N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R1, R8,R9, R10, and are as described herein. Compounds that are useful intermediates ...

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rcare defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

TRICYCLIC SULFONE COMPOUND AS A ROR GAMMA MODULATOR

or stereoisomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof. Also provided are pharmaceutical compositions comprising the same. The compound of the invention may be useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Imide and acylurea derivatives as modulators of the glucocorticoid receptor

Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF- K B activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rcare defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Pyridyl-substituted spiro-hydantoin compounds and use thereof

A class of substituted spiro-hydantoin compounds (II) having the formula: its pharmaceutically acceptable salts, enantiomers, solvates, or prodrugs thereof, wherein R₁₆ is a substituted pyridinyl group, as defined herein, is provided. Pharmaceutical compositions and methods of treating anti-inflammatory and/or immune diseases with the pyridyl-substituted spiro-hydantoin compounds are also objectives of this invention.

CYCLIC DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

This invention relates generally to modulators of chemokine receptor activity having unexpected combination of desirable pharmacological properties. Pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and prevention of inflammatory, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases, particularly diabetes, Crohn's disease, atherosclerosis, and multiple sclerosis, along with methods of preparing compounds and intermediates therefor. Metabolites of active compounds are also provided herein, pharmaceutical compositions and use thereof are also provided.

PHOSPHINE OXIDE ALKYL AMIDE SUBSTITUTED HETEROARYL COMPOUNDS AS MODULATORS OF IL-12, IL-23, AND/OR IFN ALPHA RESPONSES

Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where all substituents are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

Pyridyl-substituted spiro-hydantoin compounds and use thereof

A class of substituted spiro-hydantoin compounds (II) having the formula: its pharmaceutically acceptable salts, enantiomers, solvates, or prodrugs thereof, wherein R16 is a substituted pyridinyl group, as defined herein, is provided. Pharmaceutical compositions and methods of treating anti-inflammatory and/or immune diseases with the pyridyl-substituted spiro-hydantoin compounds are also objectives of this invention.

SUBSTITUTED HETEROCYCLIC COMPOUNDS

There are disclosed compounds of the following formula I:or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

HETEROCYCLIC COMPOUNDS COMPRISING PYRIDINE USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES

Compounds having the following formula (I) or a stereoisomer or pharmaceutically-acceptable salt thereof, where R, R, R, R, and Rare as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. 12. A compound which is{'sup': '2', 'sub': '3', '6-cyclopropaneamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methyl-6-[(pyridin-2-yl)amino]pyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '6-cyclobutaneamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methyl-6-[2-(morpholin-4-yl)acetamido]pyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '6-acetamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '6-[(5-fluoropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '6-butanamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methyl-6-propanamidopyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', 'methyl N-(5-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-6-[(H)methylcarbamoyl]pyridazin-3-yl)carbamate,'}{'sup': '2', 'sub': '3', '6-(2-cyclopropylacetamido)-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methylpyridazine-3-carboxamide,'}{'sup': '2', 'sub': '3', '4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N—(H)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,'}{'sup': ' ...

MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY CRYSTALLINE FORMS AND PROCESS

The present invention provides a novel antagonist or partial agonists/antagonists of MCP-1 receptor activity: N-((1R,2S,5R)-5-(isopropyl(methyl)amino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(isopropyl(methyl)amino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and are as described herein. Compounds that are ...

IMIDE AND ACYLUREA DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR

Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-B activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification. 4. The compound as defined in claim 3 , or an enantiomer claim 3 , diastereomer claim 3 , tautomer claim 3 , or a pharmaceutically-acceptable salt thereof claim 3 , wherein:{'sub': 11', '1-6', '3-7', '15', '16, 'Rat each occurrence is independently selected from Calkyl, Ccycloalkyl, and —NRR; and'}{'sub': 15', '16', '1-8', '1-8', '1-4', '3-7', '3-7', '15', '16, 'R, and Rare the same or different and at each occurrence are independently selected from (i) hydrogen, Calkyl, substituted Calkyl wherein the substituent is selected from OH and aryl optionally substitute with Calkoxy, Ccycloalkyl, Ccycloalkenyl, aryl, heteroaryl, and heterocyclo; or (ii) where possible, Ris taken together with Rto form a heteroaryl or heterocyclo ring.'}5. A compound as defined in claim 4 , or an enantiomer claim 4 , diastereomer claim 4 , tautomer claim 4 , or a pharmaceutically-acceptable salt thereof claim 4 , wherein:{'sub': 1', '1-6', '12', '12', '13', '12', '12', '12', '13', '12', '13', '2', '14', '12', '2', '14', '1-3, 'Ris phenyl, pyridyl or pyrimidinyl, each of which is substituted with zero to three substituents independently selected from halogen, Chydroxyalkyl, —OR, —NRR, —C(═O)R, —C(═O)OR, —C(═O)NR, R, —NRC(═O)R, —S(O)R, —NRSOR, and 5- to 6-membered heteroaryl substituted with Calkyl group.'}7. The compound as defined in or an enantiomer claim 3 , diastereomer claim 3 , tautomer claim 3 , or a pharmaceutically-acceptable salt thereof claim 3 , wherein:{'sub': 1', '1-6', '12', '12', '13', '12', '12', '12', '13', '12', '13', '2', '14', '12', ...

