SYNGENTA CROP PROTECTION AG

Compounds of formula (I), wherein the substituents are as defined in claim , and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, and their uses as insecticides. 2. The compound of formula (I) according to claim 1 , wherein Ais C—R; Ais C—H; Ais C—H; and Ais C—H claim 1 , wherein Ris halogen claim 1 , cyano claim 1 , nitro claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Chaloalkyl claim 1 , or C-Calkenyl.3. The compound of formula (I) according to claim 1 , wherein Ris halogen claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , C-Chaloalkoxy or di-C-Calkylamino claim 1 , C-Calkylthio claim 1 , C-Calkyloxycarbonyl.4. The compound of formula (I) according to claim 1 , wherein Ris C-Calkoxy.5. The compound of formula (I) according to claim 1 , wherein{'sup': 1', '1a', '1b', '1a', '1b', '1a', '1c', '1b', '1a', '1b', '1c, 'sub': 0', '4', '3', '6', '0', '4', '3', '6, 'Ris selected from —(C-Calkyl)-C(═O)—C-Ccycloalkyl, —(C-Calkyl)-O—C(═O)—C-Ccycloalkyl, —ROC(═O)R, —ROC(═O)OR, —RN(R)C(═O)ORand —ROC(═O)N(R)(R).'}6. The compound of formula (I) according to claim 1 , wherein{'sup': '3', 'sub': 1', '4, 'Ris C-Chaloalkyl.'}7. The compound of formula (I) according to claim 1 , wherein{'sup': 4', '6b, 'Ris phenyl or phenyl substituted by one to three R'}{'sup': '6b', 'sub': 1', '4', '1', '4', '1', '4', '1', '4, 'Rindependently is halogen, cyano, nitro, C-Calkyl, C-Chaloalkyl, C-Calkoxy, or C-Chaloalkoxy; more preferably bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy'}9. The compound of wherein Ris selected from —(C-Calkyl)-C(═O)—C-Ccycloalkyl claim 8 , —(C-Calkyl)-O—C(═O)—C-Ccycloalkyl claim 8 , —ROC(═O)R claim 8 , —ROC(═O)OR claim 8 , —RN(R)C(═O)ORand —ROC(═O)N(R)(R).13. The compound of claim 12 , wherein the compound is the compound of formula (Int-IV).14. A pesticidal composition claim 1 , which ...

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Номер записи: 73
15-01-2015 дата публикации

ESX-MEDIATED TRANSCRIPTION MODULATORS AND RELATED METHODS

Номер: US20150017156A1
Автор: Mapp Anna, Pan Quintin
Принадлежит:

The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating ESX-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant EGFR expression with ESX-mediated transcription modulators (e.g., ESX-mediated transcription inhibitors). 139-. (canceled)40. A method for regulating ESX-mediated transcription of a gene of interest , comprising: i) host cells expressing: ESX, an ESX transcription coactivator protein required for said ESX-mediated transcription of a gene of interest, and a gene of interest, wherein ESX has a specific region where said ESX transcription coactivator protein binds; and', 'ii) small molecules capable of binding within said specific region;, 'a) providing'}b) delivering to said host cells an effective amount of said small molecules such that expression of said gene of interest is modified.41. The method of claim 40 ,wherein said ESX transcription coactivator protein required for said ESX-mediated transcription of a gene of interest is Med23,wherein said gene of interest is selected from the group consisting of ErbB2(Her2) and EGFR, andwherein said specific region is at least a portion of an eight amino acid (137-SWIIELLE-146) (SEQ ID NO:1) α-helical region in ESX reported to mediate the interaction between ESX and Med23.42. The method of claim 40 , wherein said host cells are cancer cells.43. The method of claim 40 , wherein said small molecules are isoxazolidine compounds.45. The method of claim 44 ,wherein R is a functional group that mimics the effect of amino acid 138 within ESX, and/orwherein R is a functional group that mimics the formation of a hydrophobic surface along an amphipathic helix within amino acids 137-146 of ESX.48. A method for treating a human subject having a disorder claim 44 , administering to said human subject a pharmaceutical ...

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Номер записи: 74
21-01-2016 дата публикации

THROMBOXANE RECEPTOR ANTAGONISTS

Номер: US20160016900A1
Автор: "OConnor Barry", Guiry Patrick, Kinsella B. Therese, Reid Helen
Принадлежит:

The invention generally relates to compounds that function as TP antagonists for treating thrombosis and other cardiovascular, renal, or pulmonary diseases. In some embodiments, the invention provides a compound including a substituted nitro phenoxy phenyl, a sulfonylurea, and an alkyl group. In some embodiments, the invention provides a method of treating thrombosis by administering an antithrombotic compound that preferentially binds to a thromboxane receptor, has preferential binding for either TPalpha (TPα) or TPbeta (TPβ) receptor subtype.

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Номер записи: 75
17-01-2019 дата публикации

PROCESS FOR PREPARING SUBSTITUTED PHENYLISOXAZOLINE DERIVATIVES

Номер: US20190016691A1
Автор: Funke Christian, HEINRICH Jens Dietmar, LUI Norbert, PAZENOK Sergii
Принадлежит:

The present invention relates to a process for preparing substituted phenylisoxazoline derivatives. 2. Compound of formula (IV) according to claim 1 ,wherein{'sup': '2', 'Ris chlorine;'}{'sup': '3', 'Ris methylsulphonyloxy and'}{'sup': '4', 'Ris methyl, ethyl.'}4. Compound of formula (Ia) according to claim 3 ,wherein{'sup': '2', 'Ris chlorine and'}{'sup': '3', 'Ris methylsulphonyloxy.'}6. Compound of formula (Ib) according to claim 5 ,wherein{'sup': '2', 'Ris chlorine;'}{'sup': '3', 'Ris methylsulphonyloxy and'}X is bromine.7. A product comprising the compound of formula (Ia) according to for production of one or more active fungicidal ingredients.8. A product comprising the compound of formula (Ib) according to for production of one or more active fungicidal ingredients. This application is Divisional Application of U.S. patent application Ser. No. 15/548,216, filed Aug. 2, 2017, which is a § 371 National Stage Application of PCT/EP2016/054192, filed Feb. 29, 2016, which claims priority to European Application No. 15157803.6 filed Mar. 5, 2015. Each of these applications is incorporated by reference in its entirety.The present invention relates to a process for preparing substituted phenylisoxazoline derivatives.Substituted phenylisoxazoline derivatives are useful intermediates in the production of active agrochemical ingredients (see, for example, WO 2008/013925, WO 2009/094407, WO 2010/123791).There are various known processes for preparing such substituted phenylisoxazoline derivatives.WO 2011/085170 describes, for example, a process for preparing these phenylisoxazoline derivatives by [3+2] cycloaddition with a chloroxime with a styrene and downstream Grignard addition and halogenation (Scheme 1).A disadvantage of this process is that the use of further functional groups which can react directly with a Grignard reagent is impossible.WO 2011/085170 describes, for example, a process for preparing these phenylisoxazoline derivatives by [3+2] cycloaddition with a ...

