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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 10446. Отображено 100.
12-01-2012 дата публикации

Novel liquid-crystalline compound and organic semiconductor device containing the compound

Номер: US20120007062A1
Принадлежит: JNC Corp

Disclosed is a visible light-transmissive liquid-crystalline compound having good hole and electron-transport characteristics and useful as an organic semiconductor material. The compound is represented by a formula (1): wherein R independently represents hydrogen, or alkyl having from 1 to 24 carbon atoms, and any —CH 2 — in the alkyl may be replaced by —O—, —S—, —CO— or —SiH 2 —, any —(CH 2 ) 2 — may be replaced by —CH≡CH— or —C═C—, and any hydrogen may be replaced by halogen; Ar represents naphthylene, anthrylene, phenanthrylene, or phenylene; and every hydrogen in phenylene is replaced by halogen, and any hydrogen in naphthylene, anthrylene and phenanthrylene may be replaced by halogen.

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26-01-2012 дата публикации

Derivatives of n-(arylamino)sulfonamides as inhibitors of mek

Номер: US20120022076A1
Принадлежит: Individual

This invention concerns N-(2-arylamino)aryl sulfonamides, which are inhibitors of MEK and are useful in treatment of cancer and other hyperproliferative diseases.

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16-02-2012 дата публикации

Thiadiazole and oxadiazole derivatives, preparation thereof and therapeutic use thereof

Номер: US20120040984A1
Принадлежит: SANOFI SA

The invention relates to compounds of the formula (I) either (i) in the state of a base or an acid addition salt, or (ii) in the state of an acid or a base addition salt, as well as to a method for preparing same and to the therapeutic applications thereof.

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23-02-2012 дата публикации

Small molecule inhibitors of kynurenine-3-monooxygenase

Номер: US20120046324A1
Принадлежит: University of Maryland at Baltimore

The present invention relates to compounds of Formula I below and their tautomers or pharmaceutically acceptable salts, compositions and methods of uses thereof.

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10-05-2012 дата публикации

N,n'-diarylurea compounds and n,n'-diarylthiourea compounds as inhibitors of translation initiation

Номер: US20120115915A1
Принадлежит: Harvard College

Compositions and methods for inhibiting translation initiation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using N,N′-diarylureas and/or N,N′-diarylthiourea compounds are described.

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17-05-2012 дата публикации

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Номер: US20120122780A1
Принадлежит: Ardea Biociences Inc

Described herein are compounds useful in the reduction of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

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31-05-2012 дата публикации

Substituted Esters as Cannabinoid-1 Receptor Modulators

Номер: US20120135975A1
Принадлежит: Merck and Co Inc

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

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07-06-2012 дата публикации

Microbiocidal heterocycles

Номер: US20120142700A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to heterocyclic compounds of formula (I) which have microbiocidal activity, in particular fungicidal activity, as well as methods of using the compounds of formula (I) to control microbes.

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28-06-2012 дата публикации

Quinoline derivatives as pi3 kinase inhibitors

Номер: US20120165321A1
Принадлежит: GlaxoSmithKline LLC

Invented is a method of inhibiting the activity/function of PI3 kinases using quinoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinoline derivatives.

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19-07-2012 дата публикации

1,2,4-thiazoloidin-3-one derivatives and their use in the treatment of cancer

Номер: US20120183537A1
Принадлежит: Betagenon Ab

According to the invention there is provided a compound of formula (I) wherein: A represents C(═N—W-D) or S; B represents S or C(—NH—W-D); when: A represents C(═N—W-D) and B represents S then the bond between B and the NH atom is a single bond; or A represents S and B represents C(—NH—W-D) then the bond between B and the NH atom is a double bond; X represents -Q-[CR x R y ] n —; W represents —[CR x R y ] m — or —C(O)—[CR x R y ] p —; Q represents a bond, —N(R a )—, —S—, or —O—; A 1 to A 5 respectively represent C(R 1 ), C(R 2 ), C(R 3 ), C(R 4 ) and C(R 5 ), or, alternatively, up to two of A 1 to A 5 may independently represent N; D represents phenyl, pyridyl or pyrimidinyl optionally substituted by one or more R 6 groups, which compounds are useful in the treatment of cancer.

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30-08-2012 дата публикации

2-phenylethylamino derivatives as calcium and/or sodium channel modulators

Номер: US20120220592A1
Принадлежит: Newron Pharmaceuticals SpA

2-Phenylethylamino substituted carboxamide derivatives and their use as sodium and/or calcium channel modulators useful in preventing, alleviating and curing a wide range of pathologies are presented.

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31-01-2013 дата публикации

Methods and compounds for the targeted delivery of agents to bone for interaction therewith

Номер: US20130029901A1

Bone targeted compounds and methods are provided. Compounds can include a Bone Targeting Portion (R T ), having an affinity for bone; a Bone Active Portion (R A ) for interacting with and affecting bone; and a Linking Portion (R L ) connecting the Bone Targeting Portion and the Bone Active Portion.

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21-03-2013 дата публикации

Inhibitors of Ion Channels

Номер: US20130072471A1
Принадлежит:

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted aryl sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel. 2. The compound of claim 1 , with the proviso that the compound of formula (I) is not one of the following compounds:N-(5-methyl-3-isoxazolyl)-3-[[(5-methyl-3-isoxazolyl)amino]sulfonyl]-benzamide;3-[[(5-methyl-3-isoxazolyl)amino]sulfonyl]-N-1,3,4-thiadiazol-2-yl-benzamide;N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-(4-morpholinylcarbonyl)-benzenesulfonamide;1-[3-[[[5-(1,1-dimethylethyl)-4-methyl-2-thiazolyl]amino]sulfonyl]benzoyl]piperidine;N-(5-methyl-1,3,4-thiadiazol-2-yl)-3-(4-morpholinylcarbonyl)-benzenesulfonamide; andN-methyl-4-[[(1-methyl-1H-pyrazol-3-yl)amino]sulfonyl]-benzamide.3. The compound according to claim 2 , or a pharmaceutically acceptable salt claim 2 , wherein{'sup': '5', 'sub': 1', '10', '3', '8, 'Ris a member selected from (C-C)alkyl and (C-C)cycloalkyl,'}{'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'wherein each is optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, cyano, hydroxy, hydroxy(C-C)alkyl, hydroxy(C-C)alkoxy, (C-C)alkyl, halo(C-C)alkyl, (C-C)alkoxy, halo(C-C)alkoxy and phenyl.'}4. The compound according to claim 3 , or a pharmaceutically acceptable salt claim 3 , wherein Ris a member selected from (C-C)alkyl claim 3 , hydroxy(C-C ...

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04-04-2013 дата публикации

Gamma-glutamyl transpeptidase inhibitors and methods of use

Номер: US20130085168A1
Автор: Marie H. Hanigan
Принадлежит: University of Oklahoma

Compositions and methods for inhibiting human gamma-glutamyl transpeptidase (GGT) in vivo or in vitro and for inhibiting and killing neoplastic cancer cells, for example for the treatment, inhibition or prevention of tumors or malignant growths or other neoplasias in mammals, or sensitizing tumor to other therapies including radiation therapy. The GGT inhibitor compounds comprise a class of benzylthiadiazol benzenesulfoniamides. The compounds may also be used to treat a reversible airways obstruction in a mammal or a disease associated with reverse airways obstruction such as asthma, chronic obstructive pulmonary disease (COPD), allergic reaction, respiratory tract infection or upper respiratory tract disease. Other diseases or conditions which may be treated include, for example, degenerative diseases, renal diseases, liver diseases, cardiovascular disease and inner ear conditions or diseases.

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18-04-2013 дата публикации

POLYMERS WITH TUNABLE BAND GAPS FOR PHOTONIC AND ELECTRONIC APPLICATIONS

Номер: US20130092912A1
Автор: You Wei
Принадлежит:

The present invention provides, among other things, a copolymer comprising at least one donor monomer and at least one acceptor monomer. The polymer may optionally further comprise at least one additional comonomer. The polymers are useful as a charge-transport, semiconducting, electrochemical conducting, photoconducting, or light emitting material. Microelectronic devices comprising such polymers (e.g., as a heterojunction therein) are also described. 2. The copolymer of having a number average molecular weight of from 500 to 1 claim 1 ,000 claim 1 ,000 grams per mole.3. The copolymer of claim 1 , further comprising at least one additional comonomer.11. The copolymer of claim 10 , wherein Rand Rare fluoro.12. The copolymer of claim 10 , wherein each R and Ris C1-C20 alkyl.13. The copolymer of claim 10 , wherein R claim 10 , R claim 10 , Rand Rare each H.14. The copolymer of claim 10 , having a number average molecular weight for said polymer of from 500 to 1 claim 10 ,000 claim 10 ,000 grams per mole.16. The polymer of having a number average molecular weight of from 500 to 1 claim 15 ,000 claim 15 ,000 grams per mole.17. The polymer of claim 15 , wherein said polymer is a homopolymer.18. The polymer of claim 15 , wherein said polymer is a copolymer with at least one additional monomer.20. (canceled)21. A microelectronic device comprising a polymer of .22. The device of claim 21 , wherein said device is an optoelectronic device.23. The device of claim 21 , wherein said polymer comprises a heterojunction in said device.24. The device of claim 21 , wherein said device is a photovoltaic cell claim 21 , field effect transistor claim 21 , light emitting diode claim 21 , photodectector claim 21 , photovoltaic detector claim 21 , imaging device claim 21 , lasing device claim 21 , storage element claim 21 , amplifier claim 21 , emitter claim 21 , or electrochromic display.25. The device of claim 21 , wherein said device comprises a first electrode claim 21 , a second ...

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25-04-2013 дата публикации

METHOD OF TREATING DIABETES, METABOLIC SYNDROME AND OBESITY USING PHENYLACETAMIDE DERIVATIVE

Номер: US20130102617A1
Принадлежит: Astellas Pharma Inc.

Phenylacetamide compounds of the formula 1. (canceled)2. The method of claim 18 , wherein n is 0.3. The method of claim 2 , wherein Ris methyl claim 2 , trifluoromethyl claim 2 , or cyclopropyl.4. The method of claim 3 , wherein Ris cyclopropyl.6. The method of claim 5 , wherein Ring A is pyrazolyl claim 5 , thiazolyl claim 5 , thiadiazolyl claim 5 , pyridyl or pyrazinyl claim 5 , each of which may be substituted with up to five moieties independently selected from the group consisting of halogen claim 5 , cyano claim 5 , lower alkyl which may be substituted with —OR claim 5 , —OR claim 5 , —O-lower alkylene —OR claim 5 , and —C(O)R.7. The method of claim 6 , wherein [Chem. 21] is a single bond.8. The method of claim 6 , wherein [Chem. 22] is a double bond.9. The method of claim 18 , wherein the compound is selected from the group consisting of:(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-fluoro-1,3-thiazol-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2R)—N-(4-acetyl-1,3-thiazol-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyridin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)—N-(5-chloropyrazin-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methoxypyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-hydroxycyclopentyl]-N-(5 ...

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02-05-2013 дата публикации

Bile Acid Recycling Inhibitors for Treatment of Hypercholemia and Cholestatic Liver Disease

Номер: US20130108573A1
Принадлежит: Lumena Pharmaceuticals, Inc.

Provided herein are methods of treating or ameliorating hypercholemia or a cholestatic liver disease by administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising administering to an individual in need thereof a therapeutically effective amount of ASBTI or a pharmaceutically acceptable salt thereof. 1. A method for treating or ameliorating hypercholemia comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein the method comprises decreasing at least 20% of serum bile acid or hepatic bile acid levels in the patient.3. The method of claim 1 , wherein less than 10% of the ASBTI is systemically absorbed.5. The method of claim 4 , wherein:q is 1;n is 2;{'sup': 'x', 'sub': 3', '2, 'Ris N(CH);'}{'sup': 7', '8, 'Rand Rare independently H;'}{'sup': 1', '2, 'Rand Ris alkyl;'}{'sup': 3', '4, 'Ris H, and Ris OH;'}{'sup': 5', '6', '9', '9', '9', '9', '9, 'sub': 2', '3', 'Z', 'Z, 'claim-text': wherein z is 1, 2 or 3; each L is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted alkoxy, a substituted or unsubstituted aminoalkyl group, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl; each K is a moiety that prevents systemic absorption;', {'sup': 15', '13', '13', '14', '13', '14', '13', '13', '13', '13', '13', '14', '13', ...

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02-05-2013 дата публикации

Chemical Compounds

Номер: US20130109696A1
Принадлежит: PFIZER LIMITED

The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I) or pharmaceutically acceptable salts thereof, wherein X, Y, Y, Z, R, Rand Rare as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain. 2. A compound according to wherein X is S.3. A compound according to wherein X is CH.4. A compound according to wherein Z is either (a) a ‘C-linked’ 5-membered heteroaryl group containing two nitrogen atoms and one sulphur atom claim 1 , or (b) a ‘C-linked’ 6-membered heteroaryl group containing two nitrogen atoms.5. A compound according to wherein Z is ‘C-linked’ thiadiazolyl or ‘C-linked’ a pyrimidinyl.6. A compound according to wherein Yis Cl and Yis F.7. A compound according to wherein Yis CN and Yis H.8. A compound according to wherein Rand Rare independently H claim 1 , F claim 1 , Cl or R.9. A compound according to wherein Rand Rare independently H claim 1 , F claim 1 , CFor OCH.10. A compound according to wherein Ris H claim 1 , F claim 1 , Ror Het.11. A compound according to wherein Ris H; F; (C-C)alkyl claim 1 , optionally substituted by one to three halo atoms; (C-C)alkyloxy claim 1 , such as methoxy; or a ‘C-linked’ 6-membered heteroaryl group comprising one or two nitrogen atoms claim 1 , optionally substituted on a carbon atom by NH.12. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof together claim 1 , as defined in claim 1 , with one or more pharmaceutically acceptable excipients.13. A pharmaceutical composition according to including one or more additional therapeutic agents.14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. A method of treating a disorder in a human or animal for which a ...

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09-05-2013 дата публикации

Selective Androgen Receptor Modulators

Номер: US20130116288A1
Автор: Chris P. Miller
Принадлежит: Radius Health Inc

This invention provides compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig or salts thereof, pharmaceutical compositions comprising a compound of formulas I, Ia, Ib, Ic, Id, If or Ig and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig and intermediates useful in the preparation of same.

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16-05-2013 дата публикации

MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF USING THE SAME

Номер: US20130123246A1
Принадлежит: INCYTE CORPORATION

The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof. 2. The compound of wherein Ring A is heterocyclyl optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.3. The compound of wherein Ring A is 5- or 6-membered heterocyclyl optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.4. The compound of wherein Ring A is 5-membered heterocyclyl optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.5. The compound of wherein Ring A is 5-membered heterocyclyl containing at least one ring-forming N atom and Ring A is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.6. The compound of wherein Ring A is 5-membered heterocyclyl containing at least one ring-forming O atom and Ring A is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.7. The compound of wherein Ring A is 5-membered heterocyclyl containing at least one ring-forming O atom and containing at least one ring-forming N atom claim 1 , and Ring A is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 R.10. The compound of wherein Ris H claim 1 , C(O)R claim 1 , C(O)NRR claim 1 , or C(O)OR.11. The compound of wherein Ris H.12. The compound of wherein Ris H.13. The compound of wherein a and b are both 0.14. The compound of wherein Ris aryl claim 1 , cycloalkyl claim 1 , heteroaryl claim 1 , or heterocycloalkyl claim 1 , each optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 substituents independently selected from halo claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Chaloalkyl claim 1 , Chydroxyalkyl claim 1 , Cy claim 1 , CN claim 1 , NO claim 1 , OR claim 1 , SR claim 1 , C(O)R claim 1 , C(O)NRR claim 1 , C(O)OR claim 1 , OC(O)R claim 1 , OC(O)NRR claim 1 , NRC(O)NRR claim 1 , NRR claim 1 , NRC(O)R claim 1 , NRC(O)OR claim 1 , C(═NR)NRR claim 1 , NRC(═NR)NRR claim 1 , P(R) claim 1 , P( ...

