BROMODOMAIN INHIBITORS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 3. The compound according to claim 2 , wherein Ring A is benzo or a 5-6 membered fused heteroaryl ring having 1-2 heteroatoms independently selected from nitrogen claim 2 , oxygen claim 2 , or sulfur.4. The compound according to claim 2 , wherein Ris a 3-7 membered aryl ring; 3-7 membered saturated or partially unsaturated carbocyclic ring or a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen claim 2 , oxygen claim 2 , and sulfur claim 2 , wherein Ris optionally substituted with 1-5 independently selected R.5. The compound according to claim 2 , wherein Ris H claim 2 , halogen claim 2 , optionally substituted alkyl claim 2 , optionally substituted alkenyl claim 2 , optionally substituted alkynyl claim 2 , optionally substituted aryl claim 2 , optionally substituted aralkyl claim 2 , optionally substituted cycloalkyl claim 2 , optionally substituted heteroaryl claim 2 , optionally substituted heterocycloalkyl claim 2 , —OR claim 2 , —SR claim 2 , —CN claim 2 , —N(R′)(R″) claim 2 , —C(O)R claim 2 , —C(S)R claim 2 , —COR claim 2 , —C(O)N(R′)(R″) claim 2 , —C(O)SR claim 2 , or —(CH)R.6. The compound according to claim 2 , wherein Ris H claim 2 , halogen claim 2 , optionally substituted alkyl claim 2 , optionally substituted alkenyl claim 2 , optionally substituted alkynyl claim 2 , optionally substituted aryl claim 2 , optionally substituted aralkyl claim 2 , optionally substituted cycloalkyl claim 2 , optionally substituted heteroaryl claim 2 , optionally substituted heterocycloalkyl claim 2 , —OR claim 2 , —SR claim 2 , —CN claim 2 , —N(R′)(R″) claim 2 , —C(O)R claim 2 , —C(S)R claim 2 , —COR claim 2 , —C ...

BROMODOMAIN INHIBITORS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 2. The compound according to claim 1 , wherein Ring A is benzo claim 1 , pyrido claim 1 , pyrimidino claim 1 , pyrazino claim 1 , pyridazino claim 1 , thieno claim 1 , or isothiazolo.39-. (canceled)10. The compound according to claim 1 , wherein Ring B is phenyl.11. (canceled)12. The compound according to claim 1 , wherein Lis a covalent bond.13. The compound according to claim 1 , wherein Ris halogen or optionally substituted Caliphatic.1418-. (canceled)19. The compound according to claim 1 , wherein Rand Rof formula are taken together with their intervening atoms to form an optionally substituted 3-7 membered saturated or partially unsaturated spiro-fused ring having 0-2 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.20. (canceled)21. The compound according to claim 1 , wherein Rand X are taken together with their intervening atoms to form an optionally substituted 5-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.22. The compound according to claim 1 , wherein Rand X are taken together with their intervening atoms to form an optionally substituted triazolyl ring.25. The compound according to claim 24 , wherein Ring A is pyrimidino claim 24 , pyrazino claim 24 , isothiazolo claim 24 , or pyridazino.26. (canceled)27. (canceled)28. The compound according to claim 24 , wherein Ring B is phenyl.29. (canceled)30. The compound according to claim 24 , wherein Lis a covalent bond.31. The compound according to claim 24 , wherein Ris hydrogen claim 24 , halogen claim 24 , or optionally substituted Caliphatic.3238-. (canceled)39. The compound according to claim 24 , wherein ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

Provided herein are compounds of formula I: 23-. (canceled)4. The compound of claim 1 , wherein X is —CH— claim 1 , —CHCH— or —CHCHCH—.79-. (canceled)11. The compound of claim 1 , wherein X is or —N(R)C(R)—.1214-. (canceled)15. The compound of claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , heteroaryl claim 1 , —OR claim 1 , CN claim 1 , —C(O)—N(R)or —C(O)—OR claim 1 , wherein any heteroaryl of Ris optionally substituted with one or more Rgroups.1618-. (canceled)2022-. (canceled)2425-. (canceled)27. (canceled)2933-. (canceled)36. (canceled)40. (canceled)42. (canceled)43. A method of treating cancer in an animal comprising administering to the animal in need thereof a compound of formula I or a pharmaceutically acceptable salt thereof as described in .44. A method of treating an LSD1-mediated disorder in an animal comprising administering to the animal in need thereof a compound of formula I or a pharmaceutically acceptable salt thereof as described in .4549-. (canceled)50. A method of increasing efficacy of a cancer treatment comprising a cytotoxic agent in an animal comprising administering to the animal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof as described in .51. (canceled)52. A method of delaying or preventing development of cancer resistance to a cytotoxic agent in an animal claim 1 , comprising administering to the animal a compound of formula I or a pharmaceutically acceptable salt thereof as described in .53. A method of extending the duration of response to a cancer therapy in an animal claim 1 , comprising administering to the animal undergoing the cancer therapy a compound of formula I or a pharmaceutically acceptable salt thereof claim 1 , as described in claim 1 , wherein the duration of response to the cancer therapy when the compound of formula I is administered is extended over the duration of response to the cancer therapy in the absence of the administration of the compound of formula I or ...

Treating th2-mediated diseases by inhibition of bromodomains

The invention provides methods for treating Th2 cytokine-mediated diseases by inhibiting bromodomain function.

Therapeutic compounds and uses thereof

The present invention relates to compounds useful as inhibitors of one or more histone demethylses, such as KDM2b. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of one or more histone demethylses, such as KDM2b. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 5. The compound of wherein Ris a carbon-linked piperidine ring that is substituted on the piperidine ring nitrogen with a group Rand that is optionally further substituted with one or more groups independently selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocycle claim 1 , 3-8 membered heterocycle claim 1 , aryl claim 1 , heteroaryl claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—OR claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , and —N(R)—S(O)—R; wherein each Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocycle claim 1 , 3-8 membered heterocycle claim 1 , aryl claim 1 , and heteroaryl is optionally substituted with one or more groups independently selected from the group consisting of halo claim 1 , —NO—N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—OR claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , —N(R)—S(O)—R claim 1 , and Calkyl that is optionally substituted with one or more groups independently selected from halo.6. The compound of wherein Ris a carbon-linked piperazine ring that is substituted with one or more groups independently selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccarbocycle claim 1 , 3-8 membered heterocycle claim 1 , aryl ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The invention relates to compounds of formula (I) and salts thereof: 2. The compound of wherein Ris chloro.3. The compound of wherein Ris methyl claim 1 , isopropyl claim 1 , ethyl claim 1 , cyclopropylmethyl claim 1 , 2-buten-1-yl.4. The compound of wherein Ris a piperidyl ring or azepanyl ring claim 1 , which piperidyl ring or azepanyl ring is optionally substituted with one or more groups independently selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , oxo claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—OR claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , and —N(R)—S(O)—R claim 1 , wherein any Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , and heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of R claim 1 , oxo claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—O—R claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , and —N(R)—S(O)—R.5. The compound of wherein Ris a piperidyl ring claim 1 , which piperidyl ring is optionally substituted with one or more groups independently selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , oxo claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—OR claim 1 , —S(O)—R claim 1 , —S(O ...

