Dihydrobenzoxathiazepine compounds, a process for their preparation and pharmaceutical compositions containing them

Compounds of formula (I): wherein R 1 represents a hydrogen atom or a heterocyclic, cyano, alkoxycarbonyl, alkylsulphonylaminoalkyl or N-hydroxycarboximidamide group. Medicinal products containing the same which are useful as modulators of the AMPA receptor.

MITOTIC KINESIN INHIBITORS AND METHODS OF USE THEREOF

This invention relates to inhibitors of mitotic kinesins, particularly KSP, and methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing the inhibitors and pharmaceutical compositions in the treatment and prevention of various disorders. 23. The compound of claim 1 , wherein Ris alkyl optionally substituted with OR claim 1 , NRR claim 1 , NRC(═O)(CH)R claim 1 , NRSOR claim 1 , heterocyclyl claim 1 , —OP(═O)(OR) claim 1 , an amino acid residue claim 1 , a dipeptide or a tripeptide claim 1 , or Ris a heterocyclyl.24. The compound of claim 1 , wherein Ris (CH)—OH claim 1 , (CH)—OH claim 1 , (CH)—NH claim 1 , (CH)—NH claim 1 , (CH)—NH claim 1 , (CH)—NHCH(CH) claim 1 , (CH)—NHMe claim 1 , (CH)—NMe claim 1 , (CH)—NMe claim 1 , (CH)—NHMe claim 1 , (CH)NHC(═O)Me claim 1 , (CH)NHC(═O)CH(CH) claim 1 , (CH)NHC(═O)CHCHNMe claim 1 , (CH)NHSOMe claim 1 , (CH)-(pyrrolidin-1-yl) claim 1 , (CH)-(piperidin-1-yl) claim 1 , (CH)-(4-methylpiperidin-1-yl) claim 1 , (CH)-(morpholin-4-yl) claim 1 , (CH)-(pyrrolidin-2-yl) claim 1 , (CH)NH(C═O)CH(Me)NH(C═O)CH(Me)NH claim 1 , (CH)—OPOH claim 1 , CH—O—CHOMe or piperidin-4-yl.25. The compound of claim 1 , wherein Ris (CH)—NH.26. The compound of claim 1 , wherein Ris Z—NR—C(═NR)R claim 1 , Z—NR—C(═NR)NRR claim 1 , Z—C(═NR)NRR claim 1 , Z—O—NRC(═NR)NRR claim 1 , Z—O—NR claim 1 , —C(═NR)R claim 1 , Z—NR—NR—C(═NR)R claim 1 , or Z—NR—NR—C(═NR)NRR.27. The compound of claim 1 , wherein Aris phenyl optionally substituted with one or more groups independently selected from halogen claim 1 , alkyl claim 1 , —ORor —NROR; or Aris a heteroaryl selected from thiophenyl or pyridyl claim 1 , wherein said pyridyl is optionally substituted independently with one or more halogen.28. The compound of claim 1 , wherein Aris phenyl claim 1 , 2 claim 1 ,4-difluorophenyl claim 1 , 2-fluorophenyl claim 1 , 3-fluorophenyl claim 1 , 2-chlorophenyl claim 1 , 3- ...

KAPPA OPIOID RECEPTOR AGONISTS

The present invention relates to a series of substituted compounds having the general formula (I), including their stereoisomers and/or their pharmaceutically acceptable salts. (I) Wherein A, m, R1s, R2, R3, R4 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS. 135-. (canceled)39. The compound according to claim 38 , wherein Rrepresents hydrogen or hydroxyl.40. The compound according to claim 36 , wherein{'sub': 2', '2', 'a', 'b', 'c', '2', 'n', 'd', '2', 'n', '1', '2', 'a', 'b', 'c', 'd', '1, 'b': '1', 'Rrepresents an optionally substituted alkyl, cycloalkyl, heteroaryl or heterocyclyl group, wherein one or more optional substituents are selected from —CN, hydroxyl, —NO, —NRR, —OR, alkyl, aryl, aralkyl, heterocyclyl, heteroaryl, —(CH)COORor —(CH)CON(R), and wherein R, R, R, R, Rand n are as defined in claim .'}41. The compound according to claim 40 , wherein Rrepresents hydrogen or hydroxyl.42. The compound according to claim 40 , wherein Rrepresents an optionally substituted heteroaryl group.43. The compound according to claim 40 , wherein Rrepresents an optionally substituted heterocyclyl group.44. A compound selected from the group consisting of:(S)-1-phenyl-N-(1-phenyl-2-(pyrrolidin-1-yl)ethyl)cyclopropanecarboxamide hydrochloride;(S)—N-methyl-1-phenyl-N-(1-phenyl-2-(pyrrolidin-yl]ethyl]cyclopentanecarboxamide hydrochloride;(S)—N-methyl-1-phenyl-N-(1-phenyl-2-(pyrrolidin-1-yl]ethyl]cyclohexane carboxamide hydrochloride;(S)—N-methyl-1-phenyl-N-(1-phenyl-2-(pyrrolidin-1yl]ethyl]cyclopropane carboxamide ...

Compositions and methods for inhibition of the jak pathway

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful.

NOVEL SUBSTITUTED PHENYL-OXATHIAZINE DERIVATIVES, METHOD FOR PRODUCING THEM, DRUGS CONTAINING SAID COMPOUNDS AND THE USE THEREOF

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia. 2. The compound of claim 1 , whereinL is R1, —CH(R10)(R11);{'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5', '1', '6', '3', '8', '1', '6', '3', '8', '6', '10', '1', '6', '6', '10, 'claim-text': {'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '2', '3', '2', '2', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5, 'where the aryl radical may be mono- to trisubstituted by F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), SO—CH, SO—NH, SO—NH(C-C)-alkyl, SO—N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C-C)-alkyl, CON((C-C)-alkyl), SF;'}, 'R10 is F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C-C)-alkyl, CON((C-C)-alkyl), SF, (C-C)-alkylene-(R6), (C-C)-cycloalkylene-(R6), (C-C)-alkylene-(C-C)-cycloalkylene-(R6), (C-C)-aryl, (C-C)-alkylene-(C-C)-aryl;'}{'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5', '1', '6', '3', '8', '1', '6', '3', '8', '6', '10', '1', '6', '6', '10, 'claim-text': {'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '2', '3', '2', '2', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '5, 'where the aryl radical may be mono- to trisubstituted by F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), SO—CH, SO—NH, SO—NH(C-C)-alkyl, SO—N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C alkyl, CON((C-C)-alkyl), SF;'}, 'R11 is H, F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C ...

DI AND TRI - SUBSTITUTED OXATHIAZINE DERIVATIVES, METHOD FOR THE PRODUCTION, METHOD FOR THE PRODUCTION THEREOF, USE THEREOF AS MEDICINE AND DRUG CONTAINING SAID DERIVATIVES AND USE THEREOF

The invention relates to compounds of formula (I) and to the physiologically compatible salts thereof. Said compounds are suitable, for example, for treating hyperglycemia. 5. (canceled)6. A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salts thereof claim 1 , and a pharmaceutically acceptable carrier and/or excipient.7. The pharmaceutical composition of claim 6 , further comprising at least one further active ingredient.8. The pharmaceutical composition of claim 7 , wherein said active ingredient is one or more antidiabetics claim 7 , active hypoglycemic ingredients claim 7 , HMG-CoA reductase inhibitors claim 7 , cholesterol absorption inhibitors claim 7 , PPAR gamma agonists claim 7 , PPAR alpha agonists claim 7 , PPAR alpha/gamma agonists claim 7 , PPAR delta agonists claim 7 , fibrates claim 7 , MTP inhibitors claim 7 , bile acid absorption inhibitors claim 7 , CETP inhibitors claim 7 , polymeric bile acid adsorbers claim 7 , LDL receptor inducers claim 7 , ACAT inhibitors claim 7 , antioxidants claim 7 , lipoprotein lipase inhibitors claim 7 , ATP citrate lyase inhibitors claim 7 , squalene synthetase inhibitors claim 7 , lipoprotein(a) antagonists claim 7 , HM74A receptor agonists claim 7 , lipase inhibitors claim 7 , insulins claim 7 , sulfonylureas claim 7 , biguanides claim 7 , meglitinides claim 7 , thiazolidinediones claim 7 , α-glucosidase inhibitors claim 7 , active ingredients which act on the ATP-dependent potassium channel of the beta cells claim 7 , glycogen phosphorylase inhibitors claim 7 , glucagon receptor antagonists claim 7 , activators of glucokinase claim 7 , inhibitors of gluconeogenesis claim 7 , inhibitors of fructose 1 claim 7 ,6-biphosphatase claim 7 , modulators of glucose transporter 4 claim 7 , inhibitors of glutamine:fructose-6-phosphate amidotransferase claim 7 , inhibitors of dipeptidylpeptidase IV claim 7 , inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 claim 7 , inhibitors ...

NOVEL SUBSTITUTED PHENYL-OXATHIAZINE DERIVATIVES, METHOD FOR PRODUCING THEM, DRUGS CONTAINING SAID COMPOUNDS AND THE USE THEREOF

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia. 6. (canceled)7. A pharmaceutical compound comprising the compound of claim 1 , or pharmaceutically acceptable salts thereof claim 1 , and a pharmaceutically acceptable carrier and/or excipient.8. The pharmaceutical composition of claim 7 , further comprising at least one further active ingredient.9. The pharmaceutical composition of claim 8 , wherein said active ingredient is one or more antidiabetics claim 8 , active hypoglycemic ingredients claim 8 , HMG-CoA reductase inhibitors claim 8 , cholesterol absorption inhibitors claim 8 , PPAR gamma agonists claim 8 , PPAR alpha agonists claim 8 , PPAR alpha/gamma agonists claim 8 , PPAR delta agonists claim 8 , fibrates claim 8 , MTP inhibitors claim 8 , bile acid absorption inhibitors claim 8 , CETP inhibitors claim 8 , polymeric bile acid adsorbers claim 8 , LDL receptor inducers claim 8 , ACAT inhibitors claim 8 , antioxidants claim 8 , lipoprotein lipase inhibitors claim 8 , ATP citrate lyase inhibitors claim 8 , squalene synthetase inhibitors claim 8 , lipoprotein(a) antagonists claim 8 , HM74A receptor agonists claim 8 , lipase inhibitors claim 8 , insulins claim 8 , sulfonylureas claim 8 , biguanides claim 8 , meglitinides claim 8 , thiazolidinediones claim 8 , α-glucosidase inhibitors claim 8 , active ingredients which act on the ATP-dependent potassium channel of the beta cells claim 8 , glycogen phosphorylase inhibitors claim 8 , glucagon receptor antagonists claim 8 , activators of glucokinase claim 8 , inhibitors of gluconeogenesis claim 8 , inhibitors of fructose 1 claim 8 ,6-biphosphatase claim 8 , modulators of glucose transporter 4 claim 8 , inhibitors of glutamine: fructose-6-phosphate amidotransferase claim 8 , inhibitors of dipeptidylpeptidase IV claim 8 , inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 claim 8 , inhibitors ...

OXATHIAZINE DERIVATIVES SUBSTITUTED WITH CARBOCYCLES OR HETEROCYCLES, METHOD FOR PRODUCING SAME, DRUGS CONTAINING SAID COMPOUNDS, AND USE THEREOF

The invention relates to the compounds of formula (I) and physiologically acceptable salts thereof. The compounds are suitable, e.g., for treating hyperglycemia. 4. (canceled)5. A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salts thereof claim 1 , and a pharmaceutically acceptable carrier and/or excipient.6. The pharmaceutical composition of claim 5 , further comprising at least one further active ingredient.7. The pharmaceutical composition of claim 6 , wherein said active ingredient is one or more antidiabetics claim 6 , active hypoglycemic ingredients claim 6 , HMG-CoA reductase inhibitors claim 6 , cholesterol absorption inhibitors claim 6 , PPAR gamma agonists claim 6 , PPAR alpha agonists claim 6 , PPAR alpha/gamma agonists claim 6 , PPAR delta agonists claim 6 , fibrates claim 6 , MTP inhibitors claim 6 , bile acid absorption inhibitors claim 6 , CETP inhibitors claim 6 , polymeric bile acid adsorbers claim 6 , LDL receptor inducers claim 6 , ACAT inhibitors claim 6 , antioxidants claim 6 , lipoprotein lipase inhibitors claim 6 , ATP citrate lyase inhibitors claim 6 , squalene synthetase inhibitors claim 6 , lipoprotein(a) antagonists claim 6 , HM74A receptor agonists claim 6 , lipase inhibitors claim 6 , insulins claim 6 , sulfonylureas claim 6 , biguanides claim 6 , meglitinides claim 6 , thiazolidinediones claim 6 , α-glucosidase inhibitors claim 6 , active ingredients which act on the ATP-dependent potassium channel of the beta cells claim 6 , glycogen phosphorylase inhibitors claim 6 , glucagon receptor antagonists claim 6 , activators of glucokinase claim 6 , inhibitors of gluconeogenesis claim 6 , inhibitors of fructose 1 claim 6 ,6-biphosphatase claim 6 , modulators of glucose transporter 4 claim 6 , inhibitors of glutamine-fructose-6-phosphate amidotransferase claim 6 , inhibitors of dipeptidylpeptidase IV claim 6 , inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 claim 6 , inhibitors of protein ...

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. 4. The method according to claim 2 , wherein Ris H or R; Ris —CHOP(O)(OR); and each Ris independently for each occurrence Ror a monovalent cationic group; or two R claim 2 , together with the atoms to which they are attached claim 2 , form a 4-8 membered cyclic phosphate group claim 2 , or two Rtogether represent a divalent cationic group.6. The method according to claim 1 , comprising administering the compound in an amount effective for treating a disease selected from allergies claim 1 , autoimmune diseases claim 1 , transplant rejection claim 1 , T-cell mediated autoimmune diseases claim 1 , Type II inflammatory diseases claim 1 , delayed Type IV hypersensitivity reactions claim 1 , or hematologic malignancies.7. The method according to wherein the disease is rheumatoid arthritis claim 6 , dry eye syndrome claim 6 , uveitis claim 6 , allergic conjunctivitis claim 6 , glaucoma claim 6 , rosacea (of the eye) claim 6 , multiple sclerosis (MS) claim 6 , amyotrophic lateral sclerosis claim 6 , psoriasis claim 6 , or Sjögren's syndrome.8. The method according to wherein the method comprises contacting a JAK kinase with the compound claim 1 , or a salt thereof.98. The method according to comprising contacting the JAK kinase ex vivo.108. The method according to comprising contacting the JAK kinase in vivo.11. The method according to wherein contacting the JAK kinase comprises treating a disease selected from allergies claim 8 , autoimmune diseases claim 8 , transplant rejection claim 8 , T-cell mediated autoimmune diseases claim 8 , Type II inflammatory diseases claim 8 , delayed Type IV hypersensitivity reactions claim 8 , or hematologic malignancies.12. The method according to wherein the ...

TETRASUBSTITUTED OXATHIAZINE DERIVATIVES, METHOD FOR PRODUCING THEM, THEIR USE AS MEDICINE AND DRUG CONTAINING SAID DERIVATIVES AND THE USE THEREOF

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia. 2. The compound of claim 1 , whereinL is R1, —CH(R10)(R11);{'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5', '1', '6', '3', '8', '1', '6', '3', '8', '6', '10', '1', '6', '6', '10', '6', '10', '1', '6', '6', '10, 'claim-text': {'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '2', '3', '2', '2', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5, 'where the aryl radical or heteroaryl radical may be mono- to trisubstituted by F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), SO—CH, SO—NH, SO—NH(C-C)-alkyl, SO—N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C-C)-alkyl, CON((C-C)-alkyl), SF;'}, 'R10, R11 are each independently F, Cl, Br, I, OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C-C)-alkyl, CON((C-C)-alkyl), SF, (C-C)-alkylene-(R6), (C-C)-cycloalkylene-(R6), (C-C)-alkylene-(C-C)-cycloalkylene-(R6), (C-C)-aryl, (C-C)-alkylene-(C-C)-aryl, —(C-C)-heteroaryl, (C-C)-alkylene-(C-C)-heteroaryl;'}{'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '2', '3', '2', '2', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', '1', '6', '2', '5, 'R6 is OH, CF, CHF, CHF, NO, CN, OCF, OCHF, O—(C-C)-alkyl, (C-C)-alkyl, NH, NH(C-C)-alkyl, N((C-C)-alkyl), SO—CH, SO—NH, SO—NH(C-C)-alkyl, SO—N((C-C)-alkyl), COOH, COO—(C-C)-alkyl, CONH, CONH(C-C)-alkyl, CON((C-C)-alkyl), SF;'}{'sub': 3', '8', '3', '8, 'claim-text': {'sub': 3', '2', '2', '2', '3', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '2', '3', '2', '2', '2', '1', '6', '2', '1', '6', '2', '1', '6', '2', '1', '6', ...

