US 11,597,721 B2Granted

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

AssigneeBristol-Myers Squibb Company

InventorsZili Xiao, Michael G. Yang, Chunjian C. Liu, Trevor C. Sherwood, John L. Gilmore, David S. Weinstein

Life of this patent

Estimating the term…

Abstract

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.

Claims11

Dependent claims

A compound of the formula

wherein
X is N;
R2 is —C(O)R2a;
C1-6 alkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 R2a or a 5-12 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R2a;
R2a at each occurrence is independently H, OCF3, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, (CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, — S(O)pRc, C1-6 alkyl substituted with 0-3 Ra, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra or a —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra;
R3 is H, C1-3 alkyl or C3-6 cycloalkyl;
R4 is H, C1-3 alkyl or C3-6 cycloalkyl;
R5 is C1-4 alkyl substituted with 0-1 R5a, C1-4 alkoxy substituted with 0-1 R5a, (CH2)r-phenyl substituted with 0-3R5a or a —(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p;
R5a is is independently at each occurrence, H, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rc, —NReRe, —NReC(O)ORc, C1-6 alkyl or (CH2)r-phenyl substituted with 0-3 Rf;
R6 is C1-4 alkyl substituted with 0-1 R6a, (CH2)r-phenyl substituted with 0-3 R6a or a —(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 R6a;
R6a is H, C1-4 alkyl substituted with 0-3 Rf, CF3, C3-10 cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd;
R11 at each occurrence is independently H, C1-4 alkyl substituted with 0-3 Rf, CF3, C3-10 cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd;
Ra at each occurrence is independently H, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R11, (CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-3 Rf, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, C2-6 alkynyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf;
Rb is H, C1-6 alkyl substituted with 0-3 Rd, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rd;
Rc is C1-6 alkyl substituted with 0-3 Rf, (CH2)r—C3-6 cycloalkyl substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rf;
Rd is independently at each occurrence, hydrogen, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rc, —NReRe, —NReC(O)ORc, C1-6 alkyl or (CH2)r-phenyl substituted with 0-3 Rf;
Re is independently at each occurrence, hydrogen, C1-6 alkyl, C3-6 cycloalkyl or (CH2)r-phenyl substituted with 0-3 Rf;
Rf is independently at each occurrence, hydrogen, halo, CN, NH2, OH, C3-6 cycloalkyl, CF3, O(C1-6 alkyl) or a —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p;
p is 0, 1, or 2;
r is 0, 1, 2, 3, or 4;
or a stereoisomer or pharmaceutically acceptable salt thereof.