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30-05-2013 дата публикации

HETEROARYL (ALKYL) DITHIOCARBAMATE COMPOUNDS, PREPARATION METHODS AND USES THEREOF

Номер: US20130136794A1
Принадлежит: PEKING UNIVERSITY

Heteroaryl(alkyl)dithiocarbamate compounds represented by general formula (I) or their pharmaceutically acceptable salts, their preparing methods, and their uses for preparing antitumor medicines are disclosed, wherein each said substituent is defined as in the description. The compounds are new tyrosine kinase inhibitors useful as an anti-tumor agents, preferably useful in the preparation of medicines for treating breast cancer, liver cancer, non-small cell lung cancer, gastric cancer, colon cancer, leukaemia or nasal cancer. 2. The compound according to claim 1 , wherein the group A is substituted or unsubstituted heterocyclic group claim 1 , is the heterocyclic group being selected from pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , furyl claim 1 , oxazolyl claim 1 , pyrazolyl claim 1 , thiazolyl or oxadiazolyl; preferably the group A is substituted or unsubstituted pyridyl claim 1 , or pyridyl fused with benzene or morpholine ring claim 1 , the fused benzene or morpholine ring being unsubstituted or substituted with methyl.3. The compounds according to claim 2 , wherein the Calkyl is methyl claim 2 , the Calkoxy is methoxy claim 2 , the Calkoxycarbonyl is methoxycarbonyl claim 2 , and/or the Calkylamido is pentylamido .4. The compound according to claim 3 , wherein the Rgroup is cyano.5. The compound according to claim 1 , wherein the compound is:3-(furan-2-ylmethyl)-4-hydroxy-1,3-thiazinane-2-thione (compound 1);2-(methoxycarbonyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 2);2-cyanoethyl(furan-2-ylmethyl)dithiocarbamate (compound 3);3-(furan-2-ylmethyl)-4-hydroxy-4,5-dimethyl-3,4-dihydro-2H-1,3-thiazine-2-thione (compound 4);2-sulfamoylethyl(furan-2-ylmethyl)dithiocarbamate (compound 5);2-boronoethyl(furan-2-ylmethyl)dithiocarbamate (compound 6);2-(methylsulfinyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 7);2-(benzylsulfinyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 8);4-hydroxy-3-(pyridin-3-ylmethyl)-1,3-thiazinane-2-thione ( ...

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20-06-2013 дата публикации

HETEROCYCLIC INHIBITORS OF GLUTAMINASE

Номер: US20130157998A1
Принадлежит: CALITHERA BIOSCIENCES INC.

The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treatment using the novel heterocyclic compounds of the invention. 2. The method of claim 1 , wherein L represents CHSCH claim 1 , CHCH claim 1 , CHS or SCH.3. The method of claim 1 , wherein L represents CHCH.4. The method of any preceding claim claim 1 , wherein Y represents H.5. The method of any preceding claim claim 1 , wherein X claim 1 , independently for each occurrence claim 1 , represents S or CH═CH claim 1 , wherein any hydrogen atom of a CH unit may be replaced by alkyl.6. The method of any preceding claim claim 1 , wherein Z represents R(CO).7. The method of claim 6 , wherein each occurrence of Ris not identical.8. The method of any preceding claim claim 6 , wherein Rand Reach represent H.9. The method of any preceding claim claim 6 , wherein R claim 6 , independently for each occurrence claim 6 , represents substituted or unsubstituted arylalkyl claim 6 , heteroarylalkyl claim 6 , cycloalkyl or heterocycloalkyl.10. The method of any preceding claim claim 6 , wherein R claim 6 , independently for each occurrence claim 6 , represents C(R)(R)(R) claim 6 , wherein Rrepresents substituted or unsubstituted aryl claim 6 , arylalkyl claim 6 , heteroaryl or heteroaralkyl claim 6 , Rrepresents H claim 6 , and Rrepresents hydroxy claim 6 , hydroxyalkyl claim 6 , alkoxy or alkoxyalkyl.11. The method of claim 10 , wherein Rrepresents substituted or unsubstituted aryl claim 10 , arylalkyl claim 10 , or heteroaryl.12. The method of or claim 10 , wherein Rrepresents hydroxy claim 10 , hydroxyalkyl claim 10 , or alkoxy.13. The method of claim 1 , wherein L represents CHSCH claim 1 , CHCH claim 1 , CHS or SCH claim 1 , Y represents H claim 1 , X represents S claim 1 , Z represents R(CO) claim 1 , Rand Reach represent H claim 1 , and R claim 1 , independently for each occurrence claim 1 , represents substituted or unsubstituted ...

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20-06-2013 дата публикации

POSITIVE ALLOSTERIC MODULATORS OF MGLUR2

Номер: US20130158002A1
Принадлежит:

The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved. 3. The compound according to wherein X is C.4. The compound according to wherein X is N.5. The compound according to wherein Y is methyl.6. The compound according to wherein Ris selected from the group consisting of: cyclopropylmethyl claim 2 , 2 claim 2 ,2-difluorocyclopropylmethyl claim 2 , cyclobutylmethyl claim 2 , 2 claim 2 ,2-dimethylpropyl and benzyl claim 2 , optionally substituted with methoxy or —OCF.8. The compound according to wherein Ris selected from the group consisting of: (1) —CN claim 7 , (2) halo claim 7 , (3) —CF claim 7 , (4) 1 claim 7 ,1-dioxidothiomorpholin-4-yl claim 7 , (5) morpholin-4-ylmethyl claim 7 , (6) —C(O)—O—Calkyl claim 7 , (7) Calkoxy claim 7 , (8) Calkyl claim 7 , optionally substituted with hydroxy claim 7 , (9) piperazinyl claim 7 , optionally substituted with —C(O)—O—Calkyl or isoxazolylcarbonyl claim 7 , and (10) piperidinyl claim 7 , optionally substituted with —C(O)—O—Calkyl or isoxazolylcarbonyl.10. The compound according to wherein Ris selected from the group consisting of: (1) —CN claim 9 , (2) halo claim 9 , (3) —CF claim 9 , (4) 1 claim 9 ,1-dioxidothiomorpholin-4-yl claim 9 , (5) morpholin-4-ylmethyl claim 9 , (6) —C(O)—O—Calkyl claim 9 , (7) Calkoxy claim 9 , (8) Calkyl claim 9 , optionally substituted with hydroxy claim 9 ...

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20-06-2013 дата публикации

HETEROCYCLIC COMPOUNDS AS DGAT1 INHIBITORS

Номер: US20130158075A1
Принадлежит: Piramal Enterprises Limited

The present invention relates to heterocyclic compounds of formula 1, in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides. The invention also relates to processes for the manufacture of the heterocyclic compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1. The present invention further provides a method of treatment of such diseases or disorders by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof. 167-. (canceled)89. A compound according to claim 68 , wherein A is an aryl and said aryl is unsubstituted or substituted with one or more groups selected from halogen claim 68 , hydroxy claim 68 , (C-C)-alkoxy claim 68 , cyano claim 68 , (C-C)-alkyl claim 68 , OCF claim 68 , CF claim 68 , (C-C)-cycloalkyl claim 68 , aryl claim 68 , aryloxy claim 68 , heterocyclyl claim 68 , or O-heterocyclyl.90. A compound according to claim 68 , wherein A is an aryl group and said aryl group may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O claim 68 , N or S.91. A compound according to claim 68 , wherein A is a heterocyclyl and said heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen claim 68 , hydroxy claim 68 , (C-C)-alkoxy claim 68 , cyano claim 68 , (C-C)-alkyl claim 68 , (C-C)-cycloalkyl claim 68 , aryl claim 68 , aryloxy claim 68 , heterocyclyl or O-heterocyclyl.92. A compound according to claim 68 , wherein A is a (C-C)-cycloalkyl and said (C-C)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen claim 68 , hydroxy ...

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27-06-2013 дата публикации

CONJUGATED POLYMERS

Номер: US20130161567A1

The invention relates to novel polymers containing repeating units based on benzo[2,1,3]thiadiazole-5,6-dicarboxylic acid bis-ester, monomers and methods for their preparation, their use as semiconductors in organic electronic (OE) devices, especially in organic photovoltaic (OPV) devices, and to OE and OPV devices comprising these polymers. 2. Polymer according to claim 1 , wherein Rand Rin formula I are selected from straight-chain claim 1 , branched or cyclic alkyl with 1 to 35 C atoms claim 1 , in which one or more non-adjacent C atoms are optionally replaced by —O— claim 1 , —S— claim 1 , —C(O)— claim 1 , —C(O)—O— claim 1 , —O—C(O)— claim 1 , —O—C(O)—O— claim 1 , —CR═CR— or —C≡C— and in which one or more H atoms are optionally replaced by F claim 1 , Cl claim 1 , Br claim 1 , I or CN claim 1 , or denote aryl claim 1 , heteroaryl claim 1 , aryloxy claim 1 , heteroaryloxy claim 1 , arylcarbonyl claim 1 , heteroarylcarbonyl claim 1 , arylcarbonyloxy claim 1 , heteroarylcarbonyloxy claim 1 , aryloxycarbonyl or heteroaryloxycarbonyl having 4 to 30 ring atoms that is unsubstituted or substituted by one or more non-aromatic groups R claim 1 , wherein{'sup': 3', '0', '00', '0', '0', '0', '00', '0', '0, 'sub': 2', '3', '2', '2', '3', '5, 'Ris on each occurrence identically or differently F, Br, Cl, —CN, —NC, —NCO, —NCS, —OCN, —SCN, —C(O)NRR, —C(O)X, —C(O)R, —NH, —NRR, —SH, —SR, —SOH, —SOR, —OH, —NO, —CF, —SF, optionally substituted silyl, carbyl or hydrocarbyl with 1 to 40 C atoms that is optionally substituted and optionally comprises one or more hetero atoms, or P-Sp-,'}{'sup': 0', '00, 'sub': '1-40', 'Rand Rare independently of each other H or optionally substituted Ccarbyl or hydrocarbyl,'}P is a polymerisable or crosslinkable group,Sp is a spacer group or a single bond, and{'sup': '0', 'Xis halogen.'}4. Polymer according to claim 3 , which is selected of formula IIa{'br': None, 'sup': 4', '1', '2', '3', '5, 'sub': x', 'y', 'n, 'R—[(Ar—U—Ar)—(Ar)]—R\u2003\u2003IIa ...

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27-06-2013 дата публикации

TETRASUBSTITUTED BENZENES

Номер: US20130165486A1
Принадлежит: EnVivo Pharmaceuticals, Inc.

Tetrasubstituted benzenes that act as modulators of gamma secretase and their use in the treatment of one or more symptoms of treating neurodegenerative disorders, e.g., Alzheimer's disease, are described. 162.-. (canceled)64. The compound of claim 63 , wherein Rand Rare independently selected from the group consisting of (a) H claim 63 , (b) (C-C)alkyl and (c) (C-C)alkyl-(C-C)cycloalkyl provided that both Rand Rare not H claim 63 , wherein each alkyl or cycloalkyl of Rand Ris optionally independently substituted with one or more groups selected from the group consisting of halo claim 63 , hydroxy claim 63 , cyano claim 63 , CFand (C-C)alkyl claim 63 ,or{'sub': 1', '2', '1', '4', '3', '1', '4, 'Rand Rtaken together with the carbon to which they are attached form a 3-7 membered cycloalkyl or heterocycloalkyl ring which optionally bears a C-Calkyl substituent that can be optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, oxo, cyano, CFand (C-C)alkyl,'}or{'sub': 1', '2', '20', '21', '20', '21', '3', '1', '4, 'Rand Rare taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring substituted with Rand Rwherein Rand Rtaken together with the carbon or carbons to which they are attached form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CFand (C-C)alkyl;'}Y is —O—,{'sub': '4', 'claim-text': [{'sub': 0', '3', '3', '7, '(a) (C-C)alkyl(C-C)cycloalkyl,'}, '(b) trifluoroethyl and', '(c) trifluoropropyl;', {'sub': 6', '3', '2', '1', '4', '2', '2', '3', '6', '6', '2', '6, 'Z is a phenyl ring optionally bearing up to 3 substituents independently selected from the group consisting of halogen, R, CF, CN, NO, OH, (C-C)alkoxy, OCHCHOCH, SR, S(O)Rand S(O)R;'}], 'Ris selected from the group consisting of'}{'sub': 5', '3, 'claim-text': [{'sub': '6', 'Ris selected ...

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11-07-2013 дата публикации

N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase

Номер: US20130177590A1
Принадлежит: Incyte Corp

The present invention is directed to N-hydroxyamidino compounds which are modulators of indoleamine 2,3-dioxygenase (IDO), as well as pharmaceutical compositions thereof and methods of use thereof relating to the treatment of cancer and other diseases.

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18-07-2013 дата публикации

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

Номер: US20130184278A1
Принадлежит: ABBOTT LABORATORIES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein. 5. The compound of claim 1 , or therapeutically acceptable salt thereof claim 1 , wherein the compound is selected from the group consisting of:4-[4-(cyclohexylmethyl)-4-methoxypiperidin-1-yl]-N-{[5-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}benzamide;N-{[5-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}-4-[4-methoxy-4-(3-methylbenzyl)piperidin-1-yl]benzamide;N-{[5-({(1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}-4-[4-(3,3-diphenylprop-2-enyl)piperazin-1-yl]benzamide;4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl}-N-[(4-{[2-(phenylthio)ethyl]amino}piperidin-1-yl)sulfonyl]benzamide;N-[(4-{acetyl[2-(phenylthio)ethyl]amino}piperidin-1-yl)sulfonyl]-4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl}benzamide;4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl}-N-[(4-{methyl[2-(phenylthio)ethyl]amino}piperidin-1-yl)sulfonyl]benzamide;4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl}-N-{[5-({(1R)-3-[isopropyl(methyl)amino]-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}benzamide;4-(4-{[2-(4-chlorophenyl)cyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-{[5-({(1R)-3-[isopropyl(methyl)amino]-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}benzamide;4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-{[5-({(1R)-3-[isopropyl(methyl)amino]-1-[(phenylthio)methyl]propyl}amino)-4-nitrothien-2-yl]sulfonyl}benzamide;N-{[(5Z)-5-(acetylimino)-4-methyl-4,5-dihydro-1,3,4-thiadiazol-2-yl]sulfonyl}-4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl}benzamide;N-({5-[(benzoylamino)methyl]thien-2-yl}sulfonyl)-4-{4-[(4′-chloro-1,1′-biphenyl-2-yl)methyl]piperazin-1-yl ...

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18-07-2013 дата публикации

Sulfonyl compounds which modulate the cb2 receptor

Номер: US20130184315A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Compounds of formula (I) and formula (II) are disclosed. Compounds according to the invention bind to and are agonists, antagonists or inverse agonists of the CB2 receptor, and are useful for treating inflammation. Those compounds which are agonists are additionally useful for treating pain.

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18-07-2013 дата публикации

SMALL MOLECULE INHIBITORS OF THE PLECKSTRIN HOMOLOGY DOMAIN AND METHODS FOR USING SAME

Номер: US20130184317A1
Принадлежит:

Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein. 181-. (canceled)83. The compound of wherein{'sup': 2', '6', '6a', '6b, 'sub': 6', '20', '2, 'Ris a C-Calkyl, optionally substituted with one or more substituents independently selected from halogen, —OH, —NH, —NHC(O)R, and —NRR;'}{'sup': 6', '7', '7', '7', '7, 'sub': 3', '2', '3', '2', '2', '3', '6', '5', '6', '4', '2', '6', '5', '2', '6', '4', '1', '20', '1', '20', '2', '3', '2', '3', '2', '2', '3', '1', '6', '6', '5', '6', '4', '2', '6', '5', '2', '6', '4, 'Ris —CH, —CHCH, —CHCHCH, —CH, —CHR, —CHCH, —CHCHR, aryl, heteroaryl, or —C-Calkyl, wherein each of the aryl, heteroaryl, or —C-Calkyl may optionally be substituted with one or more substituents independently selected from —NH, —OH, —CH, —CHCH—CHCHCH—C-Calkyl, —CH, —CHR, —CHCH, —CHCHRand halogen;'}{'sup': '6a', 'Rmay be H or methyl;'}{'sup': '6b', 'sub': 6', '5, 'Rmay be methyl 7-nitrobenzene[c][1,2,5]oxadiazole-4-yl, or —C(O)CH; and'}{'sup': '7', 'sub': 3', '3', '3', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2, 'Rmay be —H, —CH, heteroaryl, —C(CH), —OH, —NH, —NHC(O)CH, —S(O)OH, —P(O))H, —As(O)OH, —NO, —OCH, —OCHCH, —C(O)OH, —C(O)NH, or halogen.'}84. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris a C-Calkyl.85. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris a straight C-Calkyl.86. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris a C-Calkyl.87. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris a C-Calkyl.88. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris a C-Calkyl.89. The compound of or pharmaceutically acceptable salt thereof claim 82 , wherein Ris —(CH)CH.92. The pharmaceutical composition of claim 91 , wherein:{'sup': 2', '6', '6a', '6b, 'sub': 6', '20', '2, 'Ris a C-Calkyl, optionally ...

