Настройки

Укажите год
-

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

Подробнее
-

Мониторинг СМИ

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

Подробнее

Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Ведите корректный номера.
Укажите год
Укажите год

Применить Всего найдено 1772. Отображено 100.
14-06-2012 дата публикации

Heterocyclic Radical or Diradical, The Dimers, Oligomers, Polymers, Dispiro Compounds and Polycycles Thereof, the Use Thereof, Organic Semiconductive Material and Electronic or Optoelectronic Component

Номер: US20120146012A1
Принадлежит: NOVALED GMBH

The present invention relates to heterocyclic radicals or diradicals, the dimers, oligomers, polymers, dispiro compounds and polycycles thereof, to the use thereof, to organic semiconductive materials and to electronic and optoelectronic components.

Подробнее
18-04-2013 дата публикации

NOVEL YELLOW PIGMENT COMPOSITION, AND METHOD FOR PRODUCING YELLOW PIGMENT MICROPARTICLES

Номер: US20130095322A1
Принадлежит: M. TECHNIQUE CO., LTD.

Disclosed are: a yellow pigment composition which contains at least one kind of yellow pigment microparticle having excellent transmission characteristics; and a method for producing the yellow pigment microparticle. Specifically disclosed are: a yellow pigment composition which contains at least one kind of yellow pigment microparticle that are characterized in that the difference between the maximum transmittance (Tmax) and the minimum transmittance (Tmin), namely (Tmax−Tmin) is 80% or more in the transmission spectrum at 350-800 nm; and a method for producing the yellow pigment microparticle. 1. A yellow pigment composition containing at least one kind of yellow pigment microparticle , wherein difference (Tmax−Tmin) between the maximum transmittance (Tmax) and the minimum transmittance (Tmin) of a transmission spectrum thereof in a region of 350 nm to 800 nm is 80% or more.2. The yellow pigment composition according to claim 1 , wherein the yellow pigment microparticle is an organic pigment.3. The yellow pigment composition according to claim 1 , wherein the yellow pigment microparticle is an azo pigment or an isoindoline pigment.4. The yellow pigment composition according to claim 1 , wherein the yellow pigment microparticle is formed by a process comprising:a fluid to be processed is supplied between processing surfaces being capable of approaching to and separating from each other and displacing relative to each other,pressure of force to move in the direction of approaching, including supply pressure of the fluid to be processed and pressure applied between the rotating processing surfaces, is balanced with pressure of force to move in the direction of separation thereby keeping a minute space in a distance between the processing surfaces,the minute space kept between two processing surfaces is used as a flow path of the fluid to be processed, thereby forming a thin film fluid of the fluid to be processed, andthe microparticle is formed in this thin film ...

Подробнее
30-05-2013 дата публикации

Inhibition and Dispersion of Bacterial Biofilms with 2-Aminobenzimidazole Derivatives

Номер: US20130136782A1
Принадлежит: Individual

Compounds described herein inhibit biofilm formation or disperse pre-formed biofilms of Gram-negative bacteria. Biofilm-inhibitory compounds can be encapsulated or contained in a polymer matrix for controlled release. Coatings, films, multilayer films, hydrogels, microspheres and nanospheres as well as pharmaceutical compositions and disinfecting compositions containing biofilm-inhibitory compounds are also provided. Methods for inhibiting formation of biofilms or dispersing already formed biofilms are provided. Methods for treating infections of gram-negative bacteria which form biofilms, particularly those of Pseudomonas and more particularly P. aeruginosa.

Подробнее
20-06-2013 дата публикации

NOVEL HETEROCYCLIC COMPOUND, AND COMPOSITION FOR TREATING INFLAMMATORY DISEASES USING SAME

Номер: US20130158047A1
Принадлежит: NEOPHARM CO., LTD.

Provided are heterocyclic compounds, having effects of treating and preventing inflammatory diseases and treating skin wounds, and particularly, exhibiting effects of recovering disrupted skin barriers, mitigating inflammation, and pruritus. Also, a composition containing the compound as an effective component can be used to mitigate various inflammatory diseases and protease activated receptor-2 (PAR-2)-overexpressed diseases, and can be particularly used as a composition having an anti-inflammatory function in inflammatory skin diseases including atopic dermatitis and the like, by inhibiting PAR-2 activity. 6. A pharmaceutical composition claim 1 , comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to and a pharmaceutically acceptable carrier.7. The pharmaceutical composition of claim 6 , which is effective in treating and preventing inflammatory skin diseases covering acne claim 6 , rosacea claim 6 , seborrheic dermatitis claim 6 , atopic dermatitis claim 6 , post-inflammatory hyperpigmentation (PIH) claim 6 , contact dermatitis claim 6 , pruritus claim 6 , psoriasis claim 6 , Lichen planus claim 6 , eczema claim 6 , skin infections claim 6 , and Netherton Syndrome.8. A method for treating skin wounds claim 1 , comprising administering an effective amount of the heterocyclic compound or a pharmaceutically acceptable salt thereof according to to a subject in need thereof.9. A method for treating and preventing metastasis of cancer claim 1 , gastrointestinal disease claim 1 , asthma claim 1 , and liver cirrhosis claim 1 , comprising administering an effective amount of the heterocyclic compound of or a pharmaceutically acceptable salt thereof according to to a subject in need thereof.10. A protease activated receptor-2 (PAR-2) inhibitor composition comprising the heterocyclic compound or a pharmaceutically acceptable salt thereof according to .11. A cosmetic composition comprising the heterocyclic compound or a ...

Подробнее
04-07-2013 дата публикации

BENZIMIDAZOLE DERIVATIVES AS SELECTIVE BLOCKERS OF PERSISTENT SODIUM CURRENT

Номер: US20130172389A1
Принадлежит: Allegan, Inc.

The present invention is directed to a compound of Formula I 2. The compound of claim 1 , wherein R is and unsubstituted straight chain or branched Calkyl.3. The compound of claim 1 , wherein R is Calkyl which is substituted with a Caryloxy group.4. The compound of claim 3 , wherein the “aryl” portion of said Caryloxy group is unsubstituted or substituted with 1-2 Calkyl or Calkoxy substitutents.5. The compound of claim 1 , wherein R is Calkyl which is substituted with a heteroaryl substitutent claim 1 , wherein said heteroaryl group is five- to six-membered ring containing 1-2 ring N atoms claim 1 , and wherein when said five- to six-membered ring containing 1-2 ring N atoms has two substituents on adjacent carbon atoms claim 1 , said substituents together with the carbon atoms to which they are attached can optionally form a phenyl ring claim 1 , and wherein said six-membered ring containing 1-2 ring N atoms claim 1 , optionally with said phenyl ring is optionally further substituted with a ring system substituent.6. The compound of claim 5 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 5 , optionally with said phenyl ring is selected from the group consisting of pyrzolyl claim 5 , imidazolyl claim 5 , pyrimidinyl claim 5 , pyrazinyl claim 5 , and benzimidazolyl.7. The compound of claim 6 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 6 , optionally with said phenyl ring is selected from the group consisting of is imidazolyl and benzimidazolyl.8. The compound of claim 1 , wherein R is Calkyl which is substituted with a —N(Calkyl)substituent.10. The compound of claim 1 , wherein Rand Rare both H.11. The compound of claim 10 , wherein m is 1 or 2.12. The compound of claim 10 , wherein m is 1 claim 10 , and X is O.13. The compound of claim 10 , wherein m is 2 claim 10 , and X is a covalent bond.14. The compound of claim 10 , wherein m is 1 claim 10 , and X is —S(═O)—.15. The compound of claim 10 , wherein m is ...

Подробнее
25-07-2013 дата публикации

PROCESSES FOR THE SYNTHESIS OF DIARYLTHIOHYDANTOIN AND DIARYLHYDANTOIN COMPOUNDS

Номер: US20130190507A1
Принадлежит:

Processes are provided for the synthesis of diarylthiohydantoin and diarylhydantoin compounds. Medicinal products containing the same find particular use in treating prostate cancer, including castration-resistant prostate cancer and/or hormone-sensitive prostate cancer. 3. The process of claim 1 , wherein X is S.4. The process of claim 1 , wherein Yand Yare both methyl.5. The process of claim 1 , wherein Yand Ytogether with the carbon to which they are attached combine to form a cyclobutyl ring or a cyclopentyl ring.6. The process of claim 1 , wherein Lis a single bond.7. The process of claim 1 , wherein Ris —C(═O)—NHCH.8. The process of claim 1 , wherein Ris —C(═O)—NH.9. The process of claim 1 , wherein Ris F.10. The process of claim 1 , wherein Yand Yare both methyl claim 1 , Ris —C(═O)—NHCH claim 1 , and Ris F.11. The process of claim 1 , wherein Yand Yare both methyl claim 1 , Ris —C(═O)—NH claim 1 , and Ris F.13. The process of claim 12 , wherein X is S.1412. The process of claim 12 , wherein Yand Yare both methyl claim 12 , Ris —C(═O)—OH claim 12 , and Ris F. This patent application is a continuation of Ser. No. 13/580,718 filed Aug. 23, 2012 as a national phase application of PCT/US2011/026135 filed on Feb. 24, 2011, which claims priority to Ser. No. 61/307,796, filed Feb. 24, 2010. Each of these applications is incorporated herein by reference in its entirety.Not applicable.The invention is in the field of cancer therapeutics, such as processes for the synthesis of prostate cancer therapeutics.According to the American Cancer Society, prostate cancer is the most commonly diagnosed cancer among men in the United States, other than skin cancer. The American Cancer Society estimates that approximately 186,000 new cases of prostate cancer were diagnosed, and approximately 29,000 men died of prostate cancer in the United States alone during 2008. Prostate cancer is thus the second-leading cause of cancer death in men in the United States, after lung cancer. ...

Подробнее
15-08-2013 дата публикации

Compounds and Their Use as BACE Inhibitors

Номер: US20130210837A1
Принадлежит: AstraZeneca Intellectual Property

The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration. 125-. (canceled)27. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Ris Calkyl.28. A compound according to or a pharmaceutically acceptable salt thereof claim 27 , wherein Ris methyl or ethyl.29. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Ris aryl claim 26 , heteroaryl claim 26 , Calkynyl claim 26 , halogen claim 26 , NHC(O)Ror ORwherein:{'sub': '2-6', 'sup': '7', 'said aryl, heteroaryl, or Calkynyl is optionally substituted with one to three R.'}30. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Rand Rare independently hydrogen or heterocyclyl wherein:{'sub': '1-6', 'sup': '8', 'said heterocyclyl is optionally substituted with one or two substituents independently selected from Calkyl or OR.'}31. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Rand R claim 26 , together with the carbon to which they are attached claim 26 , form a ring B claim 26 , wherein ring B is:{'sub': '1-6', 'sup': '8', 'a 3-14 membered cycloalkyl or heterocyclyl monocyclic ring, ...

Подробнее
05-09-2013 дата публикации

PACTAMYCIN ANALOGS AND METHODS OF USE

Номер: US20130231377A1
Автор: Mahmud Taifo
Принадлежит:

Disclosed are pactamycin analogs, pharmaceutical compositions including the analogs, and methods of using the analogs, such as to inhibit tumor growth or a pathogenic infection such as a bacterial or parasitic infection. The pactamycin analogs have a general formula 4. The method of claim 1 , wherein Rand Rtogether form a heterocyclic 5-membered ring.56-. (canceled)7. The method of claim 1 , wherein Rand Rtogether form a heterocyclic 5-membered ring.8. (canceled)9. The method of claim 1 , wherein Ris a substituted benzoyl group.10. (canceled)1213-. (canceled)17. The compound of claim 14 , wherein Rand Rtogether form a heterocyclic 5-membered ring.18. (canceled)19. The compound of claim 14 , wherein Rand Rtogether form a heterocyclic 5-membered ring.20. (canceled)21. The compound of claim 14 , wherein Ris a substituted benzoyl group.22. (canceled)24. A pharmaceutical composition claim 14 , comprising a compound according to and a pharmaceutically acceptable carrier.25. A method of inhibiting a tumor in a subject claim 14 , comprising:selecting a subject for treatment that has, or is at risk for developing, a tumor;{'claim-ref': {'@idref': 'CLM-00024', 'claim 24'}, 'administering to the subject an effective amount of the pharmaceutical composition of , thereby treating the tumor in the subject.'}26. A method of treating an infection from a pathogen of interest in a subject claim 14 , comprising:selecting a subject for treatment that has, or is at risk for developing, an infection by a pathogen of interest;{'claim-ref': {'@idref': 'CLM-00024', 'claim 24'}, 'administering to the subject an effective amount of the pharmaceutical composition of , thereby treating the infection from the pathogen of interest in the subject.'}27. The method of claim 26 , wherein the pathogen of interest is a Gram-positive or Gram-negative bacterial pathogen.28. A method of inhibiting growth of a pathogen claim 14 , comprising contacting the pathogen with a composition of claim 14 , wherein ...

Подробнее
17-10-2013 дата публикации

NOVEL INHIBITORS OF BACTERIAL BIOFILMS AND RELATED METHODS

Номер: US20130274256A1
Принадлежит: SEQUOIA SCIENCES, INC.

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

Подробнее
28-11-2013 дата публикации

Organic Electroluminescent Element

Номер: US20130313531A1
Принадлежит: UDC Ireland Ltd

Disclosed is an organic electroluminescent element which is excellent with respect to luminous efficiency and driving voltage and rarely undergoes initial luminance drop. Specifically disclosed is an organic electroluminescent element which comprises, on a substrate, a pair of electrodes composed of an anode and a cathode and a light-emitting layer arranged between the electrodes, and additionally comprises at least one organic layer arranged between the light-emitting layer and the cathode, where in the light-emitting layer contains, for example, a compound (A-1), and the at least one layer arranged between the light-emitting layer and the cathode contains, for example, a compound (e-4).

Подробнее
26-12-2013 дата публикации

Cycloalkyl Ether Compounds and Their Use as Bace Inhibitors

Номер: US20130345272A1
Принадлежит: AstraZeneca AB

Cycloalkyl ether compounds, therapeutically acceptable salts thereof, processes for preparation thereof, therapeutic uses of such compounds for treating Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy, Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration and pharmaceutical compositions containing such compounds. 2. A compound according to selected from the group consisting of:(1r,4r)-4-Methoxy-5″-methyl-6′-[(1-methylcyclopropyl)methoxy]-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1r,4r)-6′-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;(1r,4r)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1r, 1′R,4R)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1r, 1′S,4S)-6′-(Cyclopropylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1r,4r)-6′-[(2,2-Difluorocyclopropyl)methoxy]-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine;(1r,4r)-6′-(Cyclobutylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1 r, 1′R,4R)-6′-(Cyclobutylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine;(1r, 1′S,4S)-6′-(Cyclobutylmethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine, and(1r,4r)-6′-(2-Cyclopropylethoxy)-4-methoxy-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1,2″-imidazol]-4″-amine,or a pharmaceutically acceptable salt of any foregoing compound.3. A ...

Подробнее
16-01-2014 дата публикации

Benzimidazole Derivatives As PI3 Kinase Inhibitors

Номер: US20140018534A1
Принадлежит: GlaxoSmithKline LLC

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kβ, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 1. A process for the production of the compound of formulacomprising the step ofadding iron powder to a solution of methyl 3-amino-5-(4-morpholinyl)-2-nitrobenzoate in HOAc. This application is filed as a continuation application of U.S. Ser. No. 13/876,853 filed on Mar. 29, 2013, which is filed pursuant to 35 USC 371 as a United States National Phase Application of International Patent Application Serial No. PCT/US2011/052857 filed on Sep. 23, 2011, which claims priority from 61/390,314 filed on Oct. 6, 2010 and 61/528,397 filed on Aug. 29, 2011 in the United States.This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More ...

Подробнее
23-01-2014 дата публикации

Methods of Treating Neuropathic Pain with Benzimidazole Derivative Agonists of PPARgamma

Номер: US20140024692A1
Принадлежит: Aestus Therapeutics, Inc.

Embodiments of the invention relate to the treatment of neuropathic pain in mammals. Embodiments of the invention include methods for treating neuropathic pain with benzimidazole derivatives with PPARgamma agonist activity, as well as methods for preparing medicaments used in such treatments of mammalian pain. 2. The method of treating neuropathic pain of claim 1 , wherein the mammal is a human.3. The method of treating neuropathic pain of claim 2 , wherein the agonist of PPARγ is 3-(2 claim 2 ,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide or a pharmaceutically acceptable salt thereof.5. The method of treating neuropathic pain of claim 4 , wherein{'sub': '27', 'Rrepresents an aryllower alkyl group whose aryl moiety may be substituted by one or two substituents selected from the group consisting of a halogen atom, a lower alkyl group, a halo-lower alkyl group, a cyanoaryl group, an amino group, a lower alkoxy group, a nitro group, a cyano group, an aryl group, a haloaryl group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, an aryl-lower alkyloxy group, an aryl-lower alkyl group, a heterocyclic group, an arylcarbonyl group, an arylcarbonylamino group, and an aryl-lower alkyloxy group substituted by one or two halogen atoms;'}Y represents a carbonyl group; andA represents a single bond.6. The method of treating neuropathic pain of claim 5 , wherein{'sub': '27', 'Rrepresents an aryl lower alkyl group whose aryl moiety may be substituted by one or two substituents selected from a halogen atom or an aryl group;'}{'sub': '28', 'Rrepresents a lower alkyl group or a lower cycloalkyl group;'}{'sub': '25', 'Rrepresents an alkyl group having up to 8 carbon atoms or an aryl group;'}Y represents a carbonyl group; andA represents a single bond.7. The method of treating neuropathic pain of claim 2 , wherein the agonist of PPARγ is selected from the group consisting of 6-benzenesulfonylcarbamoyl-1-(2-chlorobenzyl)-2-methylbenzimidazole ...

Подробнее
20-03-2014 дата публикации

ANTIMICROBIAL AND RADIOPROTECTIVE COMPOUNDS

Номер: US20140080876A1
Принадлежит: Biodiem Ltd

The present invention relates to a method of treatment and/or prophylaxis of a microbial infection, comprising the step of administering an effective amount of a compound of formula (I), in which X and Y are either the same or different and selected from a heteroatom; is a double or single bond depending on the heteroatoms X and Y; Rto Rare either the same or different and selected from hydrogen or a non-deleterious substituent; and Rand Rare either the same or different and selected from hydrogen and a non-deleterious substituent or one of Rand Rare absent when there is a double bond present, pharmaceutically acceptable salts or derivatives, pro-drugs, tautomers and/or isomers thereof. The present invention also relates to a method for protecting a subject from radiation damage, a method of cancer radiotherapy and use as an antimicrobial or radioprotective agent of the compound of formula (I) defined above. Some of the compounds of formula (I) are novel and are also described in the present invention, together with pharmaceutical or veterinary compositions containing them. 2. A method according to claim 1 , in which the microbial infection is a bacterial infection claim 1 , fungal infection claim 1 , yeast infection claim 1 , protozoal infection or viral infection.3. A method according to or claim 1 , in which the bacterial infection is caused by a Gram Positive or Gram Negative bacterium.4Staphylococcus aureus, Enterococcus fecalis, Klebsiella pneumonia, Salmonella typhimuriumpseudotuberculosis, Acinetobacteria, Pseudomonas aeruginosa, Clostridium perfringens, Clostridium difficile, Campylobacter jejuniBacteroides fragilis.. A method according to claim 3 , in which the Gram Positive or Gram negative bacterium is or or5Trichophyton interdigitale, Aspergillus fumigatusCandida albicans.. A method according to or claim 3 , in which the fungal or yeast infection is or6Plasmodium falciparumTrichomonas vaginalis.. A method according to or claim 3 , in which the protozoal ...

Подробнее
03-04-2014 дата публикации

PRETARGETING KIT FOR IMAGING OR THERAPY COMPRISING A TRANS-CYCLOOCTENE DIENOPHILE AND A DIENE

Номер: US20140093450A1
Принадлежит: KONINKLIJKE PHILIPS N.V.

Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has a flattened structure as a result of the position of at least two exocyclic bonds. 1. A kit for targeted medical imaging and/or therapeutics , comprising at least one Pre-targeting Probe and at least one Effector Probe , wherein the Pre-targeting Probe comprises a Primary Targeting Moiety and a first Bio-orthogonal Reactive Group , and wherein the Effector Probe comprises an Effector Moiety , such as a label or a pharmaceutically active compound , and a second Bio-orthogonal Reactive Group , wherein either of the first and second Bio-orthogonal Reactive Groups is a dienophile and the other of the first and second Bio-orthogonal Reactive Groups is a diene , wherein the dienophile is a trans-cyclooctene moiety comprising at least two exocyclic bonds fixed in the same plane , and comprising at least one linkage , optionally via a spacer , to the Pre-targeting Probe or the Effector Probe.2. A kit according to claim 1 , wherein the at least two exocyclic bonds are part of a substantially flat fused ring structure.3. A kit according to claim 1 , wherein the at least two exocyclic bonds are attached to a single sp2 carbon in the trans-cyclooctene ring.4. A kit according to claim 3 , wherein the at least two exocyclic bonds are part of a carbon-to-heteroatom double bond.5. A kit according to claim 2 , wherein the at least two exocyclic bonds are part of a fused aromatic ring.7. A kit according to claim 6 , wherein the at least two exocylic bonds fixed ...