OXATHIAZINE DERIVATIVES WHICH ARE SUBSTITUTED WITH BENZYL OR HETEROMETHYLENE GROUPS, METHOD FOR PRODUCING THEM, THEIR USE AS MEDICINE AND DRUG CONTAINING SAID DERIVATIVES AND THE USE THEREOF

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia. 6. (canceled)7. A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salts thereof claim 1 , and a pharmaceutically acceptable carrier and/or excipient.8. The pharmaceutical composition of claim 7 , further comprising at least one further active ingredient.9. The pharmaceutical composition of claim 8 , wherein said active ingredient is one or more antidiabetics claim 8 , active hypoglycemic ingredients claim 8 , HMG-CoA reductase inhibitors claim 8 , cholesterol absorption inhibitors claim 8 , PPAR gamma agonists claim 8 , PPAR alpha agonists claim 8 , PPAR alpha/gamma agonists claim 8 , PPAR delta agonists claim 8 , fibrates claim 8 , MTP inhibitors claim 8 , bile acid absorption inhibitors claim 8 , CETP inhibitors claim 8 , polymeric bile acid adsorbers claim 8 , LDL receptor inducers claim 8 , ACAT inhibitors claim 8 , antioxidants claim 8 , lipoprotein lipase inhibitors claim 8 , ATP citrate lyase inhibitors claim 8 , squalene synthetase inhibitors claim 8 , lipoprotein(a) antagonists claim 8 , HM74A receptor agonists claim 8 , lipase inhibitors claim 8 , insulins claim 8 , sulfonylureas claim 8 , biguanides claim 8 , meglitinides claim 8 , thiazolidinediones claim 8 , α-glucosidase inhibitors claim 8 , active ingredients which act on the ATP-dependent potassium channel of the beta cells claim 8 , glycogen phosphorylase inhibitors claim 8 , glucagon receptor antagonists claim 8 , activators of glucokinase claim 8 , inhibitors of gluconeogenesis claim 8 , inhibitors of fructose 1 claim 8 ,6-biphosphatase claim 8 , modulators of glucose transporter 4 claim 8 , inhibitors of glutamine:fructose-6-phosphate amidotransferase claim 8 , inhibitors of dipeptidylpeptidase IV claim 8 , inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 claim 8 , ...

COMPOUNDS AND METHODS FOR THE TREATMENT OF ISOCITRATE DEHYDROGENASE RELATED DISEASES

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: 4. The compound according to claim 1 , wherein Ris an optionally substituted alkyl.5. The compound according to claim 1 , wherein Ris an optionally substituted C-Calkyl claim 1 , preferably selected from methyl claim 1 , ethyl claim 1 , propyl claim 1 , cyclopropyl claim 1 , isopropyl claim 1 , n-butyl claim 1 , tert-butyl claim 1 , cyclobutyl claim 1 , n-pentyl claim 1 , neopentyl claim 1 , cyclopentyl claim 1 , n-hexyl and cyclohexyl.8. A compound according to claim 1 , wherein q is 1.13. The method according to claim 12 , wherein said defect in isocitrate dehydrogenase is a somatic mutation at codon 132 isocitrate dehydrogenase (IDH1) or at codon 172 in isocitrate dehydrogenase 2 (IDH2) or at codon 140 of IDH2.14. The method according to claim 12 , wherein said patient has mutations on both IDH1 and IDH2.15. The method according to claim 12 , wherein said mutation is selected from R132H claim 12 , R132C claim 12 , R132S claim 12 , R132L claim 12 , R132G in IDH1 claim 12 , or R172M claim 12 , R172G claim 12 , R172K or R140Q in IDH2.16. The method according to claim 12 , wherein said disease is a cell proliferative disease.17. The method according to claim 12 , wherein said disease is selected from Grade I claim 12 , II claim 12 , III or IV glioma.18. The method according to claim 12 , wherein said disease is selected from astrocytomas claim 12 , oligodendrogliomas claim 12 , ependymomas and glioblastoma multiforme (GBM).19. A method of treating a patient exhibiting abnormal 2-hydroxyglutarate (2-HG) production comprising administering a compound according to .20. The method according to claim 19 , wherein said abnormal 2-HG production is an increase of more than about 20 fold claim 19 , or more than about 40 fold or more than about 50 fold or more than about 100 fold or more than about 200 fold compared to a corresponding normal cell or tissue or plasma ...

NRF2 Regulators

The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators. 2. The compound or pharmaceutically acceptable salt according to wherein A is —C(O)ORand Ris hydrogen claim 1 , —Calkyl-N(R) claim 1 , —(CH)-morpholinyl claim 1 , —(CH)-imidazoyl claim 1 , —(CH)-pyrrolidinyl claim 1 , or —(CH)-piperidyl.3. The compound or pharmaceutically acceptable salt according to wherein A is —C(O)OH.4. The compound or pharmaceutically acceptable salt according to wherein Ris:{'sub': 1-3', '1-3, 'phenyl substituted by one, two, or three groups independently selected from —CN, —F, —Cl, Calkyl, and —O—Calkyl;'}{'sub': 1-3', '1-3, 'benzotriazolyl substituted by one, two, or three groups independently selected from —O—Calkyl and Calkyl; or'}{'sub': 2', '2', '1-3', '2, '—(CH)-triazolyl substituted by one or two groups independently selected from Calkyl or —CH-phenyl.'}5. The compound or pharmaceutically acceptable salt according to wherein Ris benzotriazolyl substituted by one or two groups independently selected from —O—Calkyl and Calkyl.7. The compound or pharmaceutically acceptable salt according to wherein Ris hydrogen claim 1 , —Cl claim 1 , Calkyl claim 1 , or —CF.8. The compound or pharmaceutically acceptable salt according to wherein each Ris hydrogen.10. The compound according to selected from the group consisting of:3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid;3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((3-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5] ...

HYDROXYISOXAZOLINES AND DERIVATIVES THEREOF

The present disclosure relates to the use of hydroxyisoxazolines and derivatives thereof as fungicide. It also relates to new hydroxyisoxazolines derivatives, their use as fungicide and compositions comprising thereof. 2. The compound according to wherein A represents phenyl or naphthyl.3. The compound according to wherein A represents a heteroaryl selected from the group consisting of thienyl claim 1 , thiazolyl claim 1 , benzofuranyl claim 1 , indazolyl claim 1 , benzothiazolyl claim 1 , benzothiophenyl claim 1 , benzothiazolyl claim 1 , pyridyl and pyrimidinyl.4. The compound according to wherein R4 represents a substituent selected from the group consisting of halogen claim 1 , cyano claim 1 , hydroxy claim 1 , C-C-alkyl claim 1 , C-C-alkoxy claim 1 , C-C-alkylthio claim 1 , arylsulfenyl claim 1 , C-C-alkylsulfonyl claim 1 , arylsulfonyl claim 1 , C-C-alkenyl claim 1 , C-C-alkynyl claim 1 , C-C-carbocyclyl claim 1 , 3- to 10-membered-heterocyclyl claim 1 , C-C-haloalkyl claim 1 , hydroxy-C-C-alkyl claim 1 , aryl claim 1 , —SF claim 1 , —C(═O)R claim 1 , —C(═O)OR claim 1 , —C(═NR)R claim 1 , —N(R) claim 1 , —C(═NR)N(R) claim 1 , —C-C-alkyl-N(R)and —C-C-alkyl-C(═O)ORwith R claim 1 , wherein said C-C-alkyl claim 1 , C-C-alkoxy claim 1 , C-C-alkylthio claim 1 , arylsulfenyl claim 1 , C-C-alkylsulfonyl claim 1 , arylsulfonyl claim 1 , C-C-alkenyl claim 1 , C-C-alkynyl claim 1 , C-C-carbocyclyl claim 1 , 3- to 10-membered-heterocyclyl claim 1 , C-C-haloalkyl claim 1 , hydroxy-C-C-alkyl claim 1 , aryl substituent is itself optionally substituted claim 1 , one or more times claim 1 , in the same way or differently claim 1 , with R5′.5. The compound according to wherein R1 is a substituent selected from the group consisting of hydrogen claim 1 , C-C-alkyl and —C(═O)R claim 1 , wherein Rrepresent a substituent selected from the group consisting of C-C-alkyl claim 1 , C-C-haloalkyl claim 1 , C-C-carbocyclyl claim 1 , C-C-alkyl substituted by C-C-alkoxy and aryl claim 1 , ...

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

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

FUNGICIDAL 3--HETEROCYCLE DERIVATIVES

The present invention provides 3-{phenyl[(heterocyclylmethoxy)imino]methyl}-heterocyclyl derivatives of formula (I) 2. A compound according to wherein Xrepresents a hydrogen atom claim 1 , substituted or non-substituted C-C-alkyl claim 1 , substituted or non-substituted C-C-cycloalkyl or a substituted or non-substituted C-C-alkenyl.3. A compound according to wherein Xrepresents a hydrogen atom claim 2 , a methyl group claim 2 , an ethyl group claim 2 , a n-propyl group claim 2 , an isopropyl group or a cyclopropyl group.4. A compound according to wherein Xand Xindependently represent O claim 1 , S claim 1 , C═O claim 1 , C═S claim 1 , or C═NR.5. A compound according to wherein Xand Xindependently represent an O or C═S.6. A compound according to wherein Xrepresents C═S when Xrepresents O or Xrepresents C═S when Xrepresents O.7. A compound according to wherein Xor/and Xrepresents independently C═NR or S(═O)(═NR) and R represents a cyano group or substituted or unsubstituted C-C-alkyl.8. A compound according to wherein A is selected in the list consisting of Ato A.9. A compound according to wherein A is selected in the list consisting of A claim 8 , A claim 8 , A claim 8 , A claim 8 , Aand A.10. A compound according to wherein Zrepresents a hydrogen atom claim 1 , a halogen atom claim 1 , a nitro group claim 1 , an amino group claim 1 , an hydroxyamino group claim 1 , a substituted or non-substituted carbaldehyde O—(C-C-alkyl)oxime claim 1 , substituted or non-substituted C-C-alkoxyamino group claim 1 , a substituted or non-substituted (hydroxyimino)-C-C-alkyl group claim 1 , substituted or non-substituted C-C-alkenyl claim 1 , substituted or non-substituted C-C-alkynyl claim 1 , substituted or non-substituted (C-C-alkoxyimino)-C-C-alkyl claim 1 , substituted or non-substituted (C-C-alkenyloxyimino)-C-C-alkyl claim 1 , substituted or non-substituted (C-C-alkynyloxyimino)-C-C-alkyl claim 1 , substituted or non-substituted (benzyloxyimino)-C-C-alkyl claim 1 , substituted ...

Intermediates to prepare herbicidal pyrimidone derivatives

Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, X is CH or N; Y is C(O) or S(O) 2 ; provided that when Y is S(O) 2 , then X is CH; A is a radical selected from the group consisting of and B 1 , B 2 , B 3 , T, R 1 , R 2 R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling undesired vegetation comprising contacting the undesired vegetation or its environment with an effective amount of a compound or a composition of the invention.

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Compounds that regulate quorum sensing in Staphylococcal bacteria and in particular in Staphylococcus aureus are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in Staphylococcus bacteria and in particular in Staphylococcus aureus. Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of Staphylococcus bacteria and in particular of Staphylococcus aureus. Methods for treating such bacterial infections are provided.

Solid forms comprising 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and a coformer, compositions and methods of use thereof

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed.

TYROSINE KINASE INHIBITORS CONTAINING A ZINC BINDING MOIETY

The present invention relates to tyrosine kinase inhibitors that contain a zinc-binding moiety and their use in the treatment of tyrosine related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors. 1. A method of treating a disease or disorder, wherein said disease or disorder is related to a tyrosine kinase, HDAC or both HDAC and a tyrosine kinase, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound represented by formula (I) or (II):Cz is selected from aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocylic and substituted heterocyclic;Ar is aryl, substituted aryl heteroaryl or substituted heteroaryl;{'sub': '3', 'Xis NH, alkylamino, O or S;'}{'sub': '2', 'Zis O, S, NH or alkylamino;'}{'sub': 2', '20', '20, 'Yis N or CR; where Ris selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl, substituted aryl, heteroaryl, substituted heteroaryl;'}{'sub': '21', 'Ris hydrogen or aliphatic;'}B is a linker;C is selected from:or a geometric isomer, enantiomer, diastereomer, racemate, pharmaceutically acceptable salt or prodrug thereof, whereinwhere W is O or S; Y is absent, N, or CH; Z is N or CH; Rand Rare independently hydrogen, OR′, aliphatic or substituted aliphatic, wherein R′ is hydrogen, aliphatic, substituted aliphatic or acyl; provided that if Rand Rare both present, one of Ror Rmust be OR′ and if Y is absent, Rmust be OR′; and Ris hydrogen, acyl, aliphatic, or substituted aliphatic;where W is O or S; J is O, NH or NCH; and Ris hydrogen or lower alkyl;where W is O or S; Yand Zare independently N, C or CH; andwhere Z, Y, and W are as previously defined; Rand Rare independently selected from hydrogen or aliphatic; R, Rand Rare independently selected from hydrogen, hydroxy, amino, halogen, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or ...

Macrocyclic compounds and their use in the treatment of disease

The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.

INHIBITORS OF KEAP1-Nrf2 PROTEIN-PROTEIN INTERACTION

Sultam compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the KEAP1-Nrf2 interaction, such as inflammatory bowel disease, including Crohn's disease and ulcerative colitis. 164-. (canceled)65. A compound selected from the group consisting of(*R)-3-(7-(Difluoromethoxy)-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((*R)-5,5-dioxido-7,7a,8,9,10,11-hexahydro-6H-dipyrido[2,1-d:2′,3′-f][1,2,5]thiadiazepin-6-yl)methyl)-4-methylphenyl)propanoic acid;(*R)-3-(7-Cyclopropoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-5,5-dioxido-7a,8,9,10-tetrahydropyrido[2,3-f]pyrrolo[2,1-d][1,2,5]thiadiazepin-6(7H)-yl)methyl)-4-methylphenyl)propanoic acid;(*R)-3-(1-Ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-2,2-dimethyl-3-(6-methyl-5-((8′-methyl-1′,1′-dioxido-2,3,5,6-tetrahydrospiro[pyran-4,4′-pyrido[2,3-b][1,4,5]oxathiazepin]-2′(3′H)-yl)methyl)pyridin-3-yl)propanoic acid;(*S)-3-(3-((1′,1′-Dioxido-2,3,5,6-tetrahydrospiro[pyran-4,4′-pyrido[2,3-b][1,4,5]oxathiazepin]-2′(3′H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-7-yl)propanoic acid;(*R)-3-(3-((7′-(((1R,3R)-3-Hydroxycyclobutyl)amino)-8′-methyl-1′,1′-dioxido-2,3,5,6-tetrahydrospiro[pyran-4,4′-pyrido[2,3-b][1,4,5]oxathiazepin]-2′(3′H)-yl)methyl)-4-methylphenyl)-2,2-dimethyl-3-(8-methyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)propanoic acid;(*R)-2,2-Dimethyl-3-(4-methyl-3-((8′-methyl-7′-(((1-morpholinopropan-2-yl)amino)-1′,1′-dioxido-2,3,5,6-tetrahydrospiro[pyran-4,4′-pyrido[2,3-b][1,4,5]oxathiazepin]-2′(3′H)-yl)methyl)phenyl)-3-(8-methyl-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-7-yl)propanoic acid;(*S)-2,2-Dimethyl-3-(4-methyl-3-((8′-methyl-1′,1′-dioxido-7′-(2-(pyrrolidin-1-yl)ethoxy)spiro[cyclopropane-1,4′-pyrido[2,3-b][1,4,5]oxathiazepin]-2′(3′H)-yl)methyl)phenyl)-3-(8-methyl-3-(trifluoromethyl)-[1,2,4] ...

ETHER LINKED TRIAZOLES AS NRF2 ACTIVATORS

The present invention relates to ether-linked triazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof: 1. A compound selected from:(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;R)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)-3-((1-propyl-1H-1,2,3-triazol-4-yl)methoxy)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5- ...

