METHODS OF USE AND COMBINATIONS

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or —CR 0 —, where R 0 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc., Z is —CR e —, or, —N—, where R e is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 1 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 2 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl; R 3 and R 4 are independently hydrogen, C 1 C 6 linear or branched chain alkyl, etc.; R 5 and R 6 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl, etc.; R 8 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 9 and R 10 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH 2 ) q —, —(CHR s ) q —, or —(CR s R t ) q —, where R s and R t are independently C 1 -C 6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides, and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

NOVEL SELECTIVE ANDROGEN RECEPTOR MODULATORS

The present invention relates to a compound of Formula 1, 2 or 3: 2. The compound of having Formula 1 wherein Rand Rare independently C-Clinear or branched chain alkyl; and claim 1 , Rand Rare both hydrogen.3. The compound of wherein Rand Rare independently methyl claim 2 , ethyl or propyl.4. The compound of having Formula 2 wherein Q is —(CH)— claim 1 , —(CHR)— claim 1 , or (CRR)— claim 1 , where Rand Rare independently C-Clinear or branched chain alkyl; and claim 1 , q is 1 or 2.5. The compound of wherein Q is CO—.6. The compound of having Formula 3 wherein X and Y are independently —CH— claim 1 , —CHR— claim 1 , or claim 1 , —CR— claim 1 , where Rand Rare independently C-Clinear or branched chain alkyl claim 1 , aryl claim 1 , alkylaryl claim 1 , heteroaryl or claim 1 , alkylheteroaryl.7. The compound of wherein X and Y are independently —CH— claim 6 , —CHR— claim 6 , or claim 6 , —CRR— claim 6 , where Rand Rare independently methyl claim 6 , ethyl.8. The compound of selected from the group consisting of:6-[(3S)-3-methyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile;6-[(3S)-3-ethyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile6-[(3R)-1,1-dioxido-3-(2,2,2-trifluoroethyl)-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile;6-[(3R)-1,1-dioxido-3-(2-phenylethyl)-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile;6-[1-methyl-(3S)-3-methyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile;6-{(3R)-1,1-dioxido-3-[3-(trifluoromethyl)phenyl]-1,2,5-thiadiazolidin-2-yl}isoquinoline-1-carbonitrile;6-[(3S)-3-(4-chlorophenyl)-1,1-dioxido-1,2,5-thiadiazolidin-2-yl]isoquinoline-1-carbonitrile;6-[(3S)-3-methyl-1,1-dioxido-1,2-thiazolidin-2-yl]isoquinoline-1-carbonitrile;6-[(3S)-3-methyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl]naphthalene-1-carbonitrile;6-[(4R)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl]isoquinoline-1-carbonitrile;6-[(4S)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl]isoquinoline-1-carbonitrile;6-{(3R)-1,1 ...

N-SUBSTITUTED-DIOXOCYCLOBUTENYLAMINO-3-HYDROXY-PICOLINAMIDES USEFUL AS CCR6 INHIBITORS

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) 8. A compound selected from the group consisting of(R)-4-((2-(((4-Chloro-1-methyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide(R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N-isopropyl-N-methylpicolinamide;(R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(5-methylspiro[2.3]hexan-5-yl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide;4-((2-(((S)-((S)-4,4-Difluoro-2-methyltetrahydrofuran-2-yl)(4-ethyl-1-methyl-1H-pyrazol-3-yl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide;(R)-4-((2-(((2,5-Dimethylthiazol-4-yl)(1-methylcyclobutyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide;(S)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide;(R)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-N-ethyl-3-hydroxy-N-methylpicolinamide;(S)-4-((2-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-N-ethyl-3-hydroxy-N-methylpicolinamide;(R)-3-(((1,4-dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-4-((3-hydroxy-2-(morpholine-4-carbonyl)pyridin-4-yl)amino)cyclobut-3-ene-1,2-dione;(R)-3-(((1,4-Dimethyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-4-((3-hydroxy-2-(4-methylpiperazine-1-carbonyl)pyridin-4-yl)amino)cyclobut-3-ene-1,2-dione;(S)-4-((2-(((4-Chloro-1-methyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3-hydroxy-N,N-dimethylpicolinamide;(R)-4-((2-(((4-Chloro-1-methyl-1H-pyrazol-3-yl)(1-methylcyclopentyl)methyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)-3- ...