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Номер записи: 76
16-01-2020 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20200017436A1
Автор: Fleury Melissa, Hughes Adam D.
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

In one aspect, the invention relates to compounds having the formula XII: 128-. (canceled)30. The compound of claim 29 , wherein Ris H.31. The compound of claim 29 , wherein Ris selected from H claim 29 , —CHCHand —CHCH(CH).32. The compound of claim 31 , wherein Ris —CHCH.33. The compound of claim 30 , wherein Ris —CHCH.34. The compound of claim 29 , wherein P is selected from H claim 29 , t-butoxycarbonyl claim 29 , trityl claim 29 , benzyloxycarbonyl claim 29 , 9-fluorenylmethoxycarbonyl claim 29 , formyl claim 29 , trimethylsilyl and t-butyldimethylsilyl.35. The compound of claim 34 , wherein P is H.36. The compound of claim 33 , wherein P is H.37. The compound of claim 29 , wherein Ris H.38. The compound of claim 29 , wherein Ris F.39. The compound of claim 36 , wherein Ris F.40. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluoro-biphenyl-4-yl)-2-hydroxypentanoic acid or a pharmaceutically acceptable salt thereof.41. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid ethyl ester or a pharmaceutically acceptable salt thereof.42. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1 claim 29 ,3]dioxol-4-ylmethyl ester or a pharmaceutically acceptable salt thereof.43. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 2 claim 29 ,2 claim 29 ,3 claim 29 ,3 claim 29 ,3-pentafluoropropyl ester or a pharmaceutically acceptable salt thereof.44. The compound of claim 29 , wherein the compound is (2R claim 29 ,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester or a pharmaceutically acceptable salt thereof.45. A method of performing a coupling reaction claim 29 , comprising contacting the compound of with a ...

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Номер записи: 77
16-01-2020 дата публикации

COMPOUNDS AND METHODS FOR REGULATING INSULIN SECRETION

Номер: US20200017485A1
Автор: BURNS Sean M., Vetere Amedeo, WAGNER Bridget K.
Принадлежит:

Disclosed herein are methods for inducing insulin secretion in a glucose-dependent manner and compounds for use in these methods. 6. The compound of claim 1 , wherein Ris aryl substituted with one or more substitutents selected from alkyl claim 1 , cyano claim 1 , or morpholinyl.7. The compound of claim 1 , wherein the aryl of Ris a substituted phenyl claim 1 , where one or more substituents are selected from alkyl claim 1 , cyano claim 1 , or morpholinyl.8. The compound of claim 1 , wherein Ris heteroaryl.9. The compound of claim 8 , wherein the heteroaryl is a piperidinyl.1015-. (canceled)1718-. (canceled)19. The compound according to claim 1 , wherein said compound is Compound 1-7 claim 1 , or 9-99.20. A pharmaceutical composition for modulating insulation secretion comprising an effective amount of a compound of .22. (canceled)2429-. (canceled)30. A method of modulating insulin secretion comprising contacting a β-cell with a compound of claim 1 , wherein insulin secretion from said β-cell occurs only when said blood glucose levels exceed normoglycemic conditions.3136-. (canceled)3843-. (canceled)44. The method according to claim 37 , wherein said compound is selected from Compounds 1-99.4564-. (canceled)6768-. (canceled) The present application claims priority to U.S. Provisional Application Ser. No. 62/473,811, filed Mar. 20, 2017, and U.S. Provisional Application Ser. No. 62/632,865 filed Feb. 20, 2018, the contents of which are hereby incorporated by reference in their entirety.This invention was made with government support under Grant No. 1 R03 DA035188-01 awarded by the National Institutes of Health. The government has certain rights in the invention.Diabetes mellitus type 2 (type 2 diabetes) is a metabolic disorder that results in patients having high blood sugar level and insulin resistance. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow ...

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Номер записи: 78
28-01-2016 дата публикации

HETEROCYCLIC COMPOUNDS USEFUL IN THE TREATMENT OF DISEASE

Номер: US20160024031A1
Автор: Beaton Graham, Luu Hiep, RAVULA Satheesh B., Shah Chandravadan R., TUCCI Fabio C.
Принадлежит: EPIGEN BIOSCIENCES, INC.

Heterocyclic compounds are described that are lysophosphatidic acid receptor ligands that are useful in the treatment of lysophosphatidic acid receptor-dependent diseases and conditions, including but not limited to diseases involving fibrosis, such as fibrosis of the heart, kidney, liver and lung, and scleroderma; inflammatory diseases such as diabetic nephropathy and inflammatory bowel disease; ocular diseases such as diseases involving retinal degeneration; nerve diseases such as pruritus and pain. Non-limiting examples of those compounds include (RS)-3-Cyclopropyl-2-{4-[3-methyl-4((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-benzyloxy}-propionic acid and (R)-1-(4′-{5-[1-(2-Chloro-phenyl)-ethoxycarbonylamino]-4-fluoro-pyrazol-1-yl}-2-fluoro-biphenyl-4-yl)-cyclopropanecarboxylic acid. 2. The compound of wherein Ris —H claim 1 , —CN claim 1 , —F claim 1 , —Cl claim 1 , —Br claim 1 , —I claim 1 , —OC-Calkyl claim 1 , —C-Calkyl claim 1 , —C-Ccycloalkyl claim 1 , or —C-Cfluoroalkyl and Ris —N(R)—C(═O)XCH(R)—CY claim 1 , —N(R)C(═O)XC(R)—CY claim 1 , —N(R)C(═O)X—CY claim 1 , wherein Rand each Rindependently are —H or C-Calkyl.3. (canceled)5. The compound of wherein{'sup': 2', '1, 'sub': 1', '6', '3', '6', '1', '6, 'Lis absent and Lis C-Calkylene, substituted or unsubstituted C-Ccycloalkylene, or substituted or unsubstituted C-Cheteroalkylene'}{'sup': 2', '1', 'J', 'J', 'J', 'J, 'sub': n', '1', '3, 'or Land Ring C are absent and Lis —UV—Z—, wherein —UV— is defined by —OW—, —WO—, —N(R)W—, —WN(R)—, —N(R)C(═O)—, —SW—, —S(═O)W—, or —C(═O)N(R)—, wherein W is substituted or unsubstituted C-Calkylene; and n is 0, 1, or 2.'}612.-. (canceled)13. The compound of wherein Lis absent or a substituted or unsubstituted substituted C-Calkylene or a substituted or unsubstituted Ccycloalkylene (i.e. claim 2 , cyclopropyl-di-yl).15. (canceled)16. The compound of wherein Ris —H claim 14 , —CH claim 14 , —F or —CFand Ris —N(R)C(═O)XCH(R)—CY.17. The compound of wherein Ris —N(R)C(═O)XCH(R ...