18 more elements

A compound which is

6-cyclopropaneamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}—N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(pyridin-2-yl)amino]pyridazine-3-carboxamide,
6-cyclobutaneamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6]2-(morpholin-4-yl)acetamido]pyridazine-3-carboxamide,
6-acetamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(5-fluoropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}—N-(2H3)methylpyridazine-3-carboxamide,
6-butanamido-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-propanamidopyridazine-3-carboxamide,
methyl N-(5-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-6-[(2H3)methylcarbamoyl]pyridazin-3-yl)carbamate,
6-(2-cyclopropylacetamido)-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}—N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-6-[(4-methoxypyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
6-[(4-cyanopyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(5-fluoropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(4,5-dimethylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(5-fluoro-4-methylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(4-ethylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-{[5-(2-oxopyrrolidin-1-yl)pyridin-2-yl]amino} pyridazine-3-carboxamide,
6-[(4-fluoropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(5-methyl-1,3,4-thiadiazol-2-yl)amino]pyridazine-3-carboxamide,
6-[(4-chloropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(5-chloro-4-methylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-[(4-chloro-5-methylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-({2-oxo-2H-[1,3 ‘-bipyridine]-6’-yl} amino)pyridazine-3-carboxamide,
6-{[4-(2-hydroxypropan-2-yl)pyridin-2-yl] amino}-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-{[2-oxo-3-(trifluoromethyl)-2H41,3 ‘-bipyridine]-6’-yl] amino 1 pyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-6-[(6-methoxypyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-(phenylamino)pyridazine-3-carboxamide,
6-[(4-acetylpyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
6-({5-chloro-2-oxo-2H-[1,3′-bipyridine]-6′-yl}amino)-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-({[1,3]thiazolo[5,4-b]pyridin-5-yl}amino)pyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridazine-3-carboxamide,
6-{[5-(2-hydroxypropan-2-yl)pyridin-2-yl] amino}-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
6-[(4-fluorophenyl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(pyridin-4-yl)amino]pyridazine-3-carboxamide,
6-[(6-ethoxypyridazin-3-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
6-{[5-[3-tert-butyl-2-oxoimidazolidin-1-yl)pyridin-2-yl]amino}-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino 1-N-(2H3)methylpyridazine-3-carb oxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-{[5-(morpholin-4-yl)pyridin-2-yl]amino}pyridazine-3-carboxamide,
6-[(4,5-difluoropyridin-2-yl)amino]-4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl] amino 1-N-(2H3)methylpyridazine-3-carboxamide,
4-{[3-methoxy-4-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(6-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
6-cyclopropaneamido-4-({3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide,
4-[(4-cyano-3-methoxypyridin-2-yl)amino]-6-cyclopropaneamido-N-(2H3)methylpyridazine-3-carboxamide,
methyl N—{5-[(3-methoxy-4-{5-[(N-methylmethanesulfonamido)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-6-[(2H3)methylcarbamoyl]pyridazin-3-yl} carbamate,
methyl N-{5-[(3-methoxy-4-{5-[(morpholin-4-yl)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-6-[(2H3)methylcarbamoyl]pyridazin-3-yl} carbamate,
6-cyclopropaneamido-4-[(3-methoxy-4-{5-[(N-methylmethanesulfonamido)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
6-cyclopropaneamido-4-[(3-methoxy-4-{5-[(morpholin-4-yl)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
methyl N-(5-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}-6-[(2H3)methylcarbamoyl]pyridazin-3-yl)carbamate,
6-cyclopropaneamido-4[(4-{5-[(1 S)-1-hydroxyethyl]-1,2,4-oxadiazol-3-yl}-3-methoxypyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
6-cyclopropaneamido-4-[(4-{5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl}-3-methoxypyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
6-cyclopropaneamido-4-[(3-methoxy-4-{5-[(methylamino)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
4-({4-[5-(cyanomethyl)-1,2,4-oxadiazol-3-yl]-3-methoxypyridin-2-yl} amino)-6-cyclopropaneamido-N-(2H3)methylpyridazine-3-carboxamide, 60