N-ARYL PYRAZOLES AS NRF2 REGULATORS

The present invention relates to N-aryl pyrazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 regulators. In particular, the compounds of this invention include a compound of Formula (I): 3. The compound of selected from:1-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-(((S)-4-Ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid.1-(3-((8-fluoro-4,4-dimethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-((R or S)-1-((S)-4-Methyl-1,1-dioxido-8-(trifluoromethyl)-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)ethyl)phenyl)-5-((1R,2R)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid1-(3-((4,4-Dimethyl-4,5-dihydro-1H-benzo[c]azepin-2(3H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-((2,2-dimethyl-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-((2,2-dimethyl-2,3-dihydropyrido[2,3-f][1,4]oxazepin-4(5H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-(((R)-4-ethyl-4,5-dihydro-1H-benzo[c]azepin-2(3H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-(((S)-4-ethyl-4,5-dihydro-1H-benzo[c]azepin-2(3H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole-4-carboxylic acid;1-(3-((7-bromo-2,2-dimethyl-2,3-dihydrobenzo[f][1,4]oxazepin-4(5H)-yl)methyl)phenyl)-5-(trans)-2-(1-methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-1H-pyrazole- ...

ACTIVATORS OF THE RETINOIC ACID INDUCIBLE GENE "RIG-I" PATHWAY AND METHODS OF USE THEREOF

The present invention is directed to compounds of Formula (I), which are activators of the RIG-I pathway. 3. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein X is N.411.-. (canceled)13. The compound of or pharmaceutically acceptable salt thereof claim 12 , wherein Yis CR claim 12 , Yis CR claim 12 , Yis CR claim 12 , Yis CR claim 12 , Yis CR claim 12 , and Yis CR.14. The compound of or pharmaceutically acceptable salt thereof claim 13 , wherein R claim 13 , R claim 13 , R claim 13 , R claim 13 , R claim 13 , and Rare each independently selected from H claim 13 , halo claim 13 , Calkyl claim 13 , Chaloalkyl claim 13 , CN claim 13 , NO claim 13 , and OR.1534.-. (canceled)35. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or NRC(S)NRR.3637.-. (canceled)38. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein each Ris selected from H and Caryl claim 1 , wherein said Caryl is optionally substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 substituents independently selected from halo claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , CN claim 1 , OR claim 1 , and NRR.3941.-. (canceled)42. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , halo claim 1 , Calkyl claim 1 , Caryl claim 1 , Ccycloalkyl claim 1 , 5-10 membered heteroaryl claim 1 , 4-10 membered heterocycloalkyl claim 1 , Caryl-Calkyl claim 1 , Ccycloalkyl-Calkyl claim 1 , 5-10 membered heteroaryl-Calkyl claim 1 , 4-10 membered heterocycloalkyl-Calkyl claim 1 , CN claim 1 , NO claim 1 , OR claim 1 , C(O)NRR claim 1 , S(O)R claim 1 , Caryl-Calkyl claim 1 , NO claim 1 , NRR claim 1 , NRC(O)R claim 1 , NRS(O)R claim 1 , or C(O)OR.4345.-. (canceled)46. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein each Ris H or Calkyl.47. (canceled)48. The compound of or pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently ...

ETHER LINKED TRIAZOLES AS NRF2 ACTIVATORS

The present invention relates to ether-linked triazole compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof: 3. The compound of selected from:(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;R)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)-3-((1-propyl-1H-1,2,3-triazol-4-yl)methoxy)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3S)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;(3R)-((1-ethyl-1H-1,2,3-triazol-4-yl)methoxy)-2,2-dimethyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5 ...

SUBSTITUTED HETEROARYL PYRROLONES AND SALTS THEREOF AND USE THEREOF AS HERBICIDAL ACTIVE SUBSTANCES

The present invention relates to substituted heteroarylpyrrolones of the general formula (I) or salts thereof, 6. The compound of formula (I) as claimed in and/or the salt thereof claim 5 , wherein{'sup': '1', 'claim-text': [{'sup': '1', 'X represents C—H if Y represents the moiety C—Rand'}, {'sup': '1', 'X represents the moiety C—Rif Y represents C—H,'}], 'X and Y independently of one another represent C—H or the moiety C—R, where'}{'sup': '1', 'Rrepresents methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantan-1-yl, adamantan-2-yl, 1-methylcyclopropyl, 2-methylcyclopropyl, 2,2-dimethylcyclopropyl, 2,3-dimethylcyclopropyl, 1,1′-bi(cyclopropyl)-1-yl, 1,1′-bi(cyclopropyl)-2-yl, 2′-methyl-1,1′-bi(cyclopropyl)-2-yl, 1-cyanocyclopropyl, 2-cyanocyclopropyl, 1-methylcyclobutyl, 2-methylcyclobutyl, 3-methylcyclobutyl, 3,3-dimethylcyclobut-1-yl, 3,3-difluorocyclobut-1-yl, 3-fluorocyclobut-1-yl, 2,2-difluorocycloprop-1-yl, 1-fluorocycloprop-1-yl, 2-fluorocycloprop-1-yl, 1-ethylcyclopropyl, 1-methylcyclohexyl, 2-methylcyclohexyl, 3-methylcyclohexyl, 1-methoxycyclohexyl, 2-methoxycyclohexyl, 3-methoxycyclohexyl, trifluoromethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethyl, heptafluoropropyl, nonafluorobutyl, chlorodifluoromethyl, difluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, difluoro-tert-butyl, methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, tert-butyloxy, methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl, ...

COMPOUNDS AS NUCLEAR TRANSPORT MODULATORS AND USES THEREOF

Nuclear transport modulators are disclosed. The compounds can inhibit nuclear transporters such as the exportin-1 transporter. The compounds and pharmaceutical compositions comprising the compounds can be used to treat neurological diseases and cancer. 2. A pharmaceutical composition comprising the compound of .3. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition is an oral formulation.4. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of claim 1 , wherein the disease is associated with exportin-1 (XPO-1) activity.5. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of claim 1 , wherein the disease is a neurological disease or a symptom of a neurological disease.6. The method of claim 5 , wherein the neurological disease is selected from amyotrophic lateral sclerosis claim 5 , epilepsy claim 5 , a traumatic brain injury claim 5 , Huntington's disease claim 5 , Parkinson's disease claim 5 , rheumatoid arthritis claim 5 , and systemic lupus erythematosus.7. A method of treating a disease in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of the compound of claim 1 , wherein the disease is cancer.8. The method of claim 7 , wherein the cancer is a solid tumor.9. The method of claim 7 , wherein the cancer is selected from lymphoma claim 7 , liposarcoma claim 7 , multiple myeloma claim 7 , myelodysplastic syndrome claim 7 , prostate cancer claim 7 , colorectal cancer claim 7 , endometrial cancer claim 7 , pancreatic cancer claim 7 , gastric cancer claim 7 , diffuse large B-cell lymphoma claim 7 , non-small cell lung cancer claim 7 , ovarian carcinoma claim 7 , breast cancer claim 7 , acute myeloid leukemia claim 7 , thymoma claim 7 , esophageal cancer claim 7 , ...

NOVEL OXADIAZOLE COMPOUNDS FOR CONTROLLING OR PREVENTING PHYTOPATHOGENIC FUNGI

The present invention discloses a compound of formula (I),

FUSED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS

The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: 3. The compound of or , wherein Ris —Calkylene-Ror —Calkylene-L-R.4. The compound of or , wherein Ris cycloalkyl , aryl , heteroaryl or heterocyclyl;{'sub': '1-6', 'sup': 20', '22', '20', '20, 'claim-text': {'sub': 1-6', '1-6, 'claim-text': {'sub': '1-6', 'wherein said Calkyl is optionally further substituted with one, two or three halo.'}, 'wherein said Calkyl or heteroaryl are optionally further substituted with one, two or three substituents independently selected from the group consisting of halo, Calkyl and aryl; and'}, 'wherein said cycloalkyl, aryl, heteroaryl or heterocyclyl are optionally substituted with one, two or three substituents independently selected from the group consisting of Calkyl, halo, cycloalkyl, heterocyclyl, heteroaryl, —N(R)(R), —C(O)—OR, —CN and —O—R;'}5. The compound of claim 1 , wherein Rand one of Rcan join together with the atom to which they are attached to form a heterocyclyl;{'sub': '1-6', 'sup': 20', '20', '22', '20, 'claim-text': {'sub': '1-6', 'wherein said Calkyl is optionally substituted with one, two or three substituents independently selected from the group consisting of halo and heteroaryl.'}, 'wherein said heterocyclyl is optionally substituted with one, two or three substituents independently selected from the group consisting of Calkyl, —O—R, —N(R)(R) and —C(O)—OR; and'}7. The compound of claim 2 , wherein n is 1 claim 2 , 2 or 3; and{'sup': 10', '20', '20, 'sub': 2', '1-4, 'claim-text': 'wherein said alkyl and cycloalkyl are optionally substituted with one, two or three halo or —CN; and', 'each Ris independently selected from the group consisting of halo, —O—R, —O—S(O)—R, Calkyl and cycloalkyl; and'}{'sup': '20', 'sub': '1-6', 'claim-text': 'wherein the ...

COMPOUNDS AND METHODS FOR THE TREATMENT OF ISOCITRATE DEHYDROGENASE RELATED DISEASES

The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: 4. The compound according to claim 1 , wherein Ris an optionally substituted alkyl.5. The compound according to claim 1 , wherein Ris an optionally substituted C-Calkyl.8. A compound according to claim 1 , wherein q is 1.13. The method according to claim 12 , wherein said defect in isocitrate dehydrogenase is a somatic mutation at codon 132 isocitrate dehydrogenase (IDH1) or at codon 172 in isocitrate dehydrogenase 2 (IDH2) or at codon 140 of IDH2.14. The method according to claim 12 , wherein said patient has mutations on both IDH1 and IDH2.15. The method according to claim 12 , wherein said mutation is selected from R132H claim 12 , R132C claim 12 , R132S claim 12 , R132L claim 12 , R132G in IDH1 claim 12 , or R172M claim 12 , R172G claim 12 , R172K or R140Q in IDH2.16. The method according to claim 12 , wherein said disease is a cell proliferative disease.17. The method according to claim 12 , wherein said disease is selected from Grade I claim 12 , II claim 12 , III or IV glioma.18. The method according to claim 12 , wherein said disease is selected from astrocytomas claim 12 , oligodendrogliomas claim 12 , ependymomas and glioblastoma multiforme (GBM).19. A method of treating a patient exhibiting abnormal 2-hydroxyglutarate (2-HG) production comprising administering a compound according to .20. The method according to claim 19 , wherein said abnormal 2-HG production is an increase of more than about 20 fold claim 19 , or more than about 40 fold or more than about 50 fold or more than about 100 fold or more than about 200 fold compared to a corresponding normal cell or tissue or plasma concentration of 2-HG.21. The method according to claim 20 , wherein said increase is due to a mutation in IDH1.22. The method according to claim 20 , wherein said increase is due to a mutation in IDH2.23. A method of treating a disease related to a defect in isocitrate ...

QUINOLINONE CARBOXAMIDE INHIBITORS OF ENDOTHELIAL LIPASE

The present invention provides compounds of Formula (I): 3. A compound according to claim 1 , wherein:{'sup': 1', 'a', 'a', '1a, 'sub': 1-6', '2-6', '2', 'n, 'Ris independently selected from the group consisting of: Calkyl substituted with 0-2 R, Calkenyl substituted with 0-2 R, and —(CH)—W—R;'}{'sub': 1-4', '2, 'sup': 'f', 'W is independently selected from the group consisting of: a bond, CO, CONH, CON(Calkyl), SO, and CHR;'}{'sup': 1a', 'c', 'b', 'e', 'c, 'sub': 3-6', 'p, 'Ris independently selected from the group consisting of: Ccycloalkyl substituted with 0-3 R, phenyl substituted with 0-3 R, and a 5- to 6-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NR, O, and S(O); and wherein said heterocycle is substituted with 0-3 R;'}{'sup': 'g', 'sub': '2', 'L is independently a hydrocarbon or hydrocarbon-heteroatom linker optionally substituted with 0-1 R; wherein said hydrocarbon linker has one to four carbon atoms and may be straight or branched, saturated or unsaturated; and said hydrocarbon-heteroatom linker has one to four carbon atoms and one group selected from O, S, —SO—, and —SO—;'}{'sub': 1', '2, 'alternatively, L is X—Y—X;'}{'sub': 1', '2', '2', '1-4, 'sup': 'g', 'X, and Xare, independently at each occurrence, selected from the group consisting of: a bond, a hydrocarbon linker and a hydrocarbon-heteroatom linker; wherein said hydrocarbon linker and hydrocarbon-heteroatom linker may be substituted with 0-1 R; said hydrocarbon linker may be saturated or unsaturated and has one to five carbon atoms; and said hydrocarbon-heteroatom linker may be saturated or unsaturated and has zero to four carbon atoms and one group selected from O, —CO—, S, —SO—, —SO—, NH, and N(Calkyl);'}{'sub': 3-6', '4-6', '1-4', '1-4', '1-4, 'Y is independently selected from the group consisting of: Ccycloalkylene, Ccycloalkenylene, phenylene, pyridylene, azetidinylene, pyrrolidinylene, piperidinylene, pyrazolylene, thiazolylene, oxadiazolylene, ...

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed. 176-. (canceled)77. A method of treating relapsed and refractory multiple myeloma , the method comprising administering to a patient dexamethasone in combination with a solid form comprising (a) 4-amino-2-(2 ,6-dioxopiperidine-3-yl)isoindoline-1 ,3-dione (pomalidomide); and (b) a coformer; wherein:the coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 15.52, 26.16, and 26.90 degrees 2θ±0.2 degrees 2θ;the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 12.25, and 25.61 degrees 2θ±0.2 degrees 2θ;the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 18.54 degrees 2θ±0.2 degrees 2θ;the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 12.31, 20.68, and 25.52 degrees 2θ±0.2 degrees 2θ;the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 12.29, 25.23, and 25.61 degrees 2θ±0.2 degrees 2θ;the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 17.36, and 25.10 degrees 2θ±0.2 degrees 2θ;the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2θ±0.2 degrees 2θ;the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 17.16, 28.76, and 29.95 degrees 2θ±0.2 degrees 2θ;the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 13.99, 16.63, and 25.58 degrees 2θ±0.2 degrees 2θ;the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 11.87, 17.09, and 25.73 degrees 2θ±0.2 degrees 2θ;the ...

Heteroarylpiperidine and -piperazine derivatives as fungicides

Heteroarylpiperidine and -piperazine derivatives of the formula (I) in which the symbols R A1 , R A2 , X, Y, L 1 , L 2 , R B1 , R B2 , G, Q, p, R 1 , R 2 and R 10 are each as defined in the description, and salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

DEGRADERS OF KELCH-LIKE ECH-ASSOCIATED PROTEIN 1 (KEAP1)

The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by Kelch-like ECH-associated protein 1 (KEAP1). In some aspects, the present invention is directed to methods of treating diseases or disorders involving dysfunctional (e.g., dysregulated) KEAP1 activity, that entails administration of a therapeutically effective amount of a bifunctional compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof, to a subject in need thereof. 2. (canceled)5. (canceled)7. (canceled)9. The bifunctional compound of claim 1 , wherein the linker is an alkylene chain or a bivalent alkylene chain interrupted by claim 1 , and/or terminating in at least one of —O— claim 1 , —S— claim 1 , —N(R′)— claim 1 , —C≡C— claim 1 , —C(O)— claim 1 , —C(O)O— claim 1 , —OC(O)— claim 1 , —OC(O)O— claim 1 , —C(NOR′)— claim 1 , —C(O)N(R′)— claim 1 , —C(O)N(R′)C(O)— claim 1 , —C(O)N(R′)C(O)N(R′)— claim 1 , —N(R′)C(O)— claim 1 , —N(R′)C(O)N(R′)— claim 1 , —N(R′)C(O)O— claim 1 , —OC(O)N(R′)— claim 1 , —C(NR′)— claim 1 , —N(R′)C(NR′)— claim 1 , —C(NR′)N(R′)— claim 1 , —N(R′)C(NR′)N(R′)— claim 1 , —S(O)— claim 1 , —OS(O)— claim 1 , —S(O)O— claim 1 , —S(O)— claim 1 , —OS(O)— claim 1 , —S(O)O— claim 1 , —N(R′)S(O)— claim 1 , —S(O)N(R′)— claim 1 , —N(R′)S(O)— claim 1 , —S(O)N(R′)— claim 1 , —N(R′)S(O)N(R′)— claim 1 , —N(R′)S(O)N(R′)— claim 1 , Ccarbocyclene claim 1 , 3- to 12-membered heterocyclene claim 1 , 5- to 12-membered heteroarylene claim 1 , or any combination thereof claim 1 , wherein R′ is H or C-Calkyl claim 1 , wherein the interrupting group and the terminating functional groups may be the same or different.11. (canceled)13. (canceled)14. (canceled)16. (canceled)17. (canceled)20. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of the compound of claim 1 , or pharmaceutically acceptable salt or stereoisomer thereof claim 1 , and a pharmaceutically acceptable carrier.21 ...