IMIDAZOLE-DERIVED MODULATORS OF THE GLUCOCORTICOID RECEPTOR

Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-kB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

Cyclic derivatives as modulators of chemokine receptor activity

This invention relates generally to modulators of chemokine receptor activity having unexpected combination of desirable pharmacological properties. Pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and prevention of inflammatory, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases, particularly diabetes, Crohn's disease, atherosclerosis, and multiple sclerosis, along with methods of preparing compounds and intermediates therefor. Metabolites of active compounds are also provided herein, pharmaceutical compositions and use thereof are also provided.

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V):and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

There are described RORγ modulators of the formula (I), 17. A compound selected from the following:1-(4-((3R,3aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carbonyl)piperazin-1-yl)ethan-1-one,(3R,3aS,9bS)—N-((1,1-dioxidotetrahydrothiophen-3-yl)methyl)-9b-((4-fluorophenyl)sulfonyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide (diastereomeric mixture),methyl 4-((3R,3aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamido)tetrahydro-2H-thiopyran-4-carboxylate 1,1-dioxide,(3R,3 aS,9bS)—N-(2,3-dihydroxy-3-methylbutyl)-9b-((4-fluorophenyl)sulfonyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3 aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-N-(2-hydroxy-2-methylpropyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-N-((1r,4R)-4-hydroxycyclohexyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(1,1-dioxidothiomorpholino)((3R,3aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalen-3-yl)methanone,(3R,3 aS,9bS)-9b-((4-fluorophenyl)sulfonyl)-N—((R)-2-hydroxypropyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3 aS, 9bS)-9b-((4-fluorophenyl)sulfonyl)-N-((1-hydroxycyclopentyl)methyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3 aS, 9bS)-9b-((4-fluorophenyl)sulfonyl)-N-((1-hydroxycyclobutyl)methyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3 aS, 9bS)-9b-((4-fluorophenyl)sulfonyl)-N-((1-hydroxy cyclopropyl)methyl)-7-(perfluoropropan-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[a]naphthalene-3-carboxamide,(3R,3 aS, ...

Tricyclic sulfones as ROR gamma modulators

There are described RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

SULFONE PYRIDINE ALKYL AMIDE-SUBSTITUTED HETEROARYL COMPOUNDS

Compounds having the following formula I: 2. The method of wherein the inflammatory or autoimmune disease is psoriasis.3. The method of wherein the inflammatory or autoimmune disease is psoriatic arthritis.4. The method of wherein the inflammatory or autoimmune disease is systemic lupus erythematosus. This application is a divisional application of U.S. patent application Ser. No. 16/195,951, filed Nov. 20, 2018, which claims priority to U.S. Provisional Application Ser. No. 62/589,165, filed Nov. 21, 2017, the contents of which are specifically incorporated fully herein by reference.This invention relates to compounds useful in the modulation of IL-12, IL-23 and/or IFNα by acting on Tyk-2 to cause signal transduction inhibition. Provided herein are amide-substituted heterocyclic compounds, compositions comprising such compounds, and methods of their use. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention that are useful for the treatment of conditions related to the modulation of IL-12, IL-23 and/or IFNα in a mammal.The heterodimeric cytokines interleukin (IL)-12 and IL-23, which share a common p40 subunit, are produced by activated antigen-presenting cells and are critical in the differentiation and proliferation of Th1 and Th17 cells, two effector T cell lineages which play key roles in autoimmunity. IL-23 is composed of the p40 subunit along with a unique p19 subunit. IL-23, acting through a heterodimeric receptor composed of IL-23R and IL-12Rβ1, is essential for the survival and expansion of Th17 cells which produce pro-inflammatory cytokines such as IL-17A, IL-17F, IL-6 and TNF-α (McGeachy, M. J. et al., “The link between IL-23 and Th17 cell-mediated immune pathologies”, 19:372-376 (2007)). These cytokines are critical in mediating the pathobiology of a number of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and lupus. IL-12, in ...

MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY CRYSTALLINE FORMS AND PROCESS

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4 -ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and are as described herein. Compounds that are useful intermediates ...

SULFONE PYRIDINE ALKYL AMIDE-SUBSTITUTED HETEROARYL COMPOUNDS

Compounds having the following formula I: 11. A compound which is{'sup': '2', 'sub': '3', '6-cyclopropaneamido-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-[(5-fluoropyridin-2-yl)amino]-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '4-[(3-methanesulfonylpyridin-2-yl)amino]-6-[(6-methoxypyridazin-3-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methyl-6-[(1-methyl-1H-pyrazol-3-yl)amino]pyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-[(6-cyclopropyl-2-methylpyrimidin-4-yl)amino]-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-{[5-(2-hydroxypropan-2-yl)pyridin-2-yl]amino}-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-[(6-cyclopropylpyrimidin-4-yl)amino]-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-[(6-cyclopropylpyridazin-3-yl)amino]-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methyl-6-{[5-(trifluoromethyl)pyridin-2-yl]amino}pyridine-3-carboxamide;'}{'sup': '2', 'sub': '3', '4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methyl-6-{[6-(trifluoromethyl)pyridazin-3-yl]amino}pyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '4-[(3-methanesulfonylpyridin-2-yl)amino]-6-[(2-methoxypyrimidin-4-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-{[5-fluoro-4-(2-hydroxypropan-2-yl)pyridin-2-yl]amino}-4-[(3-methanesulfonylpyridin-2-yl)amino]-N-(H)methylpyridazine-3-carboxamide;'}{'sup': '2', 'sub': '3', '6-{[5-(2-aminopropan-2-yl) ...