Bromodomain inhibitors and uses thereof

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the invention. 2. The compound of claim 1 , wherein R is selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , indolyl claim 1 , and indolinyl claim 1 , wherein said phenyl claim 1 , pyridyl claim 1 , indolyl or indolinyl is optionally substituted with —R claim 1 , —OR claim 1 , —SR claim 1 , —N(R) claim 1 , —OSOR claim 1 , —SOR claim 1 , —C(O)N(R) claim 1 , halogen claim 1 , or nitrile.3. The compound of claim 1 , wherein Rtogether with Rand the nitrogen to which they are attached form a tetrahydroquinoline moiety.4. The compound of claim 1 , wherein Ris pyridyl claim 1 , wherein said pyridyl is optionally substituted with one claim 1 , two claim 1 , or three substituents each independently selected from group consisting of —OR claim 1 , halogen claim 1 , and nitrile.5. The compound of claim 1 , wherein Ris indolyl or indolinyl claim 1 , wherein said indolyl or indolinyl is optionally substituted with one claim 1 , two claim 1 , or three substituents each independently selectedfrom group consisting of —OR claim 1 , halogen claim 1 , and nitrile.6. The compound of claim 1 , Rtogether with Rand the nitrogen to which they are attached form a nitrogen ring moiety selected from the group consisting of 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinoline; 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-1 claim 1 ,5 claim 1 ,napthyridine claim 1 , dihydropyridopyrazine claim 1 , benzoimidazole claim 1 , benzoazepine claim 1 , and dihydropyridooxazine claim 1 , wherein the nitrogen ring moiety is optionally substituted with one or two substituents each independently selected from halo ...

PYRAZOLO[3,4-B]PYRAZINE SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure. 3. The compound of claim 2 , wherein X is a bond claim 2 , Ris a nitrogen containing ring moiety and Ris bound through the nitrogen.4. The compound of or claim 2 , wherein Ris selected from the group consisting of 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydroquinolin-1-yl claim 2 , 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydro-1 claim 2 ,5-naphthyridin-1-yl claim 2 , 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydroquinolin-1-yl claim 2 , 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydroquinoxalin-1-yl claim 2 , 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydropyrido[2 claim 2 ,3-b]pyrazin-1-yl claim 2 , 1H-benzo[d]imidazol-1-yl claim 2 , indolin-1-yl claim 2 , 2 claim 2 ,3-dihydro-1H-pyrrolo[3 claim 2 ,2-b]pyridin-1-yl claim 2 , 2 claim 2 ,3-dihydro-1H-pyrrolo[3 claim 2 ,2-c]pyridin-1-yl claim 2 , isoindolin-2-yl claim 2 , 2 claim 2 ,3 claim 2 ,4 claim 2 ,5-tetrahydrobenzo[f][1 claim 2 ,4]oxazepin-4-yl claim 2 , 2-(3 claim 2 ,4-dihydroisoquinolin-1(2H)-one) claim 2 , 2-(3 claim 2 ,4-dihydroisoquinolin-1(2H)-one) claim 2 , 2 claim 2 ,3-dihydro-1H-pyrido[2 claim 2 ,3-b][1 claim 2 ,4]oxazin-1-yl claim 2 , piperidin-1-yl claim 2 , 1-(1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydro-6H-pyrido[1 claim 2 ,2-a]pyrimidin-6-one) claim 2 , 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydro-1 claim 2 ,8-naphthyridin-1-yl claim 2 , 1-(3 claim 2 ,4-dihydro-1 claim 2 ,5-naphthyridin-2(1H)-one) claim 2 , 2 claim 2 ,3 claim 2 ,4 claim 2 ,5-tetrahydro-1H-benzo[b]azepin-1-yl claim 2 , 1-(2 claim 2 ,3-dihydroquinolin-4(1H)-one) claim 2 , 2 claim 2 ,3-dihydro-1H-pyrido[2 claim 2 ,3-b][1 claim 2 ,4]oxazin-1-yl claim 2 , 1 claim 2 ,2 claim 2 ,3 ...

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME

The disclosure is in part directed to crystalline forms of (R)-1′-(3-(3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3H-spiro[benzofuran-2,4′-piperidin]-3-amine, its salt, and variants thereof. 2. The solid form of claim 1 , wherein the solid form is amorphous.3. The solid form of claim 1 , wherein the solid form is crystalline.4. The solid form of claim 3 , characterized by a powder X-ray diffraction pattern having at least two characteristic peaks claim 3 , in degrees 2θ claim 3 , each selected from the group consisting of about 24.6 claim 3 , about 19.9 claim 3 , and about 16.0 2θ.5. The solid form of claim 3 , characterized by a powder X-ray diffraction pattern with at least two characteristic peaks claim 3 , in degrees 2θ claim 3 , each selected from the group consisting of about 24.6 2θ claim 3 , about 19.9 2θ claim 3 , about 16.0 2θ claim 3 , about 6.7 2θ claim 3 , about 12.8 2θ claim 3 , about 13.4 2θ and about 20.7 2θ.6. The solid form of claim 3 , wherein the solid form is characterized by an XRPD pattern substantially similar to that depicted in claim 3 , or characterized by a X-ray powder diffraction pattern having peaks claim 3 , in degrees 2θ claim 3 , at about 24.6 claim 3 , about 19.9 claim 3 , about 16.0 claim 3 , about 6.7 claim 3 , about 12.8 claim 3 , about 13.4 and about 20.7.7. The solid form of any one of - claim 3 , characterized by a differential scanning calorimetry (DSC) profile showing an endotherm with an onset of about 196° C. claim 3 , a peak of about 197° C.9. The compound of claim 8 , wherein the compound is selected from the group consisting of Compound I-2 claim 8 , Compound I-3 claim 8 , Compound I-4 claim 8 , Compound I-5 claim 8 , Compound I-6 claim 8 , Compound I-7 claim 8 , Compound I-8 claim 8 , Compound I-9 claim 8 , Compound I-10 claim 8 , Compound I-11 claim 8 , Compound I-12 claim 8 , Compound I-13 claim 8 , Compound I-14 claim 8 , Compound I-15 claim 8 , Compound I-16 claim 8 , and Compound I-17. ...

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and salts thereof, wherein: R 1 -R 4 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of BRG1, BRM and/or PB1. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various BRG1-mediated disorders, BRM-mediated disorders and/or PB1-mediated disorders.