AMINOPYRIDINE DERIVATIVES AND THEIR USE AS SELECTIVE ALK-2 INHIBITORS

The invention relates to a compound of formula (1) in free form or in pharmaceutically acceptable salt form 19-. (canceled)10. A compound which is 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1R ,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide fumarate or a hydrate thereof.11. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to and one or more pharmaceutically acceptable carriers.12. A method of inhibiting ALK-2 receptor activity in a subject claim 10 , wherein the method comprises administering to the subject a therapeutically effective amount of the compound according to .13. A method of treating a disorder or disease selected from heterotopic ossification or fibrodysplasia ossificans progressiva claim 10 , comprising administering to the subject a therapeutically effective amount of the compound according to .1416.-. (canceled)17. The compound according to claim 10 , wherein the compound is 2-amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-((1R claim 10 ,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide fumarate dihydrate.18. The compound of claim 17 , which is crystalline.19. The compound of having a DSC thermogram which is characterized by an endothermic peak at about 160° C.20. The compound of characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles (±0.2 degrees) of 7.0 claim 17 , 14.2 claim 17 , 15.6 claim 17 , 16.2 claim 17 , 18.0 claim 17 , 19.2 claim 17 , and 25.5.21. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to and one or more pharmaceutically acceptable carriers.22. A method of inhibiting ALK-2 receptor activity in a subject claim 17 , wherein the method comprises administering to the subject a therapeutically effective amount of the compound according to .23. A method of treating heterotopic ossification or fibrodysplasia ...

PROCESSES FOR PREPARING OXATHIAZIN-LIKE COMPOUNDS

Oxathiazin-like compounds, processes for making new oxathiazin-like compounds, compounds useful for making oxathiazin-like compounds, and their uses are disclosed. Processes of treating patients suffering from cancers, bacterial infections, fungal infections and/or viral infections by administering oxathiazin-like compounds are also disclosed. These compounds were found to have significantly longer half-life compared to taurolidine and taurultam. 2. The method of claim 1 , wherein the compound is administered orally claim 1 , intravenously claim 1 , topically claim 1 , or a combination thereof.4. The method of claim 1 , comprising administering 0.1 g to about 100 g of the compound per day.5. The method of claim 1 , comprising administering 5 g to about 30 g of the compound per day.6. The method of claim 1 , comprising administering the compound in a gel claim 1 , capsule claim 1 , tablet claim 1 , or solution.7. The method of claim 1 , comprising administering the compound in a pharmaceutical composition at a concentration of about 0.01 to about 3% w/v.8. The method of claim 1 , comprising administering the compound in a pharmaceutical composition at a concentration of about 0.01 μg/ml to about 1000 μg/ml.9. The method of claim 1 , comprising administering the compound in a pharmaceutical composition containing about 0.01 to about 3% taurolidine and/or taurultam.10. The method of claim 1 , wherein the subject has a tumor claim 1 , cancerous cells claim 1 , pre-cancerous cells claim 1 , or cancer stem cells claim 1 , is suspected of having a tumor claim 1 , cancerous cells claim 1 , pre-cancerous cells claim 1 , or cancer stem cells claim 1 , or is at risk of developing a tumor claim 1 , cancerous cells claim 1 , pre-cancerous cells claim 1 , cancer stem cells or metastases thereof.12. The method of claim 11 , wherein the squamous cell carcinoma is a cutaneous squamous cell carcinoma.13. The method of claim 11 , wherein the compound is administered orally claim 11 , ...

Cyclic sulfonamide containing derivatives as inhibitors of hedgehog signaling pathway

The invention relates generally to the creation and use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases.

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. 2. The compound of claim 1 , or a salt thereof claim 1 , wherein the A ring is bicyclic aryl or bicyclic heteroaryl.5. The compound of wherein the B ring is cyclopentane claim 4 , pyrrolidine claim 4 , imidazolidine claim 4 , 1 claim 4 ,3-dioxolane claim 4 , oxazolidine claim 4 , tetrahydrofuran claim 4 , cyclohexane claim 4 , morpholine claim 4 , piperidine claim 4 , dioxane claim 4 , oxathiazinane claim 4 , piperazine claim 4 , cycloheptane claim 4 , cycloheptene claim 4 , azepane claim 4 , tetrahydroazepine claim 4 , diazepane claim 4 , cyclooctane claim 4 , cyclooctene claim 4 , azocane claim 4 , hexahydroazocine claim 4 , diazocane or hexahydrodiazocine.14. The composition according to further comprising an excipient claim 11 , a second therapeutic claim 11 , or combinations thereof.18. The method according to claim 15 , comprising administering the compound in an amount effective for treating a disease selected from allergies claim 15 , autoimmune diseases claim 15 , transplant rejection claim 15 , T-cell mediated autoimmune diseases claim 15 , Type II inflammatory diseases claim 15 , delayed Type IV hypersensitivity reactions claim 15 , or hematologic malignancies.19. The method according to comprising contacting a JAK kinase ex vivo or in vivo.20. The method according to comprising administering the compound of formula I claim 15 , or a salt thereof claim 15 , in combination with or adjunctively to a second therapeutic. This application is a continuation of U.S. patent application Ser. No. 14/793,506, filed on Jul. 7, 2015, which is a continuation of U.S. patent application Ser. No. 14/250,329, filed on Apr. 10, 2014, now issued as U.S. Pat. No. 9,248,132, which is a continuation of U ...

Compositions and methods for inhibition of the jak pathway

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful.

NOVEL COMPOUND FOR INHIBITING NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE AND COMPOSITION CONTAINING SAME

The present invention relates to a novel compounds for inhibiting nicotinamide phosphoribosyltransferase (NamPT), a composition comprising the same, and various uses thereof. 130.-. (canceled)32. The method of claim 31 , wherein the compound is selected from the group of following compounds:1) N-(4-(benzo[d]oxazol-2-yl)benzyl)nicotinamide;2) N-(4-(6-methylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;3) N-(4-(6-methylbenzo[d]oxazol-2-yl)benzyl)benzamide;4) N-(4-(5-methylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;5) N-(4-(5-ethylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;6) N-(4-(6-ethylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;7) N-(4-(5-isopropylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;8) N-(4-(6-(tert-butyl)benzo[d]oxazol-2-yl)benzyl)nicotinamide;9) N-(4-(5-methoxybenzo[d]oxazol-2-yl)benzyl)nicotinamide;10) N-(4-(6-chlorobenzo[d]oxazol-2-yl)benzyl)nicotinamide;11) N-(4-(6-nitrobenzo[d]oxazol-2-yl)benzyl)nicotinamide;12) N-(4-(5-phenylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;13) N-(4-(naphtho[2,3-d]oxazol-2-yl)benzyl)nicotinamide;14) N-(4-(oxazolo[5,4-b]pyridin-2-yl)benzyl)nicotinamide;15) N-(4-(oxazolo[4,5-c]pyridin-2-yl)benzyl)nicotinamide;16) N-(4-(oxazolo[4,5-b]pyridin-2-yl)benzyl)nicotinamide;17) N-(4-(benzo[d]thiazol-2-yl)benzyl)nicotinamide; and18) N-(4-(5-isopropylbenzo[d]oxazol-2-yl)phenyl)nicotinamide. The present invention relates to novel compounds for inhibiting nicotinamide phosphorbosyltransferase (NamPT) and a composition comprising the same and various uses thereof.NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays an important role in many physiologically essential processes (Ziegkel, M. 267, 1550-1564, 2000). NAD is essential for several signaling pathways including mono-ADP-ribosylation in both the immune system and G-protein-coupled receptor signaling among other poly ADP-ribosylation in DNA repair, and is also essential for the activity of Sirtuin deacetylase (Garten, A. et al., 20, 130-138, 2008).Nicotinamide phosphoribosyltransferase (NamPT) ...

RADIOLABELLED mGluR2 PET LIGANDS

The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a mammal, in vitro or in vivo and to precursors of said compounds.

INSECTICIDAL COMPOUNDS BASED ON ISOXAZOLINE DERIVATIVES

The present invention relates to compounds of formula (I): 4. The method of wherein Ris hydrogen claim 2 , cyano-C-Calkyl claim 2 , C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , C-Ccycloalkyl where one carbon atom in the cycloalkyl group is replaced by O claim 2 , S claim 2 , S(O) or SO claim 2 , or C-Chaloalkyl claim 2 , C-Chydroxyalkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , phenyl-C-Calkyl or phenyl-C-Calkyl wherein the phenyl moiety is substituted by one to three R claim 2 , 5-6 membered heteroaryl-C-Calkyl or 5-6 membered heteroaryl-C-Calkyl wherein the heteroaryl moiety is substituted by one to three R claim 2 , and wherein the heteroaryl is pyridyl claim 2 , pyridazinyl claim 2 , pyrimidinyl claim 2 , pyrazinyl claim 2 , pyrazolyl claim 2 , furanyl claim 2 , thiophenyl claim 2 , oxazolyl claim 2 , isoxazolyl or thiazolyl.5. The method of claim 2 , wherein the animal is selected from the group consisting of a cow claim 2 , a pig claim 2 , a sheep claim 2 , a goat claim 2 , a horse claim 2 , a donkey claim 2 , a dog and a cat.6. The method of claim 2 , wherein the pest is selected from the group consisting of a nematode claim 2 , a trematode claim 2 , a cestode claim 2 , a fly claim 2 , a mite claim 2 , a tick claim 2 , a louse claim 2 , a flea claim 2 , a true bug and a maggot.7. The method of claim 2 , wherein administering is selected from the group consisting of an oral administration claim 2 , a parenteral administration claim 2 , and an external administration. This application is a continuation application of U.S. patent application Ser. No. 14/258,079, filed 22 Apr. 2014, which is a continuation application of U.S. patent application Ser. No. 13/512,820 filed May 30, 2012, which is a 371 of International Application No. PCT/EP2010/068605 filed Dec. 1, 2010, which claims priority to EP 09177640.1 filed Dec. 1, 2009, and EP 10186537.6 filed Oct. 5, 2012, the contents of which are incorporated herein by reference.The present invention relates to ...

OXATHIAZINE DERIVATIVES AS ANTIBACTERIAL AND ANTICANCER AGENTS

New oxathiazin-like compounds and their derivatives are useful as antineoplastic and antimicrobial agents. Compositions and methods of using oxathiazin-like compounds and their derivatives are disclosed. 2. The compound of claim 1 , comprising compound A3.3. The compound of claim 1 , comprising compound 2245.5. The method of claim 4 , wherein cancer cells of said cancer are killed claim 4 , or growth of said cancer cells is inhibited claim 4 , by at least one of oxidative stress claim 4 , apoptosis claim 4 , anti-angiogenesis or antitubulogenesis.6. The method of claim 4 , wherein said compound is 2245.7. The method of claim 4 , wherein said compound is 2255.8. The method of claim 4 , wherein said cancer is glioblastoma claim 4 , glioma claim 4 , neuroblastoma claim 4 , astrocytoma claim 4 , carcinomatous meningitis claim 4 , colon cancer claim 4 , rectal cancer claim 4 , colo-rectal cancer claim 4 , ovarian cancer claim 4 , breast cancer claim 4 , prostate cancer claim 4 , lung cancer claim 4 , mesothelioma claim 4 , melanoma claim 4 , renal cancer claim 4 , liver cancer claim 4 , pancreatic cancer claim 4 , gastric cancer claim 4 , esophageal cancer claim 4 , urinary bladder cancer claim 4 , cervical cancer claim 4 , cardiac cancer claim 4 , gall bladder cancer claim 4 , skin cancer claim 4 , bone cancer claim 4 , cancers of the head or neck claim 4 , leukemia claim 4 , lymphoma claim 4 , lymphosarcoma claim 4 , adenocarcinoma claim 4 , or fibrosarcoma claim 4 , or metastases thereof.9. The method of claim 8 , wherein said compound is 2245.10. The method of claim 4 , wherein said compound is 2255.11. A method of treating glioblastoma in a subject claim 1 , comprising administering to said subject the compound of .12. A method of treating glioma in a subject claim 1 , comprising administering to said subject the compound of .14. The method of wherein said compound is 2245.15S. aureus, E. coli, H. pylori. The method of wherein said bacterial infection is or MRSA ...

MIXED DISULFIDE CONJUGATES OF THIENOPYRIDINE COMPOUNDS AND USES THEREOF

This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases. 2. (canceled)3. (canceled)4. (canceled)5. The compound of claim 1 , wherein the compound has one or more of the following stereochemical configurations: a) the double bond connected with the R4 substituent is either in a Z or cis configuration; b) the C7 carbon is either in a racemic claim 1 , R or S configuration; and c) the C4 carbon is either in a racemic claim 1 , R or S configuration.7. (canceled)8. The compound of claim 1 , wherein the R4 substituent is engaged with an applicable metal to form a salt claim 1 , wherein the applicable metal is selected from Na claim 1 , K claim 1 , and Li claim 1 , orwherein the R4 substituent is engaged with an applicable halogen to form an ammonium salt.9. (canceled)12. (canceled)13. (canceled)14. The compound of claim 1 , wherein R3 is selected from the group consisting of Cl claim 1 , Br claim 1 , I claim 1 , F claim 1 , CN claim 1 , NO claim 1 , CF claim 1 , H claim 1 , and OCH.16. (canceled)17. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.18. (canceled)19. A method of treating claim 1 , ameliorating claim 1 , or preventing a cardiovascular disease in a patient comprising administering to said patient a therapeutically effective amount of the compound of claim 1 , wherein said administration is selected from the group consisting of oral administration and intravenous administration claim 1 , wherein said cardiovascular disease is selected from the group consisting of coronary artery disease claim 1 , peripheral vascular disease claim 1 , atherothrombosis claim 1 , and cerebrovascular disease.20. (canceled)21. (canceled)22. The method of claim 19 ,{'sub': '12', 'wherein said compound reduces aggregation of platelets, ...

ANTI-BIOFILM COMPOUNDS

The present invention provides non-peptide compounds that mimic the streptococcal SspB Adherence Region (BAR) and function as inhibitors of adherence to streptococci. The invention also provides methods of making and using the inhibitors. 2. (canceled)3. The compound of claim 1 , wherein Ris aryl claim 1 , or 5-6 membered heteroaryl wherein the aryl or 5-6 membered heteroaryl is optionally substituted with one or more groups independently selected from the group consisting of (C-C)alkyl claim 1 , (C-C)alkenyl claim 1 , (C-C)alkynyl claim 1 , (C-C)carbocycle claim 1 , halo(C-C)alkyl claim 1 , —CN claim 1 , NO claim 1 , halogen claim 1 , —OR claim 1 , —SR claim 1 , —S(O)NRR claim 1 , —NRR claim 1 , —NRCOR claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , and —C(O)NRR.4. The compound of claim 1 , wherein Ris phenyl or 5-6 membered heteroaryl wherein the phenyl or 5-6 membered heteroaryl is optionally substituted with one or more groups independently selected from the group consisting of (C-C)alkyl claim 1 , halo(C-C)alkyl claim 1 , or halogen.5. The compound of claim 1 , wherein Ris phenyl wherein the phenyl is optionally substituted with one or more groups independently selected from the group consisting of halogen.67-. (canceled)8. The compound of claim 1 , wherein Ris aryl claim 1 , or 5-6 membered heteroaryl wherein the aryl or 5-6 membered heteroaryl is optionally substituted with one or more groups independently selected from the group consisting of (C-C)alkyl claim 1 , (C-C)alkenyl claim 1 , (C-C)alkynyl claim 1 , (C-C)carbocycle claim 1 , halo(C-C)alkyl claim 1 , —CN claim 1 , NO claim 1 , halogen claim 1 , —OR claim 1 , —SR claim 1 , —S(O)NRR claim 1 , —NRR claim 1 , —NRCOR claim 1 , —C(O)R claim 1 , —C(O)R claim 1 , and —C(O)NRR.912-. (canceled)13. The compound of claim 1 , wherein Y is heteroaryl or aryl wherein any heteroaryl claim 1 , or aryl of Y is optionally substituted with one or more Zgroups.14. (canceled)15. The compound of claim 1 , wherein each Zis ...