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08-08-2013 дата публикации

CYCLIC AMIDE DERIVATIVE

Номер: US20130203739A1
Принадлежит: MOCHIDA PHARMACEUTICAL CO., LTD.

[Problem] 4. The compound according to claim 3 , wherein X is an oxygen atom claim 3 , k is 0 claim 3 , and any one of q and s is 1 or more claim 3 ,a salt of the compound, or a solvate of the compound or the salt.6. The compound according to claim 5 , wherein E is Formula (c2) claim 5 , and any one of q and s is 1 or more claim 5 ,a salt of the compound, or a solvate of the compound or the salt.7. The compound according to any one of to claim 5 , wherein s is 1 claim 5 , a salt of the compound claim 5 , or a solvate of the compound or the salt.10. The compound according to claim 9 , wherein Ea is Formula (c1) claim 9 , and any one of q and s is 1 or more claim 9 ,a salt of the compound, or a solvate of the compound or the salt.11. A pharmaceutical composition characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.12. A prophylactic agent and/or a therapeutic agent against a GPR40-involving disease characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.13. An insulin secretagogues characterized by comprising claim 9 , as an active ingredient claim 9 , at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.14. A GPR40 activating agent comprising at least one of the compound as claimed in any one of to claim 9 , a pharmaceutically acceptable salt of the compound claim 9 , and a pharmaceutically acceptable solvate of the compound or the salt.15. A pharmaceutical composition characterized by comprising:{' ...

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22-08-2013 дата публикации

Arylsulfonamide ccr3 antagonists

Номер: US20130217687A1
Принадлежит: Axikin Pharmaceuticals Inc

Provided herein are arylsulfonamides that are useful for modulating CCR3 activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

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29-08-2013 дата публикации

COMPOUND FOR INCREASING KINASE ACTIVE AND APPLICATION THEREOF

Номер: US20130225587A1
Принадлежит:

The compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, chelates thereof, non-covalent complexes thereof or produgs of compounds mentioned above or the mixture of any form above mentioned are provided. The use of the compounds in manufacturing a medicament for the treatment and/or prevention of diabetes, obesity and related disorders. 2. The compound of claim 1 , wherein W is C.34-. (canceled)5. The compound of claim 2 , wherein Y is C claim 2 , X is O claim 2 , and wherein Z is C.6. The compound of claim 2 , wherein Y is N.7. The compound of claim 6 , wherein X is O.8. The compound of claim 7 , wherein Z is C.911-. (canceled)12. The compound of claim 1 , wherein W is N claim 1 , Y is C claim 1 , wherein X is O claim 1 , and wherein Z is C.1319-. (canceled)20. The compound of claim 1 , wherein Ris selected from the group consisting of —H claim 1 , lower alkanyl claim 1 , substituted lower alkanyl claim 1 , lower alkenyl claim 1 , substituted lower alkenyl claim 1 , lower alkynyl claim 1 , substituted lower alkynyl claim 1 , Calkoxy and substituted Calkoxy.21. The compound of claim 20 , wherein Ris —H; Ris selected from the group consisting of cycloalkyl claim 20 , substituted cycloalkyl claim 20 , heterocycloalkyl and substituted heterocycloalkyl; and wherein Ris 5 or 6 membered heteroaryl.2324-. (canceled)25. The compound of claim 1 , wherein Ris selected from the group consisting of C(═O)R claim 1 , SR claim 1 , SORand haloalkyl; and wherein Ris selected the group consisting of Calkanyl claim 1 , substituted Calkanyl claim 1 , NRR claim 1 , Calkoxy claim 1 , and substituted Calkoxy.26. The compound of claim 25 , wherein Ris —H; wherein Ris selected from the group consisting of cycloalkanyl claim 25 , substituted cycloalkanyl claim 25 , heterocycloalkyl and substituted heterocycloalkyl; and wherein Ris substituted 5- or 6-membered heteroaryl.28. The compound of claim 27 , wherein Ris C(═O)R; Ris NRR.29. The compound of claim 27 , ...

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29-08-2013 дата публикации

SALTS OF POTASSIUM ATP CHANNEL OPENERS AND USES THEREOF

Номер: US20130225806A1
Принадлежит: Essentialis, Inc.

Provided are immediate or prolonged administration of certain salts of Kchannel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving Kchannels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals. 2. The method of wherein said cation source is an alkali metal hydroxide.3. The method of wherein said cation source is sodium hydroxide or potassium hydroxide.4. The method of wherein said solvent is selected from the group consisting of acetonitrile claim 3 , low molecular weight ketones claim 3 , and tetrahydrofuran.5. The method of wherein said cation source is an organic cation source comprising an ammonium or at least one tertiary amine group.6. The method of wherein said cation source is choline hydroxide or hexamethyl hexamethylene diammonium dihydroxide.7. The method of wherein said solvent is selected from the group consisting of acetonitrile claim 6 , low molecular weight ketones claim 6 , tetrahydrofuran claim 6 , and 2-methyl tetrahydrofuran.8. The method of wherein said cation source is choline hydroxide claim 6 , and said solvent is selected from the group consisting of acetonitrile claim 6 , low molecular weight ketones claim 6 , tetrahydrofuran claim 6 , and 2-methyl tetrahydrofuran.9. The method of wherein said compound of Formulae I-IV is dissolved in a solvent at a ratio of about 1 g compound of Formulae I-IV to about 1 to 5 mL solvent.10. The method of further comprising adding a co-solvent prior to the step of removing the solvent.11. The method of wherein said co-solvent is selected from the group consisting of methyl tert-butyl ether (MTBE) claim ...

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05-09-2013 дата публикации

ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE

Номер: US20130231342A1
Принадлежит: Oryzon Fenomics S.A.

The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX). 2. The compound of wherein (A) is an aryl group or a heteroaryl group claim 1 , wherein said aryl group or said heteroaryl group has n substituents (R3).3. The compound of wherein (A) is phenyl claim 1 , pyridinyl claim 1 , thiophenyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , or thiazolyl claim 1 , and further wherein (A) has n substituents (R3).4. The compound of wherein (A) is phenyl or pyridyl claim 1 , and further wherein said phenyl or said pyridyl has n substituents (R3).5. The compound of wherein (A) has 0 substituents (R3).6. The compound of wherein (B) is —O—CH-phenyl or phenyl claim 1 , and further wherein said phenyl or the phenyl moiety comprised in said —O—CH-phenyl has n substituents (R2).78-. (canceled)9. The compound of wherein (B) has 0 claim 1 , 1 or 2 substituents (R2).10. (canceled)11. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiadiazolyl claim 1 , triazinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , pyridinyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl claim 1 , said oxazolyl claim 1 , said isoxazolyl claim 1 , said thiadiazolyl claim 1 , said triazinyl claim 1 , said pyridazinyl claim 1 , said pyrazinyl claim 1 , said pyridinyl or said pyrimidinyl has one substituent (R1).12. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl or said pyrimidinyl has one substituent (R1).13. The compound of wherein (D) is oxadiazolyl ...

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12-09-2013 дата публикации

COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

Номер: US20130237531A1
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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12-09-2013 дата публикации

PROCESS FOR THE PREPARATION OF TAUROLIDINE AND ITS INTERMEDIATES THEREOF

Номер: US20130237700A1

The present invention relates to a process for the preparation of substantially pure Taurolidine. 1. Process for the preparation of Cbz-taurine sodium salt (II) which comprises:a. Reaction of Taurine and Cbz-cl in the presence of aqueous sodium hydroxide and toluene as solventb. Separation of aqueous and organic layerc. Addition of sodium hydroxide to make the aqueous layer highly basic (pH12-14)d. Separation of Cbz-taurine sodium salt2. Process for the preparation of Taurolidine which comprises:a. Reaction of Taurine and Cbz-cl in the presence of aqueous sodium hydroxide and toluene as solventb. Separation of Cbz-taurine sodium salt precipitated out{'sub': '5', 'c. Conversion of Cbz-taurine sodium to Cbz-Taurinamide in the presence of PClfollowed by treatment with ammonia'}d. Conversion of Cbz-Taurinamide to taurinamide in presence of Pd/C followed by in situ generation of Taurinamide Succinate by reaction of Taurinamide and succinic acide. Treatment of Taurinamide succinate with formaldehyde under basic conditions to generate Taurolidine3. Process for the purification of Taurolidine which involvesa. dissolving Taurolidine in non-aqueous aprotic solvents to obtain clear solutionb. isolation of the pure compound which precipitates from the clear solution4. Process of claim 3 , wherein the non-aqueous aprotic solvents are DMSO claim 3 , DMAc claim 3 , DMF claim 3 , Acetonitrile5. Process of wherein the purification stage has an additional step of adding antisolvent6. Process of claim 5 , wherein the anti solvents are toluene claim 5 , ethyl acetate claim 5 , diethyl ether and dichloromethane. Taurolidine is an antibacterial drug and also has antiendotoxic substance, which is used as an antiseptic solution in surgery for washing out the abdominal cavity and it also prevents septic shock. It is commercially sold as Taurolidine (Formula I). The present invention relates to a process for the preparation of Taurolidine which provides significant advantages over the ...

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03-10-2013 дата публикации

Sulfonyl semicarbazides, semicarbazides and ureas, pharmaceutical compositions thereof, and methods for treating hemorrhagic fever viruses, including infections associated with arena viruses

Номер: US20130261087A1
Принадлежит: Siga Technologies Inc

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel sulfonyl semicarbazides, carbonyl semicarbazides, semicarbazides, ureas and related compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, Pinchinde, and VSV), Filoviridae (ebola and Marburg viruses), Flaviviridae (yellow fever, omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

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03-10-2013 дата публикации

FUNGICIDAL N-(2-PHENOXYETHYL)CARBOXAMIDE DERIVATIVES AND THEIR AZA, THIA AND SILA ANALOGUES

Номер: US20130261158A1
Принадлежит:

The present invention relates to fungicide N-(2-phenoxyethyl)carboxamide derivatives of formula (I), their aza, thia and sila analogues, their process of preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. Formula (1) wherein A, T, W, X, n and Zto Zrepresent various substituents. 3. A compound according to wherein A is selected in the list consisting of A; A; Aand A.4. A compound according to wherein A represents Aand wherein Rrepresents a C-C-alkyl claim 3 , C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; or C-C-alkoxy; Rrepresents a hydrogen atom or a halogen atom; Rrepresents a C-C-alkyl.5. A compound according to wherein W represents O or S.6. A compound according to wherein n represents 0 claim 1 , 1 or 2.7. A compound according to wherein X independently represents a halogen atom; C-C-alkyl; C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; tri(C-C-alkyl)silyl; C-Calkoxy or C-C-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different or wherein two consecutive substituents X together with the phenyl ring form a substituted or non substituted 1 claim 1 ,3-benzodioxolyl; 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-quinoxalinyl; 3 claim 1 ,4-dihydro-2H-1 claim 1 ,4-benzoxazinyl; 1 claim 1 ,4-benzodioxanyl; indanyl; 2 claim 1 ,3-dihydrobenzofuranyl; or indolinyl.8. A compound according to wherein Zand Zindependently represent a C-C-alkyl.9. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.10. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.11. A compound according to wherein Zrepresents a C-Ccycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen ...

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10-10-2013 дата публикации

HETEROCYCLIC SULFONAMIDES

Номер: US20130267537A1
Принадлежит: CYTOKINETICS, INC.

Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure. 114-. (canceled)16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris a phenyl claim 15 , isoxazolyl claim 15 , oxazolyl claim 15 , pyridinyl claim 15 , pyrazinyl claim 15 , pyrimidinyl claim 15 , tetrazol-5-yl claim 15 , thiazolyl claim 15 , thiadiazolyl or imidazolyl group claim 15 , which is optionally substituted with a halogen claim 15 , lower alkoxy claim 15 , aryl or heteroaryl group.17. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris a [1 claim 15 ,3 claim 15 ,4]thiadiazol-2-yl group which is optionally substituted with a phenyl group.18. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris 5-phenyl-[1 claim 15 ,3 claim 15 ,4]thiadiazol-2-yl.19. The compound of claim 18 , or a pharmaceutically acceptable salt thereof claim 18 , wherein{'sup': '4', 'Rchloro; and'}{'sup': 5', '6', '7, 'R, Rand Rare hydrogen.'}20. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris a 1H-imidazol-2-yl group.21. The compound of claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , wherein{'sup': '4', 'Ris chloro; and'}{'sup': 5', '6', '7, 'R, Rand Rare hydrogen.'}22. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein Ris thiazol-2-yl.23. The compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein{'sup': '4', 'Ris chloro; and'}{'sup': 5', '6', '7, 'R, Rand Rare hydrogen.'}24. The compound of claim 15 , or a pharmaceutically acceptable salt thereof claim 15 , wherein{'sup': '4', 'Ris chloro; and'}{'sup': 5', '6', '7, 'R, Rand Rare hydrogen.'}25. The compound of claim 15 , or a pharmaceutically ...

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17-10-2013 дата публикации

PREMATURE-TERMINATION-CODONS READTHROUGH COMPOUNDS

Номер: US20130274283A1

Premature termination codons readthrough compounds, composition thereof, and methods of making and using the same are provided. 1. A system for high throughput assay for readthrough compound having the ability to read through premature termination codons (PTCs) in RNA , comprising high throughput reading trays and wells containing a plasmid ,wherein the plasmid comprises a fragment of ATM gene that contains a PTC mutation, which fragment being flanked by a sequence that initiates transcription of:a) a myc epitope,b) the ATM fragment, andc) a V5 epitope;wherein the assay is based on a coupled protein transcription/translation (PTT) reaction that is driven by the plasmid;wherein the reading trays are coated with an antibody to the myc epitope; andwherein an antibody to V5 is provided for attaching to readthrough proteins expressing the V5 epitope.2. The system of claim 1 , wherein the V5 epitope is conjugated to horseradish peroxidase.3. The system of claim 1 , further comprising a robot.4. A method of screening for readthrough compounds having the ability to read through premature termination codons (PTCs) in RNA claim 1 , comprising: a) a myc epitope,', 'b) the ATM fragment, and', 'c) a V5 epitope;, 'providing a plasmid template to a reaction well having a test compound to cause a coupled protein transcription/translation (PTT) reaction to occur to generate a PTT reaction product, the plasmid template comprising a fragment of ATM gene that contains a PTC mutation, which fragment being flanked by a sequence that initiates transcription ofadding the PTT reaction product to high throughput reading trays, which are coated with an antibody to the myc epitope to capture a protein fragment of the fragment of ATM gene,adding an antibody to the V5 epitope (V5 antibody) to wells in the reading trays,detecting the attachment of the V5 antibody to proteins in the PTT product, andidentifying the test compound as a readthrough compound if the attachment of the V5 antibody to ...