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R 1 is —OH or —OP(O)(OH) 2 , and X 1 , X 2 , X 3 , R 2 , R 2a , R a , R b , and R c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Imidazole-derived modulators of the glucocorticoid receptor

Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which the variables are as defined in the specification.

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 116-. (canceled)19. The compound according to or a salt thereof claim 17 , wherein:{'sub': 2a', '2', '3', '3', '2', '5-6', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2', '3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '2-4', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '1-2', '3', '2', '2', '2', '3', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '2', '4', '3', '2', '2', '4', '3', '3', '2', '4', '3', '2', '3', '2', '5', '3', '2', '2', '4-7', '3', '2', '2', '2', '2-4', '3', '2', '2', '2', '3', '2', '2', '2', '2-3', '3', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2-3', '3', ' ...

TRIAZOLOPYRIDINYL COMPOUNDS AS KINASE INHIBITORS

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY, CRYSTALLINE FORMS AND PROCESS

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin- 4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and are as described herein. Compounds that are useful intermediates ...

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R 1 is —OH or —OP(O)(OH) 2 , and X 1 , X 2 , X 3 , R 2 , R 2a , R a , R b , and R c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

TRIAZOLOPYRIDINYL COMPOUNDS AS KINASE INHIBITORS

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Phosphine oxide alkyl amide substituted heteroaryl compounds as modulators of IL-12, IL-23 and/or IFN alpha responses

Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where all substituents are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 111-. (canceled)13. The method according to wherein said autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosis claim 12 , multiple sclerosis claim 12 , inflammatory bowel disease claim 12 , ulcerative colitis claim 12 , Crohn's disease claim 12 , rheumatoid arthritis claim 12 , scleroderma claim 12 , giant cell arteritis claim 12 , and Sjögren's syndrome.17. The method according to wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosis.18. The method according to wherein said autoimmune disease or chronic inflammatory disease is ulcerative colitis.19. The method according to wherein said autoimmune disease or chronic inflammatory disease is multiple sclerosis.20. The method according to wherein said autoimmune disease or chronic inflammatory disease is inflammatory bowel disease.21. The method according to wherein said autoimmune disease or chronic inflammatory disease is rheumatoid arthritis.22. The method according to wherein said autoimmune disease or chronic inflammatory disease is Crohn's disease.23. The method according to wherein said autoimmune disease or chronic inflammatory disease is Sjögren's syndrome.24. The method according to wherein said autoimmune disease or chronic inflammatory disease is systemic lupus erythematosis.25. The method according to wherein said autoimmune disease or chronic inflammatory disease is ulcerative colitis.26. The method according to wherein said autoimmune disease or chronic inflammatory disease is multiple sclerosis.27. The method according to wherein said autoimmune disease or chronic inflammatory disease is inflammatory bowel disease.28. The method according to wherein said autoimmune disease or chronic inflammatory disease is rheumatoid arthritis.29. The method according to wherein said autoimmune disease or chronic inflammatory disease is Crohn's disease.30. The method ...

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 116-. (canceled)19. The compound according to or a salt thereof claim 17 , wherein:{'sub': 2a', '2', '3', '3', '2', '5-6', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2', '3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '2-4', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '1-2', '3', '2', '2', '2', '3', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '2', '4', '3', '2', '2', '4', '3', '3', '2', '4', '3', '2', '3', '2', '5', '3', '2', '2', '4-7', '3', '2', '2', '2', '2-4', '3', '2', '2', '2', '3', '2', '2', '2', '2-3', '3', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2-3', '3', ' ...

Tricyclic sulfone compound as a ROR gamma modulator

There is described a RORγ modulator of the formula (I), or stereoisomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof. Also provided are pharmaceutical compositions comprising the same. The compound of the invention may be useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 116-. (canceled)19. The compound according to or a salt thereof claim 17 , wherein:{'sub': 2a', '2', '3', '3', '2', '5', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3', '3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2', '3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '3', '2', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '2-4', '3', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '1-2', '3', '2', '2', '2', '3', '2', '2', '3', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '3', '2', '2', '2', '3', '3', '2', '2', '2', '2', '4', '3', '2', '2', '4', '3', '3', '2', '4', '3', '2', '3', '2', '5', '3', '2', '2', '4-7', '3', '2', '2', '2', '2-4', '3', '2', '2', '2', '3', '2', '2', '2', '2-3', '3', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2-3', '3', '2 ...