COVALENT INHIBITORS OF KRAS G12C

Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein. 231-. (canceled)35. The compound of claim 32 , wherein Gis N and Gis CR.36. The compound of claim 32 , wherein Gis CR and Gis N.37. The compound of claim 32 , wherein Gis N and Gis N.38. The compound of claim 32 , wherein nis 2 and nis 2.39. The compound of claim 32 , wherein nis 1 and nis 1.40. The compound of claim 32 , wherein nis 2 and nis 1.41. The compound of claim 32 , wherein R claim 32 , R claim 32 , R claim 32 , Rand Rare each independently H claim 32 , —OH claim 32 , halo claim 32 , oxo claim 32 , C-Calkyl claim 32 , C-Calkoxy claim 32 , heterocyclyl or aryl.42. The compound of claim 41 , wherein R claim 41 , R claim 41 , R claim 41 , Rand Rare each independently H claim 41 , —OH claim 41 , fluoro claim 41 , chloro claim 41 , bromo claim 41 , iodo claim 41 , oxo claim 41 , methyl claim 41 , methoxy claim 41 , heteroaryl or aryl.43. The compound of claim 32 , wherein Ror Ris aryl.44. The compound of claim 43 , wherein aryl is phenyl.4546-. (canceled)47. The compound of claim 43 , where the aryl is substituted with one or more halo substituents.48. The compound of claim 47 , wherein the halo substituents are selected from fluoro and chloro.49. The compound of claim 32 , wherein Ris heteroaryl.5052-. (canceled)53. The compound of claim 49 , wherein the heteroaryl is thiophenyl.54. The compound of claim 32 , wherein Ror R claim 32 , or both claim 32 , is halo.55. The compound of claim 54 , wherein halo is chloro claim 54 , bromo or iodo.57. The compound of claim 32 , wherein R claim 32 , Rand Rare each independently H or aryl.58. The compound of claim 57 , wherein R claim 57 , Rand Rare each independently H.59. The compound of claim 32 , wherein Ris aryl.60. The compound of claim 59 , wherein the aryl is substituted with one or more halo ...

Materials for organic electroluminescent devices

The present invention describes dibenzofuran derivatives substituted by electron-deficient heteroaryl groups, and electronic devices, especially organic electroluminescent devices, comprising these compounds as triplet matrix materials.

CONDENSED CYCLIC COMPOUND AND ORGANIC LIGHT-EMITTING DEVICE INCLUDING THE SAME

Provided are a condensed cyclic compound represented by Formula 1 and an organic light-emitting device including the same: 2. The condensed cyclic compound of claim 1 , wherein Ais a benzene group claim 1 , a naphthalene group claim 1 , an anthracene group claim 1 , a phenanthrene group claim 1 , a fluorene group claim 1 , a spiro-bifluorene group claim 1 , an indene group claim 1 , a pyrrole group claim 1 , a thiophene group claim 1 , a furan group claim 1 , an imidazole group claim 1 , a pyrazole group claim 1 , a thiazole group claim 1 , an isothiazole group claim 1 , an oxazole group claim 1 , an isoxazole group claim 1 , a pyridine group claim 1 , a pyrazine group claim 1 , a pyrimidine group claim 1 , a pyridazine group claim 1 , a quinoline group claim 1 , an isoquinoline group claim 1 , a benzoquinoline group claim 1 , a quinoxaline group claim 1 , a quinazoline group claim 1 , a carbazole group claim 1 , a benzimidazole group claim 1 , an imidazopyridine group claim 1 , an indolizine group claim 1 , a pyrazolopyridine group claim 1 , an indole group claim 1 , a benzofuran group claim 1 , a benzothiophene group claim 1 , an isobenzothiophene group claim 1 , a benzoxazole group claim 1 , an isobenzoxazole group claim 1 , a triazole group claim 1 , a tetrazole group claim 1 , an oxadiazole group claim 1 , a thiadiazole group claim 1 , a triazine group claim 1 , a dibenzofuran group claim 1 , a dibenzothiophene group claim 1 , or a dibenzosilole group.3. The condensed cyclic compound of claim 1 , wherein Ais a benzene group claim 1 , a naphthalene group claim 1 , a phenanthrene group claim 1 , a fluorene group claim 1 , a spiro-fluorene group claim 1 , a pyrrole group claim 1 , a thiophene group claim 1 , a furan group claim 1 , an imidazole group claim 1 , a pyrazole group claim 1 , a thiazole group claim 1 , an isothiazole group claim 1 , an oxazole group claim 1 , an isoxazole group claim 1 , a pyridine group claim 1 , a pyrimidine group claim 1 , a ...

INSECTICIDAL COMPOUNDS BASED ON ISOXAZOLINE DERIVATIVES

The present invention relates to compounds of formula (I): 4. The method of wherein Ris hydrogen claim 2 , cyano-C-Calkyl claim 2 , C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , C-Ccycloalkyl where one carbon atom in the cycloalkyl group is replaced by O claim 2 , S claim 2 , S(O) or SO claim 2 , or C-Chaloalkyl claim 2 , C-Chydroxyalkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , phenyl-C-Calkyl or phenyl-C-Calkyl wherein the phenyl moiety is substituted by one to three R claim 2 , 5-6 membered heteroaryl-C-Calkyl or 5-6 membered heteroaryl-C-Calkyl wherein the heteroaryl moiety is substituted by one to three R claim 2 , and wherein the heteroaryl is pyridyl claim 2 , pyridazinyl claim 2 , pyrimidinyl claim 2 , pyrazinyl claim 2 , pyrazolyl claim 2 , furanyl claim 2 , thiophenyl claim 2 , oxazolyl claim 2 , isoxazolyl or thiazolyl.5. The method of claim 2 , wherein the animal is selected from the group consisting of a cow claim 2 , a pig claim 2 , a sheep claim 2 , a goat claim 2 , a horse claim 2 , a donkey claim 2 , a dog and a cat.6. The method of claim 2 , wherein the pest is selected from the group consisting of a nematode claim 2 , a trematode claim 2 , a cestode claim 2 , a fly claim 2 , a mite claim 2 , a tick claim 2 , a louse claim 2 , a flea claim 2 , a true bug and a maggot.7. The method of claim 2 , wherein administering is selected from the group consisting of an oral administration claim 2 , a parenteral administration claim 2 , and an external administration. This application is a divisional of U.S. application Ser. No. 15/429,631, filed Feb. 10, 2017, which is a continuation application of U.S. patent application Ser. No. 14/258,079, filed 22 Apr. 2014, which is a continuation application of U.S. patent application Ser. No. 13/512,820 filed May 30, 2012, which is a 371 of International Application No. PCT/EP2010/068605 filed Dec. 1, 2010, which claims priority to EP 09177640.1 filed Dec. 1, 2009, and EP 10186537.6 filed Oct. 5, 2010, the ...

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Compounds that regulate quorum sensing in bacteria and in particular in are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in bacteria and in particular in Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of bacteria and in particular of Methods for treating such bacterial infections are provided. 3. The compound of claim 2 , wherein:{'sub': 1', '2', 'n, 'Lis —(CH)—, where n is 2-9 or 3-8, and all R are H;'}{'sub': 1', '2', 'n', '3, "Lis —(CH)—, where n is 2-9 or 3-8, and at least one of the R's are CH;"}{'sub': 1', '2', 'n', '3', '1', '2, "Lis —(CH)—, where n is 2-9 or 3-8, at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, benzyl, p-OH-benzyl or 3-indolylmethyl;"}{'sub': '1', 'Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and all R are H;'}{'sub': 1', '3, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CH; or"}{'sub': 1', '3', '1', '2, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, optionally-substituted benzyl, cycloalkylalkyl or 3-indolylmethyl."}4. The compound of claim 1 , wherein W is S.5. The compound of claim 1 , wherein W is NH.6. The compound of claim 1 , wherein W is NCH.7. The compound of claim 1 , where —W—CO— is a double bond.8. The compound of claim 1 , wherein Xand Xare selected from sec-butyl claim 1 , isobutyl claim 1 , benzyl claim 1 , p-OH-benzyl claim 1 , p-F-benzyl claim 1 , p-Cl-benzyl claim 1 , m-F-benzyl claim 1 , m-Cl-benzyl claim 1 , cyclohexyl claim 1 , cyclopentyl claim 1 , or 3-indolylmethyl.9. The compound of claim 1 , wherein Xis selected from optionally-substituted benzyl and Xis selected from cyclohexylmethyl or cyclopentylmethyl.10. The compound of ...

Mitotic kinesin inhibtors and methods of use thereof

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

PYRIMIDINE TBK/IKKe INHIBITOR COMPOUNDS AND USES THEREOF

The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors. 2. The compound of claim 1 , wherein Ris H.3. The compound of claim 1 , wherein Ring Z is phenyl claim 1 , pyridine claim 1 , or pyrimidine.5. The compound of claim 1 , wherein each Ris independently —R claim 1 , halogen claim 1 , —OR claim 1 , or —N(R).7. The compound of claim 1 , wherein each Ris independently —R claim 1 , halogen claim 1 , —OR claim 1 , or —N(R).8. The compound of claim 1 , wherein Ring A is phenyl or pyridyl.10. The compound of claim 1 , wherein Ris —R or —OR.11. The compound of claim 1 , wherein each Ris independently —R claim 1 , —C(O)R claim 1 , —COR claim 1 , —C(O)N(R) claim 1 , —NRC(O)R claim 1 , or —N(R).16. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or vehicle.17. A method for inhibiting TBK and IKKε activity in a patient claim 1 , comprising a step of administering to said patient a compound of claim 1 , or a pharmaceutically acceptable salt thereof.18. A method for treating a TBK/IKKε related disorder in a patient in need thereof claim 1 , comprising the step of administering to said patient a compound of claim 1 , or a pharmaceutically acceptable salt thereof.19. The method of claim 18 , wherein the disorder is selected from Rheumatoid Arthritis claim 18 , Psoriatic arthritis claim 18 , Osteoarthritis claim 18 , Systemic Lupus Erythematosus claim 18 , Lupus nephritis claim 18 , Ankylosing Spondylitis claim 18 , Osteoporosis claim 18 , Systemic sclerosis claim 18 , Multiple Sclerosis claim 18 , Psoriasis claim 18 , Type I diabetes claim 18 , Type II diabetes claim 18 , Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis) claim 18 , Hyperimmunoglobulinaemia D and periodic fever syndrome claim 18 , Cryopyrin-associated periodic syndromes ...

ENZYME INTERACTING AGENTS

The present disclosure relates generally, but not exclusively, to compounds and their use as enzyme interacting agents, in particular, agents which interact with one or more enzymes in the sphingolipid biosynthesis pathway. The disclosure further relates to the use of such compounds as research tools, use in therapy, to compositions and agents comprising said compounds, and to methods of treatment using said compounds. 2. The compound according to wherein A is N.3. The compound according to wherein A is C—R.6. The compound according to wherein Q contains 2 ring heteroatoms.7. The compound according to wherein Q contains 3 ring heteroatoms.8. The compound according to wherein Q has at least 2 nitrogen ring atoms.9. The compound according to wherein Q is an oxadiazolyl group.10. The compound according to wherein Q is 1 claim 9 ,3 claim 9 ,4-oxadiazolyl.11. The compound according to wherein L is a bivalent linker group selected from —NH— claim 1 , —*NH—CH— claim 1 , —*CH—NH— claim 1 , *NH—NH— claim 1 , and —*C(═O)—NH— claim 1 , wherein the linker atom labelled * is bonded to Q.12. The compound according to wherein Ris selected from hydrogen claim 1 , halo (chloro claim 1 , fluoro claim 1 , bromo claim 1 , iodo) claim 1 , Calkyl claim 1 , haloCalkyl claim 1 , Calkoxy claim 1 , haloCalkoxy claim 1 , Calkoxy Calkyl claim 1 , Calkoxy Calkoxy claim 1 , Ccycloalkyl claim 1 , CcycloalkylCalkyl claim 1 , Ccycloalkoxy claim 1 , phenyl claim 1 , phenylCalkyl claim 1 , 5-6 membered heterocyclyl claim 1 , and 5-6 membered heteroaryl.14. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , and a pharmaceutically acceptable additive.15. A compound according to claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , or a composition comprising said compound or a pharmaceutically acceptable salt or solvate thereof claim 1 , for use as an sphingolipid enzyme agent for interacting with an ...

Convenient process for the preparation of statins

Object of the present invention is an improved process for the preparation of key intermediates for the synthesis of statins.

Covalent inhibitors of kras g12c

Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed. 176-. (canceled)77. A method of treating multiple myeloma , the method comprising administering to a patient dexamethasone in combination with a solid form comprising (a) 4-amino-2-(2 ,6-dioxopiperidine-3-yl)isoindoline-1 ,3-dione (pomalidomide); and (b) a coformer; whereinthe coformer is gallic acid and the solid form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 22.98, 26.16, and 26.90 degrees 2θ±0.2 degrees 2θ;the coformer is vanillin and the solid form has an XRPD pattern comprising peaks at 13.09, 17.30, and 25.61 degrees 2θ±0.2 degrees 2θ;the coformer is cyclamic acid and the solid form has an XRPD pattern comprising peaks at 6.42, 7.88, and 15.73 degrees 2θ±0.2 degrees 2θ;the coformer is D-glucose and the solid form has an XRPD pattern comprising peaks at 17.09, 20.68, and 25.52 degrees 2θ±0.2 degrees 2θ;the coformer is propyl gallate and the solid form has an XRPD pattern comprising peaks at 7.78, 25.23, and 25.61 degrees 2θ±0.2 degrees 2θ;the coformer is saccharin and the solid form has an XRPD pattern comprising peaks at 15.98, 19.09, and 25.10 degrees 2θ±0.2 degrees 2θ;the coformer is sodium lauryl sulfate and the solid form has an XRPD pattern comprising peaks at 2.66, 5.30, and 7.93 degrees 2θ±0.2 degrees 2θ;the coformer is magnesium bromide and the solid form has an XRPD pattern comprising peaks at 3.23, 28.76, and 29.95 degrees 2θ±0.2 degrees 2θ;the coformer is malonic acid and the solid form has an XRPD pattern comprising peaks at 12.23, 16.63, and 25.58 degrees 2θ±0.2 degrees 2θ;the coformer is maltol and the solid form has an XRPD pattern comprising peaks at 16.51, 17.09, and 25.73 degrees 2θ±0.2 degrees 2θ;the coformer is methyl paraben and the ...

STORE OVERLOAD-INDUCED CALCIUM RELEASE INHIBITORS AND METHODS FOR PRODUCING AND USING THE SAME

The present invention provides compounds having store overload-induced Ca release (SOICR) inhibitory activity and methods for producing and using the same. In particular, compounds of the invention is of the formula: R—X-L-X—R, wherein R, X, L, X, and Rare those defined herein. 2. The compound according to claim 1 , wherein Ris selected from the group consisting of carbazol-2-yl; carbazol-3-yl; carbazol-4-yl; 2 claim 1 ,3 claim 1 ,4 claim 1 ,9-tetrahydro-1H-carbazol-6-yl; 9H-fluoren-4-yl; 9H-fluoren-9-on-4-yl; dibenzo[b claim 1 ,d]furan-2-yl; (phenylamino)phenyl; 10H-phenothiazin-2-yl; naphthalenyl; adamantanyl; (adamantanyl)alkyl; N-acyl-9H-cabazol-4-yl; 10H-5 claim 1 ,5-dioxide-phenothiazin-2-yl; 2-oxo-1 claim 1 ,2 claim 1 ,3 claim 1 ,4 claim 1 ,4a claim 1 ,8a-hexahydroquinolin-6-yl; 1H-indol-5-yl claim 1 , and 1H-indazol-6-yl claim 1 , each of which is optionally substituted;3. The compound according to claim 1 , wherein Xis O or NH.7. The compound according to claim 1 , wherein Ris selected from the group consisting of phenyl claim 1 , benzyl claim 1 , pyrid-2-yl claim 1 , benzo[d]oxazol-2-yl claim 1 , and benzofuran-2-yl claim 1 , each of which is optionally substituted.8. The compound according to claim 1 , wherein said compound is any one of the compounds in Tables 1-9.9. A method of treating cardiac arrhythmia in a heart failure patient claim 1 , said method comprising administering to a heart failure patient a therapeutically effective amount of a compound of to treat cardiac arrhythmia.10. The method of claim 1 , wherein said compound of inhibits store-overload-induced calcium release (SOICR).11. The method of claim 1 , wherein SOICR inhibition of the compound of is achieved by regulating calcium efflux through the RyR2 channel.12. The method of claim 9 , wherein calcium ion-induced calcium ion release (CICR) is minimally inhibited or not inhibited.13. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or ...