Подробнее
03-04-2014 дата публикации

SOLID FORMS OF ANTIRETROVIRAL COMPOUNDS, PROCESS FOR THE PREPARATION AND THEIR PHARMACEUTICAL COMPOSITION THEREOF

Номер: US20140094475A1
Принадлежит: LAURUS LABS PRIVATE LIMITED

Disclosed are solid forms of antiretroviral compounds and anti-oxidative acids, and processes for their preparation. Pharmaceutical compositions using the solid forms are also disclosed. 1. A solid form comprising an antiretroviral compound and an anti-oxidative acids , wherein the antiretroviral compound is selected from the group consisting of. tenofovir , lamivudine , emtricitabine , and abacavir.2. The solid form of claim 1 , which is a salt claim 1 , a co-crystal or a polymorph of a salt or a co-crystal.3. The solid form of claim 1 , wherein the anti-oxidative acids are selected from benzoic acid derivatives or cinnamic acid derivatives.4. The solid form of claim 3 , wherein the benzoic acid derivatives are selected from p-hydroxy benzoic acid claim 3 , vanillic acid claim 3 , syringic acid claim 3 , 3 claim 3 ,4-dihydroxy benzoic acid and the like.5. The solid form of claim 3 , wherein the cinnamic acid derivatives are selected from ferulic acid claim 3 , caffeic acid claim 3 , p-coumaric acid claim 3 , sinapic acid and the like.6. The solid form of claim 1 , wherein the anti-oxidative acids are selected from the group consisting of. ferulic acid claim 1 , caffeic acid claim 1 , p-coumaric acid claim 1 , sinapic acid.7. A process for preparing a solid containing an antiretroviral compound and an anti-oxidative acid claim 1 , the process comprising the step of mixing claim 1 , in solution claim 1 , the antiretroviral compound with the anti-oxidative acid compound under crystallization conditions sufficient to produce the solid form.8. The process according to claim 7 , wherein the mixing step comprises:a) dissolving antiretroviral compound in a solvent at a temperature to produce a solution;b) combining anti-oxidative acid to the solution;c) isolating the product from the solution.9. The process according to claim 8 , wherein the solvent is selected from the group consisting of. water claim 8 , lower alcohols claim 8 , ketones claim 8 , esters claim 8 , ethers ...

Подробнее
03-04-2014 дата публикации

PROCESS FOR PRODUCING 3-ALKOXY-2-AMINO-6-FLUOROBICYCLO [3.1.0] HEXANE-2,6-DICARBOXYLIC ACID DERIVATIVE AND INTERMEDIATE THEREOF

Номер: US20140094613A1
Принадлежит: TAISHO PHARMACEUTICAL CO., LTD.

A process for producing a 3-alkoxy-2-amino-6-fluoro bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative represented by the formula (I) or a salt thereof, which includes converting a compound represented by the formula (VI) or a salt thereof to the compound represented by the formula (I) or a salt thereof. 111-. (canceled) The present invention relates to a process for producing a 3-alkoxy-2-amino-6-fluoro bicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative useful as a pharmaceutical. The invention also relates to a novel intermediate compound produced in the production process.An excitatory amino acid such as glutamic acid modulates various physiological processes such as long term potentiation (learning and memory), synaptic plasticity development, motion control, respiration, cardiovascular modulation, and perception in the central nervous system (CNS) of a mammal.Presently, glutamate receptors are classified into two major groups, that is, “an ionotropic type in which the receptor has an ion channel structure”: ion channel type glutamate receptor (iGluR), and “a metabotropic type in which the receptor is coupled to a G protein”: metabotropic glutamate receptor (mGluR) (see, Non-Patent Document 1). It appears that receptors of either class mediate normal synaptic transmission in accordance with an excitatory pathway. It also appears that they are involved in modification of synaptic binding from the development stage throughout the lifetime (see, Non-Patent Document 2).Eight subtypes of the metabotropic glutamate receptor that have been identified so far are classified into three groups (group I, II, and III) depending on pharmacological characteristics and intracellular second messengers to which they are coupled. Among them, group II receptor (mGluR2/mGluR3) binds with adenylate cyclase, and inhibits the accumulation of cyclic adenosine-1-phosphate (cAMP) stimulated by forskolin (see, Non-Patent Document 3). Thus, it is suggested that compounds that ...

Подробнее
06-01-2022 дата публикации

SUBSTITUTED POLYFLUORENE COMPOUNDS

Номер: US20220002552A1
Автор: Wang Jing, Xu Xinshe
Принадлежит: BioLegend, Inc.

The present invention provides fluorescent polyfluorene polymers or macromers with unique optical properties that are stable. The polymeric fluorophores are useful in various bioassays formats. The inventive polymers are useful in assays relying on fluorescence resonance energy transfer (FRET) mechanisms where two fluorophores are used. 2. The macromer of claim 1 , wherein the macromer has a molecular weight which is a member selected from the group consisting of about 5 kDa claim 1 , about 6 kDa claim 1 , about 7 kDa claim 1 , about 8 kDa claim 1 , about 9 kDa claim 1 , about 10 kDa claim 1 , about 11 kDa claim 1 , about 12 kDa claim 1 , about 13 kDa claim 1 , about 14 kDa claim 1 , about 15 kDa claim 1 , about 16 kDa claim 1 , about 17 kDa claim 1 , about 18 kDa claim 1 , about 19 kDa claim 1 , about 20 kDa claim 1 , about 21 kDa claim 1 , about 22 kDa claim 1 , about 23 kDa claim 1 , about 24 kDa claim 1 , about 25 kDa claim 1 , about about 26 kDa claim 1 , about 27 kDa claim 1 , about 28 kDa claim 1 , about 29 kDa claim 1 , about 30 kDa claim 1 , about 31 kDa claim 1 , about 32 kDa claim 1 , about 33 kDa claim 1 , about 34 kDa claim 1 , about 35 kDa claim 1 , about 36 kDa claim 1 , about 37 kDa claim 1 , about 38 kDa claim 1 , about 39 kDa claim 1 , about 40 kDa claim 1 , about 41 kDa claim 1 , about 42 kDa claim 1 , about 43 kDa claim 1 , about 44 kDa claim 1 , about 45 kDa claim 1 , about 46 kDa claim 1 , about 47 kDa claim 1 , about 48 kDa claim 1 , about 49 kDa claim 1 , about 50 kDa claim 1 , about 51 kDa claim 1 , about 52 kDa claim 1 , about 53 kDa claim 1 , about 54 kDa claim 1 , about 55 kDa claim 1 , about 56 kDa claim 1 , about 57 kDa claim 1 , about 58 kDa claim 1 , about 59 kDa and about 60 kDa.3. The macromer of claim 1 , wherein Eand/or Eis conjugated to an organic dye.4. The macromer of claim 1 , wherein the macromer has an emission wavelength of about 300 nm to about 500 nm.5. The macromer of claim 1 , wherein each of R claim 1 , R claim 1 , R ...

Подробнее
02-01-2020 дата публикации

Benzimidazole Compound and Preparation Method Thereof

Номер: US20200002291A1
Принадлежит:

A benzimidazole compound and a preparation method thereof. Various substituted benzimidazoles are synthesized by a S2 reaction and a cyclization reaction. Namely, o-fluorinated aryl-N,N-dimethyl-formamidine and primary amine are subjected to an cyclization by a one-pot reaction, wherein a fluorine atom is substituted by an amino, and then dimethylamine is eliminated, thus forming the product. The method does not require the use of any metal catalyst and/or any toxic reagent, and has a specific selectivity. No isomer exists in the reaction product. 3. The method according to claim 2 , wherein a molar ratio of the compound of the formula (II) to the compound of the formula (III) is 1:1-12.4. The method according to claim 2 , wherein in Ris an electron withdrawing group.5. The method according to claim 4 , wherein Ris —NO—CFor —CN.6. (canceled)7. The method according to claim 6 , wherein the compound of the formula (III) is a fatty primary amine claim 6 , an aromatic primary amine or a primary amine containing a heterocyclic ring.8. The method according to claim 2 , wherein the solvent is N claim 2 ,N-dimethylformamide (DMF) claim 2 , dimethyl acetamide (DMA) claim 2 , dimethyl sulfoxide (DMSO) claim 2 , hexamethylphosphoramide (HMPA) claim 2 , tetrahydrofuran (THF) or dioxane.9. The method according to claim 2 , wherein a reaction temperature is 80° C.-220° C. claim 2 , and a reaction time is 0.2 h-5.0 h. This application is the national phase entry of International Application No. PCT/CN2017/103942, filed on Sep. 28, 2017, which is based upon and claims priority to Chinese Patent Application No. 201710589775.0, filed on Jul. 19, 2017, the entire contents of which are incorporated herein by reference.The present invention belongs to the technical field of organic synthesis, and relates to a benzimidazole compound and a preparation method thereof.The benzimidazole ring system is one of the most common core structures used for drug discovery, and has been found in many ...

Подробнее
14-01-2021 дата публикации

BICYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER

Номер: US20210008046A1
Принадлежит:

The present disclosure is directed to novel compounds of Formula I and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of cancer, including glioblastoma, bone cancer, head and neck cancer, melanoma, basal cell carcinoma, squamous cell carcinoma, adenocarcinoma, oral cancer, esophageal cancer, gastric cancer, intestinal cancer, colon cancer, bladder cancer, hepatocellular carcinoma, renal cell carcinoma, pancreatic cancer, ovarian cancer, cervical cancer, lung cancer, breast cancer, and prostate cancer. The compounds of the disclosure are selective antagonists of the EP4 receptor and useful treatment of various diseases that may be ameliorated with blockade of PGE2-mediated signaling. 2. A compound of wherein Ar is aryl or heteroaryl optionally substituted with 1 to 3 substituents independently selected from:(a) halogen,(b) cyano,{'sub': 1', '6, '(c) C-Calkyl,'}{'sub': '5', '(d) SF,'}{'sub': 1', '6, '(e) C-Chaloalkyl,'}{'sup': b', 'b, 'sub': 1', '6', '3', '6', '1', '6, '(f) ORwherein Ris C-Calkyl, aryl, heteroaryl, C-Ccycloalkyl or C-Chaloalkyl;'}(g) heterocycle,(h) aryl, and(i) heteroaryl.3. A compound of or wherein Ar is phenyl.4. A compound any one of to wherein each of X claim 1 , X claim 1 , X claim 1 , Xand Xis independently C—R claim 1 , or one of X claim 1 , X claim 1 , X claim 1 , Xand Xis N claim 1 , and the others are each independently C—R.5. A compound of wherein each of X claim 4 , X claim 4 , X claim 4 , Xand Xis independently C—R.6. A compound of any of to wherein Ris H or a halogen atom.7. A compound of any of to wherein W is selected from the group consisting of:{'sub': '2', '(a) COH; and'}(b) 1H-tetrazole.8. A compound of any of to wherein Z is —CH—.9. A compound of any of to wherein Y is a bond or —CH—.10. A compound of any of to wherein Rand ...

Подробнее
08-01-2015 дата публикации

BENZIMIDAZOLE DERIVATIVES AS SELECTIVE BLOCKERS OF PERSISTENT SODIUM CURRENT

Номер: US20150011591A1
Принадлежит:

The present invention is directed to a compound of Formula I 2. The compound of claim 1 , wherein R is and unsubstituted straight chain or branched Calkyl.3. The compound of claim 1 , wherein R is Calkyl which is substituted with a Caryloxy group.4. The compound of claim 3 , wherein the “aryl” portion of said Caryloxy group is unsubstituted or substituted with 1-2 Calkyl or Calkoxy substitutents.5. The compound of claim 1 , wherein R is Calkyl which is substituted with a heteroaryl substitutent claim 1 , wherein said heteroaryl group is five- to six-membered ring containing 1-2 ring N atoms claim 1 , and wherein when said five- to six-membered ring containing 1-2 ring N atoms has two substituents on adjacent carbon atoms claim 1 , said substituents together with the carbon atoms to which they are attached can optionally form a phenyl ring claim 1 , and wherein said six-membered ring containing 1-2 ring N atoms claim 1 , optionally with said phenyl ring is optionally further substituted with a ring system substituent.6. The compound of claim 5 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 5 , optionally with said phenyl ring is selected from the group consisting of pyrazolyl claim 5 , imidazolyl claim 5 , pyrimidinyl claim 5 , pyrazinyl claim 5 , and benzimidazolyl.7. The compound of claim 6 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 6 , optionally with said phenyl ring is selected from the group consisting of is imidazolyl and benzimidazolyl.8. The compound of claim 1 , wherein R is Calkyl which is substituted with a —N(Calkyl)substituent.10. The compound of claim 1 , wherein Rand Rare both H.11. The compound of claim 10 , wherein m is 1 or 2.12. The compound of claim 10 , wherein m is 1 claim 10 , and X is O.13. The compound of claim 10 , wherein m is 2 claim 10 , and X is a covalent bond.14. The compound of claim 10 , wherein m is 1 claim 10 , and X is —S(═O)—.15. The compound of claim 10 , wherein m ...

Подробнее
03-02-2022 дата публикации

HDAC1,2 Inhibitors

Номер: US20220033388A1
Принадлежит:

Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with HDAC1 and/or HDAC2 activity. 2. The compound of claim 1 , wherein:{'sup': '1', 'sub': '2', 'Ris selected from the group consisting of phenyl, phenyl-OH, phenyl-OSONHMe, thienyl, and furanyl;'}{'sup': '2', 'sub': 2', '1', '3, 'Ris selected from the group consisting of —H, methyl, —CH-cyclopropyl, and C-Calkyl-5-6 membered heterocycloalkyl; and'}{'sup': 3', '4, 'Rand Rare independently, at each occurrence, selected from the group consisting of —H, halo, and methyl.'}4. The compound of claim 3 , wherein:{'sup': '1', 'Ris phenyl or thienyl;'}{'sup': '2', 'sub': '2', 'Ris selected from the group consisting of absent, —H, methyl, and C-alkyl-5-6 membered heterocycloalkyl;'}{'sup': '3', 'sub': '2', 'Ris selected from the group consisting of absent, —H, and —C-alkyl-5-6 membered heterocycloalkyl; and'}{'sup': '4', 'Ris selected from the group consisting of —H, cyclopropyl, and methyl.'}7. The compound of claim 6 , wherein{'sup': '1', 'sub': '2', 'Ris —NHor —OH;'}{'sup': 2', '5, 'Ris halo or heteroaryl, wherein heteroaryl is optionally substituted by one or more R;'}{'sup': 3', '6', '6', '6', '6', '6', '5, 'sub': 1', '3', '2', '1', '3', '2', '1', '3, 'Ris independently, at each occurrence, selected from the group consisting of cycloalkyl, heterocycloalkyl, —N(R)—C-Calkyl-N(R), —O—C-Calkyl-N(R), and —N(R)—C-Calkyl-OR, wherein cycloalkyl and heterocycloalkyl are optionally substituted by one or more R;'}{'sup': '4', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}{'sup': '5', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}{'sup': '6', 'sub': 1', '6, 'Ris independently, at each occurrence, —H or C-Calkyl;'}and n is 1, 2, or 3.9. The compound of any one of - claim 6 , wherein Ris independently claim 6 , at each occurrence claim 6 , selected from the group ...

Подробнее
17-04-2014 дата публикации

Organic light emitting device and organic light emitting display device using the same

Номер: US20140103301A1
Принадлежит: LG Display Co Ltd

Disclosed is a an organic light emitting device including a first electrode and a second electrode; and an organic layer formed between the first electrode and the second electrode, in which the organic layer includes a compound represented by Formula 1 and the second electrode is a double-layer structure comprised of LiF:Mg. Accordingly, an organic light emitting device which has excellent voltage efficiency and emission efficiency and may improve service-life characteristics, and an organic light emitting display device using the same may be provided.

Подробнее
22-01-2015 дата публикации

ANTIVIRAL DRUGS FOR TREATMENT OF ARENAVIRUS INFECTION

Номер: US20150023916A1
Принадлежит: SIGA TECHNOLOGIES INC.

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain 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 the Arenavirus family such as Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever. 2. The compound of claim 1 , wherein each of E and J is N.3. The compound of claim 1 , wherein each of G claim 1 , M claim 1 , Q and L is C—R.4. The compound of claim 1 , wherein K is C.5. The compound of claim 1 , wherein D-A is RC═CRand each of Rand Rare H and the double bond in RC═CRhas a cis configuration.6. The compound of claim 1 , wherein D-A is O—CRRand each of Rand Rare H.7. The compound of selected from the group consisting of: 5-[(Z)-2-(4-tert-butylphenyl)vinyl]-1-(4-isopropoxyphenyl)-benzimidazole; 1-(4-ethoxyphenyl)-5-[(4-ethylphenyl)-methoxy]benzimidazole; and 2-[4-[(Z)-2-[1-(4-isopropoxyphenyl)benzimidazol-5-yl]vinyl]phenyl]-propan-2-ol.10. The composition of claim 9 , wherein each of E and J is N.11. The composition of claim 9 , wherein each of G claim 9 , M claim 9 , Q and L is C—R.12. The composition of claim 9 , wherein K is C.13. The composition of claim 9 , wherein D-A is RC═CRand each of Rand Rare H and the double bond in RC═CRhas a cis configuration.14. The composition of claim 9 , wherein D-A is O—CRRand each of Rand Rare H.15. The composition of claim 9 , wherein the compound of Formula I is selected from the group consisting of: 5-[(Z)-2-(4-tert-butylphenyl)vinyl]-1-(4-isopropoxyphenyl)-benzimidazole; 1-(4-ethoxyphenyl)-5-[(4-ethylphenyl)-methoxy]benzimidazole; and 2-[4-[(Z)-2-[1-(4-isopropoxyphenyl)benzimidazol-5-yl]vinyl]phenyl]-propan-2-ol.18. The method of claim 17 , wherein each of E and J is N.19. The method of claim 17 , ...

Подробнее
02-02-2017 дата публикации

HYDROXIDE-CATALYZED FORMATION OF SILICON-OXYGEN BONDS BY DEHYDROGENATIVE COUPLING OF HYDROSILANES AND ALCOHOLS

Номер: US20170029447A1
Принадлежит:

The present disclosure is directed to methods for dehydrogenatively coupled hydrosilanes and alcohols, the methods comprising contacting an organic substrate having at least one organic alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide, the contacting resulting in the formation of a dehydrogenatively coupled silyl ether. The disclosure further described associated compositions and methods of using the formed products. 1. A method comprising contacting an organic substrate having at least one alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide , the contacting resulting in the formation of a dehydrogenatively coupled silyl ether , wherein the contacting is done in the absence of a crown ether.2. The method of claim 1 , wherein the hydrosilane has a structure of Formula (I) or of Formula (II):{'br': None, 'sub': 3−m', 'm+1, '(R)Si(H)\u2003\u2003(I)'}{'br': None, 'sub': 2−m', 'm+1', '3−m', 'm, '(R)(H)Si—Si(R)(H)\u2003\u2003(II)'}{'sub': 1-24', '2-24', '2-24', '1-24', '1', '20', '5', '20', '1', '20', '5', '20', '1', '20', '1', '20', '5', '20', '2', '20', '5', '20', '1', '20, 'where: m is independently 0, 1, or 2; and each R is independently optionally substituted Calkyl or heteroalkyl, optionally substituted Calkenyl or heteroalkenyl, optionally substituted Calkynyl or heteroalkynyl, optionally substituted 6 to 18 ring membered aryl or 5 to 18 ring membered heteroaryl, optionally substituted 6 to 18 ring-membered alkaryl or 5 to 18 ring-membered heteroalkaryl, optionally substituted 6 to 18 ring-membered aralkyl or 5 to 18 ring-membered heteroaralkyl, optionally substituted —O—Calkyl or heteroalkyl, optionally substituted 6 to 18 ring-membered aryloxy or 5 to 18 ring-membered heteroaryloxy, optionally substituted 6 to 18 ring-membered alkaryloxy or 5 to 18 ring-membered heteroalkaryloxy, or optionally substituted 6 to 18 ring-membered aralkoxy or 5 to 18 ring-membered ...

Подробнее
31-01-2019 дата публикации

PHARMACEUTICAL COMPOSITION

Номер: US20190030004A1
Принадлежит:

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions. 138-. (canceled)40. The pharmaceutical composition according to claim 39 , wherein the carrier matrix consists essentially of one or both of the following:(a) d-alpha-tocopher polyethylene glycol 1000 succinate; and(b) polyglycolised glycerides.41. The pharmaceutical composition according to claim 39 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate or Lauroyl Macrogol-32 Glycerides.42. The pharmaceutical composition according to claim 39 , wherein the carrier matrix is a mixture of d-alpha-tocopheryl polyethylene glycol 1000 succinate and Lauroyl Macrogol-32 Glycerides and wherein the Lauroyl Macrogol-32 Glycerides are present in an amount to make up approximately 30-55% by weight of the carrier matrix component of the composition.43. The pharmaceutical composition according to claim 39 , wherein the carrier matrix is d-alpha-tocopheryl polyethylene glycol 1000 succinate.44. The pharmaceutical composition according to claim 43 , wherein the d-alpha-tocopheryl polyethylene glycol 1000 succinate is present in an amount to make up approximately 65 to 95% by weight of the composition.45. The pharmaceutical composition according to claim 39 , wherein greater than 90% by weight of the total amount of the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide present in the composition is dispersed within the carrier matrix.46. The pharmaceutical composition according to claim 39 , wherein the composition contains between 5 to 30% by weight of the hydrogen sulphate salt of 6-(4-bromo-2- ...

Подробнее
01-02-2018 дата публикации

DETERMINATION OF AQUEOUS NITRATE CONCENTRATION

Номер: US20180031536A1
Принадлежит:

A method of measuring nitrate concentration in an aqueous sample includes mixing the aqueous sample with a water-soluble thioether chosen to reduce nitrate in the aqueous sample to nitrite in the presence of a water soluble catalyst, and a water soluble reagent system adapted to interact with nitrite to generate a color; measuring color generation, and correlating the color generation to nitrate concentration. 1. A method of measuring nitrate concentration in an aqueous sample , comprisinga. mixing the aqueous sample with a water-soluble thioether chosen to reduce nitrate in the aqueous sample to nitrite in the presence of a water soluble catalyst, and a water soluble reagent system adapted to interact with nitrite to generate a color,b. measuring color generation, andc. correlating the color generation to nitrate concentration.2. The method of wherein the water soluble thioether comprises a thioether-containing a five-membered claim 1 , aromatic heterocyclic compound claim 1 , a phenylalkyl thioether or a substituted phenylalkyl thioether.4. The method of wherein the hydrophilic polymer is a polyalkyleneoxide.5. The method of wherein at least one of R claim 3 , R claim 3 , R claim 3 , R claim 3 , and Ris —ORwherein Ris selected from the group consisting of H claim 3 , a C-Calkyl group claim 3 , a C-Csulfonate terminated alkyl group claim 3 , a phenyl group claim 3 , and a polyalkylene oxide group claim 3 , —NRRwherein RE and Rare selected independently from the group consisting of H claim 3 , a C-Calkyl group claim 3 , a C-Csulfonate terminated alkyl group claim 3 , and a polyalkylene oxide group claim 3 , a dihydroxybenzene group claim 3 , a phenyl diamine group claim 3 , a phenyl diether group claim 3 , a carboxy late group claim 3 , and a polyalkyleneoxide group; or Rand Rtogether form a chain of four or five members selected from the group of CH claim 3 , CH claim 3 , NH claim 3 , CC(O)OH or NR claim 3 , wherein Ris an C-Calkyl group or C-Csulfonate terminated ...