SUBSTITUTED BICYCLIC COMPOUNDS

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): 3. The compound according to claim 2 , having the structure of Formula (I) or a salt thereof claim 2 , wherein:{'sub': 1', '2, 'Ris —OH or —OP(O)(OH);'}{'sub': 2', '2a', '2b, 'Ris Ror R;'}{'sub': '2a', 'claim-text': [{'sub': 2', '3', '3', '2', '5', '3', '2', '2', '3', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '2', '2', '4', '2', '2', '4', '3', '2', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '3', '2', '3', '2', '2', '2', '3, 'is —(CH)CH, —(CH)CH, —CHCH═CHCHCH, —CHCHCH═CHCHCH, —(CH)CH═CHCH, —(CH)CH═C(CH), —(CH)CH═CH, —(CH)CH═CHCH, —CH═C H(CH)CH, —CH═CH(CH)OCH, —CH═CHCHCHCH(CH), —CH═CHCHCHCHOCH, —CHCH═CHCH═CHCH, —CH═CHCHCHCH═CH, —CH═CH(phenyl) wherein said phenyl is substituted with —CH'}, {'sub': 3', '2', '1-3', '3', '3', '2', '3', '3', '2', '2', '3', '2', '2', '2', '2', '2', '2', '1-2, 'or —OCH; —CH═CH(tetrahydropyranyl), —(CH)(phenyl) wherein said phenyl is substituted with zero to 2 substituents independently selected from F, I, —CH, —OCH, —OCHCH, —OCH(CH), and —CHC(O)N(CH); —(CH)(methyl imidazolyl), —(CH)(methyl pyrazolyl), —(CH)(pyridinyl) wherein said pyridinyl is substituted with zero to 1 substituent selected'}, {'sub': 3', '2', '2', '2', '2', '2', '2-3', '2', '2', '3-4', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '3', '2', '2', '9', '3', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '3', '3', '2', '3', '3', '3', '3', '2', '1-6', '3', '3', '2', '2', '3', '2', '2', '3', '3', '3', '2', '2', '2', '3, 'from —OCH; —(CH)(pyrimidinyl), —(CH)(quinolinyl), —(CH)(tetrahydropyranyl), —CHO(CH)CH, —CHOCHCHCH(CH), —CHOCHCHC(CH), —CHO(CH)CH, —CHOCHCHCHCF, —CHOCHCH═CHCHCH, —CHOCHCH═C(CH), —CHOCHCH═CHCHCHCH, — ...

SUBSTITUTED HETEROCYCLIC COMPOUNDS

There are disclosed compounds of the following formula I: 6. A compound or a pharmaceutically acceptable salt thereof , selected from{'sup': '2', '6-cyclopropaneamido-4-{[3-(2-ethyl-2H-1,2,3-triazol-4-yl)-2-methoxyphenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '4-{[2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-6-[(6-methoxypyridazin-3-yl)amino]-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-{[5-fluoro-2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '4-{[2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-N-(H3)methyl-6-[(pyridin-2-yl)amino]pyridazine-3-carboxamide,'}{'sup': '2', 'methyl N-(5-{[2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-6-[(H3)methylcarbamoyl]pyridazin-3-yl)carbamate,'}{'sup': '2', '6-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-4-{[2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '4-{[2-methoxy-3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]amino}-N-(H3)methyl-6-[(1R)-spiro[2.2]pentane-1-amido]pyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-{[3-(2-cyclopropyl-2H-1,2,3-triazol-4-yl)-2-methoxyphenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-{[3-(2-cyclopropyl-2H-1,2,3-triazol-4-yl)-5-fluoro-2-methoxyphenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-{[3-(2-ethyl-2H-1,2,3-triazol-4-yl)-4-fluoro-2-methoxyphenyl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-{[4-(2-cyclopropyl-2H-1,2,3-triazol-4-yl)-3-methoxypyridin-2-yl]amino}-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-({3-[2-(2-fluoroethyl)-2H-1,2,3-triazol-4-yl]-2-methoxyphenyl}amino)-N-(H3)methylpyridazine-3-carboxamide,'}{'sup': '2', '6-cyclopropaneamido-4-({3-[2-(2,2-difluoroethyl)-2H-1,2,3-triazol-4-yl]-2-methoxyphenyl}amino)-N-(H3)methylpyridazine-3- ...

Substituted bicyclic compounds

Compuestos de las Fórmulas (I), (II), (III), (IV) y (V), y/o una sal de estos, en donde R1 es -OH u -OP(O)(OH)2, y X1, X2, X3, R2, R2a, Ra, Rb y Rc se definen en la presente. También se describen métodos para usar estos compuestos como agonistas selectivos del receptor S1P1 acoplado a la proteína G, y composiciones farmacéuticas que comprenden estos compuestos. Estos compuestos son útiles para el tratamiento, la prevención o la ralentización de la progresión de enfermedades o trastornos en varias áreas terapéuticas, tales como enfermedades autoinmunitarias y vasculares. Compounds of Formulas (I), (II), (III), (IV) and (V), and / or a salt thereof, wherein R1 is -OH or -OP (O) (OH) 2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also described are methods of using these compounds as selective agonists of the S1P1 receptor coupled to the G protein, and pharmaceutical compositions comprising these compounds. These compounds are useful for treating, preventing, or slowing the progression of diseases or disorders in various therapeutic areas, such as autoimmune and vascular diseases.

Cyclic derivatives as modulators of chemokine receptor activity

Modulators of chemokine receptor activity, crystalline forms and process

The present invention provides a novel antagonist or partial agonists/antagonist of MCP-1 receptor activity: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-1-yl)cyclohexyl)acetamide: (see formula I) wherein R1, R8, R9, R10, and (see formula II) are as described herein. Compounds that are useful intermediates of the process are also provided herein.

Imidazopyridazine compounds useful as modulators of il-12, il-23 and/or ifn alpha responses

Compounds having the following formula I: or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein all substituents are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα by acting on Tyk-2 to cause signal transduction inhibition.

Amide-disubstituted pyridine or pyridazine compounds

Compounds having the following formula (I): (Formula (I)) or a stereoisomer or pharmaceutically-acceptable salt thereof, are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition.

CYCLE DERIVATIVES AS MODULATORS OF THE ACTIVITY OF THE CHEMIOQUINE RECEIVER.