4-[(3-methoxy-4-{5-[(N-methylmethanesulfonamido)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
4-({3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
4-((3-methoxy-4-(5-(morpholinomethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)amino)-N-(methyl-d3)-6-(4-methylpyridin-2-yl)amino)pyridazine-3-carboxamide,
methyl N-{5-[(44 5-[(1,1-dioxo-1λ6,2-thiazinan-2-yl)methyl]-1,2,4-oxadiazol-3-yl}-3-methoxypyridin-2-yl)amino]-6-[(2H3)methylcarbamoyl]pyridazin-3-yl} carbamate,
4-[(3-methoxy-4-{5-[(morpholin-4-yl)methyl]-1,2,4-oxadiazol-3-yl} pyridin-2-yl)amino]-N-(2H3)methyl-6-propanamidopyridazine-3-carboxamide,
4-({3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methyl-6-propanamidopyridazine-3-carboxamide,
6-(2-cyclopropylacetamido)-4-[(3-methoxy-4-{5-[(N-methylmethanesulfonamido)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
4-({3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methyl-6-(3-methylbutanamido)pyridazine-3-carboxamide,
4-[(3-methoxy-4-{5-[(morpholin-4-yl)methyl]-1,2,4-oxadiazol-3-yl} pyridin-2-yl)amino]-N-(2H3)methyl-6-(3-methylbutanamido)pyridazine-3-carboxamide,
4-((3-methoxy-4-{5-[(N-methylmethanesulfonamido)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methyl-6-(3-methylbutanamido)pyridazine-3-carboxamide,
4-[(3-methoxy-4-{5-[(2-oxo-1,3-oxazolidin-3-yl)methyl]-1,2,4-oxadiazol-3-yl}pyridin-2-yl)amino]-N-(2H3)methyl-6-(3-methylbutanamido)pyridazine-3-carboxamide,
6-(2-cyclopropylacetamido)-4-({3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide,
6-(2-cyclopropylacetamido)-4-({4-[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]-3-methoxypyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide,
6-cyclopropaneamido-4-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide 74
6-(2-cyclopropylacetamido)-4-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-(}3-methoxy-4-[5-(methoxymethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl} amino)-N-(2H3)methyl-6-[2-(oxetan-3-yl)acetamido]pyridazine-3-carboxamide,
6-[(5-chloro-4-methylpyridin-2-yl)amino]-4-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
4-[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-[(6-methylpyrimidin-4-yl)amino]pyridazine-3-carboxamide,
6-[4-(2-hydroxypropan-2-yl)pyridin-2-yl] amino}-4-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl]amino}-N-(2H3)methyl-6-propanamidopyridazine-3-carboxamide,
6-[5-(2-hydroxypropan-2-yl)pyridin-2-yl] amino}-4-{[3-methoxy-4-(5-methyl-1,2,4-oxadiazol-3-yl)pyridin-2-yl] amino}-N-(2H3)methylpyridazine-3-carboxamide
6-cyclopropaneamido-4-({4-[5-(dimethylcarbamoyl)pyrazin-2-yl]-3-methoxypyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide,
6-cyclopropaneamido-4-[(4-{5-[ethyl(methyl)carbamoyl]pyrazin-2-yl}-3-methoxypyridin-2-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
6-(2-cyclopropylacetamido)-4-({4-[5-(dimethylcarbamoyl)pyrazin-2-yl]-3-methoxypyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide, 89
4-(}4-[5-(dimethyl carbamoyl)pyrazin-2-yl]-3-methoxypyridin-2-yl} amino)-N-(2H3)methyl-6-[(1-methyl-1H-pyrazol-3-yl)amino]pyridazine-3-carboxamide,
6-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-4-({4-[5-(dimethylcarbamoyl)pyrazin-2-yl]-3-methoxypyridin-2-yl} amino)-N-(2H3)methylpyridazine-3-carboxamide,
6-[(5-chloro-1-methyl-1H-pyrazol-3-yl)amino]-4-({4-[5-(dimethylcarbamoyl)pyrazin-2-yl]-3-methoxypyridin-2-yl}amino)-N-(2H3)methylpyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-6-{[5-(2-hydroxypropan-2-yl)pyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
6-{[5-(2-aminopropan-2-yl)pyridin-2-yl]amino}-4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl] amino}—N-(2H3)methyl-6-[(5-methylpyrazin-2-yl)amino]pyridazine-3-carboxamide,
6-[(6-ethoxypyridazin-3-yl)amino]-4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl] amino}—N-(2H3)methyl-6-{[5-(morpholin-4-yl)pyridin-2-yl]amino}pyridazine-3-carboxamide,
6-[(4-fluoropyridin-2-yl)amino]-4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-N-(2H3)methylpyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl] amino}—N-(2H3)methyl-6-[(4-methylpyridin-2-yl)amino]pyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-6-[(6-methoxypyridazin-3-yl)amino]-N-(2H3)methylpyridazine-3-carboxamide,
4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl]amino}-N-(2H3)methyl-6-[(pyridin-2-yl)amino]pyridazine-3-carboxamide,
6-cyclopropaneamido-4-{[4-(5-fluoropyrimidin-2-yl)-3-methoxypyridin-2-yl] amino}—N-(2H3)methylpyridazine-3-carboxamide,
or a stereoisomer or pharmaceutically acceptable salt thereof.