BENZO ISOXAZOLOAZEPINE BROMODOMAIN INHIBITORS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 7. The compound of claim 6 , wherein Ring A is pyridinyl claim 6 , pyrazolyl claim 6 , isoxazolyl claim 6 , pyridinonyl claim 6 , or pyrazinyl.8. The compound of claim 7 , wherein{'sub': 2', '4', '1', '6', '1', '6', '1', '6', '1', '6', '2', '2', 'b, 'sup': 'x', 'Rand R, if present, are each independently hydrogen, (C-C)alkyl, (C-C)haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, —N(R′), —CO, halogen, —CN, —SR, —OH, or —(CH)R;'}{'sub': 3', '5', '1', '6, 'claim-text': {'sub': 2', '3', '4', '5, 'each of Rand Ror Rand Rare taken together with their intervening atoms to form an optionally substituted 3-7 membered cycloalkyl; and'}, 'Rand R, if present, are each independently hydrogen or (C-C)alkyl; or'}{'sub': 1', '3, 'X is CO, a covalent bond, or (C-C)alkyl;'}{'sub': 6', '7', '1', '3', '1', '3', '1', '3', '1', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'each of Rand Rare independently optionally substituted phenyl, halogen, (C-C)alkyl, halogen, (C-C)haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, —OR, —SR, —N(R′), —CN, —NO, —C(O)R, —C(S)R, —COR, —C(O)N(R′), —C(O)SR, —C(O)C(O)R, —C(O)CHC(O)R, —C(S)N(R′), —C(S)OR, —S(O)R, —SOR, —SON(R′), —N(R′)C(O)R, —N(R′)C(O)N(R′), —N(R′)C(S)N(R′), —N(R′)SOR, —N(R′)SON(R′), —N(R′)N(R′), —N(R′)C(═N(R′))N(R′), —C═NN(R′), —C═NOR, —C(═N(R′))N(R′), —OC(O)R, or —OC(O)N(R′);'}{'sub': 1', '3', '1', '3', '1', '3', '1', '3', '1', '6', '1', '6', '1', '6', '1', '6', '2, 'each R and R′ are independently hydrogen, (C-C)alkyl, halogen, (C-C)haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, or phenyl optionally substituted with one or more halogen, (C-C)alkyl, (C-C)haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, —CN, —C(O)R, or —COR; and ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I) or formula (II): 39-. (canceled)11. (canceled)12. The compound of wherein Ris phenyl optionally substituted with one or more substituent groups independently selected from R claim 2 , and Ris methyl or phenyl claim 2 , wherein each methyl and phenyl of Ris optionally substituted with one or more groups R.1316-. (canceled)17. The compound of wherein Rand Rtaken together with the nitrogen to which they are attached form a 9- or 10-membered bicyclic heterocycle that is optionally substituted with one or more groups R.18. The compound of wherein Rand Rtaken together with the nitrogen to which they are attached form a 9- or 10-membered bicyclic heterocycle that is optionally substituted with one or more groups R; and wherein the 9- or 10-membered bicyclic heterocycle comprises at least one aromatic ring.1920-. (canceled)2228-. (canceled)3037-. (canceled)4148-. (canceled)5058-. (canceled)6061-. (canceled)63. (canceled)65. A composition comprising a compound of formula (I) or formula (II) as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or vehicle.6667-. (canceled)68. A method for treating a CBP and/or EP300-mediated disorder in an animal comprising administering a compound of formula (I) or formula (II) claim 1 , or a pharmaceutically acceptable salt thereof as described in claim 1 , to the animal.6975-. (canceled)76. A method of increasing efficacy of a cancer treatment comprising a cytotoxic agent in an animal comprising administering to the animal an effective amount of a compound of formula (I) or formula (II) or a pharmaceutically acceptable salt thereof as described in .77. (canceled)78. A method of extending the duration of response to a cancer therapy in an animal claim 1 , comprising administering to an animal undergoing the cancer therapy a compound of formula (I) or formula (II) or a pharmaceutically acceptable ...

PYRAZOLO[3,4-B]PYRAZINE DERIVATIVES AS SHP2 PHOSPHATASE INHIBITORS

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure 2. The compound of claim 1 , wherein Rtogether with Rand the nitrogen to which they are attached form a ring moiety selected from the group consisting of 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-1 claim 1 ,5-naphthyridin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinolin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinoxalin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydropyrido[2 claim 1 ,3-b]pyrazin-1-yl claim 1 , 1H-benzo[d]imidazol-1-yl claim 1 , indolin-1-yl claim 1 , 2 claim 1 ,3-dihydro-1H-pyrrolo[3 claim 1 ,2-b]pyridin-1-yl claim 1 , 2 claim 1 ,3-dihydro-1H-pyrrolo[3 claim 1 ,2-c]pyridin-1-yl claim 1 , isoindolin-2-yl claim 1 , 2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydrobenzo[f][1 claim 1 ,4]oxazepin-4-yl claim 1 , 2-(3 claim 1 ,4-dihydroisoquinolin-1(2H)-one) claim 1 , 2-(3 claim 1 ,4-dihydroisoquinolin-1(2H)-one) claim 1 , 2 claim 1 ,3-dihydro-1H-pyrido[2 claim 1 ,3-b][1 claim 1 ,4]oxazin-1-yl claim 1 , piperidin-1-yl claim 1 , 1-(1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-6H-pyrido[1 claim 1 ,2-a]pyrimidin-6-one) claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-1 claim 1 ,8-naphthyridin-1-yl claim 1 , 1-(3 claim 1 ,4-dihydro-1 claim 1 ,5-naphthyridin-2(1H)-one) claim 1 , 2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-benzo[b]azepin-1-yl claim 1 , 1-(2 claim 1 ,3-dihydroquinolin-4(1H)-one) claim 1 , 2 claim 1 ,3-dihydro-1H-pyrido[2 claim 1 ,3-b][1 claim 1 ,4]oxazin-1-yl claim 1 , 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-1 claim ...

BROMODOMAIN INHIBITORS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 16-. (canceled)8. The compound according to claim 7 , wherein ring A is phenyl claim 7 , napthyl claim 7 , pyridyl claim 7 , pyrimidinyl claim 7 , pyrazinyl claim 7 , pyridazinyl claim 7 , furyl claim 7 , thiophenyl claim 7 , pyrrolo claim 7 , isoxazolyl claim 7 , or isothiazolyl; each of which is optionally substituted.9. The compound according to claim 7 , wherein Ris methyl claim 7 , ethyl claim 7 , propyl claim 7 , butyl claim 7 , pentyl claim 7 , or hexyl; each of which is optionally substituted.10. The compound according to claim 7 , wherein Ris H claim 7 , methyl claim 7 , ethyl claim 7 , propyl claim 7 , butylpentyl claim 7 , hexyl claim 7 , phenyl claim 7 , or napthyl; each of which is optionally substituted.11. The compound according to claim 7 , wherein Ris H claim 7 , OR claim 7 , NRR claim 7 , N(R)C(O)R claim 7 , N(R)C(O)OR claim 7 , or OC(O)R.13. The compound according to claim 12 , wherein Ris methyl.14. The compound according to claim 12 , wherein Ris methyl.15. The compound according to claim 12 , wherein Ris methyl.16. The compound according to claim 12 , wherein Ris selected from hydrogen claim 12 , —C(O)—N(CH) claim 12 , —C(O)—NH—CHCH claim 12 , and —C(O)—O—CHCH.17. The compound according to claim 12 , wherein m is 0 or 1; and when m is 1 claim 12 , Ris a para substituent selected from fluoro and chloro.19. (canceled)20. A composition comprising a compound according to claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , and a pharmaceutically acceptable adjuvant claim 7 , carrier claim 7 , or vehicle.21. The composition according to claim 20 , further comprising an additional therapeutic agent.2227-. (canceled)28. A method for treating a ...