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24-10-2013 дата публикации

Agents for treating disorders involving modulation of ryanodine receptors

Номер: US20130281512A1
Принадлежит: Armgo Pharma Inc, Laboratoires Servier SAS

The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

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31-10-2013 дата публикации

HETEROCYCLIC FUSED ANTHRAQUINONE DERIVATIVES, MANUFACTURING METHOD AND PHARMACEUTICAL COMPOSITION USING THEREOF

Номер: US20130289028A1
Принадлежит: NATIONAL DEFENSE MEDICAL CENTER

A heterocyclic fused anthraquinone derivatives, which is represented by a formula (I): 2. The heterocyclic fused anthraquinone derivatives of claim 1 , wherein Ris aminoalkyl group claim 1 , sulfoalkyl group or haloalkyl group claim 1 , the alkyl group can be selected from the group consisting of Cstraight-chain alkyl group claim 1 , Cbranched alkyl group and Ccyclic alkyl group claim 1 , and the halogens can be selected from the group consisting of F claim 1 , Cl claim 1 , Br and I.3. The heterocyclic fused anthraquinone derivatives of claim 2 , wherein Ris Cl claim 2 , sulfonic acid sodium claim 2 , oxide potassium claim 2 , diethylamino group claim 2 , amino-propyl group claim 2 , amino-cyclobutyl group claim 2 , amino-dimethyl group claim 2 , amino-ethyl group claim 2 , ethyl piperazino group claim 2 , amimo-cyclopentylamino group claim 2 , amino-butylamino group claim 2 , amino-ethylamino claim 2 , amino-2-methylpropylamino group claim 2 , thio-morpholino group claim 2 , thio-ethyl group claim 2 , thio-n-propyl group or thio-isopropyl group.4. The heterocyclic fused anthraquinone derivatives of claim 1 , wherein the Ris amino group and the Ris 3-chlorophenylamino group claim 1 , 2-methylphenylamino group claim 1 , 3-methylphenylamono group claim 1 , 4-methylphenylamino group claim 1 , 4-chlorophenylamino group or 4-chloro-2-fluorophenylamino group.5. The heterocyclic fused anthraquinone derivatives of claim 1 , wherein the Ris oxygen and Ris para-methylphenyl-oxy group.6. The heterocyclic fused anthraquinone derivatives of claim 1 , wherein the Ris sulfur group and Ris phenylthio claim 1 , 2 claim 1 ,5-dimethylphenylthio group claim 1 , benzylthio group claim 1 , 4-chlorophenylthio group claim 1 , 2-methylphenylthio group claim 1 , 4-bromophenylthio group claim 1 , 2 claim 1 ,4-dimethylphenylthio group claim 1 , 4-isopropylphenylthio group claim 1 , 2-bromophenylthio group claim 1 , 4-fluorophenylthio group claim 1 , phenylthioethyl group claim 1 , 2 claim 1 ,3 ...

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28-11-2013 дата публикации

THIAZOLE AND THIADIAZOLE COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20130317032A1
Принадлежит: Synta Pharmaceuticals Corp.

The invention relates to compounds of structural formula (I): 1137-. (canceled)141. The compound of claim 140 , wherein Y′ is an optionally substituted phenyl or an optionally substituted pyridinyl.142. The compound of claim 141 , wherein Y′ is substituted with one to two substituents.143. The compound of claim 142 , wherein the one to two substituents are each independently a lower alkyl or a halo.144. The compound of claim 143 , wherein Y′ is 2 claim 143 ,6-difluorophenyl.145. The compound of claim 140 , wherein L′ is —NRCH— claim 140 , —CHNR— claim 140 , —C(O)— claim 140 , —NR—C(O)— claim 140 , —C(O)—NR— claim 140 , —OC(O)— claim 140 , —C(O)O— claim 140 , —C(S)— claim 140 , —NR—C(S)— claim 140 , or —C(S)—NR—.146. The compound of claim 145 , wherein L′ is —NH—C(O)—.147. The compound of claim 140 , wherein L′ is —NRS(O)— claim 140 , —S(O)NR— claim 140 , —NRS(O)NR— claim 140 , —NRC(O)CH— claim 140 , —NRC(O)CH═CH— claim 140 , —NRC(O)NR— claim 140 , —NRC(NR)NR— claim 140 , —NRC(S)NR— claim 140 , —NRCHNR— claim 140 , —NRN═CR— claim 140 , —C(NR)— claim 140 , —CR═NNR—; —CH═CH— or148. The compound of claim 140 , wherein Zis lower alkyl.149. The compound of claim 140 , wherein Zis —H.150. The compound of claim 140 , whereinY′ is a phenyl substituted with one to two substituents or a pyridinyl substituted with one to two substituents, wherein the one to two substituents are each independently a lower alkyl or a halo;L′ is —NR—C(O)—;{'sub': '1', 'Zis lower alkyl or —H; and'}{'sub': 5', '6', '3, 'Zand Zare each independently chloro, bromo, fluoro, cyano, trifluoromethyl, —C(O)CH, 2-methyl-2H-tetrazolyl, methoxy, nitro, dimethylamino, thiazol-2-yl, oxazol-2-yl, or methyl.'}153. The compound of claim 138 , wherein the compound is selected from the group consisting of:N-[4-(2,4-Dichloro-phenyl)-thiazol-2-yl]-2,6-difluoro-benzamide;N-[4-(2,5-Dimethoxy-phenyl)-thiazol-2-yl]-2,6-difluoro-benzamide;N-[5-(2,5-Dimethoxy-phenyl)-thiazol-2-yl]-2,6-difluoro-benzamide;N-[5-(2-Chloro-5- ...

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19-12-2013 дата публикации

Chemosensory Receptor Ligand-Based Therapies

Номер: US20130338095A1
Принадлежит: Elcelyx Therapeutics, Inc.

Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administering a composition comprising a chemosensory receptor ligand. Also provided herein are chemosensory receptor ligand compositions and methods for the preparation thereof for use in the methods of the present invention. 193-. (canceled)120. A composition according to claim 94 , wherein the composition further releases at least some of the chemosensory receptor ligand in the stomach.121. A composition according to claim 94 , wherein one or more regions of the intestine are the duodenum claim 94 , jejunum claim 94 , ileum claim 94 , caecum claim 94 , colon and/or rectum.122. A composition according to claim 94 , wherein the composition releases at an onset of about 5 to about 45 minutes claim 94 , about 105 to about 135 minutes claim 94 , about 165 to about 195 minutes claim 94 , about 225 to about 255 minutes or a combination of times thereof following administration to a subject.123. A composition according to claim 94 , wherein the composition releases at an onset of about pH 5.0 claim 94 , about pH 5.5 claim 94 , about pH 6.0 claim 94 , about pH 6.5 claim 94 , about pH 7.0 claim 94 , or combination thereof following administration to a subject.124. A composition according to claim 94 , the composition further comprising a second chemosensory receptor ligand selected from the group consisting of a sweet receptor ligand claim 94 , a bitter receptor ligand claim 94 , an umami receptor ligand claim 94 , a fat receptor ligand claim 94 , a sour receptor ligand and a bile acid receptor ligand.125. A composition according to claim 124 , wherein the sweet receptor ligand is selected from the group consisting of sucralose claim 124 , aspartame claim 124 , Stevioside claim 124 , Rebaudioside A claim 124 , Rebaudioside B claim 124 , Rebaudioside C claim 124 , Rebaudioside D claim 124 , ...

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19-12-2013 дата публикации

Compounds for the treatment of neurodegenerative diseases

Номер: US20130338202A1
Принадлежит: Proteo Tech Inc

Compounds and their pharmaceutically acceptable salts for treatment of synucleinopathies, such as Parkinson's disease and tauopathies.

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26-12-2013 дата публикации

COMPOUNDS AND COMPOSITIONS AS LXR MODULATORS

Номер: US20130345220A1
Принадлежит: IRM LLC

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of liver X receptors (LXRs). 3. The compound of in which{'sub': 1', '3, 'Ris selected from fluoro, chloro, methyl and —C(O)OCH; and'}{'sub': 2', '2', '3, 'Ris selected from phenyl, cyclohexyl, cyclopentyl, pyrrolyl, pyrazolyl, naphthyl, benzo[1,3]-dioxolyl, thienyl, furanyl and pyridinyl; wherein any aryl, heteroaryl or cycloalkyl of Ris optionally substituted with 1 to 4 radicals independently selected from fluoro, chloro, bromo, hydroxy, methyl, ethyl, propyl, t-butyl, amino, dimethyl-amino, methoxy, trifluoromethyl, trifluoromethoxy and —OC(O)CH.'}4. The compound of in which Ris selected from phenyl claim 3 , benzol[1 claim 3 ,3]-dioxolyl claim 3 , pyridinyl claim 3 , 2 claim 3 ,2-difluoro-benzol[1 claim 3 ,3]dioxol-5-yl and benzooxazolyl; wherein any aryl or heteroaryl of Ris substituted with 1 to 5 radicals independently selected from fluoro claim 3 , chloro claim 3 , bromo claim 3 , methoxy claim 3 , hydroxyl claim 3 , difluoromethoxy claim 3 , —OCHC(O)NH claim 3 , —OCHC(O)OCH claim 3 , —OCHC(O)NHCH claim 3 , —OCHC(O)N(CH) claim 3 , —R claim 3 , —OR claim 3 , —OCHR claim 3 , —OCHC(O)R claim 3 , —OCHC(O)NHR claim 3 , —OCHC(O)N(CH)R claim 3 , —OCHC(O)NHCHR claim 3 , —OCHCN claim 3 , —OCHCH claim 3 , —OCHCH claim 3 , —O(CH)OH claim 3 , —OCHC(O)NH(CH)C(O)OCH claim 3 , —OCHC(O)NH(CH)CHF claim 3 , —OCHC(O)NHCHCHF claim 3 , —OCHC(O)NH(CH)C(O)OH claim 3 , —OCHC(O)NHCH(CHR)C(O)OCH claim 3 , —OCHC(O)NHC(O)(CH)C(O)OCH claim 3 , —OCHC(O)NH(CH)NHC(O)CH claim 3 , —OCHC(O)NHCHC(O)CH claim 3 , —OCHC(O)NH(CH)C(O)OCH claim 3 , —OCHC(O)NHCHC(O)OCH claim 3 , —OCHC(O)NHCH[C(O)OCH] claim 3 , —S(O)CH claim 3 , —OCHC(O)NHCHCF claim 3 , —OCHC(O)NHCHC(O)(CH)C(O)OCH claim 3 , —OCHC(O)N(CH)CHC(O)OCH claim 3 , —OCHC(O)NH(CH)OCH claim 3 , —OCHC(O)NH(CH)OCH(CH) claim 3 , —OCHC(O)NH(CH)SCH claim 3 , ...

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09-01-2014 дата публикации

Compounds that Modulate EGFR Activity and Methods for Treating or Preventing Conditions Therewith

Номер: US20140011810A1
Принадлежит: Gatekeeper Pharmaceuticals, Inc.

Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith. 4. The compound of claim 1 , wherein Z is —(CH)NRC(O)R; Ris hydrogen; and Ris C-Calkenyl.6. The compound of claim 1 , wherein:X is oxygen;{'sup': '1', 'sub': 1', '6, 'Ris C-Calkoxy;'}{'sup': '2', 'sub': 1', '6, 'Ris piperazine that is substituted at the N position with C-Calkyl;'}{'sup': 2a', '2b, 'Rand Rare hydrogen;'}{'sup': 3', '4', '5', '3', '4', '5, 'one of R, R, and Ris Z, and the other two of R, R, and Rare hydrogen;'}{'sup': '7', 'sub': 1', '6, 'Ris hydrogen or C-Calkyl;'}{'sup': '8', 'sub': 2', '6, 'Ris C-Calkenyl; and'}{'sub': 2', 'n, 'sup': 7', '8, 'Z is —(CH)NRC(O)R.'}11. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.12. A kit comprising the compound of and instructions for use of the compound in treating a disease or disorder in a subject in need thereof.13. The kit of claim 12 , wherein the disease or disorder comprises a cancer or a proliferative disorder.14. A method for inhibiting a kinase claim 1 , comprising contacting the kinase with an effective amount of the compound of .15. The method of claim 14 , wherein the kinase comprises EGFR claim 14 , Jak3 claim 14 , Blk claim 14 , Bmx claim 14 , Btk claim 14 , HER2 (ErbB2) claim 14 , HER4 (ErbB4) claim 14 , Itk claim 14 , Tec claim 14 , or Txk.16. The method of claim 15 , wherein the EGFR is a mutant EGFR.17. The method of claim 16 , wherein the EGFR mutation comprises G719S claim 16 , G719C claim 16 , G719A claim 16 , L858R claim 16 , L861Q claim 16 , an exon 19 deletion mutation or an exon 20 insertion mutation.18. The method of claim 17 , wherein the EGFR mutation further comprises an EGFR T790M claim 17 , T854A or D761Y resistance mutation.19. A method for treating or preventing a disease that is mediated by a kinase comprising administering an effective amount of the compound of to a subject in need thereof.20. The method of claim 19 , wherein ...

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16-01-2014 дата публикации

MITOTIC KINESIN INHIBTORS AND METHODS OF USE THEREOF

Номер: US20140018399A1
Принадлежит: ARRAY BIOPHARMA INC.

This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders. 2. The compound of claim 1 , wherein Aris phenyl optionally substituted with one or more groups independently selected from halogen claim 1 , alkyl claim 1 , —ORor —NRR; or Aris a heteroaryl selected from thiophenyl or pyridyl claim 1 , wherein said pyridyl is optionally substituted independently with one or more halogen.3. The compound of claim 1 , wherein Aris phenyl claim 1 , 2 claim 1 ,4-difluorophenyl claim 1 , 2-fluorophenyl claim 1 , 3-fluorophenyl claim 1 , 2-chlorophenyl claim 1 , 3-chlorophenyl claim 1 , 2 claim 1 ,5-dichlorophenyl claim 1 , 2 claim 1 ,3-dichlorophenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 3 claim 1 ,5-dichlorophenyl claim 1 , 2-chloro-5-fluorophenyl claim 1 , 2-fluoro-5-chlorophenyl claim 1 , 2-chloro-5-methylphenyl claim 1 , 2-trifluoromethyl-5-fluorophenyl claim 1 , 2-fluoro-5-methoxyphenyl claim 1 , thiophen-2-yl claim 1 , thiophen-3-yl claim 1 , 5-chlorothiophen-2-yl claim 1 , 2-pyridyl claim 1 , 3-pyridyl claim 1 , 4-chloropyridin-3-yl claim 1 , 3-chloropyridin-2-yl claim 1 , 4-fluoropyridin-3-yl claim 1 , or 3 claim 1 ,6-difluoropyridin-2-yl.4. The compound of claim 1 , wherein Aris phenyl.5. The compound of claim 1 , wherein Aris phenyl optionally substituted with one or more groups independently selected from halogen claim 1 , OR claim 1 , NRR claim 1 , CN claim 1 , NO claim 1 , —OP(═O)(OR) claim 1 , C(═O)OR claim 1 , or Aris a heteroaryl selected from pyridyl claim 1 , thiophenyl optionally substituted with alkyl claim 1 , imidazolyl claim 1 , and pyrazolyl optionally substituted with NRR.6. The compound of claim 1 , wherein Aris phenyl claim 1 , 2-methylphenyl claim 1 , 3- ...

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23-01-2014 дата публикации

SULFAMIDE DERIVATIVE HAVING AN ADAMANTYL GROUP AND ITS PHARMACEUTICALLY ACCEPTABLE SALT

Номер: US20140024636A1

Provided is a sulfamide derivative having an adamantyl group represented by the following Formula 1, or a pharmaceutically acceptable salt thereof. The sulfamide derivative suppresses the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and is useful in the treatment of various diseases that are mediated by 11β-HSD1. 2. The sulfamide derivative or its pharmaceutically acceptable salt according to claim 1 , wherein Rrepresents phenyl or naphthalene group substitutued with halogen claim 1 , C-Calkyl or CF claim 1 , OCF claim 1 , cyano claim 1 , nitro claim 1 , or 5-10 membered aryl or heteroaryl; n represents an integer of 1.3. The sulfamide derivative or its pharmaceutically acceptable salt according to claim 1 , wherein the derivative represented by the Formula 1 is selected from the group consisting of:(1) N-(adamantan-2-yl)-2-(1,1-dioxido-6-(2-oxo-2-phenylethyl)-1,2,6-thiadiazinan-2-yl)acetamide;(2) N-(adamantan-2-yl)-2-(1,1-dioxido-6-phenyl-1,2,6-thiadiazinan-2-yl)acetamide;(3) tert-butyl 6-(2-(adamantan-2-ylamino)-2-oxoethyl)-1,2,6-thiadiazinan-2-carboxylate-1,1-dioxide;(4) N-(adamantan-2-yl)-2-(1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide hydro chloride;(5) N-(adamantan-2-yl)-2-(6-benzyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(6) N-(adamantan-2-yl)-2-(6-(4-fluorobenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(7) N-(adamantan-2-yl)-2-(1,1-dioxido-6-(4-(trifluoromethoxy)benzyl)-1,2,6-thiadiazinan-2-yl)acetamide;(8) N-(adamantan-2-yl)-2-(6-(4-chlorobenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(9) N-(adamantan-2-yl)-2-(6-(3-methylbenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(10) N-(adamantan-2-yl)-2-(6-(3-chlorobenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(11) N-(adamantan-2-yl)-2-(6-(3-fluorobenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(12) N-(adamantan-2-yl)-2-(6-(3-methoxybenzyl)-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamide;(13) N-(adamantan-2-yl)-2-(6-(2-chlorobenzyl)-1,1-dioxido-1,2,6- ...