Подробнее
12-02-2015 дата публикации

METHODS OF TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION, COMPOSITIONS FOR TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION, AND SCREENING ASSAYS FOR IDENTIFYING COMPOSITIONS FOR TREATING A FLAVIVIRIDAE FAMILY VIRAL INFECTION

Номер: US20150044169A1
Принадлежит:

Briefly described, embodiments of this disclosure include compositions, pharmaceutical compositions, methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of identifying a candidate agent for the treatment of hepatitis C virus (HCV) infection, and the like. 1. A method of treating a host infected with a virus from the Flaviviridae family of viruses , the method comprising administering to the host a therapeutically effective amount of an inhibiting agent to reduce the viral load in the host.2. The method of claim 1 , wherein the Flaviviridae family of viruses includes viruses selected from the group consisting of: a flavivirus claim 1 , a pestivirus claim 1 , a Hepatitis C virus claim 1 , a yellow fever virus (YFV); a Dengue virus; a Japanese Encephalitis virus; a Murray Valley Encephalitis virus; a St. Louis Encephalitis virus; a West Nile virus; a tick-borne encephalitis virus; a Hepatitis C virus; a Kunjin virus; a Central European encephalitis virus; a Russian spring-summer encephalitis virus; a Powassan virus; a Kyasanur Forest disease virus; and a Omsk hemorrhagic fever virus.3. The method of claim 1 , wherein the virus is Hepatitis C virus.4. The method of claim 1 , wherein the inhibiting agent is selected from the group consisting of: clemizole claim 1 , a clemizole analog claim 1 , and a compound having a clemizole scaffold; an H1 antagonist claim 1 , an H1 receptor antagonist that share structural similarity with clemizole; cinoxacin claim 1 , a cinoxacin analog claim 1 , and a compound having a cinoxacin scaffold; norepinephrine claim 1 , a norepinephrine analog claim 1 , and a compound having a norepinephrine scaffold; glybenclamide claim 1 , a glybenclamide analog claim 1 , and a compound having a glybenclamide scaffold; spiradoline claim 1 , a spiradoline analog claim 1 , and a compound having a spiradoline scaffold; tropicamide claim 1 , a tropicamide analog claim 1 , and a compound having a tropicamide ...

Подробнее
15-02-2018 дата публикации

COMPOUNDS FOR MODULATING MITOCHONDRIAL FUNCTION

Номер: US20180044295A1

Compounds and compositions that can modulate mitochondrial function in neuronal cells are provided herein, as are methods for using the compounds and compositions to treat or prevent conditions such as Alzheimer's disease. 2. The compound of claim 1 , wherein X is CH.3. The compound of claim 2 , wherein Ris Calkyl.4. The compound of claim 3 , wherein Ris Calkyl.5. The compound of claim 4 , wherein Ris H.6. The compound of claim 5 , wherein Ris unsubstituted 5-10 membered heteroaryl.7. The compound of claim 5 , wherein Ris aryl and Ris halo or OH.10. The compound of claim 9 , wherein X is CH.11. The compound of claim 10 , wherein Ris Calkyl.12. The compound of claim 11 , wherein Ris Calkyl.13. The compound of claim 12 , wherein Ris H.14. The compound of claim 13 , wherein Ris unsubstituted 5-10 membered heteroaryl.15. The compound of claim 13 , wherein Ris aryl and Ris halo or OH.19. A pharmaceutical composition comprising a compound of any one of - claim 13 , or a pharmaceutically acceptable salt thereof claim 13 , in combination with a pharmaceutically acceptable carrier.20. A method for modulating mitochondrial function in a subject claim 13 , comprising administering to the subject a therapeutically effective amount of a compound of any one of - claim 13 , or a pharmaceutically acceptable salt thereof.21. The method of claim 20 , wherein the subject is a human.22. The method of claim 20 , wherein the subject is diagnosed as having a neurodegenerative disorder.23. The method of claim 20 , wherein the subject is diagnosed as having diabetes claim 20 , metabolic syndrome claim 20 , cancer claim 20 , a chemotherapy-induced peripheral neuropathy claim 20 , or Down Syndrome.24. A method for treating a neurodegenerative disorder in a subject claim 20 , comprising administering to the subject a therapeutically effective amount of a compound of any one of - claim 20 , or a pharmaceutically acceptable salt thereof.25. The method of claim 24 , comprising administering the ...

Подробнее
08-05-2014 дата публикации

HDAC INHIBITORS AND THERAPEUTIC METHODS USING THE SAME

Номер: US20140128408A1

Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed. 3. (canceled)5. (canceled)9. The compound of wherein Ris selected from the group consisting of null claim 1 , hydrogen claim 1 , Calkyl claim 1 , Cheteroalkyl claim 1 , aryl claim 1 , and heteroaryl.13. A compound selected from the group consisting of compounds disclosed in paragraph [0235] and in Table 1 herein.15. A composition comprising (a) compound of claim 1 , (b) an optional second therapeutic agent useful in the treatment of a disease or condition wherein inhibition of HDAC provides a benefit claim 1 , and (c) an excipient and/or pharmaceutically acceptable carrier.16. (canceled)17. (canceled)18. A method of treating a disease or condition wherein inhibition of HDAC provides a benefit comprising administering a therapeutically effective amount of a compound of and optionally administering a therapeutically effective amount of a second therapeutic agent useful in the treatment of the disease or condition to an individual in need thereof.19. (canceled)20. (canceled)21. (canceled)22. (canceled)23. (canceled)24. The method of wherein the disease is a cancer and the second therapeutic agent is one or more of a chemotherapeutic agent claim 18 , radiation claim 18 , and an immunotherapy.25. (canceled)26. (canceled)27. (canceled)28. The method of wherein the disease or condition is a neurological disease claim 18 , a neurodegenerative disorder claim 18 , peripheral neuropathy claim 18 , stroke claim 18 , or a traumatic brain injury.29. (canceled)30. (canceled)31. The method of wherein the disease or condition is an inflammation or an autoimmune ...

Подробнее
08-05-2014 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20140128442A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 2. The process of claim 1 , wherein the suitable protecting group is selected from alkyl group; alkenyl groups; tertiary aryl-alkyls; groups that result in acetals; and silyl groups.3. (canceled)4. The process of claim 1 , further comprising isolating the intermediate.5. The process of claim 4 , wherein the isolating step comprises crystallizing the intermediate.7. (canceled)8. The process of claim 1 , wherein the suitable solvent or solvent system is a polar aprotic solvent.9. (canceled)10. The process of claim 1 , wherein the suitable deprotecting reagent is phosphoric acid.11. The process of claim 1 , wherein said compound of formula (III) or a hydrate thereof is further reacted with a suitable base claim 1 , to provide Compound A.1214-. (canceled)16. The process of claim 15 , wherein the protecting group is selected from alkyl group; alkenyl groups; tertiary aryl-alkyls; groups that result in acetals; and silyl groups.17. (canceled)18. The process of claim 15 , wherein the suitable base is selected from sodium hydroxide claim 15 , potassium hydroxide claim 15 , caesium hydroxide claim 15 , lithium hydroxide claim 15 , potassium trimethylsilanolate claim 15 , lithium trimethylsilanolate claim 15 , and sodium trimethylsilanolate.1920-. (canceled)22. The process of claim 18 , further comprising isolating the intermediate.23. The process of claim 22 , wherein the step of isolating the intermediate comprises crystallizing the intermediate.25. A process of claim 24 , wherein the solution comprises (i.) a solvent system comprising ...

Подробнее
01-03-2018 дата публикации

CDK INHIBITOR, EUTECTIC CRYSTAL OF MEK INHIBITOR, AND PREPARATION METHOD THEREFOR

Номер: US20180057498A1
Принадлежит: CRYSTAL PHARMATECH CO., LTD

The present disclosure relates to novel co-crystals of a CDK inhibitor and an MEK inhibitor and the preparation methods thereof. Specifically, the present disclosure provides hydrates or anhydrates which are named as Form I, Form II and Form III. The novel co-crystals provided in the present disclosure have good stability, low hygroscopicity and high solubility, and have an important value for further optimization and development of the drug. 2. The co-crystal according to claim 1 , wherein x is a number of 0 claim 1 , 1 claim 1 , 2 or 3.3. The co-crystal according to claim 1 , wherein the co-crystal is hydrate Form I claim 1 , having an X-ray powder diffraction pattern comprising the following 2theta values measured using CuKα radiation: 19.3°±0.2° claim 1 , 22.7°±0.2° claim 1 , 10.4°±0.2°.4. The co-crystal according to claim 3 , wherein the X-ray powder diffraction pattern of Form I further shows one or two or three characteristic peaks at 2theta values of 11.4°±0.2° claim 3 , 23.6°±0.2° claim 3 , 13.4°±0.2°.5. (canceled)6. The co-crystal according to claim 3 , wherein the X-ray powder diffraction pattern of Form I further shows one or two or three characteristic peaks at 2theta values of 21.6°±0.2° claim 3 , 26.0°±0.2° claim 3 , 8.3°±0.2°.7. (canceled)8. The co-crystal according to claim 3 , wherein the Form I contains 0.5-3 moles of water.9. The co-crystal according to claim 1 , wherein the co-crystal is anhydrous Form II claim 1 , having an X-ray powder diffraction pattern comprising the following 2theta values measured using CuKα radiation: 13.1°±0.2° claim 1 , 10.3°±0.2° claim 1 , 16.4°±0.2°.10. The co-crystal according to claim 9 , wherein the X-ray powder diffraction pattern of Form II further shows one or two or three characteristic peaks at 2theta values of 19.1°±0.2° claim 9 , 21.9°±0.2° claim 9 , 14.8°±0.2°.11. (canceled)12. The co-crystal according to claim 9 , wherein the X-ray powder diffraction pattern of Form II further shows one or two or three ...

Подробнее
04-03-2021 дата публикации

2-ARYLBENZIMIDAZOLES AS PPARGC1A ACTIVATORS FOR TREATING NEURODEGENERATIVE DISEASES

Номер: US20210061769A1

The compound 2-(4-tert-Butylphenyl)-1H-benzo[d]imidazol-5-ol: 2. A compound according to claim 1 , in free base form.3. A compound according to claim 1 , in the form of a pharmaceutically acceptable salt.4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to .5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to . This application is a continuation of U.S. application Ser. No. 16/888,040, filed May 29, 2020, which is a continuation under 35 USC § 111(a) of PCT/US2019/045229, filed Aug. 6, 2019. PCT/US2019/045229 claimed priority from U.S. Provisional application 62/714,962, which was filed Aug. 6, 2018. The contents of each of these applications are incorporated herein by reference in their entirety.The invention relates to the use of 2-arylbenzimidazole, 2-arylbenzoxazole, 2-arylbenzothiazole, 2-arylimidazo[1,2-a]pyridine, and prodrug derivatives thereof as chemical activators of Ppargc1a to treat neurodegenerative diseases.Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that is characterized by the loss of motor neurons, leading to progressive decline in motor function and ultimately death. The motor symptoms of ALS include muscle weakness, twitching and wasting, which leads to difficulties in speaking, swallowing and breathing. The cause of motor neuron death in ALS is unknown and 5-10% of the ALS cases are inherited.Activation of immune cells in the central as well as peripheral nervous system has been suggested to be a critical determinant of disease progression in ALS (Phani et al, Front Pharmacol. 3:150, 2012). Specifically, microglia and macrophages have been shown to play distinct roles in the orchestration of neuroinflammation in this disease (Dibaj et al, PLoS One. 6(3):e17910, 2011; Boillee et al, Science, 312:1389-92, 2006). Of note, bone marrow transplantation (BMT) to replace host myeloid cells has been shown to ...

Подробнее
04-03-2021 дата публикации

Synthetic Nicotine Composition

Номер: US20210061783A1
Принадлежит:

A synthetic nicotine composition comprising synthetic nicotine, a synthetic nicotine salt and a synthetic nicotine derivative, wherein the synthetic nicotine, the synthetic nicotine salt, and the synthetic nicotine derivative are in mass percentage; the synthetic nicotine accounts for 1-20%, the synthetic nicotine salt accounts for 30-70%, and the synthetic nicotine derivative accounts for 20-50%; and the synthetic nicotine is one or more of S-nicotine and a mixture of R-nicotine containing a racemate and S-nicotine. The synthetic nicotine, synthetic nicotine salt and synthetic nicotine derivative according to the present invention are proportionally mixed to prepare an existing synthetic nicotine product, which relieves the problem of the impact of impurities in natural extracted nicotine products causing an unpleasant smell, a bitter taste and a strong volatility, and can be used in the fields of low temperature heat-not-burn products, snuff, electronic cigarettes, nicotine release patches, insecticides, herbicides, microbicides, drug synthesis, etc. 1. A synthetic nicotine composition comprising synthetic nicotine , a synthetic nicotine salt and a synthetic nicotine derivative , wherein the synthetic nicotine , the synthetic nicotine salt , and the synthetic nicotine derivative are in mass percentage; the synthetic nicotine accounts for 1-20% , the synthetic nicotine salt accounts for 30-70% , and the synthetic nicotine derivative accounts for 20-50%; the synthetic nicotine is one or more of S-nicotine and a mixture of R-nicotine containing a racemate and S-nicotine; the synthetic nicotine salt is formed by reacting the synthetic nicotine with an organic acid mixture; and the nicotine derivative comprises one or more of an imidazole derivative of nicotine , an amine derivative of nicotine , and an amino acid derivative of nicotine.2. The synthetic nicotine composition according to claim 1 , wherein the synthesis organic acid mixture for the synthetic nicotine ...

Подробнее
05-03-2015 дата публикации

DIARYLHYDANTOIN COMPOUNDS

Номер: US20150065546A1

The present invention relates to diarylhydantoin compounds and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer. 19.-. (canceled)1116-. (canceled)1921-. (canceled)22. The method of claim 23 , wherein the compound is administered as a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier or diluent.24. The method of claim 23 , wherein the compound is administered at a dosage of the compound in the range of from about 0.001 mg per kg body weight per day to about 100 mg per kg body weight per day.25. The method of claim 23 , wherein the compound is administered at a dosage of the compound in the range of from about 0.01 mg per kg body weight per day to about 100 mg per kg body weight per day.26. The method of claim 23 , wherein the compound is administered at a dosage of the compound in the range of from about 0.1 mg per kg body weight per day to about 10 mg per kg body weight per day.27. The method of claim 23 , wherein the compound is administered at a dosage of the compound of about 1 mg per kg body weight per day.28. The method of claim 23 , wherein the hyperproliferative disorder is hormone refractory prostate cancer.29. The method of claim 23 , wherein the compound is administered by intravenous injection claim 23 , by injection into tissue claim 23 , intraperitoneally claim 23 , orally claim 23 , or nasally.30. The method of claim 23 , wherein the compound is administered orally.31. The method of claim 22 , wherein the pharmaceutical composition has a form selected from the group consisting of a solution claim 22 , dispersion claim 22 , suspension claim 22 , powder claim 22 , capsule claim 22 , tablet claim 22 , pill claim 22 , time release capsule claim 22 , time release tablet claim 22 , and time release pill.32. The method of claim 22 , wherein the pharmaceutical composition has a form selected from the group consisting of a capsule claim 22 , tablet claim 22 , and pill. ...

Подробнее
09-03-2017 дата публикации

NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE

Номер: US20170066712A1
Принадлежит:

This invention provides a compound having the structure: 135-. (canceled)43. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.44. A method of inhibiting the activity of a histone deactylase in a cell claim 37 , the method comprising contacting the histone deacetylase with the compound of so as to inhibit the activity of the histone deacetylase; or of increasing accumulation of acetylated alpha tubulin in a cell claim 37 , the method comprising contacting the cell with the compound of so as to increase the accumulation of acetylated alpha-tubulin in the cell.50. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.51. A method of inhibiting the activity of a histone deactylase in a cell claim 45 , the method comprising contacting the histone deacetylase with the compound of so as to inhibit the activity of the histone deacetylase; or of increasing accumulation of acetylated alpha tubulin in a cell claim 45 , the method comprising contacting the cell with the compound of so as to increase the accumulation of acetylated alpha-tubulin in the cell.53. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.54. A method of inhibiting the activity of a histone deactylase in a cell claim 52 , the method comprising contacting the histone deacetylase with the compound of so as to inhibit the activity of the histone deacetylase; or of increasing accumulation of acetylated alpha tubulin in a cell claim 52 , the method comprising contacting the cell with the compound of so as to increase the accumulation of acetylated alpha-tubulin in the cell. This application claims priority of U.S. Provisional Application No. 61/620,783, filed Apr. 5, 2012 and 61/542,598, filed Oct. 3, 2011, the contents of each of which are hereby incorporated by reference.Throughout this application, certain publications are referenced in parentheses. Full citations for ...

Подробнее
24-03-2022 дата публикации

PHARMACEUTICAL COMPOSITION

Номер: US20220087982A1
Принадлежит:

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions. 120-. (canceled)21. A pharmaceutical composition consisting essentially of:(i) from 15 to 25 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and(ii) from 75 to 85 parts of d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS);wherein both parts are by weight and the sum of the parts (i)+(ii)=100;and wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.22. A pharmaceutical composition according to claim 21 , consisting essentially of:(i) from 18 to 22 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and(ii) from 78 to 82 parts of Vitamin E TPGS;wherein both parts are by weight and the sum of the parts (i)+(ii)=100;and wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the Vitamin E TPGS, and the composition is semi-solid or solid at ambient temperature.23. A pharmaceutical composition according to claim 22 , consisting essentially of:(i) from 19 to 21 parts of a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide; and(ii) from 79 to 81 parts of Vitamin E TPGS;wherein both parts are by ...

Подробнее
25-03-2021 дата публикации

CRYSTALLINE POLYMORPHS OF PRACINOSTAT AND PRACINOSTAT SALTS

Номер: US20210087150A1
Принадлежит:

The present disclosure encompasses crystalline polymorphs of Pracinostat and of Pracinostat salts, and pharmaceutical compositions thereof. 1. A crystalline polymorph of Pracinostat , designated Form P3 , characterized by data selected from one or more of the following:{'figref': {'@idref': 'DRAWINGS', 'FIG. 3'}, 'a) an X-ray powder diffraction pattern substantially as depicted in ;'}b) an X-ray powder diffraction pattern having peaks at 5.7, 8.4, 10.2, 14.3 and 15.3 degrees 2-theta±0.2 degrees 2-theta;{'sup': '13', 'figref': {'@idref': 'DRAWINGS', 'i': a', 'b, 'FIGS. 14, 14'}, 'b': '14', 'i': 'c;', 'c) a solid state C NMR spectrum substantially as depicted in any one of and'}{'sup': '13', 'd) a solid state C NMR spectrum having peaks at the range of 100-200 ppm at 157.29, 141.28, 137.17, 130.06 and 120.57 ppm±2 ppm;'}{'sup': '13', 'e) a solid state C NMR spectrum having the following chemical shift absolute differences from a peak at 165.62 ppm±2 ppm of 8.33, 24.34, 28.45, 35.56 and 45.05±2 ppm;'}{'sup': '13', 'f) a solid state C NMR spectrum having chemical shift difference from a peak at 165.62 ppm±1 ppm to 130.06 ppm±1 ppm of 35.36 ppm±1 ppm;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 17'}, 'g) a FTIR spectrum substantially as depicted in ; and'}h) combinations of these data.2. The crystalline polymorph of Pracinostat according to claim 1 , characterized by an X-ray powder diffraction pattern having peaks at 5.7 claim 1 , 8.4 claim 1 , 10.2 claim 1 , 14.3 and 15.3 degrees 2-theta±0.2 degrees 2-theta claim 1 , and also having any one claim 1 , two claim 1 , three claim 1 , four or five additional peaks selected from the group consisting of 16.5 claim 1 , 17.8 claim 1 , 20.1 claim 1 , 20.9 and 23.3 degrees 2-theta±0.2 degrees 2-theta.3. The crystalline polymorph of Pracinostat according to claim 1 , wherein the crystalline form is anhydrous.4. A crystalline polymorph of Pracinostat claim 1 , designated Form P7 claim 1 , characterized by data selected from one or ...

Подробнее
29-03-2018 дата публикации

Diarylhydantoin Compounds

Номер: US20180086718A1

The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer. 151.-. (canceled) The present invention relates to diarylhydantoin compounds including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer. This application is a continuation of U.S. application Ser. No. 14/496,973, filed Sep. 25, 2014, which is a continuation of U.S. application Ser. No. 14/137,991, filed Dec. 20, 2013, which is a continuation of U.S. application Ser. No. 13/448,964, filed Apr. 17, 2012, which is a continuation of U.S. application Ser. No. 12/708,523, filed Feb. 18, 2010, which is a divisional of U.S. application Ser. No. 11/433,829, filed May 15, 2006, which claims the benefit of U.S. Provisional Application No. 60/786,837, filed Mar. 29, 2006, U.S. Provisional Application No. 60/756,552, filed Jan. 6, 2006, U.S. Provisional Application No. 60/750,351, filed Dec. 15, 2005, and U.S. Provisional Application No. 60/680,835, filed May 13, 2005, the specifications of which are hereby incorporated by reference in their entirety.This invention was made with Government support under Grant No. W81XWH-04-1-0129 awarded by the United States Army, Medical Research and Materiel Command and under Grant No. CA092131 awarded by the National Institutes of Health. The Government has certain rights in the invention.Prostate cancer is the most common incidence of cancer and the second leading cause of cancer death in Western men. When the cancer is confined locally, the disease can be cured by surgery or radiation. However, 30% of such cancer relapses with distant metastatic disease and others have advanced disease at diagnoses. Advanced disease is treated by castration and/or administration of antiandrogens, the so-called androgen deprivation therapy. Castration lowers the circulating levels of ...