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Номер записи: 79
17-04-2014 дата публикации

NOVEL BENZENESULFONAMIDE COMPOUNDS, METHOD FOR SYNTHESIZING SAME, AND USE THEREOF IN MEDICINE AS WELL AS IN COSMETICS

Номер: US20140107129A1
Автор: Chambon Sandrine, CHANTALAT Laurent, Clary Laurence, Pascal Jean-Claude, ROSIGNOLI Carine, ROYE Olivier, SCHUPPLI-NOLLET Marlène
Принадлежит: GALDERMA RESEARCH & DEVELOPMENT

Benzenesulfonamide compounds having a structure of formula (I) are described. Also described, are methods for synthesizing the compounds and to the use thereof in pharmaceutical compositions for human or veterinary medicine and in cosmetic compositions. 2. The method as claimed in claim 1 , wherein the disease is an inflammatory skin disease.3. The method as claimed in claim 2 , wherein the inflammatory skin disease is psoriasis claim 2 , atopic dermatitis claim 2 , or psoriatic arthritis.4. The method as claimed in claim 1 , wherein the disease or disorder is selected from the group consisting of septic shock claim 1 , hemodynamic shock claim 1 , malaria claim 1 , an inflammatory bowel disease (IBD) claim 1 , an inflammatory bone disease claim 1 , a mycobacterial infection claim 1 , meningitis claim 1 , a fibrotic disease claim 1 , a cardiac disease claim 1 , ischemic attack claim 1 , transplant rejection claim 1 , cancer claim 1 , atherosclerosis claim 1 , obesity claim 1 , a disease involving angiogenesis phenomena claim 1 , an autoimmune disease claim 1 , osteoarthritis claim 1 , rheumatoid arthritis claim 1 , ankylosing spondylitis claim 1 , juvenile chronic arthritis claim 1 , multiple sclerosis claim 1 , HIV claim 1 , non-insulin-dependent diabetes mellitus claim 1 , an allergic disease claim 1 , asthma claim 1 , chronic obstructive pulmonary disease (COPD) claim 1 , and ocular inflammation.5. The method as claimed in claim 1 , wherein the disease is a neurological pathological condition selected from the group consisting of Alzheimer's disease claim 1 , Parkinson's disease claim 1 , a Parkinsonian disorder claim 1 , amyotrophic lateral sclerosis claim 1 , an autoimmune disease of the nervous system claim 1 , an autonomic disease of the nervous system claim 1 , dorsal pain claim 1 , cerebral edema claim 1 , a cerebrovascular disorder claim 1 , dementia claim 1 , a nervous system nerve fiber demyelinating autoimmune disease claim 1 , diabetic neuropathy claim ...

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Номер записи: 80
17-04-2014 дата публикации

INSECTICIDAL COMPOUNDS BASED ON ARYLTHIOACETAMIDE DERIVATIVES

Номер: US20140107161A1
Автор: Cassayre Jerome Yves, El Qacemi Myriem, LUKSCH Torsten, Renold Peter
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention provides compounds of formula (I) wherein R, R, R, R, R, G, n, A, A, A, A, Y, Y, and Yare as defined in the claims. The invention also relates to processes and intermediates for preparing these compounds, to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising these compounds and to methods of using these compounds to control insect, acarine, nematode and mollusc pests. 2. A compound according to claim 1 , wherein Y—Y—Yis —C═N—O—.3. A compound according to claim 1 , wherein Y—Y—Yis —C═N—CH—.4. A compound according to claim 1 , wherein Y—Y—Yis —C═CH—O—.5. A compound according to claim 1 , wherein Y—Y—Yis —N—CH—CH—.6. A compound according to claim 1 , wherein Ris bromo claim 1 , chloro claim 1 , or methyl.7. A compound according to claim 1 , wherein Ris C-Calkyl or C-Calkyl substituted by one to five R claim 1 , C-Calkenyl or C-Calkenyl substituted by one to five R claim 1 , C-Calkynyl or C-Calkynyl substituted by one to five R claim 1 , C-Ccycloalkyl or C-Ccycloalkyl substituted by one to five R claim 1 , C-Ccycloalkyl-methylene or C-Ccycloalkyl-methylene substituted by one to five R claim 1 , phenyl-C-Calkylene or phenyl-C-Calkylene wherein the phenyl moiety is substituted by one to five R claim 1 , pyridyl-C-Calkylene or pyridyl-C-Calkylene wherein the pyridyl moiety is substituted by one to four R claim 1 , thietanyl or thietanyl substituted by one to five R claim 1 , oxo-thietanyl or oxo-thietanyl substituted by one to five R claim 1 , dioxo-thietanyl or dioxo-thietanyl substituted by one to five R.8. A compound according to claim 1 , wherein Ris C-Calkyl or C-Calkyl substituted by one to five halogen claim 1 , C-Ccycloalkyl or C-Ccycloalkyl substituted by one to five groups independently selected from halogen claim 1 , methyl and halomethyl claim 1 , C-Ccycloalkyl-methylene or C-Ccycloalkyl-methylene substituted by one to five groups independently selected from halogen claim 1 , methyl and halomethyl claim 1 , C- ...