COMPOUND FOR ORGANIC ELECTRIC ELEMENT, ORGANIC ELECTRIC ELEMENT USING THE SAME, AND ELECTRONIC DEVICE THEREOF

Provided is a novel compound capable of improving the luminous efficiency, stability and life span of a device, an organic electric element using the same, and an electronic device thereof. 8. The compound of claim 1 , wherein at least one of Land Lin Formula (1) is substituted at a meta position.10. An organic electric element comprising a first electrode claim 1 , a second electrode claim 1 , and an organic material layer between the first electrode and the second electrode claim 1 , wherein the organic material layer comprises one or more of a hole injection layer claim 1 , a hole transport layer claim 1 , an emitting-auxiliary layer claim 1 , an emitting layer claim 1 , an hole blocking layer claim 1 , an electronic auxiliary layer claim 1 , and an electron transport layer claim 1 , and wherein the organic material layer comprises the compound according to .11. The organic electric element of claim 10 , wherein the organic layer is a hole transport layer or an emitting-auxiliary layer claim 10 , and wherein the compound is a single compound or a mixture of two or more compounds having different structures in the hole transport layer or in the emitting-auxiliary layer.12. The organic electric element of claim 10 , wherein the organic electric element further comprises a light efficiency enhancing layer formed on the side of the first electrode and/or the second electrode claim 10 , the side being opposite to the organic material layer not facing the organic material layer.13. The organic electric element of claim 10 , wherein the organic material layer is formed by a spin coating process claim 10 , a nozzle printing process claim 10 , an inkjet printing process claim 10 , a slot coating process claim 10 , a dip coating process or a roll-to-roll process claim 10 , and since the organic material layer according to the present invention can be formed by various methods claim 10 , the scope of the present invention is not limited by the method of forming the organic ...

QUINOLONE DERIVATIVES AS ANTIBACTERIALS

This invention is in the field of medicinal chemistry and relates to compounds, and pharmaceutical compositions thereof, that inhibit bacterial gyrase. The compounds are useful as inhibitors of bacterial gyrase activity and bacterial infections, and have the structure of Formula (I) 2. The compound according to claim 1 , wherein Ris C-Ccycloalkyl or C-Calkyl.3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or halogen.4. The compound of claim 1 , wherein Ris H or F.5. The compound of claim 1 , wherein Ris methyl or methoxy.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris halo claim 1 , Calkyl claim 1 , or Chaloalkyl.8. The compound of claim 1 , wherein Ris H.9. The compound of claim 1 , wherein Ris —CHNH.11. The compound according to claim 10 , wherein Ris H.12. The compound according to claim 10 , wherein Rand Rtogether with the nitrogen atom to which they are attached form a 4- to 7-membered monocyclic heterocyclic group optionally including one additional heteroatom selected from N claim 10 , O and S as a ring member claim 10 ,or a 6-10 membered bicyclic heterocyclic group optionally including one or two additional heteroatoms selected from N, O and S as ring members,{'sup': 7A', '7B', '9', '9', '9', '9, 'sub': 2', '2', '1', '4', '1', '4', '1', '4', '3', '6, 'claim-text': {'sub': 1', '4', '3', '6', '2', '2', '1', '4', '1', '4', '1', '4, 'sup': 10', '10', '10', '10', '10, 'wherein the C-Calkyl, C-Ccycloalkyl, phenyl, and 4-6 membered heteroaryl or heterocyclyl are each optionally substituted by up to three groups independently selected from halogen, —CN, hydroxy, oxo, —OR, ═N—OR, —N(R), —COOR, —C(O)N(R, C-Calkyl, C-Chaloalkyl, and C-Calkoxy.'}, 'wherein the monocyclic or bicyclic heterocyclic group formed by Rand Rtogether with the nitrogen atom to which they are attached is optionally substituted by up to three groups selected from halogen, —CN, hydroxy, phenyl, oxo, —OR, —N(R), — ...

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. 1. A pharmaceutical composition comprising an inhibitory means for inhibiting JAK in a subject and a pharmaceutically acceptable carrier.2. The pharmaceutical composition according to claim 1 , wherein the inhibitory means is a pyrimidine diamine means.3. The pharmaceutical composition according to claim 2 , wherein the pyrimidine diamine means is a 5-halogenpyrimidine diamine means or a 5-alkylpyrimidine diamine means.4. The pharmaceutical composition according to claim 2 , wherein the pyrimidine diamine means is a 5-fluoropyrimidine diamine means or a 5-methylpyrimidine diamine means.5. The pharmaceutical composition according to claim 2 , wherein the pyrimidine diamine means is a 2 claim 2 ,4-diaminopyrimidine means.6. The pharmaceutical composition according to claim 5 , wherein the 2 claim 5 ,4-diaminopyrimidine means comprises a Caryl or a 5-10 membered heteroaryl on the 2-amino moiety.7. The pharmaceutical composition according to claim 6 , wherein the Caryl or 5-10 membered heteroaryl is a bicyclic ring moiety.8. The pharmaceutical composition according to claim 6 , wherein the Caryl or 5-10 membered heteroaryl is an optionally substituted phenyl claim 6 , optionally substituted pyridinyl claim 6 , or optionally substituted isoindolinyl moiety.9. The pharmaceutical composition according to claim 1 , wherein the inhibitory means is an aminobenzoxazolone means.10. The pharmaceutical composition according to claim 1 , wherein the inhibitory means is an (aminopyrimidin-4-yl)amino)benzo [d]oxazol-2(3H)-one means.11. The pharmaceutical composition according to claim 1 , wherein the inhibitory means is a salt.12. The pharmaceutical composition according to claim 1 , wherein the inhibitory ...

STEREOSPECIFIC PROCESS FOR 3-HETEROCYCLYLCYCLOALIPHATIC-1,2-DIOLS

A process for the stereoselective synthesis of chiral 3-heterocyclyl-1,2-dihydroxy cyclohexanes is disclosed. The process involves reacting a tricyclic nitrogenous heterocycle with an allyl carbonate in the presence of a chiral palladium catalyst followed by oxidation of the olefinic bond to provide 3-heterocyclyl-1,2-dihydroxy cyclohexanes, cyclopentanes and corresponding alicyclic heterocycles. Also disclosed are methods for converting the heterocyclyl-1,2-dihydroxy cyclohexanes to 2-amino-6-(heteroaryl)cyclohexanols (and related cyclic compounds). 2. The process of wherein said compounds II and III are reacted in the presence of a chiral palladium catalyst formed from a chiral ligand and a palladium compound chosen from tris(dibenzylideneacetone)dipalladium claim 1 , bis(dibenzylideneacetone)palladium claim 1 , tetrakis(triphenylphosphine)palladium claim 1 , and allylpalladium chloride dimer.3. The process of wherein said chiral ligand is chosen from (2 claim 2 ,2′-bis(diphenylphosphino)-1 claim 2 ,1′-binaphthyl) (BINAP) claim 2 , 5 claim 2 ,5′-bis(diphenylphosphino)-4 claim 2 ,4′-bi-1 claim 2 ,3-benzodioxole (SEGPHOS) claim 2 , 1 claim 2 ,2-diaminocyclohexane-N claim 2 ,N′-bis(2-diphenylphosphinobenzoyl) (DACH-phenyl) claim 2 , and 1 claim 2 ,2-diaminocyclohexane-N claim 2 ,N′-bis(2-diphenylphosphino-1-naphthoyl) (DACH-naphthyl).4. (canceled)5. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. The process of wherein said azide of formula VI is reduced to a rel-(1S claim 6 ,2S claim 6 ,6R)-2-amino-6-(heteroaryl)cyclohexanol of formula V using triphenyl phosphine.12. The process of wherein both of rings T and U are benzene.13. The process of wherein both of rings T and U are benzene.14. The process of claim 1 , wherein Q is chosen from —CH— claim 1 , —O— claim 1 , —N(Boc)- claim 1 , —N(Cbz)- claim 1 , —N(CH)— claim 1 , and —N(Ac)—.15. The process of wherein Q is chosen from —CH— claim 6 , —O— claim 6 , —N(Boc)- claim 6 , —N(Cbz)- claim 6 , —N(CH)— ...

DEGRADERS THAT TARGET PROTEINS VIA KEAP1

Disclosed are bifunctional compounds, pharmaceutical compositions containing them, and methods of making and using them to treat diseases and disorders characterized by aberrant protein activity wherein the protein is targeted for degradation by KEAP1 and the Cul3-based E3-ubiquitin ligase complex. 12. The bifunctional compound of claim 1 , wherein the targeting ligand binds Bruton's tyrosine kinase.14. The bifunctional compound of claim 1 , wherein the targeting ligand binds KRASG12C.16. A pharmaceutical composition comprising a therapeutically effective amount of the bifunctional compound of claim 1 , and a pharmaceutically acceptable carrier.17. A method of treating a disease or disorder characterized by an aberrant or dysfunctional protein claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the bifunctional compound of . This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/701,098, filed Jul. 20, 2018 and U.S. Provisional Application No. 62/737,514, filed Sep. 27, 2018, each of which is incorporated herein by reference in its entirety.This invention was made with government support under grant number R01 CA214608 awarded by the National Institutes of Health. The government has certain rights in the invention.The gene that encodes cereblon (CRBN) was first identified in the course of a study of genes related to memory and learning; the gene was assigned the name CRBN based on its supposed role in the development of cerebral tissues and because its expression in the hippocampus among other areas, is associated with memory and learning processes. Higgins et al., Neurol. 63(10):1927-31 (2004).Cereblon is a 442-amino acid multifunctional protein located in the cytoplasm, nucleus and peripheral membrane of the human brain and other tissues (Wada et al., Biochem. & Biophys. Res. Comm. 477:388-94 (2016)). It interacts with the DNA damage-binding protein-1 (DDB1), ...

KIF18A INHIBITORS

Compounds of formula (I): 4. The compound of claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein Ris H or methyl.5. The compound of any one of to claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris H claim 1 , halo claim 1 , Calk claim 1 , or Chaloalk; and each of Rand Rpair combine with the carbon atom attached to each of them form a saturated 3- claim 1 , 4- claim 1 , or 5-membered monocyclic ring spiro to the Rring; wherein said ring contains 0 claim 1 , 1 claim 1 , 2 or 3 N atoms and 0 claim 1 , 1 claim 1 , or 2 atoms selected from O and S.6. The compound of claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris H claim 1 , methyl claim 1 , or ethyl; and each of Rand Rpair combine with the carbon atom attached to each of them form a cyclopropyl claim 1 , cyclobutyl claim 1 , or cyclopentyl ring spiro to the IV ring.10. The compound of claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein Ris —CN claim 1 , or a group —Z—R claim 1 , wherein Z is a bond claim 1 , —NH— claim 1 , —NHSO— claim 1 , —SONH— claim 1 , —S(═O)(═NH)— claim 1 , —S— claim 1 , —S(═O)— claim 1 , —SO— claim 1 , —(C═O)— claim 1 , —(C═O)NH— claim 1 , or —NH(C═O)—; and{'sup': '12', '(a) Ris H;'}{'sup': '12', '(b) Ris oxetanyl, cyclopropyl; or'}{'sup': '12', 'sub': '1-6', '(c) Ris Calk substituted by 0, 1, 2 or 3 OH group(s).'}12. The compound of claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein Ris a group —Z—R claim 1 , wherein Z is —NHSO— or —SONH—; and Ris oxetanyl claim 1 , cyclopropyl claim 1 , or Ris Calk substituted by 0 claim 1 , 1 claim 1 , 2 or 3 OH group(s).13. The compound of claim 1 , or the pharmaceutically-acceptable salt thereof claim 1 , wherein Ris a group —Z—R claim 1 , ...

Solid forms comprising 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and a coformer, compositions and methods of use thereof

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed.

NOVEL COMPOUND FOR INHIBITING NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE AND COMPOSITION CONTAINING SAME

The present invention relates to a novel compounds for inhibiting nicotinamide phosphoribosyltransferase (NamPT), a composition comprising the same, and various uses thereof. 130.-. (canceled)36. The compound of claim 31 , wherein the Xis N claim 31 , the Xis C(R).37. The compound of claim 31 , wherein the heterocycloalkyl group and heteroaryl group of the Rare each independently unsubstituted or substituted by at least one substituents selected from the group consisting of halogen claim 31 , nitro group claim 31 , C˜Calkyl group claim 31 , C˜Calkoxy group and C˜Caryl group.38. The compound of claim 34 , wherein the Ris hydrogen or C˜Calkyl group.39. The compound of claim 31 , wherein the Ris —(CH)r-N(R)(R) claim 31 , the r is an integer of 0 to 2 claim 31 , the Rand Rare each independently hydrogen or C˜Calkyl group.40. The compound of claim 31 , wherein the Ris —(CH)r-N(R)(R) claim 31 , the r is 0 or 1 claim 31 , the Rand Rare each independently C˜Calkyl group.41. The compound of claim 31 , wherein the Ris heteroaryl group having nuclear atoms of 5 to 6 claim 31 , the heteroaryl group of Ris unsubstituted or substituted by at least one substituents of C˜Calkyl group claim 31 , and when it is substituted with a plurality of substituents which are the same as or different to each other.42. The compound of claim 31 , wherein the Ris —O—(CH)q-R claim 31 , the q is an integer of 0 to 2 claim 31 , the Ris heteroaryl group having nuclear atoms of 5 to 14.43. The compound of claim 31 , wherein the Lis oxo group claim 31 , and the Ris —O—(CH)q-Ror heteroaryl group having nuclear atoms of 5 to 14.44. The compound of claim 31 , wherein the Lis sulfonyl group claim 31 , and the Ris heterocycloalkyl group having nuclear atoms of 5 to 7.45. The compound of claim 31 , wherein the compound is selected from the group of following compounds:1) N-(4-(benzo[d]oxazol-2-yl)benzyl)nicotinamide;2) N-(4-(6-methylbenzo[d]oxazol-2-yl)benzyl)nicotinamide;3) N-(4-(6-methylbenzo[d]oxazol-2-yl) ...

RADIOLABELLED mGluR2 PET LIGANDS

The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a mammal, in vitro or in vivo and to precursors of said compounds. 3. The compound of claim 1 , wherein Ris selected from the group consisting of{'sup': 11', '11', '18, 'sub': 3', '3, '—NH[C]CH, [C]CH, and F.'}7. A pharmaceutical composition comprising a compound of Formula (I) claim 1 , and a pharmaceutically acceptable carrier or diluent.8. The pharmaceutical composition according to claim 7 , wherein the diluent is a sterile solution.9. (canceled)10. The method of claim 11 , wherein the imaging involves determining mGlu2 receptor site occupancy by other non-radiolabelled compounds.11. A method of imaging a tissue claim 1 , cells or a mammal claim 1 , comprising contacting with or providing a detectable amount of a compound of Formula (I) as defined in claim 1 , to a tissue claim 1 , cells or mammal and detecting the labelled compound associated with the mGlu2 receptor.12. The method according to wherein the compound of Formula (I) is detected by positron-emission tomography.17. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to and a pharmaceutically acceptable carrier or excipient.18. (canceled)19. A method for the treatment of a subject having a central nervous system conditions or a diseases selected from the group consisting of mood disorders; delirium claim 16 , dementia claim 16 , amnestic substance-related disorders; schizophrenia schizophrenia spectrum claim 16 , psychotic disorders other than schizophrenia or schophrenia spectrum disorders; somatoform disorders claim 16 , somatic ...