PYRAZOLO[3,4-B]PYRAZINE DERIVATIVES AS SHP2 PHOSPHATASE INHIBITORS

Disclosed herein are novel compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the disclosure. 2. The compound of claim 1 , wherein X is selected from the group consisting of a bond claim 1 , —O— claim 1 , —S— claim 1 , and —NR—.3. The compound of or claim 1 , wherein Y is selected from the group consisting of —NR— claim 1 , —CH—NR— claim 1 , and —NR—CH—.4. The compound of any one of - claim 1 , wherein Y is selected from the group consisting of —NH— claim 1 , —N(CH)— claim 1 , —N(H)—CH— claim 1 , and —N(CH)—CH—.5. The compound of any one of - claim 1 , wherein A is selected from the group consisting of phenyl claim 1 , pyridyl claim 1 , quinolinyl claim 1 , indolyl claim 1 , and indolinyl claim 1 , wherein phenyl claim 1 , pyridyl claim 1 , quinolinyl claim 1 , indolyl and indolinyl may optionally be substituted by one claim 1 , two or three substituents each independently selected from the group consisting of —R claim 1 , —OR claim 1 , —SR claim 1 , —N(R) claim 1 , —OSOR claim 1 , —SOR claim 1 , —C(O)N(R) claim 1 , halogen claim 1 , and cyano.6. The compound of any one of - claim 1 , wherein A is phenyl; wherein phenyl may optionally be substituted by one claim 1 , two claim 1 , or three substituents each independently selected from the group consisting of —OR claim 1 , halogen claim 1 , and cyano.7. The compound of any one of - claim 1 , wherein A is pyridyl; wherein pyridyl may optionally be substituted by one claim 1 , two claim 1 , or three substituents each independently selected from the group consisting of —OR claim 1 , halogen claim 1 , and cyano.8. The compound of any one of - claim 1 , wherein Rand ring A together with the nitrogen to which they are attached ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to methods for treating PCAF and GCN5 mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: 3. The compound of wherein ring A is optionally substituted with one or more groups independently selected from the group consisting of Calkyl claim 1 , phenyl claim 1 , halo claim 1 , and —O—R claim 1 , wherein any Calkyl and phenyl is optionally substituted with one or more groups independently selected from halo.4. The compound of wherein ring A is optionally substituted with one or more groups independently selected from the group consisting of methoxy claim 1 , 4-chlorophenyl claim 1 , fluoro claim 1 , and methyl.5. The compound of wherein Ris Calkyl claim 1 , optionally substituted with one or more groups independently selected from the group consisting of oxo claim 1 , halo claim 1 , amino claim 1 , hydroxy claim 1 , and Calkoxy.6. The compound of wherein Ris methyl or ethyl.7. The compound of wherein X is S.8. The compound of wherein X is N(H).9. The compound of wherein Ris hydrogen or Calkyl.10. The compound of wherein Ris hydrogen claim 1 , methyl claim 1 , or ethyl.11. The compound of wherein Ris hydrogen claim 1 , Calkyl claim 1 , carbocyclyl claim 1 , or heterocyclyl claim 1 , wherein each Calkyl claim 1 , carbocyclyl claim 1 , and heterocyclyl is optionally substituted with one or more groups R.13. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a carbocyclyl or heterocyclyl claim 1 , which carbocyclyl and heterocyclyl is optionally substituted with one or more groups R.14. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a carbocyclyl or heterocyclyl selected from the group consisting of: cyclohexane claim 1 , cyclopentane claim 1 , piperidine claim 1 , and indane claim 1 , which carbocyclyl and heterocyclyl is optionally substituted with one or more groups R.15. The compound of wherein one Rtaken ...

BROMODOMAIN INHIBITORS AND USES THEREOF

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. 17-. (canceled)916-. (canceled)17. The method according to claim 8 , wherein Ris phenyl or a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen claim 8 , oxygen claim 8 , and sulfur claim 8 , wherein Ris optionally substituted with 1-5 independently selected R.18. (canceled)19. The method according to claim 8 , wherein Ris halo claim 8 , alkyl claim 8 , aralkyl claim 8 , aryl claim 8 , or heteroaryl.20. The method according to claim 19 , wherein Ris methyl claim 19 , ethyl claim 19 , propyl claim 19 , i-propyl claim 19 , butyl claim 19 , s-butyl claim 19 , t-butyl claim 19 , pentyl claim 19 , hexyl claim 19 , or heptyl.21. The method according to claim 8 , wherein Ris H claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , i-propyl claim 8 , butyl claim 8 , s-butyl claim 8 , pentyl claim 8 , hexyl claim 8 , —OR claim 8 , —SR claim 8 , —CN claim 8 , —N(R′)(R″) claim 8 , —C(O)R claim 8 , —C(S)R claim 8 , —COR claim 8 , —C(O)N(R′)(R″) claim 8 , —C(O)SR claim 8 , or —(CH)R.22. The method according to claim 21 , wherein Ris H or —(CH)R.23. The method according to claim 22 , wherein Ris —N(R′)(R″) claim 22 , —C(O)R claim 22 , —C(S)R claim 22 , —COR claim 22 , —C(O)N(R′)(R″) claim 22 , —C(S)N(R′)(R″) claim 22 , —S(O)R claim 22 , —SOR claim 22 , —SON(R′)(R″) claim 22 , —N(R′)C(O)R claim 22 , —N(R′)SOR claim 22 , —OC(O)R claim 22 , —OC(O)N(R′)(R″) claim 22 , methyl claim 22 , ethyl claim 22 , propyl claim 22 , i-propyl claim 22 , butyl claim 22 , s-butyl claim 22 , pentyl or hexyl.24. The method according to claim 8 , wherein Ris H claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , i-propyl claim 8 ...

USE OF CBP/EP300 BROMODOMAIN INHIBITORS FOR CANCER IMMUNOTHERAPY

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer. 1. A method for treating or delaying progression of cancer in an individual comprising administering an effective amount of a CBP/EP300 bromodomain inhibitor to the individual.2. A method of enhancing immune function in an individual having cancer comprising administering an effective amount of a CBP/EP300 bromodomain inhibitor to the individual.3. The method of claim 1 , wherein CD8 T cells in the individual have enhanced priming claim 1 , activation claim 1 , proliferation and/or cytolytic activity relative to prior to the administration of the CBP/EP300 bromodomain inhibitor.4. The method of claim 3 , wherein the number of CD8 T cells is elevated relative to prior to administration of the CBP/EP300 bromodomain inhibitor.5. The method of claim 3 , wherein the CD8 T cell is an antigen-specific CD8 T cell.6. The method of claim 1 , wherein the cancer has elevated levels of T-cell infiltration.7. The method of claim 1 , wherein the cancer is associated with increased intratumoral Treg cell density.8. The method of claim 1 , wherein the cancer is selected from acoustic neuroma claim 1 , acute leukemia claim 1 , acute lymphocytic leukemia claim 1 , acute myelocytic leukemia claim 1 , acute t-cell leukemia claim 1 , basal cell carcinoma claim 1 , bile duct carcinoma claim 1 , bladder cancer claim 1 , brain cancer claim 1 , breast cancer claim 1 , bronchogenic carcinoma claim 1 , cervical cancer claim 1 , chondrosarcoma claim 1 , chordoma claim 1 , choriocarcinoma claim 1 , chronic leukemia claim 1 , chronic lymphocytic leukemia claim 1 , chronic myelocytic leukemia claim 1 , chronic myelogenous leukemia claim 1 , colon cancer claim 1 , colorectal cancer claim 1 , craniopharyngioma claim 1 , cystadenocarcinoma claim 1 , diffuse large B-cell lymphoma claim 1 , dysproliferative changes claim 1 , embryonal carcinoma claim 1 , endometrial cancer claim 1 , endotheliosarcoma ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I): 2. The compound of wherein X is NH; or a salt thereof.3. The compound of wherein X is O; or a salt thereof.4. The compound of wherein X is S; or a salt thereof.5. The compound of wherein X is CH; or a salt thereof.67-. (canceled)8. The compound wherein ring A is a benzo ring that is optionally substituted with one or more groups Rthat are independently selected from the group consisting of R claim 1 , —F claim 1 , —Cl claim 1 , —Br claim 1 , —I claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —O—C(O)—O—R claim 1 , —C(O)—R claim 1 , —C(O)—O—R claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —O—C(O)—N(R) claim 1 , —N(R)—C(O)—OR claim 1 , —N(R)—C(O)—N(R) claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—S(O)—N(R) claim 1 , —CH═C(R) claim 1 , and —N(R)—S(O)—N(R); or a salt thereof.9. The compound of wherein ring A is a benzo ring that is optionally substituted with one or more groups Rthat are independently selected from the group consisting of R claim 1 , —F claim 1 , —Cl claim 1 , —Br claim 1 , —I claim 1 , —C(O)—N(R) claim 1 , —O—R claim 1 , and —CH═C(R)or a salt thereof.11. The compound of claim 10 , wherein ring A is optionally substituted with one or more additional groups Rthat are independently selected from the group consisting of R claim 10 , —F claim 10 , —Cl claim 10 , —Br claim 10 , —I claim 10 , —C(O)—N(R) claim 10 , —O—R claim 10 , and —CH═C(R)or a salt thereof.2021-. (canceled)26. A composition comprising a compound of formula (I) as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or vehicle.2728-. (canceled)29. A method for treating a CBP and/or EP300-mediated disorder in an animal comprising administering a compound of formula (I) claim 1 , or a ...