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23-01-2014 дата публикации

Gamma-glutamyl transpeptidase inhibitors and methods of use

Номер: US20140024685A1

Compositions that are effective in inhibiting gamma-glutamyl transpeptidase are disclosed. Methods of producing and using these compositions are also disclosed.

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06-02-2014 дата публикации

Compounds and methods for kinase modulation, and indications therefor

Номер: US20140038948A1
Принадлежит: Plexxikon Inc

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.

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06-02-2014 дата публикации

SELECTIVE HETEROCYCLIC SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS

Номер: US20140039183A1
Принадлежит:

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 161-. (canceled)62. A method for the synthesis of a compound comprising an indane moiety having a chiral carbon in the five-membered ring of the indane moiety where the compound is enantiomerically enriched with respect to the chiral carbon , the method comprising the steps of(i) providing a compound comprising an indane moiety where the ring carbon of the five-membered ring of the indane moiety where chiral substitution is desired is oxo substituted at such carbon, and wherein a carbon of the phenyl ring is halo substituted;{'sub': 2', '2-6', '3-8, '(ii) reacting such compound with a chiral reagent selected from the group consisting of a Corey Bakshita Shibata-oxazaborolidine and a chiral sulfinamide of the form RS(═O)NHwhere R is selected from the group consisting of t-butyl, branched Calkyl and Ccycloalkyl; and'}(iii) forming the chiral center at the indane moiety carbon previously bound to the oxo group by either reacting such compound with a suitable reducing agent along with the chiral reagent in step (ii) or reacting the result of the reaction of such compound with a suitable reducing agent.63. The method of wherein the chiral reagent is the Corey Bakshita Shibata-oxazaborolidine.64. The method of wherein the chiral reagent is (R)-(−)-(2)-methyl-CBS-oxazaborolidine or (S)-(−)-(2)-methyl-CBS-oxazaborolidine.67. The method of wherein the protecting agent is TBSCl.69. The method of wherein the chiral reagent is RS(═O)NHand the compound comprising an ...

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13-02-2014 дата публикации

Cycloalkane Derivatives

Номер: US20140045862A1
Принадлежит: Daiichi Sankyo Company, Limited

Disclosed herein are therapeutic agents and/or preventive agents for pain or therapeutic agents and/or preventive agents for a sodium channel associated disease. The present invention provides compounds represented by the following formula (I) or pharmacologically acceptable salts thereof: 2. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein in formula (I) claim 1 ,{'sup': 1', '2, 'Arand Arare each independently a heteroaryl group;'}{'sup': 1', '2', '3, 'R, Rand Rare each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group or a C3-C7 cycloalkyl group;'}{'sup': 4', '5, 'Rand Rare each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group or a halogenated C1-C6 alkyl group; and'}the heteroaryl group is optionally substituted with one or two groups selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group, a hydroxyl group, a hydroxy C1-C6 alkyl group, a C3-C7 cycloalkyl group, an amino group, a C1-C3 alkylamino group and a di-C1-C3 alkylamino group.3. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein the heteroaryl group is a 5- or 6-membered nitrogen-containing aromatic heterocyclic group.4. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein Aris a pyridyl group claim 1 , a pyridazinyl group claim 1 , a pyrimidinyl group claim 1 , a pyrazolyl group or an imidazolyl group claim 1 , and wherein Aris optionally substituted.5. The compound or a pharmacologically acceptable salt thereof according to claim 4 , wherein Aris optionally substituted with one or two groups selected from the group consisting of a chlorine atom claim 4 , a fluorine atom claim 4 , a methyl group claim 4 , an ethyl group claim 4 , a trifluoromethyl group claim 4 , an amino group claim 4 , a methylamino group and a dimethylamino group.6. The compound or a ...

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20-02-2014 дата публикации

5-membered ring heteroaromatic derivatives having npy y5 receptor antagonistic activity

Номер: US20140051862A1
Принадлежит: Shionogi and Co Ltd

This invention provides new compounds having NPY Y5 antagonistic activity. The present inventors found that a compound of the formula (I): wherein R 1 is substituted or unsubstituted alkyl or the like; p, q and r are each independently 0 or 1; ring A is oxadiazole; and R 2 is substituted or unsubstituted alkyl or the like, has NPY Y5 antagonistic activity.

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27-02-2014 дата публикации

Novel Photoactive Polymers

Номер: US20140053905A1
Принадлежит: Merck Patent GmBH

This disclosure relates to a photovoltaic cell that includes a first electrode, a second electrode, and a photoactive layer disposed between the first and second electrodes. The photoactive layer includes a photoactive polymer containing a first monomer repeat unit, which contains a moiety of formula (1): in which A and R are defined in the specification.

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27-02-2014 дата публикации

CYCLIC AMIDE DERIVATIVE

Номер: US20140057871A1
Принадлежит: MOCHIDA PHARMACEUTICAL CO., LTD.

[Problem] 4. The compound according to claim 3 , wherein T is —CH— or an oxygen atom claim 3 , Ea is Formula (c1) claim 3 , either of q or s is 1 or more claim 3 ,or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the compound, or a pharmaceutically acceptable solvate of the salt.6. The compound according to claim 3 , whereinin Formula (III-1)-1 and Formula (III-1-A)-1,{'sup': 8', 'd', 'e1, 'sub': '1-6', 'Rs are independently a group optionally selected from Calkoxy group that is substituted with 1 to 5 substituent(s) M, a —CONRRgroup, and an aralkyloxy group,'}{'sub': 1-6', 'i', '1-6', '1-6', '2, 'sup': a', 'a', 'b1', 'c1', 'd', 'e', 'd', 'e, 'the substituents M are independently a group optionally selected from a halogen atom, —OH, a Calkoxy group, a —S(O)R(i is an integer of 0 to 2; and Ris a Calkyl group or a halogenated Calkyl group) group, a —NRRgroup, a —SONRRgroup, and a —CONRRgroup; and'}{'sup': 9', 'a', 'a', 'b1', 'c1', 'b1', 'c1', 'a', 'a', 'b1', 'c1', 'd', 'e, 'sub': 1-6', '1-6', '1-6', 'i', '1-6', '1-6', '2-6', '1-6', '1-6', '1-6', '2-7', 'i', '1-6', '1-6, 'Rs are independently a group optionally selected from a halogen atom, —OH, a cyano group, a Calkyl group (the Calkyl group is optionally substituted with 1 to 5 halogen atom(s), 1 to 5 —OH, 1 to 5 Calkoxy group(s), 1 to 5 —S(O)R(i is an integer of 0 to 2 and Ris a Calkyl group or a halogenated Calkyl group) group(s), or 1 to 5 —NRRgroup(s)), a Calkenyl group, a Calkoxy group (the Calkoxy group is optionally substituted with 1 to 5 halogen atom(s), 1 to 5 —OH, 1 to 5 Calkoxy group(s), or 1 to 5 —NRRgroup(s)), a Calkanoyl group, a —S(O)R(i is an integer of 0 to 2 and Ris a Calkyl group or a halogenated Calkyl group) group, a —NRRgroup, and a —CONRRgroup,'}or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the compound, or a pharmaceutically acceptable solvate of the salt.7. The compound according to claim 6 ...

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27-02-2014 дата публикации

PHARMACEUTICAL COMPOSITION FOR TREATING ALZHEIMER'S DISEASE

Номер: US20140058097A1
Принадлежит: Shionogi & Co., Ltd.

A pharmaceutical composition for treating Alzheimer's disease containing a compound represented by the general formula (I): 221-. (canceled) The present invention relates to a pharmaceutical composition which has reducing effect to produce amyloid β protein and is useful as an agent for treating disease induced by production, secretion and/or deposition of amyloid β protein, especially Alzheimer's disease.In the brain of Alzheimer's patient, the peptide composed of about 40 amino acids residue as is called amyloid β protein, that accumulates to form insoluble specks (senile specks) outside nerve cells is widely observed. It is concerned that this senile specks kill nerve cells to cause Alzheimer's disease. The therapeutic agents for Alzheimer's disease, such as decomposition agents of amyloid β protein and amyloid β vaccine, are under investigation.Secretase is an enzyme which cleaves amyloid 3 precursor protein (APP) in cell and produce amyloid 13 protein. The enzyme which controls the production of N terminus of amyloid β protein is called as BACE 1 (beta-site APP-cleaving enzyme 1, β-secretase). It is thought that inhibition of this enzyme leads to reduction of producing amyloid β protein and that the therapeutic agent for Alzheimer's disease will be created by the inhibition.Patent Literature 1 describes the compounds which are similar to those of the compounds contained in the pharmaceutical composition of the present invention, and the compounds have NO synthase enzyme inhibitory activity and are useful for dementia.Patent Literature 2 to 10 describes the compounds which are known as BACE 1 inhibitor, however, have different structures from the compounds contained in the pharmaceutical composition of the present invention.The present invention provides pharmaceutical compositions which have reducing effects to produce amyloid β protein, especially BACE 1 inhibitory activity, and which are useful as an agent for treating disease induced by production, secretion ...

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20-03-2014 дата публикации

Modulators of ATP-binding cassette transporters

Номер: US20140080825A1
Принадлежит: Vertex Pharmaceuticals Inc

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

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20-03-2014 дата публикации

METHODS FOR INHIBITING FASCIN

Номер: US20140080843A1
Принадлежит:

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. The method of claim 1 , wherein the compound is selected from5-(3,4-dichlorobenzyl)-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one;N-(1-(4-(trifluoromethyl)benzyl)-1H-indazol-3-yl)furan-2-carboxamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,5-dimethylbenzenesulfonamide;N-(3(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethylbenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-trimethylbenzenesulfonamide;(Z)—N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-bromobenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,4-dimethylbenzenesulfonamide;5-(3-chlorobenzyl)-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one;2-(4-oxo-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo[3,4-d]-pyrimidin-5(4H)-yl)-N-(3-( ...

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27-03-2014 дата публикации

PHENICOL ANTIBACTERIAL AGENTS

Номер: US20140088046A1
Принадлежит: Zoetis LLC

The present invention provides novel phenicol derivatives, their use for the treatment of infections in mammals, pharmaceutical composition containing these novel compounds, and methods for the preparation of these compounds. 2. A compound of wherein Het moiety is a 5- or 6-membered cyclic ring system having from 1 to 3 hetero atoms selected from N claim 1 , O claim 1 , and S claim 1 , optionally substituted with R.3. A compound of wherein Het is pyridinyl claim 2 , oxo-pyridinyl claim 2 , isoxazolyl claim 2 , thiazolyl claim 2 , thiadiazolyl claim 2 , thiophenyl claim 2 , oxazolyl claim 2 , pyrazolyl claim 2 , or thiadiazolyl.4. A compound of wherein Het is pyridinyl claim 3 , oxo-pyridinyl claim 3 , isoxazolyl claim 3 , thiazolyl claim 3 , or thiophenyl.5. A compound of wherein n is 0 or 1.6. A compound of wherein W is H claim 1 , —PO(OH) claim 1 , or —CHOPO(OH).7. A compound of selected from the group consisting of:3-[5-(4-{(1R,2S)-2-[(difluoroacetyl)amino]-3-fluoro-1-hydroxypropyl}phenyl)pyridin-2-yl]oxetan-3-yl dihydrogen phosphate;(1R,2S)-2-[(difluoroacetyl)amino]-3-fluoro-1-{4-[6-(3-hydroxyoxetan-3-yl)pyridin-3-yl]phenyl}propyl dihydrogen phosphate; and(1R,2S)-1-(4-(6-(cyanomethyl)pyridin-3-yl)phenyl)-2-(2,2-difluoroacetamido)-3-fluoropropyl dihydrogen phosphate.8. A compound of wherein W is H.9. A compound of wherein Rand Rtaken together with the carbon to which they are attached form a 4 to 6 membered heterocyclic ring moiety optionally having 1-2 hetero atoms selected from the group consisting of N claim 1 , NR claim 1 , S claim 1 , SO claim 1 , SO claim 1 , and O claim 1 , wherein the heteroatom or the heterocyclic is optionally substituted with R.10. A compound of wherein Rand Rtaken together with the carbon to which they are attached form an oxetanyl or an azetidinyl.11. A compound of wherein Ris —OW claim 1 , -Halo claim 1 , —CN claim 1 , or SOR; wherein W is hydrogen or —PO(OH); and Ris —C-Calkyl.12. A compound of wherein X claim 1 , Y and Z are ...

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03-04-2014 дата публикации

Mitotic kinesin inhibitors and methods of use thereof

Номер: US20140094603A1
Принадлежит: Array Biopharma Inc

This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders.

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10-04-2014 дата публикации

INHIBITION OF QUORUM SENSING-MEDIATED PROCESSES IN BACTERIA

Номер: US20140100242A1
Автор: Bassler Bonnie, Swem Lee
Принадлежит: THE TRUSTEES OF PRINCETON UNIVERSITY

Methods are provided for identifying molecules that can be used to positively and negatively manipulate quorum-sensing-mediated communication to control bacterial behavior. Small-molecule antagonists that disrupt quorum-sensing-mediated activities are identified. Methods are provided for disrupting detection of acyl-homoserine lactone autoinducer in Gram-negative bacteria by contacting the bacteria with the antagonists. Methods of inhibiting quorum sensing-mediated activity in Gram-negative bacteria are provided wherein the activity is pathogenicity, bioluminescence, siderophore production, type III secretion, or metalloprotease production. 2. The medical device of that is a catheter. This application is a continuation of U.S. patent application Ser. No. 12/995,476, filed Jan. 13, 2011, which is a National Stage of PCT Application No. PCT/US09/03348, which claims priority to U.S. Provisional Application No. 61/130,685, filed Jun. 2, 2008 and U.S. Provisional Application No. 61/188,310, filed Aug. 7, 2008, all of which are herein incorporated in their entirety.This invention was made with government support under Grant No. GM065859; Grant No. GM787552 and Grant No. AI054442 awarded by the National Institutes of Health and under Grant No. MCB0343821 and Grant No. MCB0639855 awarded by the National Science Foundation. The government has certain rights in the invention.The antagonist screen was partly funded with federal funds supplied to the National Cancer Institute's Initiative for Chemical Genetics, National Institutes of Health, under Contract No. N01-CO-12400 and has been performed with the assistance of the Chemical Biology Platform of the Broad Institute of Harvard and MIT. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Service, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.This invention relates to quorum sensing activities, ...

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07-01-2016 дата публикации

MODULATION OF SALTY TASTE PERCEPTION BY ALTERING THE FUNCTION OF BITTER- OR PKD2L1-EXPRESSING TASTE RECEPTOR CELLS

Номер: US20160000126A1
Автор: OKA Yuki, Zuker Charles

The current invention is in the field of taste and relates to methods and compositions to modulate the perceived taste of saltiness in food or food products where salty taste is desired. The methods and compositions relate to altering the activation and/or activity of the bitter-sensing taste receptor cells and the PKD2L1-expressing taste receptor cells. The invention also relates to food and food products containing agents and composition that alter the activation and/or activity of the bitter-sensing taste receptor cells and the PKD2L1-expressing taste receptor cells. 1. A method for modulating the perceived saltiness of a salty taste stimulant in a food or food product , comprising administering to a subject who is ingesting the food or food product , an agent that alters the activation or activity of bitter-sensing taste receptor cells (TRCs) and/or their concomitant pathway.2. The method of claim 1 , wherein the agent is administered before claim 1 , during or slightly after the subject ingests the food or food product.3. The method of claim 1 , wherein the food or food product contains sodium chloride.4. The method of claim 1 , wherein the food or food product contains a sodium substitute.5. The method of claim 4 , wherein the sodium substitute is chosen from the group consisting of potassium chloride claim 4 , magnesium chloride claim 4 , and calcium chloride.6. The method of claim 1 , wherein the food or food product is chosen from the group consisting of crackers claim 1 , potato chips claim 1 , corn chips claim 1 , tortilla chips claim 1 , sauces claim 1 , canned soups claim 1 , and canned vegetables.7. The method of claim 1 , wherein the agent is chosen from the group consisting of chemicals claim 1 , phytochemicals claim 1 , pharmaceuticals claim 1 , biologics claim 1 , small organic molecules claim 1 , antibodies claim 1 , nucleic acids claim 1 , peptides claim 1 , and proteins.8. The method of claim 1 , wherein the agent is allyl isothiocyanate.9. A ...