Un compuesto seleccionado de: (i)N-((1R,2S,5R)-2-((3S)-3-((6-terc-butilpirimido[5,4-d]pirimidin-4-il)amino)-2-oxo-1-pirrolidinil)-5-(isopropil(metil)amino)ciclohexil)acetamida; N-((1R,2S,5R)-5-(metilamino)-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)acetamida; N-((1R,2S,5R)-5-(isopropil(metil)amino)-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)formamida; N-((1R,2S,5R)-5-(dimetilamino)-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)acetamida; N-((3S)-1-((1S,2R,4R)-2-acetamido-4-(isopropil(metil)amino)ciclohexil)-2-oxo-3-pirrolidinil)-6-terc-butil-2-piridincarboxamida; N-((1R,2S,5R)-5-amino-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)propanamida; 2-terc-butil-N-((3S)-1-((1S,2R,4R)-4-(terc-butilamino)-2-(metanosulfonilamino)ciclohexil)-2-oxo-3-pirrolidinil)-4-pirimidincarboxamida; 2-terc-butil-N-((3S)-1-((1S,2R,4R)-4-(terc-butilamino)-2-(propionilamino)ciclohexil)-2-oxo-3-pirrolidinil)-4-pirimidincarboxamida; N-((1R,2S,5R)-5-(terc-butilamino)-2-((3S)-3-((6-terc-butilpirimido[5,4-d]pirimidin-4-il)amino)-2-oxo-1-pirrolidinil)ciclohexil)metanosulfonamida; y N-(((1S,2S,5R)-5-metoxi-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)metil)acetamida; N-(((1R,2S,5R)-5-(isopropilamino)-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)acetamida; N-((1R,2S,5R)-5-amino-2-((3S)-2-oxo-3-((6-(trifluorometil)-4-quinazolinil)amino)-1-pirrolidinil)ciclohexil)acetamida; N-((1R,2S,5R)-5-(isopropilo(metil)amino)-2-((3S)-2-oxo-3-((1-oxido-6-(trifluorometil)-4-quinazolinil)amino)-2-oxo-1-pirrolidinil)ciclohexil)acetamida; N-((1R,2S,5R)-5-(isopropilamino)-2-((3S)-3-((1-oxido-6-(trifluorometil)-4-quinazolinil)amino)-2-oxo-1-pirrolidinil)ciclohexil)acetamida; y N-((1R,2S,5R)-5-(terc-butilamino)-2-((3S)-3-((1-oxido-6-(trifluorometil)-4-quinazolinil)amino-2-oxo-1- ...

Amide-disubstituted pyridine or pyridazine compounds.

Compuestos que tienen la siguiente fórmula (I): (Fórmula (I) o un estereoisómero o una sal farmacéuticamente aceptable del mismo, son útiles en la modulación de IL-12, IL-23 y/o IFNa, actuando sobre Tyk-2 para provocar la inhibición de la transducción de señales. (ver Fórmula).

Substituted bicyclic compounds

<p>COMPUESTOS DE LAS FORMULAS (I), (II), (III), (IV) Y (V):</p> <p>* incluir figuras de estructuras de hoja resumen de fecha 15-02-2017, pagina 4</p> <p>Y/O UNA SAL DE ESTOS, EN DONDE R1 ES -OH U OP(O)(OH)2, Y X1, X2, X3, R2, R2A, RA, RB Y RC SE DEFINEN EN LA PRESENTE. TAMBIÉN SE DESCRIBEN MÉTODOS PARA USAR ESTOS COMPUESTOS COMO AGONISTAS SELECTIVOS DEL RECEPTOR S1P1 ACOPLADO A LA PROTEÍNA G, Y COMPOSICIONES FARMACÉUTICAS QUE COMPRENDEN ESTOS COMPUESTOS. ESTOS COMPUESTOS SON ÚTILES PARA EL TRATAMIENTO, LA PREVENCIÓN O LA RALENTIZACIÓN DE LA PROGRESIÓN DE ENFERMEDADES O TRASTORNOS EN VARIAS ÁREAS TERAPÉUTICAS, TALES COMO ENFERMEDADES AUTOINMUNITARIAS Y VASCULARES.</p> <p> COMPOUNDS OF FORMULAS (I), (II), (III), (IV) AND (V): </p> <p> * include figures of summary sheet structures dated 15-02-2017, page 4 </p> <p> AND / OR A SALT OF THESE, WHERE R1 IS -OH OR OP (O) (OH) 2, Y X1, X2, X3, R2, R2A, RA, RB AND RC SE DEFINED IN THIS. METHODS ARE ALSO DESCRIBED FOR USING THESE COMPOUNDS AS SELECTIVE AGONISTS OF THE S1P1 RECEPTOR COUPLED TO PROTEIN G, AND PHARMACEUTICAL COMPOSITIONS THAT UNDERSTAND THESE COMPOUNDS. THESE COMPOUNDS ARE USEFUL FOR THE TREATMENT, PREVENTION OR REALENTIZATION OF THE PROGRESSION OF DISEASES OR DISORDERS IN VARIOUS THERAPEUTIC AREAS, SUCH AS AUTOIMMUNITY AND VASCULAR DISEASES. </p>

Heterocyclic compounds comprising pyridine useful as modulators of IL-12, IL-23 and/or IFNα responses

Compounds having the following formula (I) or a stereoisomer or pharmaceutically-acceptable salt thereof, where R 1 , R 2 , R 3 , R 4 , and R 5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

Substituted bicyclic compounds

Amide-disubstituted pyridine or pyridazine compounds

MODULATORS OF THE ACTIVITY OF THE CHEMIOKIN RECEPTOR, CRYSTAL FORMS AND PROCEDURES.