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Номер записи: 81
22-01-2015 дата публикации

CBP AND p300-MEDIATED TRANSCRIPTION MODULATORS AND RELATED METHODS

Номер: US20150025045A1
Автор: Mapp Anna, Pan Quintin
Принадлежит:

The present invention relates to gene regulation. In particular, the present invention provides small compounds capable of modulating p300 and/or CBP-mediated transcription and related methods of therapeutic and research use. In addition, the present invention provides methods for treating conditions associated with aberrant p300 and/or CBP-mediated transcription with p300 and/or CBP-mediated transcription modulators (e.g., p300 and/or CBP-mediated transcription inhibitors). 148.-. (canceled)49. A method for regulating CBP-mediated transcription of a gene of interest , comprising: i) host cells expressing: CREB-binding protein (CBP) comprising a KIX domain, a coactivator protein known to bind the KIX domain within CBP, and a gene of interest, wherein binding of said coactivator protein within said KIX domain is required for said CBP-mediated transcription of said gene of interest, wherein said host cells are ex vivo host cells and/or cancer cells, wherein said coactivator protein is selected from the group consisting of MLL, Jun, Tat, and Tax; and', 'ii) small molecules capable of binding within said KIX domain;, 'a) providing'}b) delivering to said host cells an effective amount of said small molecules such that expression of said gene of interest is modified.50. The method of claim 49 , wherein said small molecules are isoxazolidine compounds.52. The method of claim 51 , wherein R1 is configured to mimic at least a portion of amino acid residues selected from the group consisting of:amino acid residues 2840-2858 (ILPSDIMDFLVKNTP) (SEQ ID NO:1) within MLL,amino acid residues 47-66 (VLLKLASPELERLIIQSSN) (SEQ ID NO:2) within Jun, amino acid residues 1-24 (MEPVDPRLEPWKHPGSQPKT) (SEQ ID NO:3) within Tat, andamino acid residues 76-95 (PSFPTQRTSKTLKVLPPIT) (SEQ ID NO: 4) within Tax.55. A method for regulating p300-mediated transcription of a gene of interest claim 51 , comprising: i) host cells expressing: p300 comprising a KIX domain and a CH1 domain, a coactivator ...

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Номер записи: 82
10-02-2022 дата публикации

Method for Racemisation of (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H¬isoxazol-3-yl]-2-Methyl-Benzoic Acid

Номер: US20220041564A1
Автор: Schmitt Harald
Принадлежит: Intervet Inc.

The present invention relates to a method for racemizing (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid. 2. The Method according to claim 1 , wherein the alkaline compound is an inorganic compound.3. The Method according to claim 1 , wherein the alkaline compound is selected from the group consisting of sodium hydroxide claim 1 , potassium hydroxide claim 1 , cesium hydroxide claim 1 , calcium hydroxide claim 1 , barium hydroxide claim 1 , magnesium oxide claim 1 , calcium oxide claim 1 , barium oxide claim 1 , cesium carbonate and mixtures thereof.4. The Method according to claim 1 , wherein the organic solvent is selected from the group consisting of water claim 1 , an alcohol with 1 to 5 carbon atoms claim 1 , dioxane claim 1 , tetrahydrofuran claim 1 , toluene claim 1 , ethyl acetate and mixtures thereof.5. The Method according to claim 1 , further comprising the steps of:(ii) acidifying the reacted mixture from step (i), to form a result mixture and(iii) separating the result mixture from step (ii) in a compound mixture and supernatant6. The Method according to claim 1 , wherein step (i) is carried out in the absence of phase transfer catalysts.8. The Method according to claim 1 , wherein in step (a) the solvent is selected from the group consisting of an alcohol with 2 to 5 carbon atoms claim 1 , dioxane claim 1 , tetrahydrofuran and mixtures thereof.9. The Method according to claim 7 , wherein in step (a) the solvent is 2-propanol.10. The Method according to claim 7 , wherein in step (a) R of Formula (2A) is methyl and the solvent is 2-propanol or R of Formula (2A) is ethyl and the solvent is 2-propanol.11. The Method according to claim 7 , wherein step (a) comprises heating (5RS)-4-[5-(3 claim 7 ,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]2-methyl-benzoic acid with the compound of Formula (2A) claim 7 , (2b) or (2C) in the solvent to an elevated temperature.12. The Method according to claim 7 , wherein ...

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Номер записи: 83
28-01-2021 дата публикации

PROCESS FOR THE PREPARATION OF ISOXAZOLINE COMPOUNDS

Номер: US20210022344A1
Автор: Yang ChunHua
Принадлежит: Boehringer Ingelheim Animal Health USA Inc.

This invention relates to processes for the preparation of antiparasitic isoxazoline compounds enriched in an enantiomer using quinine-based chiral phase transfer catalyst. The invention also relates to novel quinine-based phase transfer catalysts and to a toluene solvent form of the isoxazoline compound of the invention. 2. The process of claim 1 , wherein the compound of formula (I) enriched in one enantiomer is isolated by crystallizing the compound from an aromatic solvent or a mixture of solvents comprising an aromatic solvent.3. The process of claim 2 , wherein the aromatic solvent is selected from the group consisting of toluene claim 2 , ethylbenzene claim 2 , xylenes claim 2 , chlorobenzene claim 2 , o-dichlorobenzene claim 2 , fluorobenzene claim 2 , anisole and mesitylene claim 2 , or a combination thereof.4. The process of claim 3 , wherein the aromatic solvent is toluene.5. The process of claim 1 , wherein prior to isolating the compound of formula (I) enriched in an enantiomer claim 1 , the process further comprises crystallizing racemic compound of formula (I) and removing the solid.7. The process according to claim 1 , wherein Q is —C(O)NHCHC(O)NHCHCF claim 1 , —C(O)CHS(O)CH claim 1 , —C(O)NHCHCHSCHor (—CH—)(—CH—)N(CO)CHS(O)CH.8. The process according to claim 1 , wherein X in the chiral phase transfer catalyst of formula (IIIa) or (IIIb) is a halogen counter ion.9. The process according to claim 7 , wherein X is a chloride counter ion.10. The process according to claim 1 , wherein R in the chiral phase transfer catalyst of formula (IIIa) or (IIIb) is a phenyl group that is substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 aralkoxy groups.11. The process according to claim 10 , wherein the aralkoxy group is a benzyloxy group.12. The process according to claim 10 , wherein R is substituted with 3 aralkoxy groups.13. The process according to claim 12 , wherein R is 3 claim 12 ,4 claim 12 ,5-tris(benzyloxy)phenyl.1471-. (canceled)72. The process ...

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Номер записи: 84
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023667A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an effective, low-molecular-weight compound showing low reactivity with serum and low toxicity has been strongly desired.Conventionally, in search of a pharmaceutical product seed compound from microbial metabolites, terrestrial separation sources have been mainly harvested and subjected ...

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Номер записи: 85
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023668A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an effective, low-molecular-weight compound showing low reactivity with serum and low toxicity has been strongly desired.Conventionally, in search of a pharmaceutical product seed compound from microbial metabolites, terrestrial separation sources have been mainly harvested and subjected ...