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYR-ROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK. 11. The compound of selected from the group consisting of:2-(1-acryloylpiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;N-isopropyl-2-(3-(N-methylacrylamido)azetidin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((3R,4R)-1-acryloyl-3-hydroxypiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-(1-acryloylpyrrolidin-3-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-2-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((1R,3R)-3-acrylamidocyclobutylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide; and,(S)-2-((1-acryloylpyrrolidin-3-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide; or, a pharmaceutically acceptable salt thereof.12. The compound of selected from the group consisting of:(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-1-(3-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methylpiperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-hydroxypiperidin-1-yl)prop-2-en-1-one;(R)-1-(3-(5-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-(5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(hydroxymethyl)piperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-fluoropiperidin-1-yl)prop-2-en-1-one;1-((3R,4S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-methylpiperidin-1-yl)prop-2-en-1-one;1 ...

Methyl- and Trifluromethyl-Substituted Pyrrolopyridine Modulators of RORC2 and Methods of Use Thereof

The present invention provides methyl- and trifluoromethyl-substituted pyrrolopyridines, pharmaceutical compositions thereof, methods of modulating RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such pyrrolopyridines and pharmaceutical compositions thereof. Retinoid-related orphan receptors (ROR) are reported to have an important role in numerous biological processes. Scientific investigations relating to each of retinoid-related orphan receptors RORα, RORβ, and RORγ have been described in the literature. Continuing research in this field is spurred by the promise of developing new therapeutic agents to treat medical disorders associated with retinoid-related orphan receptor activity.RORγ has been reported to be expressed in high concentration in various tissues, such as thymus, kidney, liver, muscle, and certain fat tissue. Two isoforms of RORγ have been identified and are referred to as γ1 and γ2 (also referred to as RORγt). Expression of the γ2 isoform has been reported to appear in, for example, double-positive thymocytes. Compounds capable of modulating RORyt activity are contemplated to provide a therapeutic benefit in the treatment of multiple medical disorders, including immune and inflammatory disorders.Numerous immune and inflammatory disorders continue to afflict millions of patients worldwide. Significant advances have been made in treating these disorders. However, current therapies do not provide satisfactory results for all patients due to, for example, detrimental side effects or insufficient efficacy. Treatments for immune and inflammatory disorders vary depending on the particular medical disorder, and often involve use of immunosuppressive drugs. Surgery (e.g., splenectomy), plasmapheresis, or radiation can be used in certain instances.One exemplary immune disorder in need of better therapy is psoriasis. Psoriasis is a T cell-mediated inflammatory disease that affects ...

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them. 3. A compound of wherein A is a bond and Ris a C-Clinear or branched chain alkyl claim 2 , C-Ccycloalkyl or aryl.4. A compound of wherein A is a bond or —(CH)— claim 2 , and Ris C-Ccycloalkyl wherein said C-Ccycloalkyl is further optionally substituted with one or more substituents selected from the group consisting of halo claim 2 , C-Clinear or branched chain alkyl claim 2 , and CN where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo claim 2 , CN claim 2 , hydroxyl claim 2 , CONH claim 2 , and SOCH; where k is 1 claim 2 , 2 claim 2 , or 3.5. A compound of wherein A is a bond or —(CH)— claim 2 , and Ris an unsaturated claim 2 , saturated or partially saturated monocyclic or bicyclic ring structure containing a total of five to eleven atoms having one to three heteroatoms independently selected from the group consisting of oxygen claim 2 , nitrogen claim 2 , and sulfur claim 2 , wherein said alkyl claim 2 , C-Ccycloalkyl claim 2 , aryl claim 2 , or monocyclic or bicyclic ring structure is further optionally substituted with one or more substituents selected from the group consisting of deuterium claim 2 , halo claim 2 , C-Clinear or branched chain alkyl claim 2 , CN claim 2 , hydroxyl claim 2 , CF claim 2 , —NRR claim 2 , —OR claim 2 , —S(O)Rand C-Ccycloalkyl; where k is 1 claim 2 , 2 claim 2 , or 3.9. The compound of selected from the group consisting of:4-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}pyridine-2-sulfonamide;2,2,2-trifluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-ethanesulfonamide;2-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-propane-1-sulfonamide;N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide;1- ...