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. 1. A compound of formula I, or salt thereof, [{'sub': '2', 'sup': '1', 'X and Y are each independently O, S, S(O), SOor NR;'}, {'sup': 1', '50, 'sub': 1-6', '1-6', '2', '1-6, 'each Ris independently for each occurrence H, optionally substituted Calkyl, C(O)—Calkyl, CO—Calkyl or R;'}, {'sup': 50', '9', '10', '9', '9', '10', 'a', '11', '11', 'a', '11', '11, 'sub': 2', '1-6', '6-10', '7-16', '3-8', '2, 'each Ris —C(R)-A-R, where A is O or S; each Ris independently for each occurrence H, optionally substituted Calkyl, optionally substituted Caryl or optionally substituted Carylalkyl; or alternatively, two R, together with the carbon to which they are attached, form an optionally substituted Ccycloalkyl group or an optionally substituted 3-8 membered heteroalicyclyl; Ris Ror —P(O)(OR); each Ris independently for each occurrence Ror a monovalent cationic group; or two R, together with the atoms to which they are attached, form a 4-8 membered cyclic phosphate group, or two Rtogether represent a divalent cationic group;'}, 'ring A is bicyclic;', {'sup': 2', 'e', 'b', 'e', 'a', 'b', 'e', 'a', 'b', 'e', 'a', 'b', 'e', 'a', 'b', 'a', 'e', 'e', 'a', 'b', 'e', 'a', 'b', 'a', 'e', 'e', 'a', 'b', 'a', 'c', 'a', 'b', 'a', 'b', 'a', 'b', 'b', 'a', 'a', 'a', 'b', 'b', 'b', 'a', 'a', 'b', 'a', 'a', 'a', 'b', 'a', 'b', 'a', 'a', 'a', 'b', 'a', 'a', 'a', 'b', 'a', 'a', 'a', 'b', 'a', 'a', 'a', 'a', 'b, 'sub': 2', '2', '2', '2', '2', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', '2', 'm', '2', 'm', '2', 'm', '2', 'm', '2', '2', 'm', '2', 'm, 'each Ris independently for each occurrence H, R, R, Rsubstituted with one or more of the same or ...

SUBSTITUTED PYRIMIDINES FOR THE TREATMENT OF DISEASES SUCH AS CANCER

The present invention encompasses compounds of general formula (1) 1. A method for treating cancer, infections, inflammations and autoimmune diseases which comprising administering to a host suffering from such a condition a therapeutically effective amount of a compound of the formula (1c),wherein{'sub': '2', 'sup': e', 'e, 'W and Y each independently of one another represent CH, O, N—Ror N—OR;'}A denotes a group, optionally substituted by one or more identical or different R, selected from among Ccycloalkyl, 3-8 membered heterocycloalkyl, Caryl and 5-12 membered heteroaryl;Rand Reach independently of one another denote hydrogen or a group selected from among R, Rand Rsubstituted by one or more identical or different Rand/or R;Rdenotes a group selected from among hydrogen, halogen, —OR, —OCF, —SR, —NRR, —CF, —CN, —OCN, —SCN, —NO, —NO, Calkyl, Chaloalkyl and Chaloalkyloxy;each Ris selected independently of one another from among Calkyl, Ccycloalkyl, Ccycloalkylalkyl, Caryl, Carylalkyl, 2-6 membered heteroalkyl, 3-8 membered heterocycloalkyl, 4-14 membered heterocycloalkylalkyl, 5-12 membered heteroaryl and 6-18 membered heteroarylalkyl;each Ris a suitable group and is independently selected from among ═O, —OR, Chaloalkyloxy, —OCF, ═S, —SR, ═NR, ═NOR, ═NNRR, ═NN(R)C(O)NRR, —NRR, —ONRR, —N(OR)R, —N(R)NRR, halogen, —CF, —CN, —NC, —OCN, —SCN, —NO, —NO, ═N, —N, —S(O)R, —S(O)OR, —S(O)R, —S(O)OR, —S(O)NRR, —S(O)NRR, —OS(O)R, —OS(O)R, —OS(O)OR, —OS(O)NRR, —OS(O)NRR, —C(O)R, —C(O)OR, —C(O)SR, —C(O)NRR, —C(O)N(R)NRR, —C(O)N(R)OR, —C(NR)NRR, —C(NOH)R, —C(NOH)NRR, —OC(O)R, —OC(O)OR, —OC(O)SR, —OC(O)NRR, —OC(NR)NRR, —SC(O)R, —SC(O)OR, —SC(O)NRR, —SC(NR)NRR, —N(R)C(O)R, —N[C(O)R], —N(OR)C(O)R, —N(R)C(NR)R, —N(R)N(R)C(O)R, —N[C(O)R]NRR, —N(R)C(S)R, —N(R)S(O)R, —N(R)S(O)OR, —N(R)S(O)R, —N[S(O)R], —N(R)S(O)OR, —N(R)S(O)NRR, —N(R)[S(O)]R, —N(R)C(O)OR, —N(R)C(O)SR, —N(R)C(O)NRR, —N(R)C(O)NRNRR, —N(R)N(R)C(O)NRR, —N(R)C(S)NRR, —[N(R)C(O)]R, —N(R)[C(O)]R, —N{[C(O)]R}, —N(R)[C(O)]OR, —N( ...

CYCLIC SULFONAMIDE CONTAINING DERIVATIVES AS INHIBITORS OF HEDGEHOG SIGNALING PATHWAY

The invention relates generally to the creation and use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases. 10. A process for making compound of claim I or its pharmaceutically acceptable salts , hydrates , solvates , crystal forms salts and individual diastereomers thereof.11. A pharmaceutical composition comprising at least one compound of claim I or its pharmaceutically acceptable salts , hydrates , solvates , crystal forms salts and individual diastereomers thereof , and a pharmaceutically acceptable carrier.13. A process for making compound of or its pharmaceutically acceptable salts claim 12 , hydrates claim 12 , solvates claim 12 , crystal forms salts and individual diastereomers thereof.14. A pharmaceutical composition comprising at the compound of its pharmaceutically acceptable salts claim 12 , hydrates claim 12 , solvates claim 12 , crystal forms salts and individual diastereomers thereof claim 12 , and a pharmaceutically acceptable carrier. This patent application claims the benefit of U.S. Provisional Patent Applications Nos. 61/722,490, filed Nov. 5, 2012 and 61/852,112 filed Mar. 15, 2013, which are hereby incorporated by reference in their entireties.The present invention relates generally to the use of cyclic sulfonamide group containing derivatives to treat a variety of disorders, diseases and pathologic conditions, and more specifically to the use of cyclic sulfonamide containing derivatives to inhibit the hedgehog signaling pathway and to the use of those compounds for the treatment of hyperproliferative diseases and angiogenesis mediated diseases.The hedgehog (Hh) gene was first identified during a search for embryonic lethal mutants of , which found that mutation of Hh resulted in altered segment patterning of the larva (Nusslein-Volhard, C.; Wieschaus, E. 1980, 287, 795-801). Subsequently the ...

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. 2. The compound of claim 1 , or a salt thereof claim 1 , wherein the A ring is bicyclic aryl or bicyclic heteroaryl.5. The compound of wherein the B ring is cyclopentane claim 4 , pyrrolidine claim 4 , imidazolidine claim 4 , 1 claim 4 ,3-dioxolane claim 4 , oxazolidine claim 4 , tetrahydrofuran claim 4 , cyclohexane claim 4 , morpholine claim 4 , piperidine claim 4 , dioxane claim 4 , oxathiazinane claim 4 , piperazine claim 4 , cycloheptane claim 4 , cycloheptene claim 4 , azepane claim 4 , tetrahydroazepine claim 4 , diazepane claim 4 , cyclooctane claim 4 , cyclooctene claim 4 , azocane claim 4 , hexahydroazocine claim 4 , diazocane or hexahydrodiazocine.12. The pharmaceutical composition of wherein the A ring is bicyclic aryl or bicyclic heteroaryl.15. The composition according to further comprising an excipient claim 11 , a second therapeutic claim 11 , or combinations thereof.19. The method according to claim 16 , comprising administering the compound in an amount effective for treating a disease selected from allergies claim 16 , autoimmune diseases claim 16 , transplant rejection claim 16 , T-cell mediated autoimmune diseases claim 16 , Type II inflammatory diseases claim 16 , delayed Type IV hypersensitivity reactions claim 16 , or hematologic malignancies.20. The method according to comprising contacting a JAK kinase ex vivo.218. The method according to comprising contacting the JAK kinase in vivo.22. The method according to comprising administering the compound of formula I claim 16 , or a salt thereof claim 16 , in combination with or adjunctively to a second therapeutic. This application is a continuation of U.S. patent application Ser. No. 14/250,329, filed on Apr. 10, 2014, ...

FORMULATIONS CONTAINING TIOTROPIUM, AMINO ACID AND ACID AND METHODS THEREOF

A dry powder containing dry particles that contain a tiotropium salt, one or more amino acids, and acid content, and optionally, sodium chloride, and/or one or more additional therapeutic agents, wherein the molar ratio of acid to amino acid is from about 0.0005 to about 5, or 0.002 to about 1. In one aspect, the dry powder containing dry particles is suitable for administration to the respiratory tract. In one aspect, the dry powder containing dry particles is a respirable dry powder contains respirable dry particles that contain a tiotropium salt, one or more amino acids, acid content, sodium chloride, and optionally one or ore additional therapeutic agents, wherein the tiotropium salt is about 0.01% to about 0.5%, the leucine is about 5% to about 40%, the sodium chloride is about 50% to about 90%, the optional one or more additional therapeutic agents are up to about 30%, and the molar ratio of acid to amino acid is from about 0.002 to about 1, where all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%. 1. A respirable dry powder , comprising respirable dry particles that comprise a tiotropium salt , one or more amino acids , acid content , sodium chloride , and optionally one or more additional therapeutic agents , wherein the tiotropium salt is about 0.01% to about 0.5% , the amino acid is about 5% to about 40% , the sodium chloride is about 50% to about 90% , the optional one or more additional therapeutic agents are up to about 30% , and the molar ratio of acid to amino acid is from about 0.002 to about 1 , wherein all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%.2. The respirable dry powder of claim 1 , wherein when the respirable dry powder comprising respirable dry particles is sealed in a receptacle and stored for about 12 months at a temperature of about 15° C. to about 30° C. claim 1 , the purity of tiotropium ...

Novel diacylated and mono-acylated alkylated imino sugars exhibiting glucosidase inhibition and their method of use

Described herein are alkylated imino sugars derivatives having a disease-modifying action in the treatment of diseases associated with glucosidase activity that include viral hemorrhagic fevers and other enveloped viruses, and any other diseases involving glucosidase activity. 2. The compound according to claim 1 , wherein Ris COR.3. The compound according to claim 1 , wherein Ris COR.4. The compound according to claim 1 , wherein Rand Rare COR.6. The compound according to claim 4 , wherein Ris OR.7. The compound according to claim 5 , wherein Ris selected from: optionally substituted Calkyl claim 5 , optionally substituted branched Calkyl claim 5 , optionally substituted Ccycloalkyl claim 5 , and optionally substituted aryl which may be substituted by 0-5 moieties.8. The compound according to claim 1 , wherein Ris selected from: optionally substituted Calkyl claim 1 , optionally substituted Ccycloalkyl claim 1 , COR claim 1 , COR claim 1 , and CONHR.9. The compound according to claim 1 , wherein Ris selected from: optionally substituted Calkyl claim 1 , optionally substituted Ccycloalkyl claim 1 , and CONHR.10. The compound according to claim 6 , wherein Ris CONHR.11. The compound according to claim 1 , wherein Ris selected from: optionally substituted Calkyl claim 1 , optionally substituted Ccycloalkyl claim 1 , and optionally substituted aryl which may be substituted by 0-5 moieties.12. The compound according to claim 10 , wherein Ris optionally substituted Ccycloalkyl.13. The compound according to claim 1 , wherein Ris selected from: hydrogen claim 1 , optionally substituted Calkyl claim 1 , optionally substituted branched Calkyl claim 1 , and optionally substituted C3-14 cycloalkyl.14. The compound according to claim 12 , wherein Ris optionally substituted branched Calkyl.17. A composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier.18. A method for treating or preventing a disease or condition associated with a virus ...

NRF2 REGULATORS

The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators. 2. The compound or pharmaceutically acceptable salt according to wherein A is —C(O)ORand Ris hydrogen claim 1 , —Calkyl-N(R) claim 1 , —(CH)-morpholinyl claim 1 , —(CH)-imidazolyl claim 1 , —(CH)-pyrolidinyl claim 1 , or —(CH)-piperidyl.3. The compound or pharmaceutically acceptable salt according to wherein A is —C(O)OH.4. The compound or pharmaceutically acceptable salt according to wherein Ris:{'sub': 1-3', '1-3, 'phenyl substituted by one, two, or three groups independently selected from —CN, —F, —Cl, Calkyl, and —O—Calkyl;'}{'sub': 1-3', '1-3, 'benzotriazolyl substituted by one, two, or three groups independently selected from —O—Calkyl and Calkyl; or'}{'sub': 2', '2', '1-3', '2, '—(CH)-triazolyl substituted by one or two groups independently selected from Calkyl or —CH-phenyl.'}5. The compound or pharmaceutically acceptable salt according to wherein Ris benzotriazolyl substituted by one or two groups independently selected from —O—Calkyl and Calkyl.7. The compound or pharmaceutically acceptable salt according to wherein Ris hydrogen claim 1 , —Cl claim 1 , Calkyl claim 1 , or —CF.8. The compound or pharmaceutically acceptable salt according to wherein each Ris hydrogen.10. The compound according to selected from the group consisting of:3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid;3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid;3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((3-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5] ...

AMINOPYRIDINE DERIVATIVES AND THEIR USE AS SELECTIVE ALK-2 INHIBITORS

The invention relates to a compound of formula (I) in free form or in pharmaceutically acceptable salt form 111-. (canceled)12. A method of inhibiting ALK-2 receptor activity in a subject , wherein the method comprises administering to the subject a therapeutically effective amount of a compound which is amino-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-5-(4-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)nicotinamide , or a pharmaceutically acceptable salt thereof.13. A method of treating a disorder or disease selected from heterotopic ossification or fibrodysplasia ossificans progressiva , comprising administering to the subject a therapeutically effective amount of a compound which is amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)phenyl)-nicotinamide , or a pharmaceutically acceptable salt thereof.1416-. (canceled)17. The method of claim 12 , wherein the compound is amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1R claim 12 ,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide claim 12 , or a pharmaceutically acceptable salt thereof.18. The method of claim 12 , wherein the compound is amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1S claim 12 ,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide claim 12 , or a pharmaceutically acceptable salt thereof.19. The method of claim 13 , wherein the compound is amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1R claim 13 ,5S)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide claim 13 , or a pharmaceutically acceptable salt thereof.20. The method of claim 13 , wherein the compound is amino-N-(4-hydroxybicyclo-[2.2.2]octan-1-yl)-5-(4-((1S claim 13 ,5R)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl)-phenyl)nicotinamide claim 13 , or a pharmaceutically acceptable salt thereof.21. The method of claim 13 , wherein the disorder or disease ...

Formulations and Methods of Administration of Cephalotaxines, Including Homoharringtonine

The present invention is directed to compositions and methods for the treatment of patients with cephalotaxines, for example, homoharringtonine. The invention is also directed to improvements in the purity, manufacturing process, formulation and administration of homoharringtonine for the treatment of cancer and other aberrant cellular diseases. The invention also provides methods and compositions for antiparasitic, antifungal, antiviral and antibacterial treatments. 128.-. (canceled)29. An oral dosage form comprising a therapeutically effective dose of homoharringtonine and microcrystalline cellulose.30. The oral dosage form of claim 29 , comprising about 2 percent to about 60 percent by weight homoharringtonine.31. The oral dosage form of claim 29 , comprising a tablet unit form or capsule unit form.32. A liquid dosage form comprising an aqueous solution of homoharringtonine and a pH of about 4.0 claim 29 , wherein the aqueous solution of homoharringtonine exhibits less than a 5% loss of potency as measured by high performance liquid chromatography upon storage for 7 weeks at 60° C.33. The liquid dosage form of claim 32 , wherein the concentration of homoharringtonine is between 0.1 mg/mL and 50 mg/mL.34. The liquid dosage form of claim 32 , wherein the concentration of homoharringtonine is between 1 and 5 mg/mL.35. The liquid dosage form of claim 32 , comprising a phosphate buffer. This application is a continuation of U.S. patent application Ser. No. 12/698,367, filed Feb. 2, 2010, which is a continuation of U.S. patent application Ser. No. 11/497,739, filed Aug. 1, 2006 and now U.S. Pat. No. 7,683,050, issued Mar. 23, 2010, which is a continuation of U.S. patent application Ser. No. 10/617,927, filed Jul. 10, 2003 and now abandoned, which claims the benefit under 35 USC 119(e) of U.S. Provisional Patent Application 60/396,926, filed Jul. 17, 2002, all of which are incorporated by reference in their entirety for all purposes.The present invention is directed to ...