- Un compuesto que es N-((1R,2S,5R)-5-(terc-butilamino)-2-((S)-2-oxo-3-(6-(trifluorometil)quinazolin-4- ilamino)pirrolidin-1-il)ciclohexil)acetamida, o una sal farmacéuticamente aceptable del mismo. - A compound that is N - ((1R, 2S, 5R) -5- (tert-butylamino) -2 - ((S) -2-oxo-3- (6- (trifluoromethyl) quinazolin-4-ylamino) pyrrolidine -1-yl) cyclohexyl) acetamide, or a pharmaceutically acceptable salt thereof.

Modulators of chemokine receptor activity, crystalline forms and process

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Compounds having the following formula (I), or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition.

Modulators of chemokine receptor activity, crystalline forms and process

The present invention provides a novel antagonist or partial agonists,antagonists of MCP-1 receptor activity: N-((lR,2S,5R)-5- (isopropyl(methyl)amino)-2-((S)-2-0x0-3-(6- (trifluoromethyl)quinazolin-4- ylamino)pyrrolidin-1- yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. Pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((1R,2S,5R)-5-(isopropyl(methyl)amino)-2-((S)-2-oxo-3- (6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-l-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and structure (a) are as described herein. Compounds that are useful intermediates of the process are also provided herein.

Modulators of chemokine receptor activity, crystalline forms and process.

La presente invención proporciona un antagonista o agonistas/antagonistas parciales novedosos de la actividad del receptor MCP-1: N-((1R,2S,5R)-5-(isopropil(metil)amino)-2-((S)-2-o xo-3-(6-(trifluorometil)quinazolin-4-ilamino)pirrolidin-1-il)cicl ohexil)acetamida, o una sal, solvato o profármaco farmacéuticamente aceptable, de los mismos, que tienen una combinación inesperada de características farmacológicas deseables. También se proporcionan formas cristalinas de la presente invención. Las composiciones farmacéuticas que contienen los mismos y los métodos de uso de las mismas como agentes para el tratamiento de enfermedades inflamatorias, enfermedades alérgicas, autoinmunitarias metabólicas, cáncer y/o cardiovasculares también es un objetivo de esta invención. La presente descripción también proporciona un proceso para preparar los compuestos de la fórmula (I), incluyendo la N-((1R,2S,5R)-5-(isopropil(metil)amino)-2-((S)-2-oxo-3-(6-(triflu orometil)quinazolin-4-ilamino)pirrolidin-1-il)ciclohexil)acetamid a: en donde R1, R8, R9, R10 y la estructura (a) son como se describen en la presente. Los compuestos que son intermediarios útiles del proceso también se proporcionan en la presente.

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V) and/or a salt thereof, wherein R1 is OH or OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Modulators of chemokine receptor activity, crystalline forms and process.

La presente invención proporciona un antagonistas novedoso o agonista parcial/antagonista del receptor de la actividad de MCP-1; N-((1R,2S,5R)-5-(tert-butilamino)-2-((S)-2-oxo-3-(6-(triflu orometil)quinazolin-4-ilamino)pirrolidin-1-il)ciclohexil)acetamid a, o una sal, solvato o profármaco farmacéuticamente aceptable, de los mismos que tiene una combinación inesperada de características farmacológicas deseables. Las formas cristalinas de la presente invención también se proporcionan. Las composiciones farmacéuticas contienen los mismos y los métodos de uso de los mismos como agente para el tratamiento de enfermedades inflamatorias, enfermedades alérgicas, autoinmunes, metabólicos, cáncer y/o cardiovascular también es un objetivo de esta invención. La presente descripción también proporciona un proceso para preparar los compuestos de la fórmula (I), incluyendo N-((1R,S2,5R)-5-(tert-butilamino)-2-((S)-2-oxo-3-(6-(trifluoromet il)quinazolin-4-ilamino)pirrolidin-1-il)ciclohexil)acetamida: (ver fórmula (I)) en donde R1, R8, R9, R10 y HET son como se describen en la presente. Los compuestos que son intermediarios útiles de los procesos también se proporcionan en la presente.

Sulfonepyridine alkylamide-substituted heteroaryl compounds

【課題】対象における乾癬を治療するための経口医薬組成物を提供する。【解決手段】下式：TIFF2023098942000149.tif4158で示される化合物を含む、経口医薬組成物とする。【選択図】なし

Modulators of chemokine receptor activity, crystalline forms and processes

Foreliggende oppfinnelse tilveiebringer en ny antagonist eller partielle agonister/antagonist av MCP-1 reseptor aktivitet: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-okso-3-(6-(trifluormetyl)kinazolin-4-ylamino)pyrrolidin-1-yl)cykloheksyl)acetamid eller et farmasøytisk akseptabelt salt, solvat eller prodroge, derav, som har en uventet kombinasjon av ønskelige farmakologiske karakteristika. Krystallinske former ifølge foreliggende oppfinnelse er også gitt. Farmasøytiske preparater inneholdende disse og metoder for anvendelse av disse som midler for behandling av inflammatoriske sykdommer, allergiske sykdommer, autoimmune sykdommer, metabolske sykdommer, kreft og/eller kardiovaskulære sykdommer er også en hensikt ifølge foreliggende oppfinnelse. Foreliggende beskrivelse tilveiebringer også en fremgangsmåte for fremstilling av forbindelser med formel (I), omfattende N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-okso-3-(6-(trifluormetyl)kinazolin-4-ylamino)pyrrolidin-1-yl)cykloheksyl)acetamid: hvor R1, R8, R9, R10 og er som beskrevet her. Forbindelser som er anvendelige mellomprodukter av fremgangsmåten er også gitt her. 1

Tricyclic sulfones as ror gamma modulators

There are described ROR? Gamma modulators of the formula (I), (I) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating ROR? activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of ROR? activity, for example, autoimmune and/or inflammatory disorders.