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B)or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them. 119-. (canceled)22. A compound of wherein A is a bond and Ris a C-Clinear or branched chain alkyl claim 21 , C-Ccycloalkyl or aryl.23. A compound of wherein A is a bond or —(CH)— claim 21 , and Ris C-Ccycloalkyl wherein said C-Ccycloalkyl is further optionally substituted with one or more substituents selected from the group consisting of halo claim 21 , C-Clinear or branched chain alkyl claim 21 , and CN where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo claim 21 , CN claim 21 , hydroxyl claim 21 , CONH claim 21 , and SOCH; where k is 1 claim 21 , 2 claim 21 , or 3.24. A compound of wherein A is a bond or —(CH)— claim 21 , and Ris an unsaturated claim 21 , saturated or partially saturated monocyclic or bicyclic ring structure containing a total of five to eleven atoms having one to three heteroatoms independently selected from the group consisting of oxygen claim 21 , nitrogen claim 21 , and sulfur claim 21 , wherein said alkyl claim 21 , C-Ccycloalkyl claim 21 , aryl claim 21 , or monocyclic or bicyclic ring structure is further optionally substituted with one or more substituents selected from the group consisting of deuterium claim 21 , halo claim 21 , C-Clinear or branched chain alkyl claim 21 , CN claim 21 , hydroxyl claim 21 , CF claim 21 , —NRR claim 21 , —OR claim 21 , —S(O)Rand C-Ccycloalkyl; where k is 1 claim 21 , 2 claim 21 , or 3.37. A pharmaceutical composition comprising a compound of claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , and a pharmaceutically acceptable carrier. This is a Continuation of U.S. application Ser. No. 14/183,946, filed Feb. 19, 2014, which claims priority to U.S. Provisional Application Ser. No. 61/767,947, filed Feb. 22, 2013, the entire disclosure of which is incorporated ...

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them. 119-. (canceled)22. The method of wherein A is a bond and Ris a C-Clinear or branched chain alkyl claim 21 , C-Ccycloalkyl or aryl.23. The method of wherein A is a bond or —(CH)— claim 21 , and Ris C-Ccycloalkyl wherein said C-Ccycloalkyl is further optionally substituted with one or more substituents selected from the group consisting of halo claim 21 , C-Clinear or branched chain alkyl claim 21 , and CN where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo claim 21 , CN claim 21 , hydroxyl claim 21 , CONH claim 21 , and SOCH; where k is 1 claim 21 , 2 claim 21 , or 3.24. The method of wherein A is a bond or —(CH)— claim 21 , and Ris an unsaturated claim 21 , saturated or partially saturated monocyclic or bicyclic ring structure containing a total of five to eleven atoms having one to three heteroatoms independently selected from the group consisting of oxygen claim 21 , nitrogen claim 21 , and sulfur claim 21 , wherein said alkyl claim 21 , C-Ccycloalkyl claim 21 , aryl claim 21 , or monocyclic or bicyclic ring structure is further optionally substituted with one or more substituents selected from the group consisting of deuterium claim 21 , halo claim 21 , C-Clinear or branched chain alkyl claim 21 , CN claim 21 , hydroxyl claim 21 , CF claim 21 , —OR claim 21 , —NRR claim 21 , —S(O)Rand C-Ccycloalkyl; where k is 1 claim 21 , 2 claim 21 , or 3.28. The method of wherein the compound is selected from the group consisting of:4-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}pyridine-2-sulfonamide;2,2,2-trifluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-ethanesulfonamide;2-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-propane-1-sulfonamide;N-{cis-3-[methyl(7H- ...

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYRROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK. 123-. (canceled)25. The method of claim 24 , wherein the compound is selected from the group consisting of:2-(1-acryloylpiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;N-isopropyl-2-(3-(N-methylacrylamido)azetidin-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((3R,4R)-1-acryloyl-3-hydroxypiperidin-4-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-(1-acryloylpyrrolidin-3-ylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-2-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;2-((1R,3R)-3-acrylamidocyclobutylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(S)-2-((1-acryloylpyrrolidin-3-yl)methylamino)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide;(R)-4-(1-acryloylpiperidin-3-ylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile;(R)-1-(3-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-methylpiperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-hydroxypiperidin-1-yl)prop-2-en-1-one;(R)-1-(3-(5-(2-methoxyethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)prop-2-en-1-one;1-(5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-2-(hydroxymethyl)piperidin-1-yl)prop-2-en-1-one;1-((3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-5-fluoropiperidin-1-yl)prop-2-en-1-one;1-((3R,4S)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-methylpiperidin-1-yl)prop-2-en-1-one;1-((3S,4R)-3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-4-fluoropiperidin-1-yl)prop-2-en-1-one;1-((2S,5R)-5-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)- ...