HETEROCYCLIC DERIVATIVE HAVING AMPK-ACTIVATING ACTIVITY

A compound represented by formula: 2. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein Y is substituted or unsubstituted aryl claim 1 , substituted or unsubstituted heteroaryl claim 1 , substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted cycloalkenyl claim 1 , or substituted or unsubstituted heterocyclyl.3. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein Y is substituted or unsubstituted heteroaryl claim 1 , substituted or unsubstituted cycloalkyl claim 1 , substituted or unsubstituted cycloalkenyl claim 1 , or substituted or unsubstituted heterocyclyl.4. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein Y is substituted or unsubstituted heterocyclyl.613. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein Z is N═.7. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein Z is —CR═.8. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein L is NRR claim 1 , SR claim 1 , or SOR.9. The compound according to or pharmaceutically acceptable salt thereof claim 1 , wherein L is NRR.10. The compound according to or pharmaceutically acceptable salt thereof claim 9 , wherein Ris hydrogen or substituted or unsubstituted alkyl.11. The compound according to or pharmaceutically acceptable salt thereof claim 9 , wherein Ris substituted or unsubstituted alkyl claim 9 , substituted or unsubstituted cycloalkenyl claim 9 , or substituted or unsubstituted heterocyclyl.12. The compound according to or pharmaceutically acceptable salt thereof claim 11 , wherein Ris substituted alkyl claim 11 , wherein the substituent of substituted alkyl is one or more substituent(s) selected from substituted or unsubstituted aryl claim 11 , substituted or unsubstituted heteroaryl claim 11 , substituted or unsubstituted cycloalkyl claim 11 , substituted or ...

SOLID FORMS COMPRISING 4-AMINO-2-(2,6-DIOXOPIPERIDINE-3-YL)ISOINDOLINE-1,3-DIONE AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF

Provided herein are solid forms comprising (a) 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione and (b) a coformer. Pharmaceutical compositions comprising the solid forms (e.g., cocrystals) and methods for treating, preventing and managing various disorders are also disclosed. 1. A solid form comprising (a) 4-amino-2-(2 ,6-dioxopiperidine-3-yl)isoindoline-1 ,3-dione , or a pharmaceutically acceptable salt , solvate , hydrate , stereoisomer , prodrug , or clathrate thereof; and (b) a coformer.2. The solid form of claim 1 , wherein the coformer is gallic acid claim 1 , vanillin claim 1 , cyclamic acid claim 1 , D-glucose claim 1 , magnesium bromide claim 1 , malonic acid claim 1 , maltol claim 1 , methyl paraben claim 1 , propyl gallate claim 1 , saccharin claim 1 , sodium lauryl sulfate claim 1 , or zinc chloride.3. The solid form of claim 2 , wherein the coformer is gallic acid.4. The solid form of having an X-ray powder diffraction pattern comprising peaks at approximately 22.98 claim 3 , 26.16 claim 3 , and 26.90 degrees 2θ.5. The solid form of having an X-ray powder diffraction pattern further comprising peaks at approximately 15.52 claim 4 , 18.42 and 23.20 degrees 2θ.6. The solid form of having an X-ray powder diffraction pattern which matches the XRPD pattern presented in .7. The solid form of claim 2 , wherein the coformer is vanillin.8. The solid form of having an X-ray powder diffraction pattern comprising peaks at approximately 13.09 claim 7 , 17.30 claim 7 , and 25.61 degrees 2θ.9. The solid form of having an X-ray powder diffraction pattern further comprising peaks at approximately 12.25 claim 8 , 16.91 claim 8 , and 28.01 degrees 2θ.10. The solid form of having an X-ray powder diffraction pattern which matches the XRPD pattern presented in .11. The solid form of claim 2 , wherein the coformer is cyclamic acid.12. The solid form of having an X-ray powder diffraction pattern comprising peaks at approximately 6.42 claim 11 , 7.88 claim 11 , and 15 ...

Processes for preparing oxathiazin-like compounds

Oxathiazin-like compounds, processes for making new oxathiazin-like compounds, compounds useful for making oxathiazin-like compounds, and their uses are disclosed. Processes of treating patients suffering from cancers, bacterial infections, fungal infections and/or viral infections by administering oxathiazin-like compounds are also disclosed. These compounds were found to have significantly longer half-life compared to taurolidine and taurultam.

INSECTICIDAL COMPOUNDS BASED ON ISOXAZOLINE DERIVATIVES

Compounds of formula III 2. The compound according to claim 1 , wherein L is C-Calkylene.3. The compound according to claim 1 , wherein L is methylene.4. The compound according to claim 3 , wherein Yis N—Rand Ris cyano claim 3 , cyano-C-Calkyl claim 3 , C-Chaloalkyl claim 3 , C-Ccycloalkyl claim 3 , C-Ccycloalkyl where one carbon atom is replaced by S claim 3 , S(O) or SO claim 3 , or C-Ccycloalkyl-C-Calkyl claim 3 , C-Ccycloalkyl-C-Calkyl where one carbon atom in the cycloalkyl group is replaced by S claim 3 , S(O) or SO claim 3 , or C-Ccycloalkyl-C-Chaloalkyl claim 3 , C-Calkenyl claim 3 , C-Chaloalkenyl claim 3 , C-Calkynyl claim 3 , C-Chaloalkynyl claim 3 , phenyl claim 3 , phenyl substituted by one to three R claim 3 , phenyl-C-Calkyl claim 3 , phenyl-C-Calkyl wherein the phenyl moiety is substituted by one to three R claim 3 , 5-6 membered heteroaryl-C-Calkyl or 5-6 membered heteroaryl-C-Calkyl wherein the heteroaryl moiety is substituted by one to three R claim 3 , C-Calkyl-(C-Calkyl-O—N═)C—CH— claim 3 , and wherein heteroaryl refers to pyridazinyl claim 3 , pyrimidinyl claim 3 , pyrazinyl claim 3 , pyrazoyl claim 3 , furanyl claim 3 , thiophenyl claim 3 , oxazolyl claim 3 , isoxazolyl or thiazolyl.5. The compound according to claim 4 , wherein Yis N—Rand Ris cyclopropyl claim 4 , cyclobutyl claim 4 , oxetanyl claim 4 , thietanyl claim 4 , trifluoroethyl claim 4 , difluoroethyl claim 4 , allyl claim 4 , propargyl claim 4 , cyanomethyl claim 4 , benzyl claim 4 , benzyl substituted by one to three R.6. The compound according to claim 5 , wherein each Rand Ris independently hydrogen claim 5 , halogen claim 5 , C-Calkyl claim 5 , or C-Chaloalkyl.7. The compound according to claim 6 , wherein each Ris independently halogen claim 6 , cyano claim 6 , nitro claim 6 , C-Calkyl claim 6 , C-Chaloalkyl claim 6 , C-Calkoxy claim 6 , or C-Chaloalkoxy.8. The compound according to claim 7 , wherein Ris hydrogen claim 7 , C-Chaloalkyl or C-Calkyl.9. The compound according to ...

Covalent inhibitors of kras g12c

Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.

PROCESSES FOR PREPARING OXATHIAZIN-LIKE COMPOUNDS

Oxathiazin-like compounds, processes for making new oxathiazin-like compounds, compounds useful for making oxathiazin-like compounds, and their uses are disclosed. Processes of treating patients suffering from cancers, bacterial infections, fungal infections and/or viral infections by administering oxathiazin-like compounds are also disclosed. These compounds were found to have significantly longer half-life compared to taurolidine and taurultam. 151-. (canceled)54. The process of claim 53 , wherein the process comprises adding sodium 2-bromoethanesulfonate to a solution of benzyl alcohol and sodium benzyloxide to form a mixture claim 53 , boiling the mixture to reflux four times claim 53 , concentrating under vacuum until dry claim 53 , boiling with ethyl alcohol claim 53 , filtering the ethyl alcohol claim 53 , and concentrating to dryness to obtain solid sodium 2-benzyletherethanesulfonate.55. The process of claim 54 , further comprising boiling said solid sodium 2-benzylether ethanesulfonate in ethyl alcohol claim 54 , filtering claim 54 , then cooling to obtain sodium 2-benzylether ethanesulfonate crystals having increased purity.57. The process of claim 56 , which comprises the following steps sequentially: adding vinylsulphonic acid sodium to a solution of benzyl alcohol and a catalytic amount of sodium to form a mixture claim 56 , warming the mixture with stirring to dissolve most or all of the vinylsulphonic acid sodium claim 56 , cooling the warmed mixture to obtain crystals claim 56 , vacuum filtering the crystals claim 56 , suspending the filtered crystals in ethyl alcohol claim 56 , vacuum filtering the suspended crystals claim 56 , and{'br': None, 'sub': 2', '2', '2', '3, 'Ph—CH—O—CH—CH—SONa'}drying the vacuum filtered crystals to obtain64. The process of claim 63 , wherein the process comprises adding a 2-haloethanesulfonate salt to a solution of benzyl alcohol and an alkali metal salt of benzyloxide to form a mixture claim 63 , boiling the mixture to ...

Thiophene derivatives as antiviral agents for flavivirus infection

The present invention provides novel compounds represented by formula (I): or pharmaceutically acceptable salts thereof useful for treating flaviviridae viral infection.

Hepatitis c virus inhibitors

This disclosure concerns novel compounds of Formula (I) or as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.

Isoxazole derivatives

The invention relates to new isoxazoline compounds of formula (I) wherein the variables have the meaning as indicated in the claims; in free form and in salt form; and optionally the enantiomers and geometrical isomers thereof. The compounds of formula (1) are useful in the control of parasites, in particular ectoparasites, in and on vertebrates.

Aminopyridine derivatives and their use as selective alk-2 inhibitors

Oxathiazine derivatives which are substituted with benzyl or heteromethylene groups, method for producing them, their use as medicine and drug containing said derivatives and the use thereof

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable for the treatment of hyperglycemia.

Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia.

Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof

The invention relates to compounds of formula (I) and to the physiologically compatible salts thereof. Said compounds are suitable, for example, for treating hyperglycemia.

Neue substituierte phenyl-oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung

Die Erfindung betrifft die Verbindungen der Formel (I), sowie deren physiologisch verträgliche Salze. Die Verbindungen eignen sich z.B. zur Behandlung von Hyperglykämie.

Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof

The invention relates to the compounds of formula (I) and physiologically acceptable salts thereof. The compounds are suitable, e.g., for treating hyperglycemia.

Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof

The invention relates to the compounds of formula (I) and to the physiologically acceptable salts thereof. Said compounds are suitable e.g. for the treatment of hyperglycemia.

compounds, process for their production and use.

Patent RU2021111037A3

ВУ” 2021111037” АЗ Дата публикации: 10.02.2022 Форма № 18 ИЗ,ПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2021111037/04(02369Т) 18.07.2017 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [Х] подачи 18.07.2017 первоначальной заявки № 2019104609 из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 62/364,620 20.07.2016 05 Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) ПРОИЗВОДНЫЕ АМИНОПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ СЕЛЕКТИВНЫХ ИНГИБИТОРОВ АГК-2 Заявитель: НОВАРТИС АГ, СН 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты см. п см. Примечания [ ] приняты во внимание следующие пункты: р [ | принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) (0720 401/10 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) С07р 405/14, С070401/14, С07О 487/04, Аб1К 31/4427, Аб1Р 19/00 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): Езрасепеё Рабеагсп, Кеахуз 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ПРЕДМЕТУ ПОИСКА Кате- Наименование документа с указанием (где необходимо) частей, Относится к гория* относящихся к предмету ...

嘧啶ΤΒΚ/ΙΚΚε抑制剂化合物及其用途

本发明涉及式I的化合物或其药学上可接受的组合物，可用作ΤΒK/ΙKKε抑制剂。

Производные аминопиридина и их применение в качестве селективных ингибиторов alk-2

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2019 104 609 A (51) МПК C07D 401/10 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2019104609, 18.07.2017 (71) Заявитель(и): НОВАРТИС АГ (CH) Приоритет(ы): (30) Конвенционный приоритет: 20.07.2016 US 62/364,620 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 20.02.2019 (86) Заявка PCT: (87) Публикация заявки PCT: WO 2018/014829 (25.01.2018) (54) ПРОИЗВОДНЫЕ АМИНОПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ СЕЛЕКТИВНЫХ ИНГИБИТОРОВ ALK-2 R U (57) Формула изобретения 1. Соединение формулы (I) в свободной форме или в форме фармацевтически приемлемой соли где L представляет собой связь, (CH2)n, -CH(CH3)-, -O-(CH2)n-, -C(O)-, -C(O)-NH-(CH2)n-; n равняется 1, 2, 3; Стр.: 1 A 2 0 1 9 1 0 4 6 0 9 A Адрес для переписки: 129090, Москва, ул. Б. Спасская, 25, стр. 3, ООО "Юридическая фирма Городисский и Партнеры" 2 0 1 9 1 0 4 6 0 9 CN 2017/093385 (18.07.2017) R U (43) Дата публикации заявки: 20.08.2020 Бюл. № 23 (72) Автор(ы): ЛИ, Цзялян (CN), АРИСТА, Лука (CH), БАБУ, Срихари (IN), БЯНЬ, Цзяньвэй (CN), ЦУЙ, Кай (CN), ДИЛЛОН, Майкл Патрик (US), ЛАТТМАНН, Рене (CH), ЛЯО, Лв (CN), ЛИЗОС, Димитриос (CH), РАМОС, Рита (CH), ШТИФЛЬ, Николаус Йоханнес (CH), УЛЛЬРИХ, Томас (CH), УССЕЛЬМАНН, Пегги (CH), ВАН, Сяоян (CN), ВАЙКОЛЕ, Лиладхар Мурлидхар (CN), ВАЙЛЕР, Свен (DE), ЧЖАН, Юйбо (CN), ЧЖОУ, Ицзун (CN), ЧЖУ, Тинин (CN) A 2 0 1 9 1 0 4 6 0 9 A R U 2 0 1 9 1 0 4 6 0 9 Стр.: 2 R U R1 выбран из C3-C7циклоалкила, необязательно замещенного один раз или более чем один раз заместителем, независимо выбранным из гидроксила, галогена, C1-C3алкила; мостикового C5-C10циклоалкила, необязательно замещенного один раз или более чем один раз заместителем, независимо выбранным из гидроксила, гидроксиC1-C3алкила; R2 и R3 независимо выбраны из H, галогена, C1-C3алкила; R4 представляет собой N-содержащее гетероциклическое неароматическое кольцо, необязательно содержащее один или несколько ...

Tyrosine kinase inhibitors containing a zinc binding moiety

The present invention relates to tyrosine kinase inhibitors that contain a zinc-binding moiety and their use in the treatment of tyrosine related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

Organic compounds

Patent RU2019104609A3

ВИ“? 2019104609” АЗ Дата публикации: 30.09.2020 Форма № 18 ИЗ,ПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение ж 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2019104609/04(008726) 18.07.2017 РСТ/СМ№2017/093385 18.07.2017 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [ ] приоритета по первоначальной заявке № из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 62/364,620 20.07.2016 05 Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) ПРОИЗВОДНЫЕ АМИНОПИРИДИНА И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ СЕЛЕКТИВНЫХ ИНГИБИТОРОВ АГК-2 Заявитель: НОВАРТИС АГ, СН 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. Примечания) [ ] приняты во внимание следующие пункты: [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) (070 401/10 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) С07р 401/10, С07О 401/12, С07Р 401/14, С07Ь 405/14, СО7Р 409/14, С07О 411/14 , С07Б 413/109 , Аб1К 31/4427 ‚, АбТР 19/00 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы данных, использованные при поиске (название базы, и если, возможно, поисковые термины): РУ/РТ, ЕАРАТГЬ, Ебрасепеё, Соозе Раеп$, РАТЕМТЫСОРЕ, Рабеагсв, РаиБСвет, Кеахуз, Уапаех 6. ДОКУМЕНТЫ, ОТНОСЯЩИЕСЯ К ...

氨基吡啶衍生物及其作为选择性alk-2抑制剂的用途

本发明涉及氨基吡啶衍生物及其作为选择性ALK‑2抑制剂的用途。本发明涉及一种呈游离形式或药学上可接受的盐形式的式(I)的化合物、包含所述化合物的药物组合物、以及所述化合物在治疗异位骨化和进行性骨化纤维发育不良中的用途。