87 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/982,937Filed 20 Mar 2019 · us provisional application
Priority: 22 Mar 2018
Published: US 2021/0032220 A14 Feb 2021
Granted: 7 Mar 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07B 59/002
Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se: heterocyclic compounds
C07D 213/82
Amides; Imides: in position 3

Family

Application62/646,432Us provisional application · filed 22 Mar 2018
US 2021/0032220 A1Pre-grant publication · published 4 Feb 2021
US 11,597,721 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of the formula

wherein
X is N;
R2 is —C(O)R2a;
C1-6 alkyl, —(CH2)r-3-14 membered carbocycle substituted with 0-1 R2a or a 5-12 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-4 R2a;
R2a at each occurrence is independently H, OCF3, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, (CH2)rNR11R11, —(CH2)rC(O)NR11R11, —(CH2)rNRbC(O)(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, — S(O)pRc, C1-6 alkyl substituted with 0-3 Ra, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle substituted with 0-1 Ra or a —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-2 Ra;
R3 is H, C1-3 alkyl or C3-6 cycloalkyl;
R4 is H, C1-3 alkyl or C3-6 cycloalkyl;
R5 is C1-4 alkyl substituted with 0-1 R5a, C1-4 alkoxy substituted with 0-1 R5a, (CH2)r-phenyl substituted with 0-3R5a or a —(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p;
R5a is is independently at each occurrence, H, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rc, —NReRe, —NReC(O)ORc, C1-6 alkyl or (CH2)r-phenyl substituted with 0-3 Rf;
R6 is C1-4 alkyl substituted with 0-1 R6a, (CH2)r-phenyl substituted with 0-3 R6a or a —(CH2)-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 R6a;
R6a is H, C1-4 alkyl substituted with 0-3 Rf, CF3, C3-10 cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd;
R11 at each occurrence is independently H, C1-4 alkyl substituted with 0-3 Rf, CF3, C3-10 cycloalkyl substituted with 0-1 Rf, (CH)r-phenyl substituted with 0-3 Rd or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rd;
Ra at each occurrence is independently H, F, Cl, Br, OCF3, CF3, CHF2, CN, NO2, —(CH2)rORb, —(CH2)rSRb, —(CH2)rC(O)Rb, —(CH2)rC(O)ORb, —(CH2)rOC(O)Rb, —(CH2)rNR11R11, (CH2)rC(O)NR11R11, —(CH2)rNRbC(O)Rc, —(CH2)rNRbC(O)ORc, —NRbC(O)NR11R11, —S(O)pNR11R11, —NRbS(O)pRc, —S(O)Rc, —S(O)2Rc, C1-6 alkyl substituted with 0-3 Rf, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 Ra, C2-6 alkynyl substituted with 0-3 Ra, —(CH2)r-3-14 membered carbocycle or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf;
Rb is H, C1-6 alkyl substituted with 0-3 Rd, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-2 Rd, or —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rd;
Rc is C1-6 alkyl substituted with 0-3 Rf, (CH2)r—C3-6 cycloalkyl substituted with 0-3 Rf or (CH2)r-phenyl substituted with 0-3 Rf;
Rd is independently at each occurrence, hydrogen, F, Cl, Br, OCF3, CF3, CN, NO2, —ORe, —(CH2)rC(O)Rc, —NReRe, —NReC(O)ORc, C1-6 alkyl or (CH2)r-phenyl substituted with 0-3 Rf;
Re is independently at each occurrence, hydrogen, C1-6 alkyl, C3-6 cycloalkyl or (CH2)r-phenyl substituted with 0-3 Rf;
Rf is independently at each occurrence, hydrogen, halo, CN, NH2, OH, C3-6 cycloalkyl, CF3, O(C1-6 alkyl) or a —(CH2)r-5-7 membered heterocycle containing 1-4 heteroatoms selected from N, O, and S(O)p;
p is 0, 1, or 2;
r is 0, 1, 2, 3, or 4;
or a stereoisomer or pharmaceutically acceptable salt thereof.

18 more elements

Facts

Application

16/982,937Filed 20 Mar 2019 · us provisional application

Priority

22 Mar 2018

Published

US 2021/0032220 A14 Feb 2021

Granted

7 Mar 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
C07B 59/002
Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se: heterocyclic compounds
C07D 213/82
Amides; Imides: in position 3