Methyl- and Trifluromethyl-Substituted Pyrrolopyridine Modulators of RORC2 and Methods of Use Thereof

The present invention provides methyl- and trifluoromethyl-substituted pyrrolopyridines, pharmaceutical compositions thereof, methods of modulating RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such pyrrolopyridines and pharmaceutical compositions thereof. 1. 3-cyano-N-(3-((3R ,4R)-1-isobutyryl-3-methylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2 ,3-b]pyridin-5-yl)benzamide or a pharmaceutically acceptable salt thereof.3. A pharmaceutical composition comprising 3-cyano-N-(3-((3R ,4R)-1-isobutyryl-3-methylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2 ,3-b]pyridin-5-yl)benzamide , or a pharmaceutically acceptable salt thereof , and at least one pharmaceutically acceptable carrier , excipient , or diluent.4. A method of treating a disorder in a patient comprising administering to the patient in need of such treatment a therapeutically effective amount of 3-cyano-N-(3-((3R ,4R)-1-isobutyryl-3-methylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2 ,3-b]pyridin-5-yl)benzamide , or a pharmaceutically acceptable salt thereof , wherein the disorder is selected from the group consisting of inflammatory bowel disease , ulcerative colitis , and Crohn's disease.5. A method of treating a disorder in a patient comprising administering to the patient in need of such treatment a pharmaceutical composition comprising a therapeutically effective amount of 3-cyano-N-(3-((3R ,4R)-1-isobutyryl-3-methylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2 ,3-b]pyridin-5-yl)benzamide , or a pharmaceutically acceptable salt thereof , and at least one pharmaceutically acceptable carrier , excipient , or diluent , wherein the disorder is selected from the group consisting of inflammatory bowel disease , ulcerative colitis , and Crohn's disease. Retinoid-related orphan receptors (ROR) are reported to have an important role in numerous biological processes. Scientific investigations ...

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibititors

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) (see formula IA)(see formula IB) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

Carbonitrile derivatives as selective androgen receptor modulators

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYRROLO[2,3-D]PYRIDINYL ACRYLAMIDES

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Sulfonamide-substituted indole modulators of rorc2 and methods of use thereof

The present invention provides sulfonamide-substituted indoles of Formula I: (see formula I) wherein X, W and R1 are as defined herein, pharmaceutical compositions thereof, methods of modulating RORy activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such indoles and pharmaceutical compositions thereof.

Combination of pyrrolo [2, 3 -d]pyrimidine derivatives with one or more additional agents as inhibitors of janus- related kinases (jak)

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylam ides and analogues thereof, having the structure:or a pharmaceutically acceptable salt thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

N-SUBSTITUTED DIOXOCYCLOBUTENYLAMINE-3-HYDROXY-PICOLINAMIDES USEFUL AS INHIBITORS OF CCR6

La presente invención se refiere a compuestos de dioxociclobutenilamino-3-hidroxi-picolinamida N-sustituida de las Fórmulas (IA y IB) o una sal o hidrato de aquellos aceptables desde el punto de vista farmacéutico, que inhiben el receptor de quimiocinas CC 6 (CCR6), a composiciones farmacéuticas que contienen estos compuestos, y al uso de estos compuestos para tratar o prevenir enfermedades, afecciones o trastornos que mejoran mediante inhibición de CCR6.

Quinazoline Compounds

Disclosed are quinazoline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , W, W 1 , W 2 , W 3 , A, R a , R a′ , R b , R b′ , R c , R d , R d′ , R e , R f , R g , R h , R i R j , R k , R m , R n , R o , R p , R q , and n, can be, independently, as defined anywhere herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.

Combination of pyrrolo [2, 3 -d]pyrimidine derivatives with one or more additional agents as inhibitors of janus- related kinases (jak)

Carbonitrile derivatives as selective androgen receptor modulators

The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR 0 --, where R 0 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc., Z is -CR e --, or, -N--, where R e is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 1 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 2 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl; R 3 and R 4 are independently hydrogen, C 1 C 6 linear or branched chain alkyl, etc.;. R 5 and R 6 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl, etc.; R 8 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 9 and R 10 are independently hydrogen or C 1 - C 6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH 2 ) q --, --(CHR s ) q --, or -(CR s R t ) q - -, where R s and R t are independently C 1 -C 6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

Pyrrolo [2,3-d]pyrimidine derivatives as inhibitors of janus kinases (jak)

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.

Pyrrolo [2, 3 -d]pyrimidine derivatives as inhibitors of janus- related kinases (jak)

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.