Подробнее
29-03-2018 дата публикации

PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS

Номер: US20180086719A1
Принадлежит:

The present application provides the compounds of formula I 11. A pharmaceutical composition comprising the compound of and at least one pharmaceutically acceptable vehicle.12. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of claim 1 , wherein the disease or condition is selected from cancer claim 1 , hematologic malignancies claim 1 , leukemias claim 1 , lymphomas claim 1 , myeloproliferative disorders claim 1 , myelodysplastic syndromes claim 1 , plasma cell neoplasms claim 1 , or solid tumor.13. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of claim 1 , wherein the disease or condition is selected from inflammation claim 1 , fibrosis claim 1 , autoimmune disorders claim 1 , allergic conditions claim 1 , hypersensitivity claim 1 , cardiovascular diseases claim 1 , neurodegenerative diseases claim 1 , renal disorders claim 1 , viral infections claim 1 , obesity claim 1 , and autoimmune diseases.14. A method of treating prostate cancer in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of .15. A method of inhibiting the activity of phosphatidylinositol 3-kinase polypeptide by contacting the polypeptide with the compound of .16. A method of inhibiting excessive or destructive immune reactions or growth or a proliferation of cancer cells claim 1 , comprising administering an effective amount of the compound of .17. A method of treating a disease or condition in a human in need thereof comprising administering to the human a therapeutically effective amount of the compound of in combination with therapeutically effective amount of a compound that inhibits or modulates the activity of poly(ADP-ribose) polymerases (PARP) claim 1 , Tankyrases (TANKs) claim 1 , matrix ...

Подробнее
16-04-2020 дата публикации

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

Номер: US20200115333A1
Принадлежит: Roche Palo Alto LLC

The application discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt.3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This Application is a Continuation of U.S. application Ser. No. 15/597,478, filed May 17, 2017, which is a Continuation of U.S. application Ser. No. 14/531,465, filed Nov. 3, 2014, which is a Continuation U.S. application Ser. No. 13/314,525, filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459, filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706, filed Dec. 21, 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030, filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HTS, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of ...

Подробнее
31-07-2014 дата публикации

GERMINAL ALKOXY/ALKYLSPIROCYCLIC SUBSTITUTED TETRAMATE DERIVATIVES

Номер: US20140213795A1
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to novel compounds of the formula (I) 117-. (canceled)2328-. (canceled) The present invention relates to novel geminally alkoxy/alkylspirocyclically substituted tetramic acid derivatives, to a plurality of processes for their preparation and to their use as pesticides and/or herbicides. The invention also provides selective herbicidal compositions comprising, firstly, geminally alkoxy/alkylspirocyclically substituted tetramic acid derivatives and, secondly, a crop plant compatibility-improving compound.The present invention furthermore relates to the boosting of the action of crop protection compositions comprising, in particular, geminally alkoxy/alkylspirocyclically substituted tetramic acid derivatives, through the addition of ammonium salts or phosphonium salts and optionally penetrants, to the corresponding compositions, to processes for producing them and to their application in crop protection as insecticides and/or acaricides and/or for preventing unwanted plant growth.Pharmaceutical properties of 3-acyl-pyrrolidine-2,4-diones have already been described (S. Suzuki et al. Chem. Pharm. Bull. 15 1120 (1967)). Furthermore, N-phenylpyrrolidine-2,4-diones have been synthesized by R. Schmierer and H. Mildenberger (Liebigs Ann. Chem. 1985, 1095). A biological activity of these compounds has not been described.EP-A-0 262 399 and GB-A-2 266 888 disclose compounds of a similar structure (3-arylpyrrolidine-2,4-diones) of which, however, no herbicidal, insecticidal or acaricidal activity has become known. Unsubstituted bicyclic 3-arylpyrrolidine-2,4-dione derivatives (EP-A-355 599, EP-A-415 211 and JP-A-12-053 670) and substituted monocyclic 3-arylpyrrolidine-2,4-dione derivatives (EP-A-377 893 and EP-A-442 077) are known to have herbicidal, insecticidal or acaridical activity.Additionally known are polycyclic 3-arylpyrrolidine-2,4-dione derivatives (EP-A-442 073) and 1H-arylpyrrolidinedione derivatives (EP-A-456 063, EP-A-521 334, EP-A-596 298, EP ...

Подробнее
02-05-2019 дата публикации

HETEROCYCLIC CARBOXYLIC ACID AMIDE LIGAND AND APPLICATIONS THEREOF IN COPPER CATALYZED COUPLING REACTION OF ARYL HALOGENO SUBSTITUTE

Номер: US20190127337A1
Принадлежит: CE Pharm Co., Ltd.

Provided are a heterocyclic carboxylic acid amide ligand and applications thereof in a copper catalyzed coupling reaction. Specifically, provided are uses of a compound represented by formula (I), definitions of radical groups being described in the specifications. The compound represented by formula (I) can be used as the ligand in the copper catalyzed coupling reaction of the aryl halogeno substitute, and is used or catalyzing the coupling reaction for forming the aryl halogeno substitute having C—N, C—O, C—S and other bonds. 5: The method of claim 4 , wherein in the reaction claim 4 , the molar ratio of the ligand to the reactant aryl halide is 1-50:100 claim 4 , preferably 5-20:100; and/orthe molar ratio of the ligand to the copper catalyst is 1-5:1, preferably 1-2:1.7: The method of claim 4 , wherein the reaction temperature is 50-180° C. claim 4 , preferably 100-130° C.9: The method of wherein the copper catalyst is selected from the group consisting of CuI claim 4 , CuBr claim 4 , CuCl claim 4 , CuTc claim 4 , Cu(OAc) claim 4 , CuSO claim 4 , CuO claim 4 , CuBr claim 4 , CuCl claim 4 , CuO claim 4 , CuSCN claim 4 , CuCN claim 4 , Cu(acac) claim 4 , and combinations thereof; preferably CuI.10: The method of claim 4 , wherein the reaction is carried out in the presence of a base.11: The method of claim 8 , wherein claim 8 ,in the reaction (1), the ligand is preferably L-53 or L-103; and/orin the reaction (2), the ligand is preferably: L-13, L-15 or L-31; and/orin the reaction (3), the ligand is preferably: L-13, L-15 or L-35; and/orin the reaction (4), the ligand is preferably: L-92, and/or L-105; and/orin the reaction (5), the ligand is preferably L-13, L-112, L-114. The present invention relates to the field of organic synthesis. In particular, a copper-catalyzed coupling reaction of aryl halide catalyzed by a heterocyclic carboxylic acid amide ligand, especially a coupling reaction to form C—N, C—O, and C—S bonds is provided in the present invention. ...

Подробнее
21-05-2015 дата публикации

N-biphenylmethylbenzimidazole modulators of pparg

Номер: US20150141464A1

The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit cdk5 -mediated phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided.

Подробнее
18-05-2017 дата публикации

ANTIVIRAL DRUGS FOR TREATMENT OF ARENAVIRUS INFECTION

Номер: US20170137422A1
Принадлежит: Kineta Four, LLC

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain 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 the Arenavirus family such as Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, and Venezuelan hemorrhagic fever. 2. The compound of claim 1 , wherein each of E and J is N.3. The compound of claim 1 , wherein each of G claim 1 , M claim 1 , Q and L is C—R.4. The compound of claim 1 , wherein K is C.5. The compound of claim 1 , wherein D-A is RC═CRand each of Rand Rare H and the double bond in RC═CRhas a cis configuration.6. The compound of claim 1 , wherein D-A is O—CRRand each of Rand Rare H.7. The compound of claim 1 , wherein the compound is 1-(4-ethoxyphenyl)-5-[(4-ethylphenyl)-methoxy] benzimidazole.9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a compound of or a pharmaceutically acceptable salt thereof.10. The composition of claim 9 , wherein each of E and J is N.11. The composition of claim 9 , wherein each of G claim 9 , M claim 9 , Q and L is C—R.12. The composition of claim 9 , wherein K is C.13. The composition of claim 9 , wherein D-A is RC═CRand each of Rand Rare H and the double bond in RC═CRhas a cis configuration.14. The composition of claim 9 , wherein D-A is O—CRRand each of Rand Rare H.15. The composition of claim 9 , wherein the compound of Formula I is 1-(4-ethoxyphenyl)-5-[(4-ethylphenyl)-methoxy]benzimidazole.17. A method for the treatment or prophylaxis of a viral infection or disease associated therewith claim 1 , comprising administering in a therapeutically effective amount to a mammal in need thereof claim 1 , a compound of or a pharmaceutically acceptable salt thereof.1829-. (canceled)3134-. ...

Подробнее
18-05-2017 дата публикации

COMPOUNDS ACTING AT MULTIPLE PROSTAGLANDIN RECEPTORS GIVING A GENERAL ANTI-INFLAMMATORY RESPONSE

Номер: US20170137423A1
Принадлежит:

The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the following formula This application is a continuation of U.S. patent application Ser. No. 13/720,520, filed Dec. 19, 2012, which claims the benefit of U.S. Provisional Application Ser. No. 61/578,640, filed Dec. 21, 2011, the disclosures of which are hereby incorporated by reference in their entireties and serve as the basis of a priority and/or benefit claim for the present application.1. Field of the InventionThis invention relates to compounds, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine, in particular their use in the treatment of conditions mediated by the action of ligands for the DP, FP, TP, EPand EPprostaglandin (PG) receptors. The present compounds have the general structure shown below and act at different prostaglandin receptors to thereby provide a general anti-inflammatory response.2. Summary of the Related ArtThe EPreceptor is a 7-transmembrane receptor and its natural ligand is the prostaglandin PGE. PGEalso has affinity for the other EP receptors (types EP, EPand EP). The EPreceptor is associated with smooth muscle contraction, pain (in particular inflammatory, neuropathic and visceral), inflammation, allergic activities, renal regulation and gastric or enteric mucus secretion.Prostaglandin E(PGE) exerts allodynia through the EPreceptor subtype and hyperalgesia through EPand EPreceptors in the mouse spinal cord. Furthermore, it has been shown that in the EPknock-out mouse pain-sensitivity responses are reduced by approximately 50%. EPreceptor antagonist (ONO-8711) reduces hyperalgesia and allodynia in a rat model of chronic constriction injury and inhibits mechanical hyperalgesia in a rodent model of post-operative pain. The efficacy ...

Подробнее
07-08-2014 дата публикации

NOVEL HYDROGEN SULFATE SALT

Номер: US20140221443A1
Принадлежит:

The present invention relates to Compound 1 hydrogen sulfate salt and solvates, crystalline forms and amorphous forms thereof, and to processes for their preparation. 2. A hydrogen sulfate salt of Compound 1 according to in anhydrous form.3. A hydrogen sulfate salt of Compound 1 according to in the form of a solvate.4. A hydrogen sulfate salt of Compound 1 according to which is crystalline.5. A hydrogen sulfate salt of Compound 1 according to claim 4 , wherein said hydrogen sulfate salt of Compound 1 has an X-ray powder diffraction pattern with at least one specific peak at about 24.59°.6. A hydrogen sulfate salt of Compound 1 according to claim 5 , wherein said hydrogen sulfate salt of Compound 1 has an X-ray powder diffraction pattern with specific peaks at about 2-theta equal to 24.59° claim 5 , 20.97° claim 5 , 23.99° claim 5 , 27.65° claim 5 , 12.24° claim 5 , 23.49° claim 5 , 24.30° claim 5 , 17.02° claim 5 , 25.91° and 22.50°.7. A hydrogen sulfate salt of Compound 1 according to which has a powder X-ray diffraction pattern substantially the same as the X-ray powder diffraction pattern shown in .8. A hydrogen sulfate salt of Compound 1 according to in amorphous form.9. A method for preparing a hydrogen sulfate salt of Compound 1 according to claim 1 , said method comprising(i) reacting a slurry of Compound 1 in an organic liquid with at least a stoichiometric amount of sulfuric acid and water;(ii) recovering the salt from the resultant solution; and(iii) thereafter, if desired or necessary, forming a solvate thereof.10. The method according to wherein the amount of water added in step (i) is restricted to that amount necessary to ensure that the salt is formed.11. The method according to wherein step (i) is carried out at a temperature of from 40-80° C.12. The method according to claim 9 , wherein the organic liquid is a Calkyl ketone.13. The method according to claim 9 , wherein the hydrogen sulfate salt is recovered in step (ii) by cooling the reaction ...

Подробнее
28-05-2015 дата публикации

Method For Preparing Nitrogen Compounds

Номер: US20150148535A1

The present invention relates to a method for preparing nitrogen compounds using carbon dioxide, and to the use of the method in the production of vitamins, pharmaceutical products, adhesives, acrylic fibres, synthetic leathers, pesticides, herbicides, antifungal agents and fertilisers. The invention also relates to a method for producing vitamins, pharmaceutical products, adhesives, acrylic fibres, synthetic leathers, pesticides, herbicides, antifungal agents and fertilisers, which includes a step of preparing nitrogen compounds using the method of the invention. The invention further relates to a method for preparing labelled nitrogen compounds using carbon dioxide and to the uses thereof. 2. The process as claimed in claim 1 , wherein in the amine of formula (II) claim 1 , Rrepresents a hydrogen atom claim 1 , an alkyl group claim 1 , an aryl group claim 1 , a heteroaryl group claim 1 , a heterocycle or an amino group claim 1 , said alkyl claim 1 , amino claim 1 , aryl claim 1 , heterocycle and heteroaryl groups optionally being substituted.3. The process as claimed in claim 1 , wherein claim 1 , in the silane compound of formula (III) claim 1 , R claim 1 , Rand Rrepresent claim 1 , independently of one another claim 1 , a hydrogen atom claim 1 , an alkyl group claim 1 , an alkoxy group claim 1 , an aryl group claim 1 , a silyl group or a siloxy group claim 1 , said alkyl claim 1 , alkoxy claim 1 , silyl claim 1 , siloxy and aryl groups optionally being substituted.4. The process as claimed in claim 1 , wherein the nucleophilic agent E-H of formula (IV) claim 1 , E represents an RRN— group with{'sup': 5', '6, 'Rand Rrepresenting, independently of one another, a hydrogen atom, an alkyl group, an aryl group, a heteroaryl group, a heterocycle or an amino group, said alkyl, aryl, heteroaryl, heterocycle and amino groups optionally being substituted, or'}{'sup': 5', '6, 'Rand R, taken together with the nitrogen atom to which they are bonded, form an optionally ...

Подробнее
10-06-2021 дата публикации

Benzimidazole Derivatives as Modulators of Retinoid-Related Orphan Receptor Gamma (RORy) and Pharmaceutical Uses Thereof

Номер: US20210171471A1
Принадлежит:

The present invention relates to benzimidazole derivatives of formula (I) as inhibitors of retinoid-related orphan receptor gamma (RORγ) protein, pharmaceutical compositions containing the compounds, preparation methods thereof, and the use of the compounds as therapeutic agents for the treatment of RORγ-mediated diseases or disorders. 3. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is selected from the group consisting of phenyl claim 1 , Ccycloalkyl claim 1 , and or 6 member heteroaryl claim 1 , preferably piperidinyl claim 1 , phenyl claim 1 , thienyl claim 1 , furyl claim 1 , or pyridinyl.8. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rat each occurrence is independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , haloalkoxy claim 1 , cyano claim 1 , amino claim 1 , —OR claim 1 , and —NRR; and{'sub': 8', '11', '12, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R, Rand Rare as defined in .'}9. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare each independently selected from the group consisting of hydrogen claim 1 , halogen claim 1 , and alkyl.11. The compound of claim 1 , or a tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer claim 1 , or mixture thereof ...

Подробнее
24-05-2018 дата публикации

METHOD FOR PREPARING IMIDAZOLE DERIVATIVE AND INTERMEDIATE THEREOF AND CRYSTAL FORM

Номер: US20180141915A1

Disclosed are a method for preparing an imidazole derivative and crystal form A and crystal form B thereof, and also disclosed is a method for preparing a compound of formula (I) and an intermediate thereof. 4. The process according to claim 2 , wherein the acid is selected from the group consisting of trifluoroacetic acid claim 2 , acetic acid claim 2 , hydrochloric acid claim 2 , dilute sulfuric acid and p-toluenesulfonic acid.6. The process according to claim 5 , wherein the insert solvent is a single solvent or a mixed solvent for several solvents selected from the group consisting of ethyl acetate claim 5 , isopropyl acetate claim 5 , methyl tent-butyl ether claim 5 , cyclohexane and n-heptane.7. The process according to claim 6 , wherein the insert solvent is a mixed solvent of ethyl acetate and n-heptane.10. Crystal form A or Crystal form B of the compound of formula (I) claim 6 , the XRPD spectrogram is shown in and claim 6 , respectively.11. A process for preparing crystal form A according to claim 10 , comprising adding the compound of formula (I) to an organic solvent claim 10 , heating to 30° C. to the reflux temperature to dissolve claim 10 , and then cooling to 0 to 20° C. within 0.5 to 10 hours to precipitate the crystal.12. The process for preparing crystal form A according to claim 11 , wherein the organic solvent is selected from the group consisting of dichloroethane claim 11 , a Calkyl alcohol claim 11 , a Cether or cyclic ether claim 11 , a Cketone claim 11 , a Cester claim 11 , benzene optionally substituted by methyl or ethyl or halogen atom(s) claim 11 , wherein the number of the substituent(s) is selected from 1 claim 11 , 2 and/or 3.13. The process for preparing crystal form A according to claim 12 , the organic solvent is selected from the group consisting of dichloromethane claim 12 , methanol claim 12 , ethanol claim 12 , isopropanol claim 12 , tetrahydrofuran claim 12 , dioxane claim 12 , 2-methyltetrahydrofuran claim 12 , acetone claim ...

Подробнее
16-05-2019 дата публикации

NOVEL ONE-POT HOMOGENEOUS PROCESS FOR THE LARGE SCALE MANUFACTURE OF 2-SUBSTITUTED BENZIMIDAZOLES

Номер: US20190144395A1
Принадлежит: ECOLAB USA INC.

2-substituted benzimidazoles and methods of preparing the same are disclosed. The compositions may include a compound or salt thereof, an acid, and a polar aprotic solvent. The compositions may be used to inhibit corrosion of a metal surface in contact with an aqueous system, and provide enhanced protection against corrosion of metals in the aqueous system. 2. The composition of claim 1 , further comprising water.3. The composition of claim 1 , whereinX is independently hydrogen or halogen;{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'Ris absent; and'}{'sup': 3', '4, 'Ris CHR.'}4. The composition of claim 1 , wherein at least one Z is nitrogen.5. The composition of claim 1 , wherein Ris a bond and at least one Z is nitrogen.7. The composition of claim 1 , wherein the acid is selected from sulfuric acid claim 1 , hydrochloric acid claim 1 , nitric acid claim 1 , methanesulfonic acid claim 1 , phosphoric acid claim 1 , sulfamic acid claim 1 , aminomethylphosphonic acid claim 1 , p-toluenesulfonic acid claim 1 , and any combination thereof.8. The composition of claim 1 , wherein the polar aprotic solvent is selected from acetonitrile claim 1 , N claim 1 ,N-dimethylformamide claim 1 , acetone claim 1 , dimethylsulfoxide claim 1 , sulfolane claim 1 , N-methylpyrrolidinone claim 1 , methylsulfonylmethane claim 1 , chlorobenzene claim 1 , o-dichlorobenzene claim 1 , nitromethane claim 1 , an ionic liquid claim 1 , and any combination thereof.9. The composition of claim 1 , wherein the composition is homogenous liquid.10. The composition of claim 1 , further comprising a high temperature stable phase transfer catalyst.11. The composition of claim 10 , wherein the high temperature stable phase transfer catalyst is selected from the group consisting of an alkyl guanidinium salt claim 10 , an aryl guanidinium salt claim 10 , an alkyl phosphonium salt claim 10 , an aryl phosphonium salt claim 10 , a peralkylated phosphazenium salt claim 10 , and any combination thereof.13. The ...

Подробнее
09-06-2016 дата публикации

METHOD FOR PREPARATION OF BENZIMIDAZOLE DERIVATIVES

Номер: US20160159747A1
Принадлежит:

The present invention provides a method for preparing a compound with a benzimidazole structure with an excellent yield using a low-cost starting material, not requiring an additional separation process, or not using a dangerous reagent during the manufacturing process. Furthermore, the present invention also provides an intermediate and a final product produced by the preparing method. 5. The method of claim 1 , wherein Rand Rare independently methyl claim 1 , ethyl claim 1 , propyl or tert-butyl.6. The method of claim 1 , wherein Ris methyl claim 1 , trifluoromethyl or phenyl.7. The method of claim 1 , wherein step 1) is performed in the presence of a base selected from the group consisting of potassium tert-butoxide claim 1 , sodium ethoxide and sodium methoxide.8. The method of claim 1 , wherein step 1) is performed using a solvent selected from the group consisting of methanol claim 1 , ethanol claim 1 , acetonitrile and methylene chloride.9. The method of claim 1 , wherein step 2) is performed using acetonitrile as a solvent.11. The method of claim 10 , wherein Ris methyl claim 10 , ethyl claim 10 , propyl or tert-butyl.12. The method of claim 10 , wherein Ris methyl or ethyl.13. The method of claim 10 , wherein hydrochloric acid claim 10 , bromic acid or acetic acid is added in step a).14. The method of claim 10 , wherein acetyl chloride is added in step a).15. (canceled)16. The method of claim 10 , wherein step c) is performed in the presence of a base selected from the group consisting of potassium carbonate claim 10 , triethylamine claim 10 , sodium hydroxide and diisopropylethylamine.17. (canceled)18. (canceled)19. The method of claim 3 , wherein the reaction is performed using a solvent selected from the group consisting of methanol claim 3 , ethanol claim 3 , water and a mixed solution thereof.21. The compound of claim 20 , wherein Rand Rare independently methyl claim 20 , ethyl; propyl or tert-butyl.22. The compound of claim 20 , wherein Ris methyl ...

Подробнее
28-08-2014 дата публикации

SUBSTITUTED HYDOXAMIC ACIDS AND USES THEREOF

Номер: US20140243334A1
Принадлежит: Millennium Pharmaceuticals, Inc.