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Номер записи: 86
24-01-2019 дата публикации

METHOD FOR PRODUCING KAKEROMYCIN AND DERIVATIVES THEREOF

Номер: US20190023669A1
Автор: ISHIKAWA Teruhiko, IWAMI Morita
Принадлежит:

Provided is a production method of kakeromycin and a derivative thereof showing an antifungal activity and cytotoxicity and expected as a new antifungal agent or anticancer agent, by chemical synthesis. A production method of a compound represented by the formula (1): 1. A compound represented by the formula (6):whereinR is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,{'sup': '4', 'Ris an optionally substituted hydrocarbon group or an optionally substituted hydrocarbon-oxy group, and'}n is 0 or 1, This patent application is a divisional of copending U.S. patent application Ser. No. 15/554,002, filed on Aug. 27, 2017, which the U.S. national phase of International Patent Application No. PCT/JP2016/055891, filed on Feb. 26, 2016, which claims the benefit of Japanese Patent Application No. 2015-039363, filed Feb. 27, 2015, the disclosures of which are incorporated herein by reference in their entireties for all purposes.The present invention relates to a production method of kakeromycin and a derivative thereof.In recent years, along with an increase in elderly people, progress of advanced medicine, immunodeficiency of late stage cancer patients and the like, infections with fungi have been increasing. These infections provide serious effects, often causing death. Since there are not many kinds of existing antifungal agents, and their toxicity is high, the mother nucleus of a new antifungal agent, which is different from that of conventional medicaments, has been desired. In addition, since the use of antifungal agents causes increased emergence of resistant bacteria, the development of a new medicament has been earnestly desired. While candin-based antifungal agents show low toxicity, since the molecular weight thereof is large, reactivity with serum poses problems. Azole-based antifungal agents have a problem in that administration at a high concentration is difficult in view of the toxicity thereof. Therefore, an ...

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Номер записи: 87
28-01-2021 дата публикации

COMPOUND WITH ANTICANCER ACTIVITY

Номер: US20210024540A1
Автор: IKOTA Hideo, IMAEDA Takashi, KANAI Toshimi, KAWAI Ryohei, Uchida Kenji, YAMAMOTO Keisuke, YOSHIDA Kei
Принадлежит: Kyowa Kirin Co., Ltd.

A compound having anticancer activity, or a pharmaceutically acceptable salt thereof is provided. Used is a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Lis a member selected from formula (A) claim 1 , (B) claim 1 , (C) claim 1 , (D) claim 1 , or (F) claim 1 , Lis a member selected from formula (A) claim 1 , (B) claim 1 , (C) claim 1 , or (D) claim 1 , and S is a member selected from formula (S1).3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Land Lare independently a member selected from formula (A) claim 1 , and S is a member selected from formula (S2).4. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Lrepresents a member selected from formula (A) claim 1 , (B) claim 1 , or (C) claim 1 , Lis a member selected from formula (A) or (B) claim 1 , and S is a member selected from formula (S3).5. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Land Lindependently represent a member selected from formula (A) claim 1 , and S is a member selected from formula (S4) or (S5).6. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Lis a group member selected from formula (A) claim 1 , (B) claim 1 , (C) claim 1 , or (D) claim 1 , Lis a member selected from formula (A) claim 1 , (B) claim 1 , or (D) claim 1 , and S is a member selected from formula (S6).7. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Lis a member selected from formula (A) or (B) claim 1 , Lis a member selected from formula (A) claim 1 , and S is a member selected from formula (S7).8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Lis a member selected from formula (A) or (B) claim 1 , Lis a member selected from formula (A) claim 1 , and S is a member-selected from formula (S8).9 ...

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Номер записи: 88
24-04-2014 дата публикации

Naphthalene Isoxazoline Invertebrate Pest Control Agents

Номер: US20140113943A9
Автор: Lahm George Philip, Long Jeffrey Keith, Xu Ming
Принадлежит:

Disclosed are compounds of Formula 1, 2. A compound of wherein{'sup': '4', 'Ris H; and'}{'sup': '5', 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '2', '7', '2', '7, 'Ris C-Calkyl substituted with one substituent independently selected from C-Calkylthio, C-Calkylsulfinyl, C-Calkylsulfonyl, C-Calkylaminocarbonyl and C-Chaloalkylaminocarbonyl.'}3. A compound of wherein{'sup': '1', 'sub': '3', 'Ris Cl, Br or CF;'}{'sup': '2', 'Ris H; and'}{'sup': '3', 'sub': '3', 'Ris H, F, Cl, Br or CF.'}4. A compound of wherein{'sup': '1', 'sub': '3', 'Ris CF.'}5. A compound of wherein{'sup': '3', 'sub': '3', 'Ris Cl, Br or CF.'}6. A compound of wherein{'sup': '5', 'sub': 1', '6', '2', '7', '3', '7, 'Ris C-Calkyl substituted with one C-Calkylaminocarbonyl or C-Chaloalkylaminocarbonyl.'}7. A compound of that is selected from the group consisting of4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylsulfonyl)ethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylamino)-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(ethylamino)-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-[(1-methylethyl)amino]-2-oxoethyl]-1-naphthalenecarboxamide,4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide,4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-(methylamino)-2-oxoethyl]-1- ...

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Номер записи: 89
29-01-2015 дата публикации

HERBICIDAL SULFINIMIDOYL- AND SULFONIMIDOYL BENZOYL DERIVATIVES

Номер: US20150031536A1
Автор: AHRENS HARTMUT, Dietrich Hansjoerg, Doerner-Rieping Simon, GATZWEILER ELMAR, LEHR Stefan, ROSINGER CHRISTOPHER HUGH, SCHMUTZLER Dirk
Принадлежит:

The invention relates to sulfmimidoyl- and sulfonimidoylbenzoyl derivatives of the general formula (I). In said formula (I), R, R′, X, W and Z represent radicals such as hydrogen, organic radicals such as alkyl, and other radicals such as halogens. Q represents a cyclohexandionyl-, pyrazolyl-oder isoxazolyl radical. 4. A herbicidal composition which comprises a herbicidally active amount of at least one compound of formula (I) and/or salt as claimed in .5. The herbicidal composition as claimed in in a mixture with one or more formulation auxiliaries.6. The herbicidal composition as claimed in which comprises at least one further pesticidally active compound selected from the group consisting of insecticides claim 4 , acaricides claim 4 , herbicides claim 4 , fungicides claim 4 , safeners and growth regulators.7. The herbicidal composition as claimed in which comprises a safener.8. The herbicidal composition as claimed in which comprises cyprosulfamide claim 7 , cloquintocet-mexyl claim 7 , mefenpyr-diethyl or isoxadifen-ethyl.9. The herbicidal composition as claimed in which comprises a further herbicide.10. A method of controlling unwanted plants claim 1 , which comprises applying an effective amount of at least one compound of the formula (I) and/or salt thereof as claimed in to the plants and/or to a location of unwanted plant growth.11. A compound of formula (I) and/or salt as claimed in capable of being used for controlling one or more unwanted plants.12. The compound and/or salt as claimed in claim 11 , wherein the compound of formula (I) and/or salt is employed for controlling unwanted plants in one or more crops of useful plants.13. The compound and/or salt as claimed in claim 12 , wherein the useful plants are transgenic useful plants. The invention relates to the technical field of the herbicides, in particular to that of the herbicides for the selective control of broad-leafed leaves and weed grasses in crops of useful plants.WO 03/014071 A1 and WO 2011/ ...