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03-01-2019 дата публикации

Compounds for the Detection, Capture and/or Separation of Polluting Gases

Номер: US20190001252A1

A subject of the present invention is the use of a compound having the general formula (I): (I) wherein V, W, X 4 , X 5 , X 6 , X 7 , X′ 4 , X′ 5 , X′ 6 , X′ 7 , Y, Y′, R 3 , R′ 3 , R 4 and R′ 4 are as defined in any one of claims 1 to 11 , for the detection, capture and/or separation of polluting gases, in particular those selected from the group comprising carbon dioxide, methane, sulfur dioxide, nitrogen oxides, carbon monoxide, linear hydrocarbons, linear mono-olefins and their mixtures, and preferably carbon dioxide. Another subject of the invention is a compound of formula (I) wherein V, W, X 4 , X 5 , X 6 , X 7 , X′ 4 , X′ 5 , X′ 6 , X′ 7 , Y, Y′, R 3 , R′ 3 , R 4 and R′ 4 are as defined in any one of claims 12 to 21 .

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05-01-2017 дата публикации

CYCLOPROPANAMINE COMPOUND AND USE THEREOF

Номер: US20170001994A1
Принадлежит:

The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula 2. The compound according to claim 1 , wherein A is(1) an optionally substituted heterocyclic group, or{'sub': '3-10', '(2) an optionally substituted Ccycloalkyl group,'}or a salt thereof.3. The compound according to claim 1 , wherein B is a ring selected from(1) a 5- or 6-membered aromatic heterocycle, and(2) a benzene ring fused with an optionally substituted 5- or 6-membered ring,wherein the ring represented by B is optionally substituted, and binds, via two adjacent carbon atoms with one atom in between, to a group represented by the formula (II), and a group represented by the formula (III),or a salt thereof.5. The compound according to claim 1 , wherein R claim 1 , Rand Rare each independently a hydrogen atom or an optionally substituted Calkyl group claim 1 ,or a salt thereof.6. The compound according to claim 1 , wherein Ris(1) a hydrogen atom,{'sub': '1-6', '(2) an optionally substituted Calkyl group,'}{'sub': '3-10', '(3) an optionally substituted Ccycloalkyl group, or'}(4) an optionally substituted heterocyclic group,or a salt thereof.8. The compound according to claim 1 , wherein A is{'sub': '1-6', '(1) a piperidinyl group, an isoxazolyl group, a pyrazolyl group, a thiadiazolyl group, a thiazolyl group, a tetrahydropyranyl group ...

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04-01-2018 дата публикации

COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

Номер: US20180002298A1
Принадлежит:

Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia. 2. A method of disrupting or inhibiting the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of tau fibrils and/or aggregates claim 1 , comprising administering a therapeutically effective amount of the compounds of .3. The method of claim 2 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.4. The method of claim 2 , where the compound is administered in an amount between 1 mg/Kg/day and 100 mg/Kg/day.5. The method of claim 2 , where amount of compound administered is in an amount between 10 mg/Kg/day and 100 mg/Kg/day.6. A method resulting in neuroprotection from a tauopathy in a mammal comprising the step of administrating a therapeutically effective amount of a compound of .7. The method of where the tauopathy is one selected from; Alzheimer's disease claim 6 , Pick's disease claim 6 , progressive supranuclear palsy claim 6 , corticobasal degeneration claim 6 , familial frontotemporal dementia/Parkinsonism linked to chromosome 17 claim 6 , amyotrophic lateral sclerosis/Parkinsonism-dementia complex claim 6 , argyrophilic grain dementia claim 6 , dementia pugilistic claim 6 , diffuse neurofibrillary tangles with calcification claim 6 , progressive subcortical gliosis and tangle only dementia.8. An article of manufacture claim 1 , comprising packaging material claim 1 , the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , contained within packaging material claim 1 , which is used for treating ...

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02-01-2020 дата публикации

CRYSTAL MODIFICATIONS OF ODEVIXIBAT

Номер: US20200002299A1
Принадлежит:

The present invention relates to crystal modifications of 1,1-dioxo-3,3-dibutyl-5-phenyl-7-methylthio-8-(N—{(R)-α-[N—((S)-1-carboxypropyl)carbamoyl]-4-hydroxybenzyl}carbamoylmethoxy)-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepine (odevixibat), more specifically crystal modifications 1 and 2 of odevixibat. The invention also relates to a process for the preparation of crystal modification 1 of odevixibat, to a pharmaceutical composition comprising crystal modification 1, and to the use of this crystal modification in the treatment of various conditions as described herein. 1. A crystalline hydrate of odevixibat.2. The hydrate according to claim 1 , which is a channel hydrate.3. The hydrate according to claim 1 , which comprises from about 0 to about 2 moles of water associated with the crystal per mole of odevixibat.4. The hydrate according to claim 1 , which is a sesquihydrate.5. The hydrate according to claim 1 , having an XRPD pattern claim 1 , obtained with CuKα1-radiation claim 1 , with peaks at °2θ positions 5.6±0.2 claim 1 , 6.7±0.2 and/or 12.1±0.2.6. The hydrate according to claim 5 , having an XRPD pattern claim 5 , obtained with CuKα1-radiation claim 5 , with specific peaks at °2θ positions 5.6±0.2 claim 5 , 6.7±0.2 and 12.1±0.2 and one or more of the characteristic peaks: 4.1±0.2 claim 5 , 4.6±0.2 claim 5 , 9.3±0.2 claim 5 , 9.4±0.2 and 10.7±0.2.7. (canceled)8. The crystal modification according to claim 5 , having a crystallinity of greater than about 99%.9. A mixed solvate of odevixibat claim 5 , containing about two moles of water per mole of odevixibat.10. The mixed solvate according to claim 9 , wherein the organic solvent is methanol claim 9 , ethanol claim 9 , 2-propanol claim 9 , acetone claim 9 , acetonitrile claim 9 , 1 claim 9 ,4-dioxane claim 9 , DMF or DMSO.11. The mixed solvate according to claim 9 , wherein the organic solvent is ethanol.12. The mixed solvate according to claim 9 , having an XRPD pattern claim 9 , obtained with CuKα1-radiation ...

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05-01-2017 дата публикации

BICYCLOAMINE-SUBSTITUTED-N-BENZENESULFONAMIDE COMPOUNDS WITH SELECTIVE ACTIVITY IN VOLTAGE-GATED SODIUM CHANNELS

Номер: US20170002008A1
Принадлежит: Merck Sharp & Dohme Corp.

Disclosed are compounds of Formula A-a, or a salt thereof: Where “B” and “R” through “R” are as defined herein, which compounds have properties for blocking Na1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A-a or their salts, and methods of treating neuropathic pain disorders using the same. 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 4', '5, 'Rand Rare independently: —H; or a cyclic-, branched- or linear-alkyl moiety of up to 6 carbon atoms; and'}{'sup': 1', '2, 'sub': '3', 'Rand Rare independently: —H; —F; —Cl; —Br; —CN; a cyclic-, branched, or linear-alkyl moiety comprising up to 6 carbon atoms; or —CF.'}34-. (canceled)5. A compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein:{'sup': '1', 'sub': '3', 'Ris: —H; —F; —Cl; —Br; —CN; or —CH;'}{'sup': '2', 'sub': 3', '2', '3', '3, 'Ris: —H; —F; —Cl; —Br; —CN; CH; —CHCH; or —CF; and'}{'sup': 4', '5, 'sub': '3', 'Rand Rare independently: (i) —H; or (ii) —CH.'}6. (canceled)8. A compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein:{'sup': 3', '4', '5, 'sub': '2', 'A, Aand Aare each [—CH—]; and'} [{'sup': '1', 'sub': '3', 'Ris independently: —H; —F; —Cl; —Br; —CN; or CH;'}, {'sup': '2', 'sub': 3', '3', '2', '3, 'Ris independently: —H; —F; —Cl; —Br; —CN; —CF, —CH; or —CHCH.'}], 'in the structure of Formula A-a9. (canceled)10. A compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein:{'sup': 10a2', '11a2, 'claim-text': [{'sup': 10a2', '11a2, 'claim-text': (a) hydrogen;', '(b) halogen;', {'sub': 1-6', '3-6', '3-6', '1-4', '3-4, '(c) an alkyl moiety which is —C-linear-alkyl, —C-branched-alkyl, or —C-cycloalkyl, which alkyl moiety is optionally substituted with one or more: (i) halogen; (ii) an aryl moiety optionally substituted with C-linear-alkoxy or C-branched-alkoxy; or (iii) —OH; ...

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05-01-2017 дата публикации

Benzothiadiazole-based conjugated molecules capable of forming films on conductive surfaces by electrochemical method

Номер: US20170002024A1

The present disclosure provides new materials that combine the advantages of well-defined polymeric starting materials and the convenience of surface modification by physical methods into one package and, thus, offers a general and powerful platform suitable for use in numerous applications.

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05-01-2017 дата публикации

NOVEL THERAPEUTICS FOR THE TREATMENT OF GLAUCOMA

Номер: US20170002040A1
Принадлежит:

The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure. 1. A pharmaceutical composition comprising a benzothiadiazine or chroman derivative disposed in an ophthalmically acceptable aqueous carrier.4. A unit dose container comprising the pharmaceutical composition according to .5. The unit dose container according to claim 4 , wherein the unit dose container is an eye drop dispenser.8. A pharmaceutical composition of claim 6 , wherein the benzothiadiazine or chroman derivative is comprise a 3S claim 6 ,4R stereo chemistry or a 3R claim 6 ,4S stereo chemistry.9. The pharmaceutical composition of claim 6 , wherein the compound is administered by topical application to the eye or administered by injection into the anterior chamber.10. The pharmaceutical composition of claim 6 , wherein the compound is administered using an ocular insert.11. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is a prodrug that is activated by removing one or more groups from the pharmaceutical composition.13. A composition as in claim 12 , wherein the R2 is a 2-pyrrolidinone group; R4 and R5 are —CH; and R6 claim 12 , R7 and R8 are —H. The present invention relates generally to benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives and methods for treating glaucoma and reducing intraocular pressure. It also relates to a process for their preparation and pharmaceutical compositions in which they are present.Without limiting the scope of the ...

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03-01-2019 дата публикации

IDO INHIBITORS

Номер: US20190002402A1
Принадлежит:

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention. 2. The compound according to wherein Rand Rare independently H claim 1 , Cto Calkyl claim 1 , Cto Calkoxy claim 1 , or join together to form cyclopropyl or cyclobutyl.3. The compound according to wherein Z is —NH— and Ris —SOR claim 1 , halo (C-Calkyl) claim 1 , thiazolyl or oxazolyl claim 1 , wherein Ris Cto Calkyl claim 1 , Cto Ccycloalkyl4. The compound according to wherein Z is O and Ris H.5. The compound according to wherein Ris —COR.6. The compound according to wherein Ris a 5 membered heterocycle containing from 1 to 4 heteroatoms selected from N claim 1 , O claim 1 , and S.7. The compound according to wherein Ris H and Ris —CORor —CONRR; Ris H claim 1 , and Ris phenyl claim 1 , pyridyl claim 1 , isoxazolyl claim 1 , thiadiazolyl claim 1 , indolinyl claim 1 , or benzyl claim 1 , wherein Rmay optionally be substituted with from 1 to 3 substituents selected from the group consisting of halo claim 1 , amino claim 1 , phenoxy claim 1 , benzoxy claim 1 , isoxalyl claim 1 , Cto Calkoxy claim 1 , Cto Calkyl claim 1 , halo-Cto Calkyl claim 1 , and CN.8. The compound according to wherein Ris Cto Ccycloalkyl optionally substituted with halo claim 1 , —OH or Cto Calkoxy; Cto Calkyl optionally substituted with halo claim 1 , —OH or phenyl claim 1 , wherein said phenyl is optionally substituted with Cto Chaloalkyl claim 1 , Cto Calkoxy claim 1 , halo or Cto Calkyl; Cto Calkenyl; Cto Calkoxy; or benzyl optionally substituted with Cto Calkyl claim 1 , halo claim 1 , Cto Calkoxy claim 1 , or haloalkyl.9. The compound according to wherein Ris a Cto Cheterocycloalkyl containing from 1 to 4 heteroatoms selected from O claim 1 , N or S.10. The compound ...

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07-01-2021 дата публикации

SULPHONYL UREA DERIVATIVES AS NLRP3 INFLAMMASOME MODULATORS

Номер: US20210002261A1
Принадлежит:

The present disclosure relates to compounds of Formula (I): 2. The compound of any one of the preceding claims , wherein Ris C-Cbicyclic cycloalkyl.6. The compound of any one of the preceding claims , wherein Ris C-Ctricyclic cycloalkyl.9. The compound of any one of the preceding claims , wherein , Ris C-Caryl optionally substituted by one or more R.10. The compound of any one of the preceding claims , wherein Ris phenyl is substituted by one , two , or three R.15. The compound of any one of the preceding claims , wherein Ris cyclopentyl , cyclohexyl , or cycloheptyl , wherein the cyclopentyl , cyclohexyl , or cycloheptyl is optionally substituted by one or more R.17. The compound of any one of the preceding claims , wherein at least one Ris methyl , ethyl , isopropyl , isobutyl , secbutyl , methoxy , ethoxy , —CF , —OCF , —OCHCF , F , or Cl.18. The compound of any one of the preceding claims , wherein Ris —R.19. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.20. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.21. The compound of any one of the preceding claims , wherein each Xis H.22. In some embodiments , at least one Xis C-Calkyl , C-Calkenyl , or C-Calkynyl , wherein the C-Calkyl , C-Calkenyl , or C-Calkynyl is optionally substituted with one or more halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.23. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl optionally substituted with one or more C-Calkyl , C-Calkenyl , C-Calkynyl , C-Chaloalkyl , halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.24. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl.25. The compound of any one of the preceding claims , wherein Ris 5- to 8-membered heterocycloalkyl.26. The compound of any one of the preceding claims , wherein Ris 5- to 7-membered heterocycloalkyl.27. The compound of any one of ...

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01-01-2015 дата публикации

TREATMENT OF CANCER WITH HETEROCYCLIC INHIBITORS OF GLUTAMINASE

Номер: US20150004134A1
Принадлежит: CALITHERA BIOSCIENCES, INC.

The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention. 223-. (canceled)2548-. (canceled)49. The method of any preceding claim , wherein the cancer is selected from breast cancer , colorectal cancer , endocrine cancer , lung cancer , melanoma , mesothelioma , renal cancer and a B cell malignancy.50. (canceled)51. The method of claim 49 , wherein the breast cancer comprises basal-type breast cancer cells claim 49 , triple-negative breast cancer cells or claudin-low breast cancer cells.5256-. (canceled)57. The method of claim 49 , wherein the endocrine cancer is selected from adrenal cortex adenoma claim 49 , adrenal cortex carcicnoma claim 49 , adrenal gland pheochromocytoma and parathyroid gland adenoma.5860-. (canceled)61. The method of claim 49 , wherein the B cell malignancy is selected from multiple myeloma claim 49 , leukemia and lymphoma.6263-. (canceled)64. The method of claim 61 , wherein the leukemia is selected from acute lymphoblastic leukemia and chronic lymphoblastic leukemia.65. (canceled)66. The method of claim 61 , wherein the lymphoma is selected from Burkitt's lymphoma claim 61 , Diffuse large B cell lymphoma claim 61 , follicular lymphoma and Hodgkin's lymphoma.67. The method of or claim 61 , further comprising conjointly administering one or more additional chemotherapeutic agents.6872-. (canceled)73. The method of claim 67 , wherein the one or more additional chemotherapeutic agents are selected from aminoglutethimide claim 67 , amsacrine claim 67 , anastrozole claim 67 , asparaginase claim 67 , bcg claim 67 , bicalutamide claim 67 , bleomycin claim 67 , bortezomib claim 67 , buserelin claim 67 , busulfan claim 67 , campothecin claim 67 , capecitabine claim 67 , carboplatin claim 67 , carfilzomib claim 67 , carmustine claim 67 , chlorambucil claim 67 , chloroquine claim 67 , ...