This invention provides compounds of formula (I): 2. The compound of claim 1 , wherein G is —R claim 1 , —V—R claim 1 , —V-L-R claim 1 , -L-V—R claim 1 , or -L-R.3. The compound of claim 2 , wherein:{'sup': 2a', '1, 'Ris R;'}{'sup': '2b', 'Ris G;'}{'sup': 2c', '1, 'Ris R; and'}{'sup': '2d', 'sub': '1', 'Ris R.'}4. The compound of claim 2 , wherein:{'sup': 2a', '1, 'Ris R;'}{'sup': 2b', '1, 'Ris R;'}{'sup': '2c', 'Ris G; and'}{'sup': 2d', '1, 'Ris R.'}5. The compound of claim 2 , wherein:{'sub': 1', '1, 'sup': 3', '3', '3, 'G is —V—R, -L-R, or —R;'}{'sub': 1', '2', '2', '2, 'Lis —CH— or —CHCH—; and'}{'sub': 1', '2, 'sup': 4a', '4a', '4a', '4a', '4a', '4a', '4a, 'Vis —N(R)—, —N(R)—C(O)—, —C(O)—N(R)—, —N(R)—SO—, —O—, —N(R)—C(O)—O—, or —N(R)—C(O)—N(R)—.'}6. The compound of claim 2 , wherein:{'sup': '1a', 'each occurrence of Ris independently hydrogen, fluoro, trifluoromethyl, or methyl;'}{'sup': '1b', 'each occurrence of Ris hydrogen;'}{'sup': '1c', 'Ris hydrogen, hydroxy, fluoro, trifluoromethyl, or methyl;'}{'sup': '1', 'each occurrence of Ris independently hydrogen, chloro, fluoro, cyano, hydroxy, methoxy, ethoxy, trifluoromethyl, methyl, or ethyl.'}7. The compound of claim 2 , wherein:{'sup': 3', '5dd, 'each substitutable carbon chain atom in Ris unsubstituted or substituted with 1-2 occurrences of R;'}{'sup': 3', '5', '5aa, 'sub': '2', 'each substitutable saturated ring carbon atom in Ris unsubstituted or substituted with ═O, ═C(R), or —R;'}{'sup': 3', '5a, 'each substitutable unsaturated ring carbon atom in Ris unsubstituted or is substituted with —R;'}{'sup': 3', '9b, 'claim-text': [{'sup': 5a', '5', '5', '5', '5', '6', '6', '6', '4', '4', '4', '6', '4', '4', '4', '6', '4', '6', '4', '4', '6', '4', '4', '5a, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '1-6, 'each Ris independently halogen, —NO, —CN, —C(R)═C(R), —C≡C—R, —OR, —SR, —S(O)R, —SOR, —SON(R), —N(R), —NRC(O)R, —NRC(O)N(R), —NRCOR, —OC(O)N(R), —C(O)R, —C(O)N(R), —N(R)SOR, —N(R) ...

Подробнее
16-06-2016 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20160168102A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 2. A process of claim 1 , wherein the solution comprises (i.) a solvent system comprising an ether and an alcohol claim 1 , and (ii.) water.312.-. (canceled)13. The process of claim 2 , wherein the alcohol is methanol claim 2 , ethanol or isopropanol.14. The process of claim 13 , wherein the alcohol is methanol.15. The process of claim 2 , wherein Compound A is dissolved in a solution comprising (i) a solvent system comprising tetrahydrofuran and methanol and (ii) water.16. The process of claim 2 , further comprising the step of heating the solution of step a) to an internal temperature of about 52-56° C. prior to addition of the seed crystal suspension.17. The process of claim 16 , further comprising the step of cooling the solution to 47-48° C. after heating to an internal temperature of about 52-56° C. and before the seed crystal is added.18. The process of claim 2 , wherein the water in step d) is added over a period of 10 to 25 hours.19. The process of claim 2 , wherein the treated mixture of step d) has a ratio of alcohol/ether/water in a range between 40/40/20 and 15/15/70 w/w/w.20. The process of claim 19 , wherein the treated mixture has a ratio of alcohol/ether/water of about 20/20/60 w/w/w.21. The process of claim 2 , wherein the treated mixture of step e) is cooled to an internal temperature of about 1-10° C.22. The process of claim 2 , further comprising the step of drying the crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.23. The process ...

Подробнее
16-06-2016 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20160168103A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 2. The crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide of claim 1 , further comprising the step of milling the crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.3. A pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide claim 1 , at least one sugar claim 1 , and at least one cellulose-derivative excipient.4. The pharmaceutical composition of claim 3 , wherein the at least one sugar is lactose monohydrate.5. The pharmaceutical composition of claim 3 , wherein the at least one cellulose-derivative excipient is microcrystalline cellulose claim 3 , microfine cellulose claim 3 , powdered cellulose claim 3 , methyl cellulose claim 3 , hydroxyethyl cellulose claim 3 , hydroxymethyl cellulose claim 3 , hydroxypropyl cellulose claim 3 , or hydroxypropylmethyl cellulose.6. The pharmaceutical composition of claim 3 , wherein at least one cellulose-derivative excipient is microcrystalline cellulose.7. The pharmaceutical composition of claim 3 , further comprising one or more of croscarmellose sodium claim 3 , magnesium stearate claim 3 , and silicon dioxide.8. The pharmaceutical composition of claim 3 , comprising 5-35 weight percent crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.9. The pharmaceutical ...

Подробнее
16-06-2016 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20160168104A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro -3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 1. (canceled)2. A method of treating a proliferative disease in a patient in need thereof , comprising administering to said mammal a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient.3. The method according to claim 2 , wherein the proliferative disease is cancer.4. The method according to claim 3 , wherein the cancer is selected from melanoma claim 3 , pancreatic cancer claim 3 , ovarian cancer claim 3 , carcinoma of the fallopian tubes claim 3 , peritoneal cancer claim 3 , biliary cancer claim 3 , colon cancer claim 3 , or rectal cancer.5. The method according to claim 4 , wherein the cancer is melanoma.6. The method according to claim 5 , wherein said melanoma is BRAFV600 or NRAS-mutant melanoma.7. The method according to claim 6 , wherein the pharmaceutical composition is formulated as a tablet.8. The method according to claim 7 , wherein the pharmaceutical composition comprises approximately 15 mg crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.9. The method according to claim 8 , wherein the pharmaceutical composition further comprises lactose monohydrate claim 8 , microcrystalline cellulose claim 8 , colloidal silicon dioxide claim 8 , croscarmellose sodium claim 8 , and magnesium stearate.10. The method according to claim 9 , wherein said melanoma is NRAS-mutant melanoma.11. The ...

Подробнее
04-09-2014 дата публикации

N-BENZYLBENZIMIDAZOLE MODULATORS OF PPARG

Номер: US20140249196A1
Принадлежит:

The invention provides molecular entities that bind with high affinity to PPARG (PPARγ), inhibit cdk5-mediated phosphorylation of PPARG, but do not exert an agonistic effect on PPARG. Compounds of the invention can be used for treatment of conditions in patients wherein PPARG plays a role, such as diabetes or obesity. Methods of preparation of the compounds, bioassay methods for evaluating compounds of the invention as non-agonistic PPARG binding compounds, and pharmaceutical compositions are also provided. 2. The compound of wherein Ris H or methyl.3. The compound of wherein Ris an unsubstituted or substituted benzyl claim 1 , α-phenethyl claim 1 , or α-phenpropyl.4. The compound of wherein Ris unsubstituted or substituted cycloalkyl or cycloalkylalkyl.5. The compound of wherein Ris unsubstituted or substituted naphthyl or naphthylalkyl.6. The compound of wherein Ris unsubstituted or substituted heterocyclyl claim 1 , heterocyclylalkyl claim 1 , heteroaryl claim 1 , or heteroarylalkyl.8. The compound of wherein YRRis SO.9. The compound of wherein Y is C-alkyl; and Rand Rare H; or wherein Y is C-alkyl claim 1 , and Rand Rare H.11. The compound of wherein n is 1 and Ris disposed para to Y.14. A pharmaceutical composition claim 1 , comprising a compound of ; and a pharmaceutically acceptable excipient.15. A method of inhibiting cdk5-mediated phosphorylation of PPARG in a mammal claim 1 , comprising administering to the mammal an effective amount of a compound of .16. The method of wherein the effective amount of the compound for inhibiting cdk5-mediated phosphorylation of PPARG does not produce an agonistic effect on PPARG.17. A method of treating a condition in a mammal claim 1 , wherein binding of a ligand to PPARG or inhibition of cdk5-mediated phosphorylation of PPARG claim 1 , or both claim 1 , is medically indicated claim 1 , comprising administering to the mammal an effective amount of a compound of at a frequency of dosing and for a duration of dosing ...

Подробнее
06-06-2019 дата публикации

Methods of Forming Carbene-Functionalized Composite Materials

Номер: US20190169132A1
Принадлежит:

Deposition of carbene monolayers that excluded starting anions, such as iodide ions, has been achieved. Anions such as iodide are a typical contaminant in carbene hydrogen carbonate salts when synthesized using the state-of-the-art method. A method is described for eliminating substantially all starting anion (e.g., iodide) contamination from the monolayer. Air stable, purified carbenes precursors were used to deposit an intact monolayer on the surface of some industrially relevant metals. The monolayer's ability to protect these metals against, for example, oxidation has been demonstrated. 1. A method for forming a carbene-functionalized composite material , comprising:forming a carbene precursor by{'sub': '2', 'claim-text': forming a purified carbene precursor comprising a final hydrogen carbonate anion that is substantially free of the starting anion;', 'placing a material having at least a metal surface in fluid communication with the purified carbene precursor, thermally decomposing the purified precursor in the presence of a material having at least a metal surface, or vacuum depositing the purified carbene precursor in the presence of a material having at least a metal surface; and', 'forming a carbene monolayer on the metal surface, the monolayer being uniform, stable, substantially free of contamination, and substantially free of the starting anion., 'oxidizing a starting anion of a carbene precursor in the presence of water and CO, or exchanging a starting anion of a carbene salt via a hydrogen carbonate-anion exchange resin, and'}2. The method of claim 1 , wherein the purified carbene precursor comprises ≤10% of the starting anion; or claim 1 , ≤5%; or claim 1 , ≤2%; or claim 1 , ≤1%; or claim 1 , ≤1.5%; or claim 1 , ≤0.1%.35.-. (canceled)7. The method of claim 6 , wherein for{'sup': o', 'q', '1', '2', '7', '8, 'claim-text': {'sup': 2', '3', '5', '6', '11', '12', '3', '4', '9', '10, 'Formula (IIa) or Formula (Va): m is 1; each Y is N; Yand Yare C; Rand ...

Подробнее
04-06-2020 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20200171002A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 1. (canceled) This application is a continuation of U.S. application Ser. No. 15/842,715, filed Dec. 14, 2017, which is a continuation of U.S. application Ser. No. 15/445,393, filed Feb. 28, 2017, which continuation of U.S. application Ser. No. 15/053,441, filed Feb. 25, 2016, which is a continuation of U.S. application Ser. No. 14/974,655, filed Dec. 18, 2015, which is a divisional application of U.S. application Ser. No. 14/057,498, filed Oct. 18, 2013, which claims priority to U.S. Provisional Application No. 61/716,169, filed Oct. 19, 2012, which are incorporated herein by reference in their entirety.Provided herein are processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound.Growth factor-mediated proliferative signals are transmitted from the extracellular environment to the nucleus through several pathways, including the RAS/RAF/MEK pathway. The RAS/RAF/MEK kinase signal transduction pathway is activated through initial extracellular binding and stimulation of tyrosine receptor kinases (RTKs) by their respective cognate ligands. Upon autophosphorylation of specific tyrosine residues in the cytosolic domain of RTKs, the Grb2-Sos complex translocates to the plasma membrane, ...

Подробнее
04-06-2020 дата публикации

MODULATORS OF RESISTANT ANDROGEN RECEPTOR

Номер: US20200172504A1
Принадлежит:

The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same. 113-. (canceled)15. The method of claim 14 , wherein Z is Ring B.16. The method of claim 15 , wherein Ring B is an optionally substituted cyclohexyl ring.17. The method of claim 16 , wherein X is CH.19. The method of claim 14 , wherein the secondary agent is a second AR modulator claim 14 , an anti-cancer agent claim 14 , a cytotoxin claim 14 , a chemotherapeutic agent claim 14 , a radiotherapeutic agent claim 14 , a palliative agent claim 14 , a pain reliever claim 14 , an anti-emetic agent claim 14 , an anti-nausea agent claim 14 , or an anti-inflammatory agent.20. The method of claim 19 , wherein the secondary agent is a second AR modulator.21. The method of claim 19 , wherein the second AR modulator is selected from the group consisting of non-steroidal antiandrogens claim 19 , aminoglutethimide claim 19 , enzalutamide claim 19 , bicalutamide claim 19 , nilutamide claim 19 , flutamide claim 19 , steroidal antiandrogens claim 19 , finasteride claim 19 , dutasteride claim 19 , bexlosteride claim 19 , izonsteride claim 19 , turosteride claim 19 , epristeride claim 19 , inhibitors of 5-alpha-reductase claim 19 , 3 claim 19 ,3′-diindolylmethane (DIM) claim 19 , and N-butylbenzene-sulfonamide (NBBS).22. The method of claim 14 , wherein the secondary agent is an anti-cancer agent.24. The conjugate of claim 23 , wherein Z is Ring B.25. The conjugate of claim 24 , wherein Ring B is an optionally substituted cyclohexyl ring.26. The conjugate of claim 25 , wherein X is CH.28. The conjugate of claim 23 , wherein the multifunctional agent is an anti-cancer agent claim 23 , an antiemetic claim 23 , a photosensitizer claim 23 , a radiosensitizer claim 23 , or a detection entity.29. The conjugate of claim 28 , wherein the multifunctional agent is an anti-cancer agent.30. The conjugate of claim 29 , ...

Подробнее
11-06-2020 дата публикации

PHARMACEUTICAL COMPOSITION

Номер: US20200179344A1
Принадлежит:

The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament; and to processes for the preparation of said compositions. 120-. (canceled)21. A pharmaceutical composition comprising a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide , and a carrier matrix , wherein the carrier matrix comprises a polyglycolised glyceride; and wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix.22. The pharmaceutical composition of claim 21 , wherein the polyglycolised glyceride comprises stearoyl macrogolglycerides.23. The pharmaceutical composition of claim 22 , wherein the composition comprises approximately 5% to approximately 30% by weight of the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide.24. A pharmaceutical composition comprising a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide claim 22 , and a carrier matrix claim 22 , wherein the carrier matrix comprises d-alpha-tocopheryl polyethylene glycol 1000 succinate; and wherein the hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide is dispersed within the carrier matrix.25. The pharmaceutical composition according to claim 24 , wherein the d-alpha-tocopheryl polyethylene glycol 1000 succinate is present in an amount of approximately 65% to approximately 95% by weight of the composition.26. The ...

Подробнее
22-07-2021 дата публикации

COMPOUNDS ACTING AT MULTIPLE PROSTAGLANDIN RECEPTORS GIVING A GENERAL ANTI-INFLAMMATORY RESPONSE

Номер: US20210221810A1
Принадлежит:

The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the following formula 27. The compound according to claim , wherein the compound is:2-(5-Chloro-2-Isobutoxy-Benzyl)-2H-Indazole-5-Carboxylic Acid;2-(5-Bromo-2-Isobutoxy-Benzyl)-2H-Indazole-5-Carboxylic Acid;2-(5-Chloro-2-Cyclopropylmethoxy-Benzyl)-2H-Indazole-4-Carboxylic Acid;2-(5-Chloro-2-Isobutoxy-Benzyl)-2H-Indazole-4-Carboxylic Acid;2-[5-Chloro-2-(2-Ethyl-Butoxy)-Benzyl]-2H-Indazole-4-Carboxylic Acid;2-[5-Chloro-2-(4-Chloro-Benzyloxy)-Benzyl]-2H-Indazole-4-Carboxylic Acid;2-(5-Bromo-2-Isobutoxy-Benzyl)-2H-Indazole-6-Carboxylic Acid;2-(5-Bromo-2-Cyclopentylmethoxy-Benzyl)-2H-Indazole-6-Carboxylic Acid;or a pharmaceutically acceptable salt thereof.3. A compound selected from the group consisting of:1-(3-Isobutoxy-6-Methyl-Pyridin-2-Ylmethyl)-1H-Indazole-5-Carboxylic Acid;1-(5-Bromo-2-Isobutoxy-Benzyl)-1H-Pyrrolo[3,2-B]Pyridine-5-Carboxylic Acid;or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. patent application Ser. No. 16/539,835, filed Aug. 13, 2019, which is a continuation of U.S. patent application Ser. No. 15/406,295, filed Jan. 13, 2017, now U.S. Pat. No. 10,392,382, issued Aug. 27, 2019, which is a continuation of U.S. patent application Ser. No. 13/720,520, filed Dec. 19, 2012, now U.S. Pat. No. 9,567,328, issued Feb. 14, 2017, which claims the benefit of U.S. Provisional Application Serial No. 61,578,640, filed Dec. 21, 2011, the disclosures of which are hereby incorporated by reference in their entireties and serve as the basis of a priority and/or benefit claim for the present application.This invention relates to compounds, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine, in particular their use in the ...

Подробнее
25-09-2014 дата публикации

NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE 1

Номер: US20140288119A1
Принадлежит:

This invention provides a compound having the structure: 2. (canceled)4. (canceled)6. (canceled)1112-. (canceled)1821-. (canceled)23. (canceled)27. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.28. A method of inhibiting the activity of a histone deactylase in a cell comprising contacting the histone deacetylase with the compound of so as to inhibit the activity of the histone deacetylase.29. (canceled)30. A method of inhibiting the activity of a histone deacetylase 6 (HDAC6) in a cell comprising contacting the histone deacetylase 6 with the compound of so as to inhibit the activity of the histone deacetylase 6 in the cell.31. A method of increasing accumulation of acetylated alpha tubulin in a cell comprising contacting the cell with the compound of so as to increase the accumulation of acetylated alpha-tubulin in the cell.32. A method of treating a neurodegenerative disease in a subject comprising administering an effective amount of the compound of to the subject so as to treat the neurodegenerative disease in the subject.33. (canceled)34. A method of treating a disease associated with defective lipid transport in a subject comprising administering an effective amount of the compound of to the subject so as to treat the disease in the subject.35. (canceled) This application claims priority of U.S. Provisional Application Nos. 61/620,783, filed Apr. 5, 2012 and 61/542,598, filed Oct. 3, 2011, the contents of each of which are hereby incorporated by reference.Throughout this application, certain publications are referenced in parentheses. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention relates.To date, eighteen histone deacetylases (HDACs) have been identified in humans. Eleven HDACs ( ...

Подробнее
26-07-2018 дата публикации

2-ARYL- AND 2-ARYLALKYL-BENZIMIDAZOLES AS MIDH1 INHIBITORS

Номер: US20180207137A1
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The present invention relates to 2-Aryl- and 2-Arylalkyl-benzimidazoles of general formula (I): in which A, R, R, R, R, R, R, R, Rand Rare as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients. 2. The compound according to claim 1 , wherein:{'sub': 2', '2', '2, 'claim-text': and', {'sup': '5', 'Rrepresents a group selected from, {'sup': 12', '12', '12, 'sub': 1', '6', '1', '6', '2', '6', '2', '6, '—C(O)OH, —C(═O)OR, HOC(═O)—(C-C-alkyl)-, ROC(═O)—(C-C-alkyl)-, HOC(═O)—(C-C-alkenyl)-, ROC(═O)—(C-C-alkenyl)-,'}, {'sub': 1', '6', '1', '6, 'sup': '12', 'HOC(═O)—(C-C-alkoxy)-, ROC(═O)—(C-C-alkoxy)- and cyano;'}], 'A represents a bond or a —CH— or a —(CH)— group,'}or{'sub': 3', '3', '2, 'claim-text': and', {'sup': '5', 'Rrepresents a group selected from, {'sub': 1', '6', '1', '6', '2', '6', '2', '6', '1', '6', '1', '6, 'sup': 12', '12', '12, '—C(═O)OH, HOC(═O)—(C-C-alkyl)-, ROC(═O)—(C-C-alkyl)-, HOC(═O)—(C-C-alkenyl)-, ROC(═O)—(C-C-alkenyl)-, HOC(═O)—(C-C-alkoxy)-, ROC(═O)—(C-C-alkoxy)- and cyano;'}], 'A represents a —CH(CH)— or a —C(CH)— group,'}{'sup': '1', 'claim-text': [{'sub': 1', '6', '3', '6', '1', '6', '3', '6', '1', '6', '1', '6, 'which phenyl group is optionally substituted with one, two or three substituents, which are, independently of each other, a halogen atom or a group selected from: C-C-alkyl, C-C-cycloalkyl, C-C-alkoxy, C-C-cycloalkyloxy, C-C-haloalkyl, C-C-haloalkoxy and cyano;'}, 'and', {'sub': 1', '3, 'which heteroaryl group is optionally substituted with one, two or three substituents, which are, independently of each other, a halogen atom or a group selected from: C-C-alkyl and phenyl;'}]}, ' ...

Подробнее
04-08-2016 дата публикации

A PROCESS FOR THE PREPARATION OF INTERMEDIATE FOR THE PREPARATION OF OSELTAMIVIR PHOSPHATE

Номер: US20160222029A1

The present invention discloses an economic, simple, azide and aziridine complexity free process for the synthesis of osletamivir phosphate (Tamiflu) by stereospecific amidoalkylation of imidazothiazolone from easily available L-cysteine via Ramberg-Backlund reaction and Sharpless-Reich protocol. 2. The process as claimed in claim 1 , wherein refluxing in step b) is carried for 6 to 7 hrs.3. The process as claimed in claim 1 , wherein stirring in step c) is carried for 4 to 5 hrs. The present invention relates to an economic, simple, azide and aziridine complexity free process for the synthesis of osletamivir phosphate (Tamiflu). Particularly, the present invention relates to process for the synthesis of osletamivir phosphate (Tamiflu) by stereospecific amidoalkylation of imidazothiazolone from easily available L-cysteine via Ramberg-Backlund reaction and Sharpless-Reich protocol.Influenza, commonly referred to as flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses). Influenza spreads around the world in seasonal epidemics, resulting in the deaths of between 200,000 and 500,000 to people every year, up to millions in some pandemic years. The development of effective antiviral medicines is hampered by the exceptionally high mutation rates of influenza virus. Therefore, in order to be successful, new drugs should target the molecular mechanisms specific to the proliferation of the virus.H5N1 and H1N1 strains of virus have shown pandemic disease threat worldwide and has been the cause of death of thousands of people till date by viral flu. These viruses actually cut surface protein of infected host cell and allow spreading to other cell. Oseltamivir phosphate (1, Tamiflu, Ro 64-0796, GS4104) and Zanamivir (2, Relenza, GG 167) are currently used as neuraminidase inhibitor drugs. Oseltamivir phosphate is recommended as the best choice due to its oral active form and bioavailability (). The anti-influenza drug 1 was ...