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Номер записи: 90
02-02-2017 дата публикации

ISOXAZOLINE HYDROXAMIC ACID DERIVATIVES AS LpxC INHIBITORS

Номер: US20170029415A1
Автор: FU Jiping, Jin Xianming, KARUR Subramanian, Lapointe Guillaume, Lee Patrick, Sweeney Zachary Kevin
Принадлежит: NOVARTIS AG

This invention pertains generally to compounds of Formula I and compositions containing such compounds, as well as methods of using such compounds to treat bacterial infections. In certain aspects, the invention pertains to methods and compositions for treating infections caused by Gram-negative bacteria. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein X is H or F.3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris methyl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris methyl.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Z is CH or CF.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Z is N.9. The compound of or a pharmaceutically acceptable salt thereof claim 8 , wherein A is Calkyl or cyclopropyl and is optionally substituted with F claim 8 , OH claim 8 , or OMe.11. A pharmaceutical composition claim 8 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound according to , or a pharmaceutically acceptable salt thereof, and'}a pharmaceutically acceptable carrier.12. A pharmaceutical combination comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound according to , or a pharmaceutically acceptable salt thereof,'}an antibacterially effective amount of a second therapeutic agent, anda pharmaceutically acceptable carrier.13. The pharmaceutical combination composition according to claim 12 , wherein the second therapeutic agent is selected from the group consisting of Ampicillin claim 12 , Piperacillin claim 12 , Penicillin G claim 12 , Ticarcillin claim 12 , Imipenem claim 12 , Meropenem claim 12 , Azithromycin claim 12 , erythromycin claim 12 , Aztreonam claim 12 , Cefepime claim 12 , Cefotaxime claim 12 , Ceftriaxone claim 12 , ...

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Номер записи: 91
04-02-2016 дата публикации

BIOMARKER

Номер: US20160031836A1
Автор: CHEN Jinyun, CHEN Yaoyu, Wilson Christopher, ZHOU Wenlai
Принадлежит: NOVARTIS AG

The invention is directed, in part, to selective cancer treatment regimes based on assaying for the presence or absence of a mutation in a nucleic acid that encodes MLL1 or for the presence of reduced levels of MLL1. 1. A method of selectively treating a subject having cancer , including selectively administering a therapeutically effective amount of (5-(2 ,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide , or a pharmaceutically acceptable salt thereof , to the subject on the basis of the subject having reduced levels of MLL12. A method according to further comprising:a) assaying a biological sample from the subject for the level of MLL1; andb) selectively administering a therapeutically effective amount of (5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide or a pharmaceutically acceptable salt thereof, to the subject on the basis that the sample has reduced levels of MLL1.3. (canceled)4. A method according to further comprising:a) assaying a biological sample from the subject for the levels of MLL1;b) thereafter selecting the subject for treatment with (5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide (AUY922), or a pharmaceutically acceptable salt thereof, on the basis that the subject has reduced levels of MLL1; andc) thereafter administering (5-(2,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4-ylmethyl-phenyl)-isoxazole-3-carboxylic acid ethylamide or a pharmaceutically acceptable salt thereof to the subject on the basis that the subject has reduced levels of MLL1.57-. (canceled)8. A method of genotyping an individual including detecting a genetic variant that results in an amino acid variant at position 859 of the encoded catalytic p110α subunit of PI3K claim 2 , wherein a lack of variant at position 859 indicates that (5-(2 claim 2 ,4-Dihydroxy-5-isopropyl-phenyl)-4-(4-morpholin-4- ...

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Номер записи: 92
01-02-2018 дата публикации

Process for preparing substituted phenylisoxazoline derivatives

Номер: US20180030002A1
Автор: Funke Christian, HEINRICH, II JENS DIETMAR, LUI Norbert, PAZENOK Sergii
Принадлежит:

The present invention relates to a process for preparing substituted phenylisoxazoline derivatives. 2. Process according to claim 1 , wherein{'sup': '1', 'Ris methyl, bromomethyl, chloromethyl;'}{'sup': '2', 'Ris chlorine or bromine;'}{'sup': '3', 'Ris methylsulphonyloxy or ethylsulphonyloxy;'}{'sup': '4', 'sub': 1', '4, 'Ris C-C-alkyl and'}X is chlorine or bromine.3. Process according to claim 1 , wherein{'sup': '1', 'Ris methyl, bromomethyl;'}{'sup': '2', 'Ris chlorine;'}{'sup': '3', 'Ris methylsulphonyloxy;'}{'sup': '4', 'Ris methyl, ethyl and'}X is bromine.4. Process according to claim 1 , wherein claim 1 , in (ii) claim 1 , triethylamine is used as base and methylmagnesium bromide or methylmagnesium chloride as organometallic reagent.6. Compound of formula (IV) according to claim 5 ,wherein{'sup': '2', 'Ris chlorine;'}{'sup': '3', 'Ris methylsulphonyloxy and'}{'sup': '4', 'Ris methyl, ethyl.'}8. Compound of the formula (Ia) according to claim 7 ,wherein{'sup': '2', 'Ris chlorine and'}{'sup': '3', 'Rmethyl sulphonyloxy.'}10. Compound of formula (Ib) according to claim 9 ,wherein{'sup': '2', 'Ris chlorine;'}{'sup': '3', 'Ris methylsulphonyloxy and'}X is bromine.11. A product comprising the compound of formula (Ia) according to for production of one or more active fungicidal ingredients.12. A product comprising the compound of formula (Ib) according to for production of one or more active fungicidal ingredients. The present invention relates to a process for preparing substituted phenylisoxazoline derivatives.Substituted phenylisoxazoline derivatives are useful intermediates in the production of active agrochemical ingredients (see, for example, WO 2008/013925, WO 2009/094407, WO 2010/123791).There are various known processes for preparing such substituted phenylisoxazoline derivatives.WO 2011/085170 describes, for example, a process for preparing these phenylisoxazoline derivatives by [3+2] cycloaddition with a chloroxime with a styrene and downstream Grignard ...