Triazolopyridinyl compounds as kinase inhibitors

Compuestos que tienen la Fórmula (I) y enantiómeros y diastereómeros, estereoisómeros, sales farmacéuticamente aceptables de los mismos, (I) son útiles como moduladores de quinasas, incluida la modulación RIPK1. Todas las variables son como se definen en el presente documento. Compounds having Formula (I) and enantiomers and diastereomers, stereoisomers, pharmaceutically acceptable salts thereof, (I) are useful as kinase modulators, including RIPK1 modulation. All variables are as defined in this document.

Modulators of chemokine receptor activity, crystalline forms and process

Substituted heterocyclic compounds

There are disclosed compounds of the following formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Compostos heterocíclicos substituídos

compostos heterocíclicos substituídos. a presente invenção refere-se a compostos da fórmula (i) que segue ou um estereoisômero ou sal farmaceuticamente aceitável dos mesmos, em que todos os substituintes são como definidos na presente invenção, que são úteis na modulação de il-12, il-23 e/ou ifna, através da ação sobre tyk-2 para causar inibição de transdução de sinal. os compostos da invenção podem ser úteis para tratamento de doenças ou distúrbios neurodegenerativos.

Cyclische derivate als modulatoren der chemokinrezeptoraktivität

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Compounds having the following formula I:or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Substituted heterocyclic compounds

There are disclosed compounds of the following formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Composés hétéroaryle substitués par un amide alkyle d'oxyde de phosphine en tant que modulateurs des réponses il-12, il-23 et/ou ifn alpha

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

SULFONE PYRIDINE ALKYL AMIDE-SUBSTITUTED HETEROARYL COMPOUNDS ABSTRACT 5 Compounds having the following formula I: R 4 R 3 0 'N' N H | N N R5 or a stereoisomer or pharmaceutically-acceptable salt thereof, where R', R2, R3 , R4, and 10 R 5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition. - 171-

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Compounds having the following formula I:or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

Modulatoren der chemokinrezeptoraktivität, kristalline formen und verfahren

Compuestos de triazolopiridinilo como inhibidores de quinasas

La presente invencion se refiere a un compuesto derivado de triazolopiridinilo de formula (I), o una sal del mismo; en donde R1 es H, alquilo C1-3, alcoxilo C1-3, entre otros; R2 es H o halo; R3 es H, halo o alquiloC1-3 o deuteroalquiloC1-3; R4 es H o F; R5a y R5b son cada uno independientemente H, deuterio, alquiloC1-3 o haloalquiloC1-3 alternativamente; R6a y R6b son cada uno independientemente H, deuterio, OH, F, entre otros; R7a y R7b son cada uno independientemente H, deuterio, OH, OP(O)(OR)2, entre otros; R es H o alquiloC1-3; R8 es H, F, Cl, alquiloC1-3, entre otros; R9 es H o CH3; el anillo Z es fenilo, un anillo heteroarilo de 6 miembros, ciclohexilo, ciclopentilo o ciclobutilo; Y es F, Cl, alquiloC1-3, alcoxiC1-3, entre otros; n es 0 a 3. Un compuesto seleccionado es (S)-5-(2-amino-[1,2,4]triazolo[1,5-?]piridin-7-il)-N-(3-(4-clorofenil)-3-hidroxipropil)-4-fluoro-2-metilbenzamida. Dichos compuestos son inhibidores de quinasas, incluida la modulacion de la actividad de RIPK1. Tambien se refiere a una composicion farmaceutica que comprende dicho compuesto, siendo util en el tratamiento de enfermedades inflamatorias, isquemias, neurodegeneracion y enfermedad de Gaucher.

Compostos bicíclicos substituídos, uso dos mesmos e composição farmacêutica

COMPOSTOS BICÍCLICOS SUBSTITUÍDOS. São descritos compostos de fórmulas (I), (II), (III), (IV), e (V): e/ou um sal do mesmo, em que R1 é -OH ou -OP(O)(OH)2, e X1, X2, X3, R2, R2a, Ra, Rb, e Rc são definidos aqui. São também descritos méto-dos de uso de tais compostos como agonistas seletivos para receptor S1P1 de proteína G, e composições farmacêuticas compreendendo tais compostos. Estes compostos são úteis no tratamento, prevenção, ou retardo da progressão de doenças ou distúrbios em uma variedade de áreas terapêuticas, tais como doenças autoimunes e doença vascular.

Υποκατεστημενες δικυκλικες ενωσεις

Αποκαλύπτονται ενώσεις των Τύπων (Ι), (II), (III), (IV), και (V) ή/και άλας αυτών, όπου το R1 είναι ΟΗ ή ΟΡ{Ο)(ΟΗ)2, και τα Χ1, Χ2, Χ3, R2, R2a, Ra, Rb, και Rc ορίζονται στο παρόν. Επίσης αποκαλύπτονται μέθοδοι χρήσης τέτοιων ενώσεων ως εκλεκτικών αγωνιστών για συνδεδεμένο με G πρωτεΐνη υποδοχέα S1Ρ1, και φαρμακευτικές συνθέσεις που περιλαμβάνουν τέτοιες ενώσεις. Αυτές οι ενώσεις είναι χρήσιμες στη θεραπεία, αποτροπή, ή επιβράδυνση της εξέλιξης ασθενειών ή διαταραχών σε μία ποικιλία θεραπευτικών περιοχών, όπως αυτοάνοσων ασθενειών και αγγειακής ασθένειας.