Подробнее
11-07-2019 дата публикации

DIARYLHYDANTOIN COMPOUNDS

Номер: US20190210974A1

The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer. 151.-. (canceled) This application is a continuation of U.S. application Ser. No. 15/655,458, filed Jul. 20, 2017, which is a continuation of U.S. application Ser. No. 14/496,973, filed Sep. 25, 2014, which is a continuation of U.S. application Ser. No. 14/137,991, filed Dec. 20, 2013, which is a continuation of U.S. application Ser. No. 13/448,964, filed Apr. 17, 2012, which is a continuation of U.S. application Ser. No. 12/708,523, filed Feb. 18, 2010, which is a divisional of U.S. application Ser. No. 11/433,829, filed May 15, 2006, which claims the benefit of U.S. Provisional Application No. 60/786,837, filed Mar. 29, 2006, U.S. Provisional Application No. 60/756,552, filed Jan. 6, 2006, U.S. Provisional Application No. 60/750,351, filed Dec. 15, 2005, and U.S. Provisional Application No. 60/680,835, filed May 13, 2005, the specifications of which are hereby incorporated by reference in their entirety.This invention was made with Government support under Grant No. W81XWH-04-1-0129 awarded by the United States Army, Medical Research and Materiel Command and under Grant No. CA092131 awarded by the National Institutes of Health. The Government has certain rights in the invention.The present invention relates to diarylhydantoin compounds including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.Prostate cancer is the most common incidence of cancer and the second leading cause of cancer death in Western men. When the cancer is confined locally, the disease can be cured by surgery or radiation. However, 30% of such cancer relapses with distant metastatic disease and others have advanced disease at diagnoses. Advanced disease is treated by castration and/or administration of antiandrogens, the so- ...

Подробнее
23-10-2014 дата публикации

ANDROGEN RECEPTOR ANTAGONISTS AND USES THEREOF

Номер: US20140315957A1
Автор: Tong Youzhi
Принадлежит:

The present invention relates to novel substituted thioimidazolidinone compounds and pharmaceutical compositions comprising such compounds for treatment of androgen receptor-associated diseases or disorders, such as prostate cancer, benign prostatic hypertrophy, male hair loss, muscle loss, acne and hirsutism. 2. The compound of wherein Ris an aryl group substituted with one or more C-Calkyl claim 1 , C(O)NHR″ claim 1 , SOR″ claim 1 , SONHR″ claim 1 , cyano claim 1 , hydroxyl claim 1 , alkoxy claim 1 , C(S)NHR″ claim 1 , C(O)OR″ claim 1 , CH(CH)Q claim 1 , halogen or a 5-6 membered heteroaryl group claim 1 , where R″ is selected from hydrogen claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl and C-Calkenyl; m is an integer selected from 0 to 6; and Q is selected from C(O)NHR″ claim 1 , SOR″ claim 1 , SONHR″ claim 1 , cyano claim 1 , hydroxyl claim 1 , alkoxy claim 1 , C(S)NHR″ and C(O)OR″.3. The compound of wherein Ris a heteroaryl group substituted with one or more C-Calkyl claim 1 , C(O)NHR″ claim 1 , SONHR″ claim 1 , cyano claim 1 , C(S)NHR″ claim 1 , C(O)OR″ claim 1 , hydroxyl claim 1 , alkoxy claim 1 , CH(CH)Q claim 1 , halogen or a 5-6 membered heteroaryl group claim 1 , where R″ is selected from hydrogen claim 1 , C-Calkyl claim 1 , C-Ccycloalkyl and C-Calkenyl; m is an integer selected from 0 to 6; and Q is selected from C(O)NHR″ claim 1 , SOR″ claim 1 , SONHR″ claim 1 , cyano claim 1 , hydroxyl claim 1 , alkoxy claim 1 , C(S)NHR″ and C(O)OR″.4. The compound of wherein Rand Rare independently selected from methyl claim 1 , ethyl claim 1 , or methyl optionally substituted with one or more fluoro groups.5. The compound of wherein Rand Rand the carbon to which they are attached together form a cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl or cyclohexyl ring which may be optionally substituted with one or more fluoro or hydroxyl groups.8. The compound of wherein Ris an aryl group substituted with one or more C-Calkyl claim 7 , C(O)NHR″ claim 7 , SOR″ claim 7 , ...

Подробнее
18-07-2019 дата публикации

CRYSTAL FORM A OF 1-ISOBUTYRYL-1'-((1-(4,4,4-TRIFLUOROBUTYL)-4,5,6,7-TETRAHYDRO-1H-BENZO[D]IMIDAZOL-2-YL)METHYL)SPIRO[AZETIDINE-3,3'-INDOLIN]-2'-ONE

Номер: US20190218189A1

Disclosed are a method for preparing an imidazole derivative and crystal form A and crystal form B thereof, and also disclosed is a method for preparing a compound of formula (I) and an intermediate thereof. 3. A process for preparing the crystal form B according to claim 1 , wherein the process comprises the following steps:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(1) admixing the compound of formula (I) according to with a polar organic solvent to form a mixture, and'}(2) then slowly dropping water to the mixture formed in step (1) to precipitate the crystal.4. The process according to claim 3 , wherein the polar organic solvent is selected from the group consisting of a Calkyl alcohol claim 3 , a Calkyl ether or a Ccyclic ether and a Cketone.5. The process according to claim 4 , wherein the polar organic solvent is selected from the group consisting of methanol claim 4 , ethanol claim 4 , isopropanol claim 4 , tetrahydrofuran claim 4 , 2-methyltetrahydrofuran claim 4 , dioxane and acetone.6. A method for inhibiting respiratory syncytial virus activity in a subject claim 1 , comprising administering to the subject in need thereof a therapeutically effective amount of the crystal form B according to .7. The method according to claim 6 , wherein the subject has respiratory virus infection.8. A pharmaceutical composition comprising a therapeutically effective amount of the crystal form B according to as an active ingredient and a pharmaceutically acceptable carrier.9. A method for inhibiting respiratory syncytial virus activity in a subject claim 8 , comprising administering to the subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to .10. The method according to claim 9 , wherein the subject has respiratory virus infection. The present application is a Divisional of U.S. application Ser. No. 15/580,167, filed Dec. 6, 2017, which is a 371 National Stage application of PCT/CN2016/085104, filed Jun. 7, 2016, ...

Подробнее
16-07-2020 дата публикации

PROCESS FOR PREPARING 1-ISOBUTYRYL-1'-((1-(4,4,4-TRIFLUORO-BUTYL)-4,5,6,7- TETRAHYDRO-1H-BENZO[D]IMIDAZOL-2-YL)METHYL)SPIRO[AZETIDINE-3,3'-INDOLIN]-2'-ONE

Номер: US20200223802A1

Disclosed are a method for preparing an imidazole derivative and crystal form A and crystal form B thereof, and also disclosed is a method for preparing a compound of formula (I) and an intermediate thereof. 4. The process according to claim 2 , wherein the acid is selected from the group consisting of trifluoroacetic acid claim 2 , acetic acid claim 2 , hydrochloric acid claim 2 , dilute sulfuric acid and p-toluenesulfonic acid.7. The process according to claim 5 , wherein the insert solvent is a single solvent or a mixed solvent for several solvents selected from the group consisting of ethyl acetate claim 5 , isopropyl acetate claim 5 , methyl tert-butyl ether claim 5 , cyclohexane and n-heptane.8. The process according to claim 7 , wherein the insert solvent is a mixed solvent of ethyl acetate and n-heptane. The present application is a Continuation of U.S. application Ser. No. 16/242,753, filed Jan. 8, 2019, which is a Divisional of U.S. application Ser. No. 15/580,167, filed Dec. 6, 2017, which is a 371 National Stage application of PCT/CN2016/085104, filed Jun. 7, 2016, which claims priority from Chinese Application No. 201510309106.4, filed Jun. 8, 2015, the entire contents of which is hereby incorporated by reference.The present invention relates to a method for preparing an imidazole derivative, crystal form A, crystal form B, and the corresponding preparation process thereof, the present invention also relates to a method for preparing an intermediate of the compound of formula (I).Respiratory syncytial virus (RSV) is the main cause of severe lower respiratory tract infection in infants, children, the elderly and those with impaired immunity. Severe viral infections can cause bronchiolitis or pneumonia that require hospitalization or cause death (JAMA, 1997, 277, 12). Recently, Ribavirin has been approved for the treatment of the virus infection. Ribavirin is a nucleoside analog that is administered intranasally in the form of an aerosol. And the toxicity ...

Подробнее
03-09-2015 дата публикации

ENOYL REDUCTASE INHIBITORS WITH ANTIBACTERIAL ACTIVITY

Номер: US20150246888A1
Принадлежит:

Disclosed are compounds and compositions useful as antibacterials. In particular, disclosed are enoyl reductase (FabI) inhibitors, compositions comprising such compounds, processes for producing such compounds, and methods of using such compounds. 2. The compound of claim 1 , wherein{'sup': 1', '1, 'Xis CR;'}{'sup': 2', '2, 'Xis CR;'}{'sup': 3', '3, 'Xis CR;'}{'sup': 4', '4, 'Xis CR;'}{'sup': 5', '5, 'Xis CR;'}{'sup': 8', '8, 'Xis CR;'}{'sup': 9', '9, 'Xis CR;'}{'sup': 10', '10, 'Xis CR;'}{'sup': 11', '11, 'Xis CR; and'}{'sup': 12', '12, 'Xis CR.'}3. The compound of claim 1 , wherein{'sup': '8', 'Ris —H; and'}R11 is —H.4. The compound of claim 1 , wherein{'sup': '1', 'Ris —H; and'}{'sup': '5', 'Ris —H.'}5. The compound of claim 1 , wherein{'sup': '12', 'Ris —H.'}6. The compound of claim 1 , wherein{'sup': '6', 'Ris —H; and'}{'sup': '7', 'Ris —H.'}7. The compound of claim 1 , wherein{'sup': '6', 'Ris —H; and'}{'sup': '7', 'Ris methyl.'}8. The compound of claim 1 , wherein{'sup': '4', 'Ris hydrogen.'}9. The compound of claim 1 , wherein{'sup': 2', '3, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '6', '2', '6', '3', '6, 'Rand Rare each independently selected from the group consisting of halo, C-C-alkyl, halo-C-C-alkyl, hydroxy-C-C-alkyl, amino-C-C-alkyl, C-C-alkylamino-C-C-alkyl, di(C-C-alkyl)amino-C-C-alkyl, C-C-alkoxy-C-C-alkyl, C-C-alkoxy, halo-C-C-alkoxy, hydroxy-C-C-alkoxy, C-C-alkoxy-C-C-alkoxy, C-C-alkylcarbonyl, C-C-alkoxycarbonyl, C-C-alkylcarbonyloxy, C-C-alkyl-S—, C-C-alkyl-NHSO—, C-C-alkyl-SONH—, C-C-alkyl-SO—, C-C-alkylamino, di(C-C-alkyl)amino, C-C-alkenyl, C-C-alkynyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aryl, or ...

Подробнее
31-08-2017 дата публикации

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

Номер: US20170247321A1
Принадлежит: Roche Palo Alto LLC

The application discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt.3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This application is a Continuation of U.S. application Ser. No. 14/531,465 filed Nov. 3, 2014 which is a Continuation U.S. application Ser. No. 13/314,525 filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459 filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706 filed Dec. 21, 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030 filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of central nerve system disorders. In particular, 5-HT2-selective and 5-HT6 selective ligands have ...

Подробнее
17-09-2015 дата публикации

INHIBITORS OF BETA-SECRETASE

Номер: US20150259325A1
Принадлежит: Vitae Pharmaceuticals, Inc.

The present invention relates to spirocyclic indane imidazole 4-amines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates. 4. The compound of claim 1 , wherein:{'sup': 3', '4', '3', '4', '7, 'sub': 1-4', '1-4, 'Rand Rare each independently —H or Calkyl, with the proviso that Rand Rcannot both be —H; and Ris —H or Calkyl.'}5. The compound of claim 4 , wherein:{'sup': 3', '4', '3', '4', '7, 'Rand Rare each independently H, methyl or ethyl, with the proviso that Rand Rcannot both be —H; and Ris —H or methyl.'}6. The compound of claim 5 , wherein:{'sup': '2', 'sub': 1-6', '2-6', '2-6, 'Ris —CN, halo, phenyl or a 6 membered heteroaryl, which two latter groups are optionally substituted with one or more groups selected from halo, —CN, Calkyl, Calkenyl and Calkynyl; or —NHC(O)-(6 membered heteroaryl) optionally substituted with one or more halo groups.'}7. The compound of claim 6 , wherein:{'sup': '2', 'sub': 1-6', '2-6', '2-6, 'Ris —CN, halo, phenyl or pyridyl which latter two groups are optionally substituted with one or more groups selected from halo, —CN, Calkyl, Calkenyl or Calkynyl; or —NHC(O)-pyridyl optionally substituted with one or more halo groups.'}8. The compound of claim 7 , wherein:{'sup': '2', 'sub': '2-', 'Ris —CN, halo or pyridinyl, the latter group of which is optionally substituted with halo or Calkynyl; or —NHC(O)-pyridyl optionally substituted with halo.'}9. The compound of claim 8 , wherein Ris —CN or halo.12. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.13. A method of treating a BACE1 mediated disease or disorder in a subject ...

Подробнее
08-09-2016 дата публикации

MODULATORS OF RESISTANT ANDROGEN RECEPTOR

Номер: US20160257666A1
Принадлежит:

The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same. 26-. (canceled)8. The method of claim 7 , wherein the cancer is a castration-resistant prostate cancer.9. The method of claim 8 , wherein the castration-resistant prostate cancer bears one or more mutations in the androgen receptor.10. The method of claim 9 , wherein the one or more mutations in the androgen receptor comprises a mutation of Phe876.11. The method of claim 10 , wherein the mutation is Phe876 to Leu claim 10 , Ile claim 10 , Val claim 10 , Ser claim 10 , Cys claim 10 , or Tyr.12. The method of claim 10 , wherein the mutations further comprise one or more mutations to residues selected from the group consisting of E566 claim 10 , E589 claim 10 , E669 claim 10 , C687 claim 10 , A700 claim 10 , N772 claim 10 , H777 claim 10 , C785 claim 10 , F877 claim 10 , and K911.13. The method of claim 8 , wherein the castration-resistant prostate cancer is resistant to Enzalutamide. The present application claims priority to U.S. provisional application Ser. No. 61/719,117, filed Oct. 26, 2012, the entirety of which is incorporated herein by reference.Prostate cancer is the ninth-most-common cancer in the world, but is the number-one non-skin cancer in men from the United States. As of 2011, prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males worldwide. In 2008, there were 186,000 new diagnoses and 28,600 deaths attributable to prostate cancer. In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years. The continuing and highly prevalent problem of prostate cancer highlights the overwhelming need for new drugs to treat this condition and its underlying causes.It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are ...

Подробнее
08-08-2019 дата публикации

Hydroxide-Catalyzed Formation Of Silicon-Oxygen Bonds By Dehydrogenative Coupling Of Hydrosilanes And Alcohols

Номер: US20190241587A1
Принадлежит:

The present disclosure is directed to methods for dehydrogenatively coupled hydrosilanes and alcohols, the methods comprising contacting an organic substrate having at least one organic alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide, the contacting resulting in the formation of a dehydrogenatively coupled silyl ether. The disclosure further described associated compositions and methods of using the formed products. 1. A composition comprising (a) at least one hydrosilane; (b) sodium and/or potassium hydroxide; (c) an organic substrate having at least one organic alcohol moiety; and optionally (d) an aprotic polar solvent and/or (e) a silyl ether derived or derivable from the dehydrogenative coupling of the at least one hydrosilane and the at least one alcohol moiety , the composition being substantially devoid of crown ether , transition metal ions or complexes , alkoxides , hydrides , alkyl lithium reagents , or fluoride ion.2. The composition of claim 1 , further comprising the silyl ether derived or derivable from the dehydrogenative coupling of the at least one hydrosilane and the at least one alcohol moiety.3. The composition of claim 1 , wherein the aprotic polar solvent is present as an aprotic oxygen donor solvent claim 1 , the composition containing less than 500 ppm water.4. The composition of claim 1 , wherein the aprotic polar solvent is present and comprises acetonitrile claim 1 , dimethylacetamide claim 1 , dimethyl formamide claim 1 , dimethylsulfoxide claim 1 , dimethoxyethane (DME) claim 1 , an optionally substituted dioxane claim 1 , a dialkyl dialkyl ether claim 1 , hexamethylphosphoramide (HMPA) claim 1 , and optionally substituted THF claim 1 , furans claim 1 , or N-methylpyrrolidone (NMP).5. The composition of claim 1 , wherein the hydrosilane has a structure of Formula (I) or of Formula (II):{'br': None, 'sub': 3−m', 'm+1, '(R)Si(H)\u2003\u2003(I)'}{'br': None, 'sub': 2−m', 'm+1', '3−m', 'm, '(R ...

Подробнее
20-11-2014 дата публикации

DIARYLTHIOHYDANTOIN COMPOUNDS

Номер: US20140343111A1

The present invention relates to diarylthiohydantoin compounds and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer. 2. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier or diluent.39-. (canceled)10. A method for treating a hyperproliferative disorder comprising administering a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof to a subject in need of such treatment claim 1 , thereby treating the hyperproliferative disorder.11. The pharmaceutically acceptable composition of claim 2 , wherein the composition has a form selected from the group consisting of a solution claim 2 , dispersion claim 2 , suspension claim 2 , powder claim 2 , capsule claim 2 , tablet claim 2 , pill claim 2 , time release capsule claim 2 , time release tablet claim 2 , and time release pill.12. The method of claim 10 , wherein the compound is administered by intravenous injection claim 10 , by injection into tissue claim 10 , intraperitoneally claim 10 , orally claim 10 , or nasally.13. The method of claim 10 , wherein the compound is administered at a dosage of the compound in the range of from about 0.001 mg per kg body weight per day to about 100 mg per kg body weight per day.14. The method of claim 10 , wherein the compound is administered at a dosage of the compound in the range of from about 0.01 mg per kg body weight per day to about 100 mg per kg body weight per day.15. The method of claim 10 , wherein the compound is administered at a dosage of the compound in the range of from about 0.1 mg per kg body weight per day to about 10 mg per kg body weight per day.16. The method of claim 10 , wherein the compound is administered at a dosage of the compound of about 1 mg per kg body weight per day.17. A method for treating hormone ...

Подробнее
23-09-2021 дата публикации

ACID ADDITION SALTS OF BENZIMIDAZOLE DERIVATIVE

Номер: US20210292307A1
Принадлежит: HK INNO.N CORPORATION

The present invention relates to a pidolate salt and malate salt of a compound represented by a formula 1 with an excellent liquid-phase stability, solid-phase stability, water solubility, precipitation stability and hygroscopicity all together as a compound for preventing and treating diseases mediated by an acid pump antagonistic activity, as well as a method for preparing the same. 4. The salt according to claim 1 , wherein the salt is noncrystalline.5. The salt according to claim 1 , wherein the salt is partially crystalline.6. A pharmaceutical composition for preventing or treating diseases mediated by an acid pump antagonistic activity claim 1 , wherein the pharmaceutical composition comprises a salt according to .7Helicobacter pylori. The pharmaceutical composition according to claim 6 , wherein the diseases mediated by an acid pump antagonistic activity are one selected from the group consisting of a gastroesophageal diseases claim 6 , a gastroesophageal reflux disease (GERD) claim 6 , a peptic ulcer claim 6 , a gastric ulcer and a duodenal ulcer claim 6 , an ulcer induced by NSAID claim 6 , a gastritis claim 6 , a infection claim 6 , a dyspepsia and a functional dyspepsia claim 6 , Zollinger-Ellison syndrome claim 6 , a nonerosive reflux disease (NERD) claim 6 , a visceral pain claim 6 , a purosis claim 6 , a nausea claim 6 , an esophagitis claim 6 , a dysphagia claim 6 , a salivation claim 6 , an airway lesion and an asthma.8. The pharmaceutical composition according to claim 6 , wherein a formulation of the composition is one selected from the group consisting of powder claim 6 , granule claim 6 , tablet claim 6 , capsule claim 6 , suspension claim 6 , emulsion claim 6 , syrup claim 6 , aerosol claim 6 , ointment claim 6 , cream claim 6 , suppository and injection.10. The method according to claim 9 , wherein the organic solvent of the step a) is methanol and added by 10 times (volume/weight) compared to a compound represented by the formula 1.11. The ...

Подробнее
14-09-2017 дата публикации

Tricyclic Compounds as Inhibitors of Immunosuppression Mediated By Tryptophan Metabolization

Номер: US20170260188A1
Принадлежит:

Presently provided are inhibitors of IDO and TDO and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase and tryptophan 2,3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease. 131.-. (canceled)33. The composition of wherein bond α is a single bond.34. The composition of wherein V and X are N claim 32 , W and Z are CH and Y is C.35. The composition of wherein V claim 32 , Y and Z are N claim 32 , W is CH and X is C.36. The composition of wherein V claim 32 , W and Y are N claim 32 , X is C and Z is CH.37. The composition of wherein V and W are N or NH claim 32 , X and Y are C and Z is CH.38. The composition of claim 32 , wherein Ris —Calkyl-R.39. The composition of claim 32 , wherein Ris —CH—R claim 32 , —CHCH—R claim 32 , —C(H)(CH)CH—R claim 32 , or —C(H)═C(H)R.40. The composition of claim 39 , wherein Ris —CH—R.41. The composition of claim 32 , wherein Ris —C(O)Ror —C(OR)(R)(R).42. The composition of claim 32 , wherein Ris —C(NHR)(R)(R) claim 32 , or —C(═N—OR)R.43. The composition of claim 32 , wherein Ris —C(NHR)(R)(R) claim 32 , wherein Ris hydrogen claim 32 , Calkyl claim 32 , or —C(O)Calkyl.44. The composition of claim 32 , wherein Ris —C(OR)(R)(R).45. The composition of claim 32 , wherein Ris —CH(OH)(R).46. The composition of claim 32 , wherein Ris hydrogen.47. The composition of claim 32 , wherein Ris aryl claim 32 , heteroaryl claim 32 , Ccycloalkyl claim 32 , Ccycloalkenyl claim 32 , 3-10 membered heterocyclyl claim 32 , or CcycloalkylCalkyl- claim 32 , wherein{'sub': 3-8', '3-8', '3-8', '1-6, 'sup': 32', '31, 'the Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, and CcycloalkylCalkyl-, are ...