Pyrrolo (2, 3 -d)pyrimidine derivatives as inhibitors of janus kinases (jak)

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as CCR6 inhibitors

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

? PIRROLO ACRYLAMIDS [2,3-D] PIRIMIDINI LO, PIRROLO [2,3-B] IRAZINYL AND PIRROLO [2,3-D] PIRIDINYL?

La presente invención provee acrilamidas farmacéuticamente activas de pirrolo[ 2,3-d]pirimidinilo y pirrolo [2,3-d]piridinilo y análogos de las mismas. Dichos compuestos son útiles para inhibir quinasa de Janus. Esta invención también está dirigida a composiciones que comprend en métodos para hacer dichos compuestos, y métodos para tratar y preven ir condiciones mediadas por JAK.

Combination of pyrrolo [2,3-d] pyrimidine derivatives with one or more additional agents such as janus kinase inhibitors (JAK)

Un compuesto de fórmula IA que tiene la estructura:**Fórmula** o una sal farmacéuticamente aceptable del mismo, en la que Y es -A-R5, en el que A es un enlace, --(CH2)k-- o --(CD2)k-- y R5 es un alquilo cadena de cadena lineal o ramificada C1-C6, cicloalquilo C3-C6, arilo o --NRa'Rb', o es una estructura de anillo monocíclico o bicíclico, insaturado, saturado o parcialmente saturado que contiene un total de cinco a once átomos que tiene de uno a tres heteroátomos seleccionados independientemente entre el grupo que consiste en oxígeno, nitrógeno y azufre, en el que dicho alquilo, cicloalquilo C3-C6, arilo o estructura de anillo monocíclico o bicíclico además se sustituye opcionalmente con uno o más sustituyentes seleccionados entre el grupo que consiste en deuterio, halo, alquilo de cadena lineal o ramificada C1-C6, CN, hidroxilo, CF3, --ORe, --NReRf, --S(O)pRe y cicloalquilo C3- C6, en los que dicho alquilo y cicloalquilo pueden sustituirse opcionalmente con uno o más sustituyentes seleccionados entre el grupo que consiste en halo, CN, hidroxilo, CONH2 y SO2CH3, en el que (a) Ra' y Rb' son independientemente hidrógeno, deuterio, alquilo de cadena lineal o ramificada C1-C6, cicloalquilo C3-C6, arilo, (alquilo de cadena lineal o ramificada C1-C6)arilo, heteroarilo o (alquilo de cadena lineal o ramificada C1- C6)heteroarilo, en el que dicho alquilo y cicloalquilo pueden sustituirse opcionalmente con uno o más Rc', o (b) Ra' y Rb' juntos forman una cadena que comprende --(CRc'Rd')y--, en el que Rc' y Rd' son independientemente hidrógeno, deuterio, alquilo de cadena lineal o ramificada C1-C6, arilo, (alquilo de cadena lineal o ramificada C1- C6)arilo, heteroarilo, (alquilo de cadena lineal o ramificada C1-C6)heteroarilo, halo, CN, hidroxilo, CF3, CONH2, -- 20 ORe, --NReRf o --S(O)pRe; en el que Re y Rf son independientemente hidrógeno, deuterio, alquilo de cadena lineal o ramificada C1-C6 o cicloalquilo C3-C6, en los que dicho ...

Pyrrolo [2,3-d] pyrimidine derivatives

EN LA PRESENTE, SE DESCRIBEN DERIVADOS DE PIRROLO [2,3-D]PIRIMIDINA, SU USO COMO INHIBIDORES DE LA QUINASA JANUS (JAK) Y COMPOSICIONES FARMACEUTICAS QUE LOS CONTIENEN. THEREOF, PIRROLO [2,3-D] PYRIMIDINE, ITS USE AS INHIBITORS OF THE JANUS KINASE (JAK) AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM ARE DESCRIBED.

Carbonitrile derivatives as selective androgen receptor modulators

CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS Abstract The present invention relates to a compound of Formula 1, 2 or 3: R9 R10 R, R1 HO HO Y\ CR R R 3 N R3 n Formula I A4 Formula 2 o z R3 (CR5 R) Formula 3 wherein A is N or -CRo--, where Ro is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is CRe --, or, -N--, where Re is hydrogen, C1-C6 linear or branched chain alkyl,etc.; R1 is hydrogen, C1-C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1-C6 linear or branched chain alkyl, etc;. R5and R6 are independently hydrogen or C1-C linear or branched chain alkyl, etc.; R8 is hydrogen, C1-C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1-C linear or branched chain alkyl, etc.; Q is --CO--, -- (CH2)q--, --(CHRs)q--, or (CRsR)q--, where Rs and R, are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