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01-01-2015 дата публикации

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20150005320A9
Принадлежит: Synta Pharmaceuticals Corp.

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

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04-01-2018 дата публикации

SPIRO-TYPE COMPOUND AND ORGANIC LIGHT EMITTING ELEMENT COMPRISING SAME

Номер: US20180006233A1
Принадлежит: LG CHEM, LTD.

The present specification provides a compound having a spiro structure, and an organic light emitting device including the same. 3. The compound of claim 1 , wherein HAr is a substituted or unsubstituted pyridyl group; a substituted or unsubstituted pyrimidyl group; a substituted or unsubstituted triazinyl group; a substituted or unsubstituted furan group; a substituted or unsubstituted thiophene group; a substituted or unsubstituted oxadiazole group; a substituted or unsubstituted thiadiazole group; a substituted or unsubstituted phenanthroline group; a substituted or unsubstituted quinolinyl group; a substituted or unsubstituted isoquinolinyl group; a substituted or unsubstituted quinazoline group; a substituted or unsubstituted benzoxazole group; a substituted or unsubstituted benzothiazole group; a substituted or unsubstituted benzimidazole group; a substituted or unsubstituted phenoxazine group; a substituted or unsubstituted phenothiazine group; a substituted or unsubstituted dibenzofuran group; a substituted or unsubstituted dibenzothiophene group; a substituted or unsubstituted carbazole group; or a substituted or unsubstituted diarylphosphine oxide group.7. An organic light emitting device comprising:a first electrode;a second electrode provided opposite to the first electrode; andone or more organic material layers provided between the first electrode and the second electrode,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'wherein one or more layers of the organic material layers include the compound of .'}8. The organic light emitting device of claim 7 , wherein the organic material layer includes a light emitting layer claim 7 , and the light emitting layer includes the compound.9. The organic light emitting device of claim 8 , wherein the light emitting layer further includes a light emitting dopant.10. The organic light emitting device of claim 7 , wherein the organic material layer includes an electron injection layer claim 7 , an electron transfer ...

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09-01-2020 дата публикации

METHODS, COMPOUNDS, COMPOSITIONS AND VEHICLES FOR DELIVERING 3-AMINO-1-PROPANESULFONIC ACID

Номер: US20200009086A1
Принадлежит:

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease 5. A method for treating Alzheimer's disease claim 1 , mild cognitive impairment claim 1 , Down's syndrome claim 1 , Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type claim 1 , cerebral amyloid angiopathy claim 1 , a degenerative dementia claim 1 , a dementia of mixed vascular and degenerative origin claim 1 , dementia associated with Parkinson's disease claim 1 , dementia associated with progressive supranuclear palsy claim 1 , dementia associated with cortical basal degeneration claim 1 , or diffuse Lewy body type of Alzheimer's disease claim 1 , comprising administering a therapeutically effective amount of a compound of to a human subject in need thereof.6. The method of claim 5 , which is for treating Alzheimer's disease claim 5 , mild cognitive impairment claim 5 , cerebral amyloid angiopathy claim 5 , or degenerative dementia.7. The method of claim 6 , which is for treating Alzheimer's disease.8. The method of wherein the compound is administered intratracheally claim 5 , intranasally claim 5 , ontologically claim 5 , rectally claim 5 , vaginally claim 5 , or orally.9. A pharmaceutical composition comprising a compound of together with a pharmaceutically acceptable carrier.10. The pharmaceutical composition of which is suitable for oral administration.11. The pharmaceutical composition of claim 9 , which is in the form of a hard shell gelatin capsule claim 9 , soft shell gelatin capsule claim 9 , cachet claim 9 , pill claim 9 , tablet claim 9 , lozenge claim 9 , powder claim 9 , granule claim 9 , pellet claim 9 , dragee claim 9 , which is ...

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14-01-2021 дата публикации

PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

Номер: US20210009542A1
Принадлежит:

Provided herein are compounds, compositions, and methods useful for inhibiting protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases, disorders and conditions favorably responsive to PTPN1 or PTPN2 inhibitor treatment, e.g., a cancer or a metabolic disease. This application is a continuation of International Patent Application No. PCT/US2019/038459, filed on Jun. 21, 2019, which claims the benefit of, and priority to, U.S. Provisional Application No. 62/688,226, filed on Jun. 21, 2018, the contents of each of which are incorporated herein by reference in their entirety.Cancer immunotherapy regimens targeting immune evasion mechanisms including checkpoint blockade (e.g. PD-1/PD-L1 and CTLA-4 blocking antibodies) have been shown to be effective in treating in a variety of cancers, dramatically improving outcomes in some populations refractory to conventional therapies. However, incomplete clinical responses and the development of intrinsic or acquired resistance will continue to limit the patient populations who could benefit from checkpoint blockade.Protein tyrosine phosphatase non-receptor type 2 (PTPN2), also known as T cell protein tyrosine phosphatase (TC-PTP), is an intracellular member of the class 1 subfamily of phospho-tyrosine specific phosphatases that control multiple cellular regulatory processes by removing phosphate groups from tyrosine substrates. PTPN2 is ubiquitously expressed, but expression is highest in hematopoietic and placental cells (Mosinger, B. Jr. et al., 89:499-503; 1992). In humans, PTPN2 expression is controlled post-transcriptionally by the existence of two splice variants: a 45 kDa form that contains a nuclear localization signal at the C-terminus upstream of the splice junction, and a 48 kDa canonical form which has a C-terminal ER retention motif (Tillmann U. et al., 14:3030-3040; 1994). The 45 kDa ...

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14-01-2021 дата публикации

Calpain modulators and therapeutic uses thereof

Номер: US20210009564A1
Принадлежит: Blade Therapertics Inc

Small molecule calpain modulator compounds, including their pharmaceutically acceptable salts, can be included in pharmaceutical compositions. The compounds can be useful in inhibiting calpain, or competitive binding with calpastatin, by contacting them with CAPN1, CAPN2, and/or CAPN9 enzymes residing inside a subject. The compounds and composition can also be administered to a subject in order to treat a fibrotic disease or a secondary disease state or condition of a fibrotic disease.

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10-01-2019 дата публикации

SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS

Номер: US20190010126A1
Принадлежит:

Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper-mineralization. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. The method of claim 1 , wherein Xis ═C(R)—.9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The method of claim 1 , wherein Ris optionally substituted phenyl or optionally substituted 5- or 6-membered heteroaryl.14. (canceled)15. The method of claim 1 , wherein Rand Rare independently selected from the group consisting of —F claim 1 , —Cl claim 1 , —Br claim 1 , —CN claim 1 , —OMe claim 1 , and —OCF.16. (canceled)17. (canceled)18. (canceled)21. (canceled)22. The method of claim 20 , wherein: A is —C(O)—O—R claim 20 , wherein Ris selected from hydrogen claim 20 , optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , and optionally substituted phenyl.23. (canceled)24. (canceled)25. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rtogether with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino.26. The method of claim 25 , wherein the optionally substituted heterocycloamino is an optionally substituted pyrrolidine claim 25 , an optionally substituted piperidine claim 25 , an optionally substituted morpholine claim 25 , or an optionally substituted piperazine.27. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Ris hydrogen and Ris optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , or optionally substituted phenyl.28. (canceled)29. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rare hydrogen.30. (canceled)31. (canceled)32. (canceled)33. The method of claim 1 , wherein the vascular calcification is an arterial calcification.34. The method of ...

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09-01-2020 дата публикации

METHOD FOR PREPARING 3,7-BIS(DIMETHYLAMINO)PHENOTHIAZIN-5-YLIUM IODIDE

Номер: US20200010438A1
Принадлежит: PROVEPHARM LIFE SOLUTIONS

Method for preparing 3,7-bis(dimethylamino)phenothiazin-5-ylium iodide, the method resulting in a high purity while being very simple to implement and producing high yields. The method uses phenothiazine as a starting material and includes the following steps: a) treating phenothiazine with diiodine, b) treating the reaction medium directly obtained from step a) with dimethylamine. 111-. (canceled)12. A process for preparing 3 ,7-bis(dimethylamino)phenothiazin-5-ylium iodide , this process using phenothiazine as starting product and comprising the following steps:a) treating phenothiazine with diiodine,b) treating the reaction medium directly resulting from step a) with dimethylamine.13. The process as claimed in claim 12 , wherein the treatment with diiodine is carried out with an amount of diiodine claim 12 , relative to the phenothiazine claim 12 , ranging from 2.5 molar equivalents to 3.5 molar equivalents.14. The process as claimed in claim 12 , wherein claim 12 , before step b) claim 12 , the reaction medium resulting from step a) is conditioned at a temperature ranging from 5° C. to 50° C.15. The process as claimed in claim 12 , wherein the treatment with dimethylamine is carried out with at least 7 molar equivalents of dimethylamine relative to the phenothiazine.16. The process as claimed in claim 12 , wherein claim 12 , in step a) claim 12 , the solvent is chosen from: an aromatic solvent or acetonitrile claim 12 , or mixtures thereof.17. The process as claimed in claim 16 , wherein in step a) claim 16 , the solvent is chosen from: toluene or acetonitrile claim 16 , or mixtures thereof.18. The process as claimed in claim 12 , wherein claim 12 , in step b) claim 12 , the dimethylamine is introduced into the reaction medium in the form of a solution in water.19. The process as claimed in claim 12 , wherein a precipitate forms at the outcome of the treatment of step b) claim 12 , said precipitate being recovered by filtration.20. The process as claimed in ...

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21-01-2016 дата публикации

FLUORINE ATOM-CONTAINING DISULFIDE COMPOUND

Номер: US20160016922A1
Принадлежит: FUJIFILM Corporation

A disulfide compound represented by formula (1):

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21-01-2016 дата публикации

S-imino-s-oxo-iminothiadiazine compounds as bace inhibitors, compositions, and their use

Номер: US20160016923A1
Принадлежит: Merck Sharp and Dohme LLC

In its many embodiments, the present invention provides certain S-imino-S-oxo iminothiadiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein R N , R 1 , R 2 , R 3 , R 4 , ring A, R A , m, L 1 , and R L are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

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21-01-2016 дата публикации

PREPARATION METHOD OF OPTICALLY ACTIVE DIAMINE COMPOUND

Номер: US20160016974A1
Принадлежит: Daiichi Sankyo Company, Limited

The problem to be solved is to provide a method for efficiently producing compounds (1) and (1a) that are important intermediate compounds in the production of FXa inhibitors (X) and (X-a). The solutions thereto are a method for producing a compound represented by the formula (8d) using a stereoselective intramolecular cyclization reaction, and a method for producing a compound (1f) or a salt thereof, or a hydrate thereof, which is characterized by desulfonylation of the compound (8d). In each formula, Rrepresents a C1-C6 alkyl group, a benzyl group, etc. 2. The production method according to claim 1 , wherein the desulfonylation is carried out by treating the compound with water and a base.3. The production method according to claim 2 , wherein the base is a pyridine.6. The production method according to claim 1 , wherein Rand Reach represent an ethyl group.8. The production method according to claim 1 , wherein Rrepresents a C1-C6 alkyl group.9. The production method according to claim 1 , wherein Rrepresents a methyl group.12. The production method according to claim 11 , wherein the desulfonylation is carried out by treating the compound with water and a base.13. The production method according to claim 12 , wherein the base is a pyridine.14. The production method according to claim 1 , wherein Ris a di(methyl)amino group.15. The production method according to claim 1 , wherein Ris a tert-butyl group or a benzyl group.16. The production method according to claim 14 , wherein the compound represented by the formula (1d) or a salt thereof claim 14 , or a hydrate thereof is a sulfate of the compound represented by the formula (1d) claim 14 , an oxalate monohydrate of the compound represented by the formula (1d) claim 14 , or an oxalate of the compound represented by the formula (1d).21. The compound according to claim 20 , wherein Rrepresents a C1-C6 alkyl group.22. The compound according to claim 20 , wherein Rrepresents a methyl group.24. The compound according ...

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18-01-2018 дата публикации

HUMAN HELICASE DDX3 INHIBITORS AS THERAPEUTIC AGENTS

Номер: US20180016243A1
Принадлежит:

The present invention refers to compounds endowed with RNA helicase DDX3 inhibitory activity of formula I and II and their therapeutic use, in particular for the treatment of viral diseases. 2. The compound according to wherein X and Y are C.3. The compound according to or wherein A is substituted aryl.4. The compound according to wherein the substituted aryl is phenyl.5. The compound according to wherein the phenyl is substituted by one claim 4 , two or more groups independently selected from methyl claim 4 , isopropyl claim 4 , CF claim 4 , F claim 4 , Cl claim 4 , OH claim 4 , OMe.6. The compound according to or wherein A is unsubstituted or substituted heteroaryl.7. The compound according to wherein the substituted heteroaryl is pyridinyl or isoquinolinyl.10. The compound or pharmaceutical acceptable salt claim 6 , solvate claim 6 , stereoisomer thereof according to any one of previous claim being an inhibitor of DDX3.11. The compound or pharmaceutical acceptable salt claim 6 , solvate claim 6 , stereoisomer thereof according to any one of previous claim for medical use.12. The compound or pharmaceutical acceptable salt claim 11 , solvate claim 11 , stereoisomer thereof according to for use in the treatment of a viral disease.13. The compound for use according to wherein the viral disease is modulated by DDX3.14. The compound for use according to or wherein the viral disease is caused by a virus that is resistant to at least one compound selected from the group consisting of: protease inhibitor; nucleoside reverse transcriptase inhibitor claim 12 , non-nucleoside reverse transcriptase inhibitor or integrase inhibitor.15. The compound according to to for use in the treatment of a viral disease is caused by a virus selected from the group consisting of: Human Immunodeficiency Virus 1 (HIV-1) claim 12 , Hepatitis C Virus claim 12 , Hepatitis B Virus claim 12 , Eastern Equine Encephalitis Virus claim 12 , Western Equine Encephalitis Virus claim 12 , Venezuelan ...

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15-01-2015 дата публикации

ANTIBACTERIAL AGENTS

Номер: US20150018331A1
Принадлежит: Achaogen, Inc.

Antibacterial compounds of formula (I) are provided: 137-. (canceled)39. A compound of wherein A is —C(R claim 38 ,R)N(R claim 38 ,R).40. A compound of wherein A is —C(CH)NH.41. A compound of wherein A is —C(R claim 38 ,R)OR.42. A compound of wherein A is selected from the group consisting of:{'sub': 3', '10, '(1) substituted or unsubstituted C-C-cycloalkyl,'}(2) substituted or unsubstituted heterocyclyl, and(3) substituted or unsubstituted heteroaryl.44. (canceled)45. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,{'sup': 3G', '3G, '(3) —CR═CR—C≡C—, and'}{'sup': 3G', '3G, '(4) —C≡C—CR═CR—.'}46. A compound of wherein G is selected from the group consisting of:(1) —C≡C—,(2) —C≡C—C≡C—,(3) —CH═CH—C≡C—, and(4) —C≡C—CH═CH—.47. A compound of wherein G is —C≡C—.48. A compound of wherein G is —C≡C—C≡C—.49. A compound of wherein G is —CH═CH—C≡C—.50. (canceled)51. A compound of wherein G is —C≡C—CH═CH—.5257-. (canceled)58. A compound of wherein Ris H.59. A compound of wherein Y is substituted or unsubstituted aryl.60. A compound of wherein Y is substituted or unsubstituted phenyl.61. A compound of wherein Y is unsubstituted phenyl.62. (canceled)63. A compound of wherein D is substituted or unsubstituted heteroaryl.6467-. (canceled)68. A compound of wherein D is absent.6972-. (canceled)73. A compound of wherein L is absent.74. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier or diluent.75. A method for treating a subject with a gram-negative bacterial infection comprising administering to the subject in need thereof an antibacterially effective amount of a compound of or a pharmaceutical composition of .76. (canceled) This application is a continuation of U.S. patent application Ser. No. 12/635,551, filed Dec. 10, 2009, now pending, which is a continuation of International PCT Application No. PCT/US2008/066766, filed Jun. 12, 2008, which claims the benefit under 35 U.S.C. §119(e) of U.S. ...