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer. 2. The compound of claim 1 , wherein Ris phenyl claim 1 , pyridyl claim 1 , or indolyl claim 1 , wherein said phenyl claim 1 , pyridyl claim 1 , or indolyl is optionally substituted with —R claim 1 , —OR claim 1 , —SR claim 1 , —N(R) claim 1 , —OSOR claim 1 , —SOR claim 1 , —C(O)N(R) claim 1 , halogen claim 1 , or nitrile.3. The compound of claim 1 , wherein Ris phenyl claim 1 , pyridyl claim 1 , or indolyl claim 1 , wherein said phenyl claim 1 , pyridyl claim 1 , or indolyl is optionally substituted with —OR claim 1 , halogen claim 1 , or nitrile.4. The compound of claim 1 , wherein Ris pyridyl claim 1 , wherein said pyridyl is optionally substituted with —OR claim 1 , halogen claim 1 , or nitrile.5. The compound of claim 1 , wherein Ris indolyl claim 1 , wherein said indolyl is optionally substituted with —OR claim 1 , halogen claim 1 , or nitrile.6. The compound of any of - claim 1 , wherein m is an ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I) or formula (II): 1. A method for treating a CBP and/or EP300-mediated disorder in an animal comprising administering a CBP and/or EP300 inhibitor , or a pharmaceutically acceptable salt thereof , to the animal.2. The method of wherein the CBP and/or EP300-mediated disorder is a fibrotic disease.3. The method of wherein the fibrotic disease is selected from the group consisting of pulmonary fibrosis claim 2 , silicosis claim 2 , cystic fibrosis claim 2 , renal fibrosis claim 2 , liver fibrosis claim 2 , liver cirrhosis claim 2 , primary sclerosing cholangitis claim 2 , primary biliary cirrhosis claim 2 , endomyocardial fibrosis claim 2 , mediastinal fibrosis claim 2 , myelofibrosis claim 2 , retroperitoneal fibrosis claim 2 , progressive massive fibrosis claim 2 , nephrogenic systemic fibrosis claim 2 , Crohn's disease claim 2 , keloid claim 2 , myocardial infarction claim 2 , systemic sclerosis and arthro fibrosis.4. The method of wherein the CBP and/or EP300-mediated disorder is a fibrotic lung disease.5. The method of wherein the fibrotic lung disease is selected from the group consisting of idiopathic pulmonary fibrosis claim 4 , fibrotic interstitial lung disease claim 4 , interstitial pneumonia claim 4 , fibrotic variant of non-specific interstitial pneumonia claim 4 , cystic fibrosis claim 4 , lung fibrosis claim 4 , chronic obstructive pulmonary lung disease (COPD) claim 4 , and pulmonary arterial hypertension.6. The method of wherein the fibrotic lung disease is idiopathic pulmonary fibrosis. This application is a continuation of U.S. application Ser. No. 14/952,821, filed Nov. 25, 2015, which claims priority to International Application No. PCT/CN2014/092380, filed Nov. 27, 2014, and International Application No. PCT/CN2015/092965, filed Oct. 27, 2015, which are hereby incorporated by reference.The present invention relates to compounds useful as inhibitors of CBP/EP300 and methods of treating cancer ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to methods for treating PCAF mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: 131-. (canceled)3355-. (canceled)58. The compound of wherein Ris hydrogen or methyl.59. The compound of wherein Ris selected from the group consisting of H claim 32 , 4-fluorophenyl claim 32 , 4-methoxyphenyl claim 32 , 3-chlorophenyl claim 32 , benzyl claim 32 , 4-(trifluoromethyl)phenyl claim 32 , phenyl claim 32 , and 4-(phenylsulfonyl)phenyl.60. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a carbocyclyl or heterocyclyl claim 32 , which carbocyclyl and heterocyclyl is optionally substituted with one or more groups R.61. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a cyclohexane claim 32 , which is optionally substituted with one or more groups R.62. The compound of wherein Rand one Rtaken together with the atoms to which they are attached form a 5-membered or 6-membered heterocyclyl claim 32 , which 5-membered and 6-membered heterocyclyl is optionally substituted with one or more groups R.63. The compound of wherein Rand one Rtaken together with the atoms to which they are attached form a 6-membered heterocyclyl.64. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a 5-membered or 6-membered heterocyclyl claim 32 , which 5-membered and 6-membered heterocyclyl is optionally substituted with one or more groups R.65. The compound of wherein Rand Rtaken together with the atoms to which they are attached form a 6-membered heterocyclyl.66. The compound of wherein or Rand Rtaken together with the atoms to which they are attached form a 5-membered or 6-membered heterocyclyl claim 32 , which 5-membered and 6-membered heterocyclyl is optionally substituted with one or more groups R.67. The compound of wherein Rtaken together with Rand the atoms to which they are attached form a ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I): 2. (canceled)3. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and claim 1 , Calkenyl is optionally substituted with one or more groups R.4. (canceled)5. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and Calkenyl is optionally substituted with one or more groups independently selected from carbocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —O—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , and —C(O)—O—R.6. The compound of wherein Ris Calkyl or Calkenyl claim 1 , wherein each Calkyl and Calkenyl is optionally substituted with one or more groups independently selected from Ccycloalkyl.7. The compound of wherein Ris methyl claim 1 , butyl claim 1 , 2-propenyl claim 1 , 2-buten-1-yl claim 1 , 3-buten-1-yl or 2-cyclopropylethyl.8. (canceled)9. The compound of wherein Ris H or Calkyl wherein each Calkyl is optionally substituted with one or more groups R.1013-. (canceled)14. The compound of wherein Ris hydrogen claim 1 , Calkyl claim 1 , or Ccycloalkyl claim 1 , wherein each Calkyl and Ccycloalkyl is optionally substituted with one or more substituent groups independently selected from —O—R.15. The compound of wherein Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , or 2-methoxyethyl.1618-. (canceled)19. The compound of wherein Ris Calkyl that is optionally substituted with one or more substituent groups independently selected from oxo claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —Br claim 1 , —I claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —O—R claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —O—C(O)—O—R claim 1 , —C(O)—R claim 1 , —C(O)—O—R claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —O—C(O)—N(R) claim 1 , —N(R)—C(O)—OR claim 1 , —N(R)—C(O)—N(R ...