Pyrrolo[2,3-D]pyrimidine derivatives

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors

Methods of use and combinations

The present invention relates to a compound of Formula 1, 2 or 3: wherein A is N or —CR 0 —, where R 0 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc., Z is —CR e —, or, —N—, where R e is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 1 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 2 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl; R 3 and R 4 are independently hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 5 and R 6 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl, etc.; R 8 is hydrogen, C 1 -C 6 linear or branched chain alkyl, etc.; R 9 and R 10 are independently hydrogen or C 1 -C 6 linear or branched chain alkyl, etc.; Q is —CO—, —(CH 2 ) q —, —(CHR s ) q —, or —(CR s R t ) q —, where R s and R t are independently C 1 -C 6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to combinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

Novel selective androgen receptor modulators

The present invention relates to a compound of Formula 1, 2 or 3: wherein A is N or -CR0 --, where R0 is hydrogen, C1 -C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl,etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1 -C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1 -C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1 -C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1 -C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2 )q --, --(CHRS )q --, or -(CRS Rt )q--, where RS and Rt are independently C1 -C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.

N-SUBSTITUTED DIOXOCYCLOBUTENYLAMINO-3-HYDROXY-PICOLINAMIDES USEFUL AS CCR6 INHIBITORS

La presente invención se refiere a compuestos de dioxociclobutenilamino-3-hidroxi-picolinamida N-sustituida de las Fórmulas (IA y IB) o una sal o hidrato de aquellos aceptables desde el punto de vista farmacéutico, que inhiben el receptor de quimiocinas CC 6 (CCR6) , a composiciones farmacéuticas que contienen estos compuestos, y al uso de estos compuestos para tratar o prevenir enfermedades, afecciones o trastornos que mejoran mediante inhibición de CCR6.

Diazepino-thieno-quinoxaline compounds and their use in therapy

The invention provides diazepino-thieno-quinoxaline compounds, pharmaceutical compositions, their use for inhibiting MK2, and their use in the treatment of a disease or condition, such as an inflammatory disorder.

Ακρυλαμιδια πυρρολο[2,3-d]πυριμιδινυλιου, πυρρολo[2,3-β]πυραζινυλιου και πυρρολο[2,3-d]πυριδινυλιου

Η παρούσα εφεύρεση παρέχει φαρμακευτικώς ενεργά ακρυλαμίδια πυρρολο[2,3-d]πυριμιδινυλίου και πυρρολο[2,3-d]πυριδινυλίου και ανάλογα εξ' αυτών. Τέτοιες ενώσεις είναι χρήσιμες για αναστολή της Κινάσης Janus [Ιανός] (JAK). Αυτή η εφεύρεση απευθύνεται επίσης και σε συνθέσεις περιλαμβάνοντας μεθόδους για παρασκευή τέτοιων ενώσεων, και μεθόδους για αγωγή και πρόληψη καταστάσεων που μεσολαβούνται από JAK.

Compounds for the activation of ampk

Described herein are compounds of Formula I, wherein the variables are defined herein, their use as activators from AMPK, pharmaceutical compositions containing such compounds and their use to treat, for example, heart failure or peripheral vascular disease.

Compounds for the activation of ampk

Described herein are compounds of Formula I,wherein the variables are defined herein, their use as activators from AMPK, pharmaceutical compositions containing such compounds and their use to treat, for example, heart failure or peripheral vascular disease.

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B) or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3- b]pyrazinyl,and pyrrolo[2,3-b]pyridinyl acrylamides, epoxides,and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides a method for treating alopecia using certain pharmaceutically active pyrrolo[2,3-d]pyrimidinyl acrylamides having the structure:or a pharmaceutically acceptable salt thereof, as set forth in the Description.

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors

N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamides useful as ccr6 inhibitors

The present invention relates to N-substituted-dioxocyclobutenylamino-3-hydroxy-picolinamide compounds of Formulae (IA and 1B)or a pharmaceutically acceptable salt or hydrate thereof, that inhibit CC chemokine receptor 6 (CCR6), pharmaceutical compositions containing these compounds, and the use of these compounds for treating or preventing diseases, conditions, or disorders ameliorated by inhibition of CCR6.

Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof, having the structure: or a pharmaceutically acceptable salt or solvate thereof, or an enantiomer or diastereomer thereof, as set forth in the Description. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Pyrrolo[2,3-D]pyrimidine derivatives

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.

Pyrrolo[2,3-D]pyrimidine derivatives

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.