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Номер записи: 93
01-02-2018 дата публикации

TRICYCLIC COMPOUNDS AND USES THEREOF IN MEDICINE

Номер: US20180030003A1
Автор: CHENG Changchung, GUO Rui, PAN Shengqiang, Wang Xiaojun, WU Junwen, YANG Xinye, ZHANG Yingjun
Принадлежит: SUNSHINE LAKE PHARMA CO., LTD.

The present invention relates to novel tricyclic compounds which can bind to FXR and act as modulators of the FXR, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and the uses of the compounds for the treatment of diseases and/or conditions mediated by FXR. The invention further provides a pharmaceutical composition containing the compound disclosed herein and a method of treatment of diseases and/or conditions mediated by FXR comprising administering the compound or the pharmaceutical composition. 2. (canceled)3. The compound of claim 1 , wherein{'sup': '1', 'sub': 1-6', '1-6', '1-6', '3-6', '2-6', '2-6', '2-6', '1-6', '1-6', '6-10', '1-9, 'each Ris independently H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, Ccycloalkyl, Cheterocyclyl, Calkenyl, Calkynyl, Calkylamino, Calkoxy, Caryl or Cheteroaryl;'}{'sup': '2', 'sub': 1-6', '1-6', '1-6', 'C1-6', '1-6', '3-6', '1-6', '2-6', '1-6', '1-6, 'Ris H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, alkoxy—C-alkyl, Ccycloalkyl, Chydroxyalkyl, Cheterocyclyl, Calkylamino or Calkoxy; and'}{'sub': 1-6', '2-6', '2-6', '3-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '2-9', '6-10', '1-9, 'sup': I', '2', '9, 'Wherein each of said hydroxy, amino, Calkyl, Calkenyl, Calkynyl, Ccycloalkyl, Chaloalkyl, Calkylamino, Calkoxy, Chaloalkoxy, Chydroxyalkyl, Calkoxy—C-alkyl, Cheterocyclyl, Caryl and Cheteroaryl of Rand Ris independently and optionally substituted with one or more R; or'}{'sup': '1', 'sub': 1-3', '1-3', 'h3', 'C3-6', '2-9', '2-4', '2-4', '1-3', '1-3', '6-10', '1-9, 'wherein each Ris independently H, deuterium, F, Cl, Br, I, hydroxy, amino, nitro, cyano, Calkyl, Chaloalkyl, Chaloalkoxy, cycloalkyl, Cheterocyclyl, Calkenyl, Calkynyl, Calkylamino, Calkoxy, Caryl or Cheteroaryl;'}{'sup': '2', 'sub': 1-3', '1-3', '1-3', '1-3', '1-3', ...

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Номер записи: 94
01-02-2018 дата публикации

ISOXAZOLE HYDROXAMIC ACID COMPOUNDS AS LpxC INHIBITORS

Номер: US20180030004A1
Автор: FU Jiping, Jin Xianming, KARUR Subramanian, Lapointe Guillaume, Madera Ann Marie, Sweeney Zachary Kevin
Принадлежит:

This invention pertains generally to compounds of Formula I as described herein and compositions containing such compounds, as well as methods of using such compounds to treat bacterial infections. In certain aspects, the invention provides methods and compositions comprising these compounds for treating infections caused by Gram-negative bacteria. 2. The compound of claim 1 , wherein Ris —CH(OH)—Y.3. The compound of claim 1 , wherein Ris —SOR.4. The compound of claim 1 , wherein X is —CH—.5. The compound of claim 1 , wherein X is —NH—.6. The compound of claim 1 , wherein Y is isoxazole claim 1 , optionally substituted with one or two R.8. The compound of claim 1 , wherein Z is phenyl substituted with up to three groups selected from halogen claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , CN claim 1 , and Calkyl optionally substituted with one to three groups selected from halogen claim 1 , hydroxy claim 1 , amino claim 1 , CN claim 1 , and Calkoxy.9. The compound of claim 1 , wherein Z is C-Calkyl or C-Ccycloalkyl claim 1 ,{'sub': 1-4', '1-4', '1-4', '1-3, 'and Z is optionally substituted with up to three groups selected from halogen, Calkoxy, Chaloalkoxy, CN, and Calkyl optionally substituted with one to three groups selected from halogen, hydroxy, amino, CN, and Calkoxy.'}10. The compound of claim 1 , wherein L is —C≡C—.13. A pharmaceutical composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound of and'}a pharmaceutically acceptable carrier.14. A pharmaceutical combination composition claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound of ,'}an antibacterially effective amount of a second therapeutic agent, anda pharmaceutically acceptable carrier.15. The pharmaceutical combination composition of claim 14 , wherein the second therapeutic agent is selected from the group consisting of Ampicillin claim 14 , Piperacillin claim 14 , Penicillin G claim 14 , Ticarcillin claim 14 , Imipenem claim 14 ...

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Номер записи: 95
01-02-2018 дата публикации

ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS

Номер: US20180030007A1
Автор: Bell Ian M., CAMPBELL BRIAN T., Crowley Brendan M., Duffy Joseph L., Greshock Thomas J., Guiadeen Deodial G., Harvey Andrew John, HUFF BELINDA C., Leavitt Kenneth J., Rada Vanessa L., Sanders John M., Shipe William D., SUEN LINDA M.
Принадлежит: Merck Sharp & Dohme Corp.

The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation 116-. (canceled)19. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of .20. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of .21. A method of treating a patient with mild to moderate dementia of the Alzheimer's type claim 17 , the method comprising administering to the patient the compound of in an amount effective to treat the patient. The present disclosure relates to compounds that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia.The α7 nAChR is a fast desensitizing ligand-gated ion channel that has high permeability to Ca. In human brain, α7 nAChRs are highly expressed in the cortex and hippocampus, regions associated with cognition, see for example, Breese et al. (1997) 387: 385-398. In neurons, α7 nAChRs are localized in both pre-synaptic and post-synaptic structures, where activation of the receptor can modulate neurotransmitter release, neuronal excitability, and intracellular signalling, see for example, Frazier et al. (1998) 18: 1187-1195.Cognitive impairments are prevalent in many neurological and psychiatric diseases, including Alzheimer's disease (AD), schizophrenia, and Parkinson's disease, and dysfunction in cholinergic signalling contributes to ...