Подробнее
01-10-2015 дата публикации

MODULATORS OF RESISTANT ANDROGEN RECEPTOR

Номер: US20150274693A1
Принадлежит:

The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same. Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful in medicine, and particularly for treating any of a variety of diseases, disorders or conditions. 6. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , adjuvant claim 1 , or vehicle.7. A method of treating or lessening the severity of a cancer or another proliferative disease claim 1 , disorder or condition claim 1 , comprising administering to a patient in need thereof a compound according to .8. The method of claim 7 , wherein the cancer is a castration-resistant prostate cancer.9. The method of claim 8 , wherein the castration-resistant prostate cancer bears one or more mutations in the androgen receptor.10. The method of claim 9 , wherein the one or more mutations in the androgen receptor comprises a mutation of Phe876.11. The method of claim 10 , wherein the mutation is Phe876 to Leu claim 10 , Ile claim 10 , Val claim 10 , Ser claim 10 , Cys claim 10 , or Tyr.12. The method of claim 10 , wherein the mutations further comprise one or more mutations to residues selected from the group consisting of E566 claim 10 , E589 claim 10 , E669 claim 10 , C687 claim 10 , A700 claim 10 , N772 claim 10 , H777 claim 10 , C785 claim 10 , F877 claim 10 , and K911.13. The method of claim 8 , wherein the castration-resistant prostate cancer is resistant to Enzalutamide. The present application claims priority to U.S. provisional application Ser. No. 61/719,117, filed Oct. 26, 2012, the entirety of which is incorporated herein by reference.Prostate cancer is the ninth-most-common cancer in the world, but is the number-one non-skin cancer in men from the United States. As of ...

Подробнее
18-11-2021 дата публикации

CARBENE COMPOUND, CARBENE-METAL NANOPARTICLE COMPLEX AND PREPARATION METHOD THEREOF

Номер: US20210356461A1

The present invention relates to a carbene compound having substituted at the terminal polyethylene glycol (PEG) having nitrogen-containing functional groups, a carbene-metal nanoparticle complex in which the carbene compound and metal nanoparticles are bounded, a preparation method thereof, and a biosensor using same. 2. The carbene compound of claim 1 , wherein the nitrogen-containing functional group is at least one selected from the group consisting of azide claim 1 , phthalimide and amine.3. The carbene compound of claim 1 , wherein at least one of the R1 and R2 and at least one of the R5 and R6 are equal to or different from each other claim 1 , and each independently an alkyl group having 1 to 20 carbon atoms claim 1 , a cycloalkyl group of 3 to 20 carbon atoms claim 1 , an aryl group having 6 to 30 carbon atoms claim 1 , or a heteroaryl group of 2 to 30 carbon atoms.4. A carbene-metal nanoparticle complex in which the carbene compound according to binds to metal nanoparticles.5. The carbene-metal nanoparticle complex of claim 4 , wherein the particle size of the metal nanoparticle is 1 nm to 40 nm.6. The carbene-metal nanoparticle complex of claim 4 , wherein the metal is any one selected from the group consisting of copper (Cu) claim 4 , cobalt (Co) claim 4 , bismuth (Bi) claim 4 , silver (Ag) claim 4 , aluminum (Al) claim 4 , gold (Au) claim 4 , hafnium (Hf) claim 4 , chromium (Cr) claim 4 , indium (In) claim 4 , manganese (Mn) claim 4 , molybdenum (Mo) claim 4 , magnesium (Mg) claim 4 , nickel (Ni) claim 4 , niobium (Nb) claim 4 , lead (Pb) claim 4 , palladium (Pd) claim 4 , platinum (Pt) claim 4 , rhenium (Re) claim 4 , rhodium (Rh) claim 4 , antimony (Sb) claim 4 , tantalum (Ta) claim 4 , titanium (Ti) claim 4 , tungsten (W) claim 4 , vanadium (V) claim 4 , zirconium (Zr) claim 4 , zinc (Zn) claim 4 , iron (Fe) claim 4 , and mixtures thereof.7. A preparation method of a carbene-metal nanoparticle complex comprising:preparing sulfur-metal nanoparticles ...

Подробнее
25-11-2021 дата публикации

Hydroxide-Catalyzed Formation Of Silicon-Oxygen Bonds By Dehydrogenative Coupling Of Hydrosilanes And Alcohols

Номер: US20210363164A1
Принадлежит:

The present disclosure is directed to methods for dehydrogenatively coupled hydrosilanes and alcohols, the methods comprising contacting an organic substrate having at least one organic alcohol moiety with a mixture of at least one hydrosilane and sodium and/or potassium hydroxide, the contacting resulting in the formation of a dehydrogenatively coupled silyl ether. The disclosure further described associated compositions and methods of using the formed products. 2. The compound according to claim 1 , wherein X is H.3. The compound according to claim 1 , wherein X is OH.4. The compound according to claim 1 , wherein p is 0.5. The compound according to claim 1 , wherein p is 1.6. The compound according to claim 1 , wherein at least one Ris tert-butyl.7. The compound according to claim 1 , wherein the optional substituent is independently halo claim 1 , optionally protected hydroxyl claim 1 , sulfhydryl claim 1 , C-Calkoxy claim 1 , C-Calkenyloxy claim 1 , C-Calkynyloxy claim 1 , C-Caryloxy claim 1 , C-Caralkyloxy claim 1 , C-Calkaryloxy claim 1 , C-Calkylcarbonyl (—CO-alkyl) claim 1 , C-Carylcarbonyl (—CO-aryl)) claim 1 , C-Calkylcarbonyloxy (—O—CO-alkyl) claim 1 , C-Carylcarbonyloxy (—O—CO-aryl)) claim 1 , C-Calkoxycarbonyl ((CO)—O-alkyl) claim 1 , C-Caryloxycarbonyl (—(CO)—O-aryl) claim 1 , halocarbonyl (—CO)-X where X is halo) claim 1 , C-Calkylcarbonato (—O—(CO)—O-alkyl) claim 1 , C-Carylcarbonato (—O—(CO)—O-aryl) claim 1 , optionally protected carboxy (—COOH) claim 1 , carboxylato (—COO—) claim 1 , optionally protected carbamoyl (—(CO)—NH) claim 1 , mono-(C-Calkyl)-substituted carbamoyl (—(CO)NH(C-Calkyl)) claim 1 , di-(C-Calkyl)-substituted carbamoyl (—(CO)—N(C-Calkyl)) claim 1 , mono-(C-Chaloalkyl)-substituted carbamoyl (—(CO)—NH(C-Calkyl)) claim 1 , di-(C-Chaloalkyl)-substituted carbamoyl (—(CO)—N(C-Calkyl)) claim 1 , mono-(C-Caryl)-substituted carbamoyl (—(CO)—NH-aryl) claim 1 , di-(C-Caryl)substituted carbamoyl (—(CO)—N(C-Caryl)) claim 1 , di-N—(C-Calkyl) ...

Подробнее
18-12-2014 дата публикации

IMIDAZOLIDINEDIONE COMPOUNDS AND THEIR USES

Номер: US20140371284A1
Автор: Chen Yuanwei
Принадлежит: HC PHARMACEUTICAL CO., LTD.

Provided are imidazolidinedione compounds of formula (I), processes for preparation, uses and pharmaceutically compositions thereof. Said imidazolidinedione compounds posses androgen receptor antagonist activity and can be used for preventing and treating diseases and disorders related to androgen receptor, such as prostate cancer, alopecia, hair regeneration, acne and adolescent acne. 2. The compound of claim 1 , wherein Rand Rare independently selected from hydrogen claim 1 , deuterated methyl claim 1 , and deuterated ethyl.3. The compound of claim 1 , wherein when Ris hydrogen claim 1 , Ris selected from the group consisting of mono-deuterated methyl claim 1 , bi-deuterated methyl claim 1 , tri-deuterated methyl claim 1 , mono-deuterated ethyl claim 1 , bi-deuterated ethyl claim 1 , tri-deuterated ethyl claim 1 , tetra-deuterated ethyl claim 1 , and penta-deuterated ethyl.4. The compound of claim 1 , wherein when Ris hydrogen claim 1 , Ris tri-deuterated methyl.76. A method for preparing a pharmaceutical composition claims 1 , comprising mixing the compound of any one of the - claims 1 , or a crystal form claims 1 , pharmaceutically acceptable salt claims 1 , hydrate or solvate thereof and a pharmaceutically acceptable carrier to form a pharmaceutical composition.86. A pharmaceutical composition claims 1 , comprising (1) the compound of any one of the - claims 1 , or a crystal form claims 1 , pharmaceutically acceptable salt claims 1 , hydrate or solvate thereof claims 1 , and (2) a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 8 , wherein the composition further comprises an additional therapeutic agent; preferably claim 8 , the additional therapeutic agent is the therapeutic agent for treating alopecia claim 8 , hair regeneration claim 8 , pimples claim 8 , acne or prostate cancer.106. A use of the compound of any one of the - or a crystal form claims 1 , pharmaceutically acceptable salt claims 1 , hydrate or solvate thereof as ...

Подробнее
25-12-2014 дата публикации

Benzimidazole Derivatives As PI3 Kinase Inhibitors

Номер: US20140378456A1
Принадлежит:

This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazoles in the treatment of 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. More suitably, the present invention relates to PI3Kβ selective benzimidazoles compounds for treating cancer. 2. A combination according to wherein compound (I) is in the form of the 2-amino-2-(hydroxymethyl)-1 claim 1 ,3-propanediol salt.3. A combination kit comprising a combination according together with a pharmaceutically acceptable carrier or carriers.4. Use of a combination according to in the manufacture of a medicament for the treatment of cancer.5. A combination according to for use in therapy.6. A combination according to for use in treating cancer.7. A pharmaceutical composition comprising a combination according to together with a pharmaceutically acceptable diluent or carrier.9. The method of claim 8 , wherein the cancer is selected from head and neck cancer claim 8 , breast cancer claim 8 , lung cancer claim 8 , colon cancer claim 8 , ovarian cancer claim 8 , prostate cancer claim 8 , gliomas claim 8 , glioblastoma claim 8 , astrocytomas claim 8 , glioblastoma multiforme claim 8 , Bannayan-Zonana syndrome claim 8 , Cowden disease claim 8 , Lhermitte-Duclos disease claim 8 , inflammatory breast cancer claim 8 , Wilm's tumor claim 8 , Ewing's sarcoma claim 8 , Rhabdomyosarcoma claim 8 , ependymoma claim 8 , medulloblastoma claim 8 , kidney cancer claim 8 , liver cancer claim 8 , melanoma claim 8 , pancreatic ...

Подробнее
22-10-2015 дата публикации

Crystal containing unsaturated carboxylic acid amide compound and method for producing same

Номер: US20150299135A1
Принадлежит: Daicel Corp

Provided is a high-purity crystal of an unsaturated carboxylic acid amide compound which is useful as or for fine chemicals such as pharmaceuticals, agricultural chemicals, polymeric materials, functional materials, and intermediates of them. The crystal includes an unsaturated carboxylic acid amide compound represented by Formula (1) in an amount of 95 percent by area or more. In X-ray diffraction, the crystal exhibits peaks at 2θ in the range of 29.0 to 30.0 and in at least one range selected from 6.0 to 8.0, 12.0 to 13.5, and 16.5 to 17.5 and exhibits approximately no peak at 2θ in the range of 14.0 to 15.0.

Подробнее
13-10-2016 дата публикации

Benzimidazoles and Their Use in the Treatment of Tuberculosis

Номер: US20160297769A1
Автор: AWASTHI Divya, Ojima Iwao
Принадлежит:

The present invention relates to novel 2,5,6-benzimidazole derivatives and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to methods of treating a patient infected by by administering to the patient a 2,5,6-benzimidazole derivative or a pharmaceutically acceptable salt thereof. This application claims priority to International Application No. PCT/US2014/066286 filed Nov. 19, 2014, which claims priority to U.S. Provisional Application No. 61/907,610, filed Nov. 22, 2013, and 62/033,808, filed Aug. 6, 2014, which are incorporated herein by reference.This invention was made with government support under grant number AI078251 awarded by the National Institute of Health. The government has certain rights in the invention.Tuberculosis (TB) was one of the first infectious diseases to be identified. More than fifty years of research has been directed to controlling and eliminating this disease. However, the eradication of TB is still one of the most prominent challenges for basic and clinical research scientists.Once thought to be under control, TB case reports in the U.S. increased sharply in the early 1990's. Although, this trend has reversed and the reported numbers of new cases has steadily declined in industrialized countries, TB remains a major global public health threat. Recent statistics from the WHO estimate that there are approximately 8.4 million new cases every year with a global mortality rate of 23% or approximately 2 million deaths per year.Poor chemotherapeutics and inadequate local-control programs contribute to the inability to manage TB and lead to the emergence of drug resistant strains of the bacteria that cause (Mtb). A survey conducted at 58 international sites between 1996 and 1999 found exceptionally high rates of single and multidrug-resistant strains in Estonia, Latvia and Russia, and revealed that countries such as China and Iran were developing a high prevalence of multidrug-resistance (MDR-TB). See Kruuner, ...

Подробнее
19-09-2019 дата публикации

BENZIMIDAZOLE DERIVATIVES: PREPARATION AND PHARMACEUTICAL APPLICATIONS

Номер: US20190282547A1
Принадлежит:

The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to benzimidazole containing compounds and methods for their preparation. These compounds may be useful as medicaments for the treatment of proliferative disorders as well as other diseases involving, relating to or associated with dysregulation of histone deacetylase (HDAC). 142.-. (canceled)44. The method of claim 43 , wherein Ris C-Calkyl substituted with one or more substituents independently selected from the group consisting of: alkylamino and aminoalkyl; Ris unsubstituted C-Calkyl; Ris H; and X and Y are H; or a pharmaceutically acceptable salt thereof.45. The method of claim 44 , wherein Ris selected from the group consisting of: 2-diethylamino-ethyl claim 44 , 3-dimethylamino-propyl claim 44 , 3-dimethylamino-2 claim 44 ,2-dimethyl-propyl claim 44 , and 4-dimethylamino-butyl.46. The method of claim 44 , wherein Ris 2-diethylamino-ethyl.47. The method of claim 44 , wherein Ris selected from the group consisting of methyl claim 44 , ethyl claim 44 , n-propyl claim 44 , 2-propyl claim 44 , n-butyl claim 44 , sec-butyl claim 44 , isobutyl claim 44 , t-butyl claim 44 , hexyl claim 44 , and octyl.48. The method of claim 44 , wherein Ris n-butyl.49. The method of claim 44 , wherein the method is for treating acute myeloid leukemia.50. The method of claim 44 , wherein the method is for treating myelodysplastic syndromes.52. The method of claim 51 , wherein Ris selected from the group consisting of: 2-diethylamino-ethyl claim 51 , 3-dimethylamino-propyl claim 51 , 3-dimethylamino-2 claim 51 ,2-dimethyl-propyl claim 51 , and 4-dimethylamino-butyl.53. The method of claim 51 , wherein Ris 2-diethylamino-ethyl.54. The method of claim 51 , wherein Ris selected from the group consisting of methyl claim 51 , ethyl claim 51 , n-propyl claim 51 , 2-propyl claim 51 , n-butyl claim 51 , sec-butyl claim 51 , isobutyl claim 51 , t- ...

Подробнее
19-09-2019 дата публикации

Processes For The Preparation Of A Diarylthiohydantoin Compound

Номер: US20190284156A1
Принадлежит:

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer. 3. The process of claim 2 , wherein the solvent is diglyme claim 2 , dioxane claim 2 , butyronitrile claim 2 , or propionitrile.4. The process of claim 3 , wherein compound (VII) is reacted in the presence of norbornadiene claim 3 , tetrabutylammonium bromide claim 3 , and DABCO.6. The process of claim 5 , wherein the palladium catalyst is added to the reaction mixture as a pre-formed palladium catalyst or is generated in situ.12. The process of claim 11 , wherein the organomagnesium halide is a Calkylmagnesium halide or a Ccycloalkylmagnesium halide; wherein the lithium halide is lithium chloride claim 11 , lithium bromide claim 11 , or lithium iodide; and the aprotic organic solvent is tetrahydrofuran claim 11 , 2-methyl-tetrahydrofuran claim 11 , methyl tert-butylether (MTBE) claim 11 , cyclopentyl methylether (CPME) claim 11 , or toluene.13. The process of claim 12 , wherein the Calkylmagnesium halide is a Calkylmagnesium chloride or Calkylmagnesium bromide and the Ccycloalkylmagnesium halide is a Ccycloalkylmagnesium chloride or a Ccycloalkylmagnesium bromide.14. The process of wherein the Calkylmagnesium halide is isopropylmagnesium chloride claim 12 , sec-butylmagnesium chloride claim 12 , n-pentylmagnesium chloride claim 12 , hexylmagnesium chloride claim 12 , ethylmagnesium chloride claim 12 , ethylmagnesium bromide claim 12 , n-butylmagnesium chloride claim 12 , or isopropylmagnesium chloride and the Ccycloalkylmagnesium halide is cyclohexylmagnesium chloride.19. The process of claim 10 , wherein compound (1c) is converted to compound (X) by reacting compound (1c) with methylamine in a solvent claim 10 , in the presence of a coupling agent claim 10 , to yield compound (X).20. The method of claim 19 , wherein the coupling agent is 1 claim 19 ,1′-carbonyldiimidazole (CDI) and the solvent is tetrahydrofuran ...

Подробнее
10-09-2020 дата публикации

Autotaxin Inhibitory Compunds

Номер: US20200283435A1
Принадлежит:

The present invention relates to compounds of formula I 144.-. (canceled)46. A compound according to wherein Ais CH claim 45 , Ais N and Ais N.47. A compound according to claim 45 , wherein L is methylene.48. A compound according to claim 45 , wherein Rand R are H.50. A compound according to claim 45 , wherein Ais N or CH.51. A compound according to claim 45 , wherein Ais N or CH.52. A compound according to claim 45 , wherein Rand R are independently selected from H claim 45 , fluoro claim 45 , methyl claim 45 , OCFor methoxy.53. A compound according to claim 45 , wherein Ris selected from is H claim 45 , halo claim 45 , hydroxyl claim 45 , (1-2C)fluoroalkyl claim 45 , (1-2C)alkoxy claim 45 , (1-2C)fluoroalkoxy claim 45 , or{'sub': 'c', 'claim-text': {'br': None, 'sub': '1', '-L-B'}, 'Ris a group of the formulawherein:{'sub': '1', 'Lis (1-2C)alkylene or —O-(1-2C)alkylene optionally substituted by methyl or oxo; and'}B is phenyl optionally substituted with fluoro or methyl.54. A compound according to claim 45 , wherein Q is either a group of the formula:{'br': None, 'sub': 2', 'k, '—CH—R—'} {'sub': k', '2', 'l', 'l, 'Ris CH, NRor O, wherein Ris selected from H or methyl;'}, 'wherein {'br': None, 'sub': m', 'y, '—R—CHR—'}, 'or Q is a group of the formula [{'sub': m', '2, 'Ris O, S, SO or SO; and'}, {'sub': 'y', 'Ris H or methyl.'}], 'wherein55. A compound according to claim 45 , wherein Rand Rare H claim 45 , methyl or fluoro.56. A compound according to claim 45 , wherein Ris selected from H or (1-4C)alkyl.57. A compound according to claim 45 , wherein Ris (1-4C)alkyl claim 45 , carboxyl claim 45 , wherein said (1-4C)alkyl claim 45 , is optionally substituted with one or more substituents selected from amino claim 45 , mercapto or hydroxyl.58. A compound according to claim 45 , wherein Ris selected from a group of formula claim 45 , Z claim 45 , wherein:{'sub': 3', '3', 's', 't', 's', 's', 'y', 's', 's', 't, 'Z is phenyl, heteroaryl, heterocycyl or (3-6C)carbocyclyl, ...

Подробнее
18-10-2018 дата публикации

PREPARATION OF AND FORMULATION COMPRISING A MEK INHIBITOR

Номер: US20180296533A1
Принадлежит:

The present invention relates to processes for preparing 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, processes for preparing crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide, and intermediates useful therefore. Also provided herein are pharmaceutical compositions comprising this crystallized compound. 1. (canceled)2. A method of treating colon cancer in a patient in need thereof , the method comprising: (i) a pharmaceutical composition comprising crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide and a pharmaceutically acceptable carrier or excipient; and', '(ii) an additional therapeutic agent which is a chemotherapeutic agent or anti-tumor agent., 'administering to said patient an effective amount of3. The method according to claim 2 , wherein the pharmaceutical composition is formulated as a tablet.4. The method according to claim 3 , wherein the pharmaceutical composition comprises approximately 15 mg of crystallized 6-(4-bromo-2-fluorophenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxyethyoxy)-amide.5. The method according to claim 2 , wherein the pharmaceutical composition is administered daily.6. The method according to claim 2 , wherein the additional therapeutic agent is selected from mitotic inhibitors claim 2 , alkylating agents claim 2 , anti-metabolites claim 2 , intercalating antibiotics claim 2 , growth factor inhibitors claim 2 , cell cycle inhibitors claim 2 , enzyme inhibitors claim 2 , topoisomerase inhibitors claim 2 , biological response modifiers claim 2 , anti-hormones claim 2 , angiogenesis inhibitors claim 2 , and anti-androgens.7. The method according to claim 5 , wherein the additional therapeutic agent is a growth factor inhibitor.8. The method according to claim 7 , wherein the pharmaceutical ...