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds of formula (I): 2. The compound of wherein Ris methyl that is substituted with one or more groups R.3. The compound of wherein Ris ethyl that is substituted with one or more groups R.47-. (canceled)8. The compound of wherein Ris butyl claim 1 , 2-cyclopropylethyl claim 1 , cyclopentylmethyl claim 1 , 2-penten-1-yl claim 1 , cyclohexylmethyl claim 1 , cyclobutylmethyl claim 1 , 2-cyclohexylethyl claim 1 , pentyl claim 1 , 2-methylpropyl claim 1 , 2-buten-1-yl claim 1 , butyl claim 1 , 2-furylmethyl claim 1 , 3-methylbut-1-yl claim 1 , 2-propenyl claim 1 , 3-methyl-2-buten-1-yl claim 1 , 3-buten-1-yl claim 1 , 2-methoxyethyl claim 1 , 3-methoxypropyl claim 1 , or 4-methoxybenzyl.910-. (canceled)11. The compound of wherein Ris methyl.1213-. (canceled)14. The compound of wherein Q is C-Ccycloalkyl that is optionally substituted with one or more groups R.15. The compound of wherein Q is aryl that is optionally substituted with one or more groups R.16. The compound of wherein Q is phenyl that is optionally substituted with one or more groups R.17. The compound of wherein Q is C-Cheterocycloalkyl that is optionally substituted with one or more groups R.18. The compound of wherein Q is heteroaryl that is optionally substituted with one or more groups R.2024-. (canceled)25. The compound of claim 1 , wherein each Ris independently selected from oxo claim 1 , Calkyl claim 1 , heterocyclyl claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —O—R claim 1 , and —N(R)—S(O)—R claim 1 , wherein any Calkyl or heterocyclyl is optionally substituted with one or more groups independently selected from —O—Rand Calkyl that is optionally substituted with one or more groups independently selected from oxo and halo.2627-. (canceled)30. A composition comprising a compound of formula (I) as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or ...

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and to salts thereof, wherein R 1 , R 2 , and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure. 3. The compound of claim 2 , wherein X is selected from the group consisting of a bond claim 2 , —O— claim 2 , —NR— and —NR—.4. The compound of or claim 2 , wherein A is selected from the group consisting of phenyl claim 2 , pyridyl claim 2 , quinolinyl claim 2 , indolyl claim 2 , and indolinyl claim 2 , wherein phenyl claim 2 , pyridyl claim 2 , quinolinyl claim 2 , indolyl and indolinyl may optionally be substituted by one claim 2 , two or three substituents each independently selected from the group consisting of —R claim 2 , —OR claim 2 , —SR claim 2 , —N(R) claim 2 , —OSOR claim 2 , —SOR claim 2 , —C(O)N(R) claim 2 , halogen claim 2 , and cyano.5. The compound of any one of - claim 2 , wherein A is phenyl; wherein phenyl may optionally be substituted by one claim 2 , two claim 2 , or three substituents each independently selected from the group consisting of —OR claim 2 , halogen claim 2 , and cyano.6. The compound of any one of - claim 2 , wherein A is pyridyl; wherein pyridyl may optionally be substituted by one claim 2 , two claim 2 , or three substituents each independently selected from the group consisting of —OR claim 2 , halogen claim 2 , and cyano.7. The compound of or claim 2 , wherein Rand ring A together with the nitrogen to which they are attached form a 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydro-1 claim 2 ,5-naphthyridine moiety.8. The compound of or claim 2 , wherein Rand ring A together with the nitrogen to which they are attached form a 1 claim 2 ,2 claim 2 ,3 claim 2 ,4-tetrahydro-1 claim 2 ,5-naphthyridine moiety.9. The compound of or claim 2 , wherein ...

Therapeutic compounds and uses thereof

Phthalazine derivatives of formula (i) as pcaf and gcn5 inhibitors for use in the treatment of cancer

The present invention relates to methods for treating PCAF and GCN5 mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein ring A, R 1, R 3 , R 4 , R 5 , and each R e have any of the values defined in the specification. Also included are novel compounds of Formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Therapeutic compounds and uses thereof

The invention relates to compounds of formula (I) and salts thereof: wherein R 1 -R 3 have any of the values defined in the specification. The compounds and salts are useful for treating PCAF mediated disorders and/or GCN5 mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as and methods of using said compounds, salts, or compositions in the treatment of various disorders.

Therapeutic compounds and uses thereof

The present invention relates to methods for treating PCAF mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein R 1 , R 3 -R 6 , X, and each R e have any of the values defined in the specification. Also included are novel compounds of formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Therapeutic compounds and uses thereof

The present invention relates to methods for treating PCAF and GCN5 mediated disorders using a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein ring A, R 1 , R 3 , R 4 , R 5 , and each R e have any of the values defined in the specification. Also included are novel compounds of Formula (I) and salts thereof, as well as pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Use of CBP/EP300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

PI3K-α INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-α enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-α signaling with the compounds and compositions of the disclosure.

Use of cbp/ep300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure

Pyridazinone derivatives and their use in the treatment of cancer

The invention relates to compounds of formula (I) and salts thereof: wherein R 1 -R 3 have any of the values defined in the specification. The compounds and salts are useful for treating PCAF mediated disorders and/or GCN5 mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as and methods of using said compounds, salts, or compositions in the treatment of various disorders.

Bromodomain inhibitors and uses thereof

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Bromodomain inhibitors and uses thereof

Shp2 phosphatase inhibitors and methods of making and using the same

The disclosure is in part directed to crystalline forms of (R)- 1'-(3 -(3,4-dihydro- 1,5- naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3H-spiro[benzofuran-2,4'- piperidin]-3 -amine, its salt, and variants thereof.

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and to salts thereof, wherein R 1 , R 2 , and Q have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of bromodomains. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various bromodomain-mediated disorders.

Bromodomain inhibitors and uses thereof

Use of cbp/ep300 bromodomain inhibitors for cancer immunotherapy

The present invention relates to use of CBP/EP300 bromodomain inhibitors for the treatment of cancer.

Bromodomain inhibitors and uses thereof

The present invention relates to compounds useful as inhibitors of bromodomain-containing proteins. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders. Such compounds may be exemplified by the compounds of the following formula: (see above formula)

use of cbp / ep300 bromodomain inhibitors for cancer immunotherapy

a presente invenção refere-se ao uso de inibidores de bromodomínio cbp/ep300 para o tratamento de câncer. The present invention relates to the use of cbp / ep300 bromodomain inhibitors for the treatment of cancer.

SHP2 phosphatase inhibitors and methods of use thereof

The present invention relates to novel compounds having the general formula: and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer.

SUBSTITUTED PYRROLOPYRIDINES USED AS BROMODOMA INHIBITORS

4,5,6,7-tetrahydro-1h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors

Therapeutic compounds and uses thereof

The present invention relates to compounds of formula (I): and to salts thereof, wherein A has any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors

The present invention relates to compounds of formula (I) or formula (II): and to salts thereof, wherein R 1 -R 4 of formula (I) and R 1 -R 3 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.

Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors

Disclosed herein are novel compounds of formula (I) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds ad compositions of the disclosure.

fgfr inhibitors and methods of using them

inibidores de fgfr e métodos de uso dos mesmos. a presente invenção refere-se a novos compostos e composições farmacêuticas dos mesmos, e métodos para inibir a atividade de enzimas de fgfr com os compostos e composições da invenção. a presente invenção também se refere a, mas não está limitada a, métodos para o tratamento de distúrbios associados com sinalização de fgfr com o compostos e composições da invenção. fgfr inhibitors and methods of using them. The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods of inhibiting the activity of fgfr enzymes with the compounds and compositions of the invention. the present invention also relates to, but is not limited to, methods for treating disorders associated with fgfr signaling with the compounds and compositions of the invention.

Pi3k-alpha inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K? enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K? signaling with the compounds and compositions of the disclosure.

Pi3k.alpha. inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K? enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K? signaling with the compounds and compositions of the disclosure.

Phthalazine derivatives of formula (i) as pcaf and gcn5 inhibitors for use in the treatment of cancer

Fgfr inhibitors and methods of use thereof

Shp2 phosphatase inhibitors and methods of use thereof

Ｓｈｐ２ホスファターゼ阻害剤およびこれらの使用方法

【課題】ＳＨＰ２ホスファターゼ阻害剤およびこれらの使用方法を提供すること。【解決手段】本開示は、新規化合物およびその薬学的組成物、ならびに本開示の化合物および組成物を用いてＳＨＰ２ホスファターゼの活性を阻害するための方法に関する。本開示はさらに、ＳＨＰ２脱調節に関連する障害を、本開示の化合物および組成物を用いて処置するための方法に関するが、これらに限定されない。TIFF2023166614000567.tif1533本明細書中に記載される方法はまた、治療有効量の抗体、抗体－薬物結合体、免疫調節薬、またはヒストンデアセチラーゼ阻害剤をさらに投与する工程を包含し得る。【選択図】なし

Inhibidores de la fosfatasa shp2 y metodos para su uso.

Nuevos compuestos y composiciones farmacéuticas de los mismos, y métodos para inhibir la actividad de la fosfatasa SHP2 con los compuestos y las composiciones de la invención. Además, se relaciona, no taxativamente, con métodos para tratar trastornos asociados con la desregulación de la SHP2, mediante los compuestos y las composiciones de la invención.

Shp2 phosphatase inhibitors and methods of use thereof

Pi3k-alpha inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Ka enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Ka signaling with the compounds and compositions of the disclosure.

Fgfr inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.

SHP2 phosphatase inhibitors and methods of making and using the same

The disclosure is in part directed to crystalline forms of (R)-1′-(3-(3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3H-spiro[benzofuran-2,4′-piperidin]-3-amine, its salt, and variants thereof.

Cdk inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of CDK enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with CDK signaling with the compounds and compositions of the disclosure.

INHIBIDORES DE PI3Ka Y MÉTODOS DE USO DE LOS MISMOS

La presente divulgación se refiere a nuevos compuestos y composiciones farmacéuticas de los mismos, y a métodos para inhibir la actividad de las enzimas PI3Ka con los compuestos y composiciones de la divulgación. La presente divulgación se refiere, además, pero sin limitación, a métodos para tratar trastornos asociados con la señalización de PI3Ka con los compuestos y las composiciones de la divulgación.

4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors

The present invention relates to compounds of formula (I), wherein: X is C(=O) or S(O) 2 ; R 1 is selected from the group consisting of N-linked piperazinyl, relinked piperidine, and N-linked diazabicyclo[3.2.1]octane, wherein R 1 is optionally substituted with one or more groups; R 2 and R 3 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl, wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl is optionally substituted with one or more groups; or R 2 and R 3 taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring that is optionally substituted with one or more groups; R 4 and R 5 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl, wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl is optionally substituted with one or more groups; or R 4 and R 5 taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring that is optionally substituted with one or more groups; and R 6 is a 5-10 membered heteroaryl, 5-10 membered heterocycle, or a 6-10 membered aryl, which 5-10 membered heteroaryl, 5-10 membered heterocycle, and 6-10 membered aryl is optionally substituted with one or more groups; useful as inhibitors of one or more histone demethylases, such as KDM2b. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors

The present invention relates to compounds of formula (I), (formula I) wherein: X is C(=0) or S(0) 2 ; R 1 is selected from the group consisting of N-linked piperazinyl, relinked piperidine, and N-linked diazabicyclo[3.2.1]octane, wherein R 1 is optionally substituted with one or more groups; R 2 and R 3 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl, wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl is optionally substituted with one or more groups; or R 2 and R 3 taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring that is optionally substituted with one or more groups; R 4 and R 5 are each independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl, wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-8 cycloalkyl is optionally substituted with one or more groups; or R 4 and R 5 taken together with the carbon to which they are attached form a 3-, 4-, 5-, or 6-membered carbocyclic ring that is optionally substituted with one or more groups; and R 6 is a 5-10 membered heteroaryl, 5-10 membered heterocycle, or a 6-10 membered aryl, which 5-10 membered heteroaryl, 5-10 membered heterocycle, and 6-10 membered aryl is optionally substituted with one or more groups; useful as inhibitors of one or more histone demethylses, such as KDM2b. The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

Estrogen receptor alpha degraders and medical use thereof

The application relates to bifunctional compounds which act as degraders of the estrogen receptor alpha (ERα) and are useful for treating disorders associated with ERα-mediated transcription regulation such as endometriosis and cancer. The compounds are bifunctional molecules comprising a cereblon- binding moiety LBM linked to a ligand ERBM that binds ERα and comprises a benzofused 7-membered ring.

Estrogen receptor alpha degraders and use thereof

The application relates to bifunctional compounds of the general formula I-3' which act as degraders of the estrogen receptor alpha(ERα) and are useful for treating disorders associated with ERα-mediated transcription regulation such as endometriosis and cancer. The compounds are bifunctional molecules comprising a cereblon-binding moiety LBM linked to a ligand ERBM that binds ERα and comprises a benzofused partially saturated 6-membered carbocyclic or heterocyclic ring. [I-3'] wherein ERBM is delected from

Inhibidores de fosfatidilinositol 3 cinasa (pi3k) alfa y metodos de uso de los mismos.

La presente invención se refiere a nuevos compuestos y composiciones farmacéuticas de los mismos, y a métodos para inhibir la actividad de las enzimas PI3Ka con los compuestos y composiciones de la invención. La presente invención además se refiere, pero no se limita, a métodos para tratar trastornos asociados con la señalización de PI3Ka con los compuestos y composiciones de la invención.

PI3K-a INHIBITORS AND METHODS OF USE THEREOF

SHP2 phosphatase inhibitors and methods of use thereof

The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.

PI3Kα INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Kα enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Kα signaling with the compounds and compositions of the disclosure.

Inhibidores de cinasas dependientes de ciclinas (cdk) y metodos de uso de estos.

La presente descripción se refiere a compuestos novedosos y composiciones farmacéuticas de estos, y métodos para inhibir la actividad de las enzimas CDK con los compuestos y las composiciones de la descripción. Además, la presente descripción se refiere, de modo no taxativo, métodos para tratar trastornos asociados con la señalización de CDK con los compuestos y las composiciones de la descripción.

Inhibidores de la fosfatasa shp2 y métodos para su uso (divisional de la solicitud no. 202002419)

Nuevos compuestos y composiciones farmacéuticas de los mismos, y métodos para inhibir la actividad de la fosfatasa SHP2 con los compuestos y las composiciones de la invención. Además se relaciona, no taxativamente, con métodos para tratar trastornos asociados con la desregulación de la SHP2, mediante los compuestos y las composiciones de la invención.