Substituted bicyclic compounds

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V) and/or a salt thereof, wherein R1 is OH or OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Tricyclic sulfone compound as a ror gamma modulator

There is described a RORγ modulator of the formula (I), or stereoisomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof. Also provided are pharmaceutical compositions comprising the same. The compound of the invention may be useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Modulatoren der chemokinrezeptoraktivität, kristalline formen und verfahren

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,Formula (I): are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Compuestos de triazolopiridinilo como inhibidores de cinasas.

La presente invención se refiere a compuestos que tienen la Fórmula (I) y enantiómeros y diastereómeros, estereoisómeros, sales farmacéuticamente aceptables de los mismos, (ver Fórmula) (I) son útiles como moduladores de cinasas, incluida la modulación de RIPK1. Todas las variables son como se definen en el presente documento.

Compuestos de triazolopiridinilo como inhibidores de quinasas

Compuestos que tienen la Fórmula (I) y enantiómeros y diastereómeros, estereoisómeros, sales farmacéuticamente aceptables de los mismos, son útiles como moduladores de quinasas, incluida la modulación RIPK1. Todas las variables son como se definen en el presente documento.

Triazolopyridinyl compounds as kinase inhibitors

Substituted heterocyclic compounds

Compuestos heterocíclicos sustituidos

Se describen compuestos de la siguiente fórmula I: o un estereoisómero o sal farmacéuticamente aceptable del mismo, en donde todos los sustituyentes son como se definen aquí, que son útiles en la modulación de IL-12, IL-23 y/o IFN-alfa, actuando sobre Tyk-2 para provocar la inhibición de la transducción de señales. Los compuestos de la invención pueden ser útiles para tratar enfermedades o trastornos neurodegenerativos.

Związki triazolopirydynylu jako inhibitory kinaz

Triazolopiridinilo junginiai kaip kinazės inhibitoriai

Triatsolopyridinyyliyhdisteitä kinaasiestäjinä

Compuestos heterociclicos sustituidos.

La presente invención se refiere a compuestos de la siguiente fórmula I: (ver Fórmula) I o un estereoisómero o sal farmacéuticamente aceptable del mismo, en donde todos los sustituyentes son como se definen aquí, que son útiles en la modulación de IL-12, IL-23 y/o IFNa, actuando sobre Tyk-2 para provocar la inhibición de la transducción de señales. Los compuestos de la invención pueden ser útiles para tratar enfermedades o trastornos neurodegenerativos.

Triazolopiridinilne spojine kot inhibitorji kinaze

Phosphine oxide alkyl amide substituted heteroaryl compounds as modulators of il-12, il-23, and/or ifn alpha responses

Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where all substituents are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.

Compuestos heterocíclicos sustituidos

Se describen compuestos de la siguiente fórmula I: I o un estereoisómero o sal farmacéuticamente aceptable del mismo, en donde todos los sustituyentes son como se definen aquí, que son útiles en la modulación de IL-12, IL-23 y/o IFNα, actuando sobre Tyk-2 para provocar la inhibición de la transducción de señales. Los compuestos de la invención pueden ser útiles para tratar enfermedades o trastornos neurodegenerativos.

Substituted heterocyclic compounds

There are disclosed compounds of the following formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Substituted heterocyclic compounds

There are disclosed compounds of the following formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Substituted heterocyclic compounds

There are disclosed compounds of the following formula I: or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Triazolpyridinylforbindelser som kinasehæmmere

Triazolopyridinyl compounds as kinase inhibitors

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,Formula (I): are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Triazolopiridinil jedinjenja kao inhibitori kinaze

Imidazopyridazine compounds useful as modulators of il-12, il-23 and/or ifn alpha responses

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Spojevi triazolopiridinila kao inhibitori kinaze

Substituted heterocyclic compounds

There are disclosed compounds of the following formula (I) or a stereoisomer or pharmaceutically acceptable salt thereof, wherein all substituents are as defined herein, which are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition. The compounds of the invention may be useful for treating neurodegenerative diseases or disorders.

Sulfone pyridine alkyl amide-substituted heteroaryl compounds

Compounds having the following formula (I), or a stereoisomer or pharmaceutically-acceptable salt thereof, where R

Triazolopyridinyl compounds as kinase inhibitors

Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof,are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.

Method, device, medium and apparatus for controlling running of gantry

The present invention provides a method, a device, a medium and an apparatus for controlling running of a gantry. The method comprises: determining road information at the current moment(Sl 10); controlling running of the gantry according to a predicted value of a state parameter at the current moment predicted at the previous moment and the road information at the current moment(S120); determining an actual value of the state parameter at the current moment(S130); calculating a difference value between the predicted value of the state parameter at the current moment predicted at the previous moment and the actual value of the state parameter at the current moment, and using the difference value as a feedback value corresponding to the current moment(S140); and determining a predicted value of the state parameter at the next moment, according to the feedback value corresponding to the current moment and the actual value of the state parameter at the current moment, to control running of the gantry at the next moment according to the predicted value of the state parameter at the next moment(S150). With the present invention, it is possible to improve the rectification precision during running of the gantry.