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Номер записи: 96
17-02-2022 дата публикации

PESTICIDALLY ACTIVE CYCLOPROPYL METHYL AMIDE DERIVATIVES

Номер: US20220048873A1
Автор: BIGOT Aurelien, El Qacemi Myriem, Jeanguenat Andre
Принадлежит: SYNGENTA CROP PROTECTION AG

The present invention relates to compounds of formula (I) wherein the substituents are as defined in claim , and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds; to intermediates for preparing compounds of formula (I), to compositions comprising them and to methods of using them to combat and control insect, acarine, nematode and mollusc pests. 2. A compound of formula (I) according to claim 1 , wherein Ris —ROC(═O)OR.3. A compound of formula (I) according to claim 2 , wherein Ris —CH—O—C(═O)—O—CHor —CH—O—C(═O)—O—CH—CH.4. A compound of formula (I) according to claim 1 , wherein Ris cyano.5. A compound of formula (I) according to claim 1 , wherein Ris C-Chaloalkyl.6. A compound of formula (I) according to claim 1 , wherein Ris aryl or aryl substituted by one to three R claim 1 , wherein Ris independently halogen claim 1 , cyano claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy or C-Chaloalkoxy.7. A compound of formula (I) according to claim 1 , wherein Ris phenyl or phenyl substituted by one to three R claim 1 , wherein Ris independently halogen.8. A compound according to selected from[(1-cyanocyclopropyl)methyl-[4-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoyl]amino]methyl methyl carbonate, and[(1-cyanocyclopropyl)methyl-[4-[(5S)-5-(3,5-dichloro-4-fluoro-phenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoyl]amino]methyl ethyl carbonate.11. The compound of claim 10 , wherein the compound is the compound of formula (Int-III).12. A pesticidal composition claim 1 , which comprises at least one compound of formula (I) according to or claim 1 , where appropriate claim 1 , a tautomer thereof claim 1 , in each case in free form or in agrochemically utilizable salt form claim 1 , as active ingredient and at least one auxiliary.13. A method for controlling pests claim 12 , which comprises applying a composition according to to the pests or their ...

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Номер записи: 97
17-02-2022 дата публикации

Method for Producing (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-Benzoic Acid

Номер: US20220048874A1
Автор: Harald Schmitt
Принадлежит: Intervet Inc

The present invention relates to a novel method for preparing (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid, which can preferably be used in the synthesis of (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]-2-methyl-benzamide.

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Номер записи: 98
17-02-2022 дата публикации

INSECTICIDAL COMPOUNDS

Номер: US20220048876A1
Автор: Cassayre Jerome Yves, El Qacemi Myriem, Pitterna Thomas, Stoller Andre
Принадлежит: SYNGENTA PARTICIPATIONS AG

Compounds of formula (I), wherein the substituents are as defined in claim , and the agrochemically acceptable salts salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, and their uses as insecticides. 2. The compound according to claim 1 , wherein Ais C—R; Ais C—H; Ais C—H; and Ais C—H claim 1 , wherein Ris halogen claim 1 , cyano claim 1 , nitro claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Chaloalkyl or C-Calkenyl.3. The compound of formula (I) according to claim 1 , wherein Ris halogen claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , C-Chaloalkoxy or di-C-Calkylamino claim 1 , C-Calkylthio or C-Calkyloxycarbonyl.4. The compound of formula (I) according to claim 1 , wherein Ris hydrogen claim 1 , formyl claim 1 , C-Calkyl claim 1 , C-Calkylcarbonyl- or C-Calkoxycarbonyl-.5. The compound of formula (I) according to claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkylcarbonyl- claim 1 , C-Ccycloalkylcarbonyl claim 1 , C-Calkoxy claim 1 , C-Calkoxy-C-Calkyl claim 1 , C-Calkoxycarbonyl claim 1 , C-CalkylcarbonyloxyC-Calkyl claim 1 , C-Calkoxycarbonylsulfanyl claim 1 , C-CalkylaminocarbonyloxyC-Calkyl claim 1 , C-CdialkylaminocarbonyloxyC-Calkyl claim 1 , C-CalkylaminocarbonylC-Calkyl claim 1 , C-CdialkylaminocarbonylC-Calkyl claim 1 , or C-CalkoxycarbonylC-CalkylaminoC-Calkyl claim 1 , wherein each alkyl or alkoxy group may be optionally substituted with from one to three halogen atoms6. The compound of formula (I) according to claim 4 , wherein Ris C-Ccyanoalkyl claim 4 , C-Calkoxy-C-Calkyl claim 4 , C-Calkoxycarbonyl or C-CalkylcarbonyloxyC-Calkyl.7. The compound of formula (I) according to claim 6 , wherein Ris cyanomethyl claim 6 , methoxymethyl claim 6 , ethoxymethyl claim 6 , methoxycarbonyl claim 6 , ethoxycarbonyl claim 6 , methylcarbonyloxymethyl claim 6 , 1-methylethylcarbonyloxymethyl or 1 claim 6 ,1-dimethylethylcarbonyloxymethyl.8. The compound according to claim 1 , wherein ...

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Номер записи: 99
17-02-2022 дата публикации

PROCESS FOR THE CYCLOADDITION OF A (HETERO)ARYL 1,3-DIPOLE COMPOUND WITH A (HETERO)CYCLOALKYNE

Номер: US20220048920A1
Автор: Dommerholt Frederik Jan, van Delft Floris Louis
Принадлежит: SynAffix B.V.

A process is provided, comprising reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne, wherein the (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound; wherein: 1. A process for preparing a product of a 1 ,3-dipolar cycloaddition reaction comprising reacting a (hetero)aryl 1 ,3-dipole compound with a (hetero)cycloalkyne , wherein:{'claim-text': ['wherein:', {'sub': ['p', 'm'], '#text': '(i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises one or more substituents having a positive value for the para-Hammett substituent constant σand/or the meta-Hammett substituent constant σ, and/or'}, {'claim-text': ['(ii-a) a (hetero)aryl group wherein the (hetero)aromatic ring system is bearing a positive charge, and/or', '(ii-b) a (hetero)aryl group wherein the ratio {number of it-electrons present in the (hetero)aromatic ring system}:{number of protons present in the nuclei of the (hetero)aromatic ring system} is lower than 0.167 for a 6-membered ring, or lower than 0.200 for a 5-membered ring;'], '#text': '(ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group, wherein an electron-poor (hetero)aryl group is:'}], '#text': 'the (hetero)aryl 1,3-dipole compound is defined as a compound comprising a 1,3-dipole functional group, wherein the 1,3-dipole functional group is bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound;'}{'sup': ['1', '3'], '#text': 'the (hetero)cycloalkyne is an aliphatic (hetero)cycloalkyne, wherein an aliphatic (hetero)cycloalkyne is defined as a (hetero)cycloalkyne wherein both spC-atoms of the (hetero)cycloalkyne carbon-carbon triple bond are bonded to an spC-atom.'}2. The process according to claim 1 , wherein the (hetero) ...

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Номер записи: 100