Inhibidores de cdk y métodos de uso de estos

La presente descripción se refiere a compuestos novedosos y composiciones farmacéuticas de estos, y métodos para inhibir la actividad de las enzimas CDK con los compuestos y las composiciones de la descripción. Además, la presente descripción se refiere, de modo no taxativo, métodos para tratar trastornos asociados con la señalización de CDK con los compuestos y las composiciones de la descripción.

Inhibidores de cdk y metodos de uso de estos

La presente invencion se refiere a un compuesto de formula I-A, o una sal farmaceuticamente aceptable de este, en donde: Q es L1; CyA es un heteroarileno de 5-6 miembros que tiene 1-4 heteroatomos seleccionados de nitrogeno, oxigeno y azufre; CyB es un anillo carbociclico saturado o parcialmente insaturado de 3-14 miembros, un anillo heterociclico saturado o parcialmente insaturado de 3-14 miembros que tiene 1-4 heteroatomos seleccionados de nitrogeno, oxigeno y azufre, fenileno, entre otros; Z es hidrogeno o L2-Rz; Rz es hidrogeno, fenilo, entre otros; W es hidrogeno o Cyc; Cyc es un anillo carbociclico saturado o parcialmente insaturado de 3-14 miembros, fenilo, entre otros. Tambien se refiere a compuestos de formula I a VII, donde los sustituyentes son tal como se definen en la descripcion. Tambien se refiere a una composicion farmaceutica. Dichos compuestos son inhibidores de la actividad de las cinasas dependientes de ciclinas (CDK), siendo utiles en el tratamiento del cancer.

Inibidores de cdk e métodos de uso destes

inibidores de cdk e métodos de uso destes. a presente invenção refere-se a novos compostos e composições farmacêuticas destes e métodos para inibir a atividade de enzimas cdk com os compostos e composições da invenção. a presente invenção refere-se ainda a, mas não está limitada a, métodos para o tratamento de distúrbios associados à sinalização de cdk com os compostos e composições da invenção.

PI3Ka INHIBITORS AND METHODS OF USE THEREOF

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Kα enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Kα signaling with the compounds and compositions of the disclosure.

Shp2 phosphatase inhibitors and methods of making and using the same

The disclosure is in part directed to crystalline forms of (R)-1′-(3-(3,4-dihydro-1,5-naphthyridin-1(2H)-yl)-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3H-spiro[benzofuran-2,4′-piperidin]-3-amine, its salt, and variants thereof.

Inhibidores de cdk y métodos de uso de estos

La presente descripción se refiere a compuestos novedosos y composiciones farmacéuticas de estos, y métodos para inhibir la actividad de las enzimas CDK con los compuestos y las composiciones de la descripción. Además, la presente descripción se refiere, de modo no taxativo, métodos para tratar trastornos asociados con la señalización de CDK con los compuestos y las composiciones de la descripción.

Cdk inhibitors and methods and use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of CDK enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with CDK signaling with the compounds and compositions of the disclosure.

Inhibidores fgfr y métodos de uso de estos

Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, en donde: CyA es un compuesto seleccionado del grupo de fórmulas (2) en donde * representa un enlace a R⁵ y línea ondulada representa un enlace a Cy⁶; R⁵ es R⁵A-L⁵-R⁵B; R⁵A es un radical bivalente de RB, en donde R⁵A está sustituido con m casos de R⁵C además de -L⁵-R⁵B; R⁵B es hidrógeno o RB, en donde R⁵B está sustituido con n casos de R⁵D; Cy⁶ es fenileno; un anillo carbocíclico de 3 - 14 miembros saturado o parcialmente insaturado bivalente; un anillo heterocíclico de 3 - 14 miembros saturado o parcialmente insaturado bivalente que tiene 1 - 4 heteroátomos independientemente seleccionados entre nitrógeno, oxígeno, y azufre; o un heteroarileno de 5 - 14 miembros que tiene 1 - 4 heteroátomos independientemente seleccionados entre nitrógeno, oxígeno, y azufre; en donde Cy⁶ está sustituido con p casos de R⁶ además de -L⁶-RW; RW es halógeno, -CN, o un compuesto del grupo de fórmulas (3); cada caso de R⁶ es independientemente RA o RB, en donde R⁶ está sustituido por q casos de RC; o dos casos de R⁶, un caso de R⁶ y un caso de RL, un caso de R⁶ y un caso de RWA, o un caso de R⁶ y un caso de R⁷ᵃ se toman junto con sus átomos intervinientes para formar un anillo parcialmente insaturado o aromático de 4 - 8 miembros que tiene 0 - 4 heteroátomos independientemente seleccionados entre nitrógeno, oxígeno, y azufre; en donde dicho anillo está sustituido con r casos de RC; R⁷ es H o RB, en donde R⁷ está sustituido con t casos de R⁷A; R⁸ es H, -NR₂, halógeno, -OH, o C₁₋₆ alifático opcionalmente sustituido con 1 - 3 halógenos; R⁹ es H, -NR₂, halógeno, o C₁₋₆ alifático opcionalmente sustituido con 1 - 3 halógenos; R¹⁰ es H o C₁₋₆ alifático opcionalmente sustituido con 1 - 3 halógenos; cada uno de L⁵ y L⁶ es independientemente un enlace covalente, o una cadena de hidrocarburos lineal o ramificada saturada o insaturada bivalente C₁₋₄ en donde una o dos unidades de metileno de la cadena ...

Jak2 inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of JAK2 enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with JAK2 signaling with the compounds and compositions of the disclosure.

Cdk inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of CDK enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with CDK signaling with the compounds and compositions of the disclosure.

Fgfr inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of FGFR enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with FGFR signaling with the compounds and compositions of the disclosure.

Pi3k-alpha inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Kα enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Kα signaling with the compounds and compositions of the disclosure.

Inhibidores de fgfr y métodos de uso de los mismos

La presente invención se refiere a nuevos compuestos y composiciones farmacéuticas de los mismos, y a métodos para inhibir la actividad de las enzimas FGFR con los compuestos y composiciones de la invención. La presente invención además se refiere, pero no se limita, a métodos para tratar trastornos asociados con la señalización de FGFR con los compuestos y composiciones de la invención.

Pyrazolo[3,4-b]pyrazine derivatives as shp2 phosphatase inhibitors

Pi3k-alpha inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3K-α enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3K-α signaling with the compounds and compositions of the disclosure.

Pi3k-alpha inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of PI3Ka enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with PI3Ka signaling with the compounds and compositions of the disclosure.

Therapeutic compounds and uses thereof

Provided herein are compounds of formula I: and salts thereof and compositions and uses thereof. The compounds are useful as inhibitors of LSD1. Also included are pharmaceutical compositions comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various LSD1-mediated disorders.

Cdk inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of CDK enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with CDK signaling with the compounds and compositions of the disclosure.

SHP2 phosphatase inhibitors and methods of use thereof

The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.

Inhibidores de pi3k y métodos de uso de los mismos div 2985-22

La presente invención se refiere a nuevos compuestos y composiciones farmacéuticas de los mismos, y a métodos para inhibir la actividad de las enzimas PI3Ka con los compuestos y composiciones de la invención. La presente invención además se refiere, pero no se limita, a métodos para tratar trastornos asociados con la señalización de PI3Ka con los compuestos y composiciones de la invención.

Shp2 phosphatase inhibitors and methods of use thereof

Jak2 inhibitors and methods of use thereof

The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of JAK2 enzymes with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with JAK2 signaling with the compounds and compositions of the disclosure.