Подробнее
17-09-2020 дата публикации

PREPARATION METHOD FOR ZEOLITIC IMIDAZOLATE FRAMEWORKS

Номер: US20200291046A1
Принадлежит:

The present invention provides a preparation method for zeolitic imidazolate frameworks. The preparation method comprises: adding a metal carbonate or oxide, an organic ligand to a hydrophilic liquid to obtain a mixture; introducing an acidic gas to reach a reaction pressure of 0.1 MPa to 2.0 MPa, and reacting for a predetermined time; heating to 30° C.-60° C. and vacuuming to obtain the zeolitic imidazolate framework. The present invention also provides a zeolitic imidazolate framework obtained by the above preparation method. The preparation method according to the present invention is environmentally friendly and has a high yield.

Подробнее
26-10-2017 дата публикации

PREPARATION METHOD FOR BEMACICLB

Номер: US20170305884A1
Автор: Xu Xuenong
Принадлежит: SUZHOU MIRACPHARMA TECHNOLOGY CO., LTD.

Disclosed are an intermediate of bemaciclib or abemaciclib and a preparation method therefor. The preparation method comprises condensation, amidine reaction, cyclization and other unit reactions. Serving the intermediate of bemaciclib as a raw material, bemaciclib is obtained through the guanidination reaction and the cyclization reaction. According to the preparation method, the raw material is easily available, the procedure is simple, and the preparation method is economical, environmentally friendly and suitable for industrial production. 2. A Bemaciclib intermediates according to claim 1 , wherein its preparation method I comprises the following steps: 1-(4-amidogen-2 claim 1 ,6-difluoro-phenyl)-2-fluoro-ethanone and N claim 1 ,N-dimethyl formamide dimethyl acctel go through primary condensation reaction to obtain 1-(4-amidogen-2 claim 1 ,6-difluoro-phenyl)-3-N claim 1 ,N-dimethylammonium-2-fluoro-2-acrylketone; 1-(4-amidogen-2 claim 1 ,6-difluoro-phenyl)-3-N claim 1 ,N-dimethylammonium-2-fluoro-2-acrylketone and N-isopropyl acetamide go through primary amidine reaction under actions of primary halogenating agent and primary acid-binding agent to obtain N-[2 claim 1 ,6-difluoro-4-(3-N claim 1 ,N-dimethylammonium-2-fluoro-2-acrylketone-1-yl)phenyl]-N′-isopropyl-ethanamidine; N-[2 claim 1 ,6-difluoro-4-(3-N claim 1 ,N-dimethylammonium-2-fluoro-2-acrylketone-1-yl)phenyl]-N′-isopropyl-ethanamidine goes through primary cyclization reaction under actions of primary alkali accelerant to obtain Bemaciclib intermediate 6-(3-N claim 1 ,N-dimethylammonium-2-fluoro-2-acrylketone-1-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzimidazole (II).3. A preparation method for Bemaciclib intermediates according to claim 2 , wherein molar ratio of raw materials of the aforesaid primary condensation reaction claim 2 , 1-(4-amidogen-2 claim 2 ,6-difluoro-phenyl)-2-fluoro-ethanone and N claim 2 ,N-dimethyl formamide dimethyl acctel is 1:2-6; Temperature of aforesaid primary condensation ...

Подробнее
24-09-2020 дата публикации

2-ARYLBENZIMIDAZOLES AS PPARGC1A ACTIVATORS FOR TREATING NEURODEGENERATIVE DISEASES

Номер: US20200299244A1

The compound 2-(3-tert-Butylphenyl)-4,6-difluoro-1H-benzo[d]imidazole and its use are disclosed: 2. A compound according to claim 1 , in free base form.3. A compound according to claim 1 , in the form of a pharmaceutically acceptable salt.4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to .5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to . This application is a continuation claiming priority under 35 USC § 365(c) of PCT/US2019/045229, which was filed Aug. 6, 2019, and published on Feb. 13, 2020, as WO 2020/033359. PCT/US2019/045229 claimed priority from U.S. Provisional application 62/714,962, which was filed Aug. 6, 2018. The contents of both are incorporated by reference herein in their entirety.The invention relates to the use of 2-arylbenzimidazole, 2-arylbenzoxazole, 2-arylbenzothiazole, 2-arylimidazo[1,2-a]pyridine, and prodrug derivatives thereof as chemical activators of Ppargc1a to treat neurodegenerative diseases.Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that is characterized by the loss of motor neurons, leading to progressive decline in motor function and ultimately death. The motor symptoms of ALS include muscle weakness, twitching and wasting, which leads to difficulties in speaking, swallowing and breathing. The cause of motor neuron death in ALS is unknown and 5-10% of the ALS cases are inherited.Activation of immune cells in the central as well as peripheral nervous system has been suggested to be a critical determinant of disease progression in ALS (Phani et al, Front Pharmacol. 3:150, 2012). Specifically, microglia and macrophages have been shown to play distinct roles in the orchestration of neuroinflammation in this disease (Dibaj et al, PLoS One. 6(3):e17910, 2011; Boillee et al, Science, 312:1389-92, 2006). Of note, bone marrow transplantation (BMT) to replace host myeloid cells has been ...

Подробнее
09-11-2017 дата публикации

MODULATORS OF RESISTANT ANDROGEN RECEPTOR

Номер: US20170320849A1
Принадлежит:

The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same. 4. (canceled)6. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier claim 1 , adjuvant claim 1 , or vehicle.7. A method of treating or lessening the severity of a cancer or another proliferative disease claim 1 , disorder or condition claim 1 , comprising administering to a patient in need thereof a compound according to .8. The method of claim 7 , wherein the cancer is a castration-resistant prostate cancer.9. The method of claim 8 , wherein the castration-resistant prostate cancer bears one or more mutations in the androgen receptor.10. The method of claim 9 , wherein the one or more mutations in the androgen receptor comprises a mutation of Phe876.11. The method of claim 10 , wherein the mutation is Phe876 to Leu claim 10 , Ile claim 10 , Val claim 10 , Ser claim 10 , Cys claim 10 , or Tyr.12. The method of claim 10 , wherein the mutations further comprise one or more mutations to residues selected from the group consisting of E566 claim 10 , E589 claim 10 , E669 claim 10 , C687 claim 10 , A700 claim 10 , N772 claim 10 , H777 claim 10 , C785 claim 10 , F877 claim 10 , and K911.13. The method of claim 8 , wherein the castration-resistant prostate cancer is resistant to Enzalutamide.21. The composition of claim 20 , wherein the payload is a photosensitizer or a radiosensitizer. The present application is a divisional application of U.S. patent application Ser. No. 15/158,432, filed May 18, 2016 (now U.S. Pat. No. 9,650,359), which is a divisional application of U.S. patent application Ser. No. 14/438,584, filed Apr. 24, 2015 (now U.S. Pat. No. 9,365,542), which is the national stage entry of PCT App. No. PCT/US13/66875, filed Oct. 25, 2013, which claims priority to U.S. ...

Подробнее
17-11-2016 дата публикации

NOVEL COMPOUND AND EPOXY RESIN COMPOSITION CONTAINING SAME

Номер: US20160333138A1
Принадлежит:

An epoxy resin composition excellent in storage stability and curability is provided. Particularly, a compound of general formula (I) and an epoxy resin composition containing the compound as a curing agent are provided. 5. The epoxy resin composition of claim 3 , being a one-pack type thermosetting epoxy resin composition.6. The epoxy resin composition of claim 4 , being a one-pack type thermosetting epoxy resin composition. This invention relates to a novel compound and an epoxy resin composition containing the same. More particular, it relates to a specific dicyanamide or thiocyanate salt and a one-pack type thermosetting epoxy resin composition containing the salt and having excellent storage stability and curability.Epoxy resins exhibit high adhesion to various substrates. Cured products of epoxy resins have relatively excellent properties, such as heat resistance, chemical resistance, electric characteristics, and mechanical characteristics, and, are useful in a wide range of applications, including coatings, adhesives, and molding materials.Conventional epoxy resin compositions are mostly of two-pack type in which an epoxy resin component is mixed with a curing agent or a curing accelerator on use. A two-pack type epoxy resin composition is characterized by curability at ambient or low temperature. Nevertheless, a two-pack epoxy resin composition is disadvantageous in that the two packs must be metered and mixed immediately before use and that the pot life of the composition is short and therefore has a limited use, for example, meeting difficulty in applying to automatic machinery. To eliminate these disadvantages, a one-pack type epoxy resin composition has been demanded.In order to develop a one-pack type curing resin composition, a curing agent that does not react at room temperature but commences reaction to cure upon heating, i.e., a latent curing agent is necessary. Latent curing agents so far proposed include dicyandiamide, dibasic acid hydrazides, ...

Подробнее
08-11-2018 дата публикации

TETRALIN AND INDANE DERIVATIVES AND USES THEREOF

Номер: US20180319743A1
Принадлежит: Roche Palo Alto LLC

The applicaton discloses pharmaceutical compounds of formula I useful for treating CNS diseases wherein m, s, RR, Rand Rare as defined herein. 2. The method of wherein m is 0 claim 1 , s is 1 claim 1 , Ris 3-fluoro claim 1 , Ris hydrogen and Ris acetyl claim 1 , aminocarbonyl or methylsulfonyl or a pharmaceutically acceptable salt..3. The method of wherein the compound is (R)-[6-(3-fluoro-benzenesulfonyl)-1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-naphthalen-1-ylmethyl]-urea or a pharmaceutically acceptable salt.4. The method of claim 3 , wherein the central nervous system disease state is depression.5. The method of claim 3 , wherein the central nervous system disease state is a memory disorder.6. The method of claim 3 , wherein the central nervous system disease state is Parkinson's disease. This Application is a Continuation of U.S. application Ser. No. 15/597,478, filed May 17, 2017, which is a Continuation of U.S. application Ser. No. 14/531,465, filed Nov. 3, 2014, which is a Continuation U.S. application Ser. No. 13/314,525, filed on Dec. 8, 2011, which is a Continuation of U.S. application Ser. No. 11/985,459, filed on Nov. 15, 2007, which is a continuation of U.S. patent application Ser. No. 11/315,706, filed Dec. 21 2005, which claims the benefit under Title 35 U.S.C. 119(e) of U.S. Provisional Patent Application Ser. No. 60/638,030, filed Dec. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety.This invention relates to substituted indane and tetralin compounds, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.The actions of 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of ...

Подробнее
08-10-2020 дата публикации

SULFONYLDIAZOLES AND N-(FLUOROSULFONYL)AZOLES, AND METHODS OF MAKING THE SAME

Номер: US20200317700A1
Автор: JOHNSON Martin Reid
Принадлежит: Trinapco, Inc.

The present disclosure provides methods for producing N-(fluorosulfonyl)azoles, sulfonyldiazoles, or related derivatives thereof; and the related products including N-(fluorosulfonyl)azoles, sulfonyldiazoles, and related derivatives thereof. For example, an N-(fluorosulfonyl)azole is obtained by reaction of sulfuryl fluoride with an azoles, an azole anion compound, a silylazole, or a combination thereof. Symmetric and asymmetric sulfonyldiazoles are obtained by further reaction of such an N-(fluorosulfonyl)azole with azoles, azole anion compounds, or silylazoles. A sulfonyldiazole can be also produced by reacting sulfuryl fluoride with an azole, a silylazole, or a combination thereof in one pot. 1. A method , comprising:{'sub': '2', 'reacting a N-(fluorosulfonyl)azole (Azole 1-SOF) having a first azole base structure (Azole 1) with a protic azole or an azole anion compound having a second azole base structure (Azole 2); and'}{'sub': '2', 'isolating an N,N′-sulfonyldiazole (Azole 1-SO-Azole 2).'}2. The method of claim 1 , wherein the first and the second azole base structures are independently selected from the group consisting of imidazole claim 1 , pyrazole claim 1 , 1 claim 1 ,2 claim 1 ,4-triazole claim 1 , benzimidazole claim 1 , benzotriazole claim 1 , indazole claim 1 , 2-methylimidazole claim 1 , 2-methylbenzimidazole claim 1 , and 3 claim 1 ,5-dimethylpyrazole.3. The method of claim 1 , wherein the first azole base structure (Azole 1) and the second azole base structure (Azole 2) are the same.4. The method of claim 1 , wherein the azole anion compound is an azole anion salt having an cation of a metal selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim 1 , cesium claim 1 , and magnesium.5. The method of claim 1 , wherein the azole anion compound is derived from the protic azole (Azole 2) and a metal carbonate claim 1 , the metal being selected from the group consisting of lithium claim 1 , sodium claim 1 , potassium claim ...

Подробнее
22-10-2020 дата публикации

TOTAL SYNTHESIS METHOD OF PACTALACTAM

Номер: US20200331863A1
Принадлежит:

The present invention relates to a method of preparing pactalactam represented by Formula 5 below using a total synthesis method: 5. The method of claim 1 , wherein the second step comprises a second-first step of adding Ito the compound of Formula 2 above to form a compound of Formula 2-1 below; a second-second step of adding PMBNHto the compound of Formula 2-1 above to form the compound of Formula 3. The present invention relates to a novel method of preparing pactalactam using a total synthesis method.Natural products play an important role in medicine. About two-thirds of recently approved drugs are natural products or chemicals inspired by nature.Natural products are emphasized as essential components of our therapeutics due to abundant biological activity and structural diversity.Among a very large number of natural bioactive materials, compounds include aminocyclopentitol-containing natural products representing sugar-derived microbial secondary metabolites.While natural products are relatively rare, they are attractive research subjects because of their biological activity and unique structure.One of the major members of natural products is soil bacterium (). A large number of pactamycin analogs separated from and related strains have been reported.Pactamycin is composed of a steric center, two aromatic rings, and a 5-membered amino cycle site rich in 1,1-dimethylurea. This compound is an aminocyclopentitol-derived natural product having a strong antibacterial effect and a strong anticancer effect.Since pactamycin has strong cytotoxicity, its use as an anticancer drug is inadequate. Accordingly, it has been necessary to discover novel materials.According to the present invention, analogs similar to pactamycin could alternatively be approached to extend a range and find characterized nontoxic compounds.Among the compounds, pactalactam is a natural product reported from and related strains in a trace amount. The present invention provides a total synthesis ...

Подробнее
08-12-2016 дата публикации

BENZIMIDAZOLE DERIVATIVES AS SELECTIVE BLOCKERS OF PERSISTENT SODIUM CURRENT

Номер: US20160355485A9
Принадлежит:

The present invention is directed to a compound of Formula I 2. The compound of claim 1 , wherein R is and unsubstituted straight chain or branched Calkyl.3. The compound of claim 1 , wherein R is Calkyl which is substituted with a Caryloxy group.4. The compound of claim 3 , wherein the “aryl” portion of said Caryloxy group is unsubstituted or substituted with 1-2 Calkyl or Calkoxy substitutents.5. The compound of claim 1 , wherein R is Calkyl which is substituted with a heteroaryl substitutent claim 1 , wherein said heteroaryl group is five- to six-membered ring containing 1-2 ring N atoms claim 1 , and wherein when said five- to six-membered ring containing 1-2 ring N atoms has two substituents on adjacent carbon atoms claim 1 , said substituents together with the carbon atoms to which they are attached can optionally form a phenyl ring claim 1 , and wherein said six-membered ring containing 1-2 ring N atoms claim 1 , optionally with said phenyl ring is optionally further substituted with a ring system substituent.6. The compound of claim 5 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 5 , optionally with said phenyl ring is selected from the group consisting of pyrazolyl claim 5 , imidazolyl claim 5 , pyrimidinyl claim 5 , pyrazinyl claim 5 , and benzimidazolyl.7. The compound of claim 6 , wherein said five- to six-membered ring containing 1-2 ring N atoms claim 6 , optionally with said phenyl ring is selected from the group consisting of is imidazolyl and benzimidazolyl.8. The compound of claim 1 , wherein R is Calkyl which is substituted with a —N(Calkyl)substituent.10. The compound of claim 1 , wherein Rand Rare both H.11. The compound of claim 10 , wherein m is 1 or 2.12. The compound of claim 10 , wherein m is 1 claim 10 , and X is O.13. The compound of claim 10 , wherein m is 2 claim 10 , and X is a covalent bond.14. The compound of claim 10 , wherein m is 1 claim 10 , and X is —S(═O)—.15. The compound of claim 10 , wherein m ...

Подробнее
29-10-2020 дата публикации

Non-Coordinating Anion Type Benzimidazolium Activators

Номер: US20200339517A1
Принадлежит:

The present disclosure provides benzimidazolium borate activators comprising benzimidazolium cations having linear alkyl groups, catalyst systems comprising, and processes for polymerizing olefins using such activators. Specifically, the present disclosure provides polymerization activator compounds which may be prepared in, and which are soluble in aliphatic hydrocarbon and alicyclic hydrocarbon solvents. 3. The compound of claim 2 , wherein at least one of R claim 2 , R claim 2 , R claim 2 , and Rcomprises a perfluoro substituted phenyl moiety claim 2 , a perfluoro substituted naphthyl moiety claim 2 , a perfluoro substituted biphenyl moiety claim 2 , a perfluoro substituted triphenyl moiety claim 2 , or a combination thereof.4. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , and Rare perfluoro substituted phenyl radicals or perfluoro substituted naphthyl radicals.5. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rtogether comprise 10 or more carbon atoms.6. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rtogether comprise 18 or more carbon atoms.7. The compound of claim 1 , wherein Ris a C-Calkyl radical.8. The compound of claim 1 , wherein Ris a methyl radical.9. The compound of claim 1 , wherein Ris a C-Clinear alkyl radical.10. The compound of claim 1 , wherein a 1 millimole per liter mixture of the compound in n-hexane claim 1 , isohexane claim 1 , cyclohexane claim 1 , methylcyclohexane claim 1 , or a combination thereof claim 1 , forms a clear homogeneous solution at 25° C.13. The process of further comprising the step of filtering the mixture to remove the salt to produce a clear homogeneous solution comprising the activator compound according to formula (AI) and optionally removing at least a portion of the solvent.14. The process of claim 11 , wherein the solvent is methylene chloride claim 11 , toluene claim 11 , xylene claim 11 , ...

Подробнее
28-12-2017 дата публикации

FIVE-MEMBERED C-N-ATTACHED ARYL SULPHIDE AND ARYL SULPHOXIDE DERIVATIVES AS PESTICIDES

Номер: US20170367333A1
Принадлежит: Bayer CropScience Aktiengesellschaft

Provided are compounds of the formula (I) 2. A compound according to wherein the structural elements are defined as follows:W represents hydrogen or halogen;n represents the number 0 or 1;{'sub': 1', '3', '1', '3', '1', '3', '1', '3, 'claim-text': represents NR′″R″″,', {'sub': 1', '4', '2', '4, 'where R′″ and R″″ independently of one another represent hydrogen, (C-C)-alkyl or (C-C)-haloalkyl;'}], 'Y represents hydrogen, halogen, (C-C)-alkyl, (C-C)-haloalkyl, (C-C)-alkoxy, (C-C)-haloalkoxy or amino; or'}{'sub': 1', '3', '1', '3', '1', '3, 'X represents hydrogen, halogen, cyano, (C-C)-alkyl, (C-C)-haloalkyl or (C-C)-alkoxy;'}{'sup': 1', '2, 'Vand Vindependently of one another represent oxygen or sulphur;'}{'sup': 1', '2, 'sub': 1', '3, 'claim-text': {'sup': 1', '2, 'sub': 3', '6, 'or Rand Rtogether with the carbon atom to which they are attached represent a (C-C)-cycloalkyl ring;'}, 'Rand Rindependently of one another represent hydrogen or (C-C)-alkyl;'}{'sup': '3', 'sub': 1', '6', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '1', '6', '1', '3', '1', '6', '1', '3', '1', '3', 'm', '1', '3', '1', '3', 'm', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3, 'claim-text': [{'sub': 3', '6', '3', '6', '1', '3', '3', '6', '3', '6', '1', '3', '1', '4', '1', '3', '1', '3', '1', '3, 'represents (C-C)-cycloalkyl, (C-C)-cycloalkyl-(C-C)-alkyl, (C-C)-cycloalkenyl or (C-C)-cycloalkenyl-(C-C)-alkyl which is optionally mono- or disubstituted by identical or different substituents from the group consisting of halogen, cyano, nitro, hydroxy, amino, (C-C)-alkyl, halo-(C-C)-alkyl, (C-C)-alkoxy, halo-(C-C)-alkoxy and cyclopropyl, or'}, {'sub': 1', '3', '1', '3', '1', '3', '1', '4', '1', '3', '1', '3', '1', '3, 'represents heterocyclyl, heterocyclyl-(C-C)-alkyl, aryl, aryl-(C-C)-alkyl, hetaryl or hetaryl-(C-C)-alkyl which is optionally mono- or disubstituted by identical or different substituents from the group consisting of halogen, cyano, nitro, hydroxy, amino, (C-C)-alkyl, halo-(C-C ...

Подробнее
12-11-2020 дата публикации

Process For The Preparation Of A Diarylthiohydantoin Compound

Номер: US20200354334A1
Принадлежит:

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer. 2. The process of claim 1 , comprising:reacting compound VII with an organomagnesium halide; in the presence or absence of a lithium halide; andadding carbon dioxide gas; in an aprotic organic solvent; at a temperature of about 0° C. to yield compound 1c.3. The process of claim 1 , comprising reacting compound VII under a carbon monoxide atmosphere; in the presence of a palladium catalyst; in the presence of one or more phosphorus ligands; in the presence of water; in a solvent; at a temperature of about 0° C. to about 100° C. to yield the compound 1c. This application is a continuation of U.S. patent application Ser. No. 16/427,637, filed May 31, 2019, which is a continuation of U.S. patent application Ser. No. 15/537,859, filed Jun. 19, 2017, which is the U.S. national stage of International Patent Application No. PCT/US2015/066345, filed Dec. 17, 2015, which claims priority to U.S. Provisional Patent Application No. 62/094,425, filed Dec. 19, 2014, all disclosures of which are hereby incorporated by reference in their entireties.The research and development of the invention described below was not federally sponsored.The present invention is directed to the preparation of compound (X) and intermediates in its synthesis. More specifically, the present invention is directed to processes for the preparation of compound (X), disclosed in U.S. Pat. No. 8,445,507, issued on May 21, 2013, which is hereby incorporated by reference in its entirety.Compound (X) of the present invention is currently being investigated for use in the treatment of prostate cancer. The present invention describes processes and intermediates for the preparation of such compound.The present invention is directed to a process for the preparation of compound (X)Comprising, consisting of, and/or consisting essentially ofreacting compound (V) with ...

Подробнее