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18-01-2018 дата публикации

Ionic Liquid, Lubricant, and Magnetic Recording Medium

Номер: US20180016510A1
Принадлежит: Dexerials Corp

A lubricant, which includes an ionic liquid including a conjugate base and a conjugate acid including 2 or more cations in a molecule of the conjugate acid, wherein the conjugate acid includes a monovalent group including a straight-chain hydrocarbon group having 6 or more carbon atoms, and an acid that is a source of the conjugate base has a pKa in acetonitrile of 10 or less.

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15-01-2015 дата публикации

CYCLOALKANE DERIVATIVES

Номер: US20150018551A1
Принадлежит:

Disclosed herein are therapeutic agents and/or preventive agents for pain or therapeutic agents and/or preventive agents for a sodium channel associated disease. The present invention provides compounds represented by the following formula (I) or pharmacologically acceptable salts thereof: 131-. (canceled)33. The method of claim 32 , wherein the removal of the protecting group is conducted by reacting an acid and the compound represented by formula (VI) in a solvent.34. The method of claim 33 , wherein the solvent is selected from the group consisting of an ethers claim 33 , a halogenated hydrocarbon claim 33 , tetrahydrofuran claim 33 , 1 claim 33 ,4-dioxane and dichloromethane.35. The method of claim 33 , further comprising a scavenger.36. The method of claim 35 , wherein the scavenger is selected from the group consisting of trialkylsilane claim 35 , aryl ether claim 35 , triethylsilane and anisole.37. The method of claim 33 , wherein the acid is selected from the group consisting of an organic acid claim 33 , an inorganic acid claim 33 , trichloroacetic acid claim 33 , trifluoroacetic acid claim 33 , acetic acid claim 33 , sulfuric acid and hydrochloric acid.38. The method of claim 32 , wherein the reaction temperature is 0° C. to 200° C.39. The method of claim 32 , wherein the reaction time is from 1 hour to 48 hours.40. The method of claim 32 , wherein the deprotecting of the compound of formula (VI) is in a solvent and in the presence of a palladium catalyst under hydrogen atmosphere.41. The method of claim 40 , wherein the solvent is selected from the group consisting of ethers claim 40 , alcohols claim 40 , tetrahydrofuran claim 40 , methanol and ethanol.42. The method of claim 40 , wherein the catalyst is selected from the group consisting of a zero-valent palladium catalyst claim 40 , a palladium-activated carbon and a palladium hydroxide-activated carbon.43. The method of claim 40 , wherein the reaction temperature is from −20° C. to 120° C.44. The ...

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17-01-2019 дата публикации

METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF

Номер: US20190016715A1
Принадлежит:

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions. 162.-. (canceled)65. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein X is —O—.66. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris substituted or unsubstituted heteroaryl.67. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein n is 1 and Ris halogen or —CH.68. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris —CF.69. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein m is 0.71. A pharmaceutical composition comprising a compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , and at least one pharmaceutically acceptable excipient.72. A method of treating a central nervous disorder (CNS) claim 63 , the method comprising the step of administering to a subject in need thereof claim 63 , an effective amount of a compound of claim 63 , thereby treating the disorder.75. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein X is —O—.76. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris substituted or unsubstituted heteroaryl.77. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein n is 1 and Ris halogen or —CH.78. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris —CF.79. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein m is 0.81. A pharmaceutical composition comprising a compound of claim 73 , or a pharmaceutically acceptable salt claim 73 , and at least one pharmaceutically acceptable excipient.82. A method of treating ...

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21-01-2021 дата публикации

BENZOTHIA(DI)AZEPINE COMPOUNDS AND THEIR USE AS BILE ACID MODULATORS

Номер: US20210017141A1
Принадлежит:

The invention relates to 1,5-benzothiazepine and 1,2,5-benzothiadiazepine derivatives of formula (I). These compounds are bile acid modulators having apical sodium-dependent bile acid transporter (ASBT) and/or liver bile acid transport (LBAT) inhibitory activity. The invention also relates to pharmaceutical compositions comprising these compounds and to the use of these compounds in the treatment of cardiovascular diseases, fatty acid metabolism and glucose utilization disorders, gastrointestinal diseases and liver diseases. 1. (canceled)3. The method of claim 2 , wherein Rand Rare each n-butyl.4. The method of claim 2 , wherein Rand Rare each ethyl.5. The method of claim 2 , wherein Ris n-butyl and Ris ethyl.6. The method of claim 2 , wherein Ris selected from the group consisting of hydrogen claim 2 , bromo claim 2 , hydroxy claim 2 , methoxy claim 2 , amino claim 2 , tert-butoxycarbonylamino claim 2 , methylsulfonamido and cyclopropylsulfonamido.7. The method of claim 2 , wherein Ris selected from the group consisting of hydrogen claim 2 , bromo claim 2 , ethyl claim 2 , cyclopropyl claim 2 , methoxy claim 2 , methylthio and dimethylamino.8. The method of claim 2 , wherein Ris selected from the group consisting of hydrogen and fluoro.9. The method of claim 2 , wherein Ris carboxy.11. The method of claim 2 , wherein the a liver disease or disorder is selected from the group consisting of inherited metabolic disorder of the liver; inborn errors of bile acid synthesis; congenital bile duct anomalies; biliary atresia; neonatal hepatitis; neonatal cholestasis; hereditary forms of cholestasis; cerebrotendinous xanthomatosis; a secondary defect of BA synthesis; Zellweger's syndrome; cystic fibrosis-associated liver disease; alpha1-antitrypsin deficiency; Alagilles syndrome (ALGS); Byler syndrome; a primary defect of bile acid (BA) synthesis; progressive familial intrahepatic cholestasis (PFIC); autoimmune hepatitis; primary biliary cirrhosis (PBC); liver fibrosis; non- ...

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16-01-2020 дата публикации

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

Номер: US20200017488A1
Принадлежит:

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome. This application is a continuation of U.S. patent application Ser. No. 15/122,085 filed Aug. 26, 2016 which is a national phase application of PCT/US2015/017806 filed Feb. 26, 2014 which claims benefit to U.S. Provisional Patent Application No. 61/945,309 filed Feb. 27, 2014, and which is hereby incorporated by reference in its entirety.The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention relates to heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of diseases and conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.Voltage-gated sodium (Nav) channels are present in neurons and excitable tissues where they contribute to processes such as membrane excitability and muscle contraction (Ogata et al., 88:365-77, 2002). Nine different transmembrane 3-subunits (Nav1.1-1.9) from a single Nav1 family combine with auxiliary β-subunits that modify channel ...

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16-01-2020 дата публикации

METHODS FOR INHIBITING FASCIN

Номер: US20200017506A1
Принадлежит:

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. (canceled)16. The method of claim 15 , wherein Wis S.17. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.18. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.19. The method of claim 14 , wherein Rand Rare phenyl.20. The method of claim 14 , wherein Ris methyl claim 14 , phenyl claim 14 , or benzyl.2122-. (canceled)2467-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/972,649, filed on Aug. 21, 2013, which claims the benefit of U.S. Provisional Patent Application No. 61/692,177, filed on Aug. 22, 2012, and U.S. Provisional Patent Application No. 61/778,015, filed on Mar. 12, 2013. The entire contents of the foregoing applications are hereby incorporated herein by reference in their entireties.The technology described herein was developed with funds from National Institutes of Health Grant No. R01 CA136837. The United States Government has certain rights to the technology.The present technology relates generally to methods for treating or preventing cancer.In recent years, progress has ...

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25-01-2018 дата публикации

Novel glp-1 receptor modulators

Номер: US20180021346A1
Принадлежит: Celgene International II SARL

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

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26-01-2017 дата публикации

COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

Номер: US20170022174A1
Принадлежит:

Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia. 2. A method of disrupting or inhibiting the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of tau fibrils and/or aggregates claim 1 , comprising administering a therapeutically effective amount of the compounds of .3. The method of claim 2 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.4. The method of claim 2 , where the compound is administered in an amount between 1 mg/Kg/between 10 mg/Kg/day and 100 mg/Kg/day.5. The method of claim 2 , where amount of compound administered is in an amount between 10 mg/Kg/day and 100 mg/Kg/day.6. A method resulting in neuroprotection from a tauopathy in a mammal comprising the step of administrating a therapeutically effective amount of a compound of .7. The method of where the tauopathy is one selected from; Alzheimer's disease claim 6 , Pick's disease claim 6 , progressive supranuclear palsy claim 6 , corticobasal degeneration claim 6 , familial frontotemporal dementia/Parkinsonism linked to chromosome 17 claim 6 , amyotrophic lateral sclerosis/Parkinsonism-dementia complex claim 6 , argyrophilic grain dementia claim 6 , dementia pugilistic claim 6 , diffuse neurofibrillary tangles with calcification claim 6 , progressive subcortical gliosis and tangle only dementia.8. An article of manufacture claim 1 , comprising packaging material claim 1 , the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , contained within packaging material claim 1 , which is ...

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17-04-2014 дата публикации

NOVEL PROSTAMIDES FOR THE TREATMENT OF GLAUCOMA AND RELATED DISEASES

Номер: US20140107124A1
Принадлежит: ALLERGAN, INC.

Disclosed herein are compositions comprising an amide related to a prostaglandin and a biogenic amine. Other aspects relate to certain chemical compounds, pharmaceutical compositions, and methods of treating glaucoma. 1. A composition comprising an amide related toa. a prostaglandin; andb. a biogenic amine.2. The composition of wherein the prostaglandin is a natural prostaglandin selected from the group consisting of prostaglandin E claim 1 , prostaglandin E claim 1 , prostaglandin F claim 1 , prostaglandin F claim 1 , and prostaglandin D claim 1 , or is an analog thereof.3. The composition of wherein the biogenic amine is selected from the group consisting of cholinomimetics claim 1 , antimuscarinics claim 1 , adrenergics claim 1 , dopaminergics claim 1 , α-adrenoreceptor antagonists claim 1 , β-adrenergic antagonists claim 1 , monoamine oxidase inhibitors claim 1 , histaminergics claim 1 , serotonergics claim 1 , and thyroid drugs.4. The composition of wherein the biogenic amine is selected from the group consisting of tropicamide claim 1 , epinephrine claim 1 , isoprotenenol claim 1 , dopamine claim 1 , phentolamine claim 1 , timolol claim 1 , trancylpromine claim 1 , histamine claim 1 , dimaprit claim 1 , thyroxine claim 1 , and serotonin claim 1 , or is an analog claim 1 , a pharmaceutically acceptable salt claim 1 , or a prodrug thereof.5. The composition of wherein the prostaglandin is prostaglandin F and the amine is dopamine.6. The composition of wherein the prostaglandin is prostaglandin F and the amine is diacetyl dopamine.7. The composition of wherein the prostaglandin is prostaglandin F and the amine is serotonin.8. A compound comprising an amide related to a prostaglandin and a biogenic amine claim 1 , wherein said compound is not naturally occurring.9. The compound of wherein said biogenic amine is selected from the group consisting of cholinomimetics claim 8 , antimuscarinics claim 8 , adrenergics claim 8 , dopaminergics claim 8 , α-adrenoreceptor ...

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17-04-2014 дата публикации

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20140107134A1
Принадлежит: Synta Pharmaceuticals Corp.

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

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17-04-2014 дата публикации

Processes and intermediates for making sweet taste enhancers

Номер: US20140107370A1
Принадлежит: Senomyx Inc

The present invention includes methods/processes and intermediates for preparing compounds having structural Formula (I): wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

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25-01-2018 дата публикации

METHOD OF PRODUCING BENZO[1,2-B:4,5-B']DITHIOPHENE AND BENZOTHIADIAZOLE-BASED MOLECULAR COMPLEXES

Номер: US20180022717A1
Принадлежит: Phillips 66 Company

A method of forming a molecular complex. The method proceeds by reacting 5-chloro-2,1,3-benzothiadiazole with N-bromosuccinimide to produce 4,7-dibromo-5-chlorobenzo[c][1,2,5]thiadiazole. 4,7-dibromo-5-chlorobenzo[c][1,2,5]thiadiazole is then reacted with trimethyl[4-(2-octyldodecyl)thiophen-2-yl]stannane to produce 5-chloro-4,7-bis(4-(2-octyldodecyl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole. 4, 7-bis(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-5-chlorobenzo[c][1,2,5]thiadiazole is subsequently synthesized from 5-chloro-4,7-bis(4-(2-octyldodecyl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole. 4,7-bis(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-5-chlorobenzo[c][1,2,5]thiadiazole with tributyl(thiophen-2-yl)stannane is then reacted to produce 4-bromo-5,6-difluoro-7-(thiophen-2-yl)benzo[c][1,2,5]thiadiazole. This is followed by reacting 4,7-dibromo-5-chloro-2,1,3-benzothiadiazole with tributyl(thiophen-2-yl)stannane to produce 4-bromo-5-chloro-7-(thiophen-2-yl)benzo[c][1,2,5]thiadiazole. trimethyl[4-(2-octyldodecyl)thiophen-2-yl]stannane is then reacted with and 4-bromo-5-chloro-7-(thiophen-2-yl)benzo[c][1,2,5]thiadiazole to produce 5-chloro-4-(4-(2-octyldodecyl)thiophen-2-yl)-7-(thiophen-2-yl)benzo[c][1,2,5]thiadiazole. 5-chloro-4-(4-(2-octyldodecyl)thiophen-2-yl)-7-(thiophen-2-yl)benzo[c][1,2,5]thiadiazole is then reacted with N-bromosuccinimide to produce the co-monomer 4-(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-7-(5-bromothiophen-2-yl)-5-chlorobenzo[c][1,2,5]thiadiazole. A 2. The method of claim 1 , wherein the molecular complex is used as photovoltaic material in one or more photovoltaic devices.3. The method of claim 2 , wherein the one or more photovoltaic devices are polymer solar cell devices or photodetector devices.4. The method of claim 1 , wherein the molecular complex is used as an active layer material in one or more electronic devices.5. The method of claim 4 , wherein the one or more electronic devices are field effect transistors claim 4 , light emitting devices ...

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25-01-2018 дата публикации

UNSYMMETRICAL BENZOTHIADIAZOLE-BASED MOLECULAR COMPLEXES

Номер: US20180022718A1
Принадлежит: Phillips 66 Company

A molecular complex comprising 2. The molecular complex of claim 1 , wherein the molecular complex is part of an oligomer.3. The molecular complex of claim 1 , wherein the molecular complex is part of a polymer with a molecular weight ranging from about 1 claim 1 ,000 to about 100 claim 1 ,000 kDa.5. The molecular complex of claim 1 , wherein the molecular complex is used as photovoltaic material in one or more photovoltaic devices.6. The molecular complex of claim 5 , wherein the one or more photovoltaic devices are polymer solar cell devices or photodetector devices.7. The molecular complex of claim 1 , wherein the molecular complex is used as an active layer material in one or more electronic devices.8. The molecular complex of claim 4 , wherein the one or more electronic devices are field effect transistors claim 4 , light emitting devices and sensors claim 4 , electrochromic devices and capacitors.9. The molecular complex of claim 1 , wherein when used as a photovoltaic polymer produces a power conversion efficiency greater than 7.0%.10. The molecular complex of claim 1 , wherein when used as a photovoltaic polymer produces a fill factor greater than 69%.11. The molecular complex of claim 1 , wherein R1 and R1′ are not identical.12. The molecular complex of claim 1 , wherein R2 and R2′ are not identical.13. The molecular complex of claim 1 , wherein both R1 and R1′ are not identical and R2 and R2′ are not identical. This application is a non-provisional application which claims the benefit of and priority to U.S. Provisional Application Ser. No. 62/364,088 filed Jul. 19, 2016, entitled “Unsymmetrical Benzothiadiazole-Based Molecular Complexes,” which is hereby incorporated by reference in its entirety.None.This invention relates to unsymmetrically substituted benzothiadiazole-based molecular complexes.Solar energy using photovoltaic effect requires active semiconducting materials to convert light into electricity. Currently, solar cells based on silicon are the ...

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25-01-2018 дата публикации

Ibat inhibitors for the treatment of liver diseases

Номер: US20180022776A1
Принадлежит: ALBIREO AB

The present invention regards specific IBAT inhibitors useful in the prophylaxis and/or treatment of a liver disease. It also relates to compositions comprising these IBAT inhibitors, a method for treatment of the disorders and a kit comprising the substances or the compositions.

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