| 主权项 |
1. A compound of formula I having the structure:or a pharmaceutically acceptable salt thereof, wherein
R1 is hydrogen C1-C4 alkyl, wherein said alkyl is further optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, methoxy, amino, CF3, and C3-C6 cycloalkyl; R2 and R3 are each independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, C1-C6 linear or branched chain perfluoroalkyl, C1-C6 linear or branched chain alkoxy, C1-C6 linear or branched chain perfluoroalkoxy, halogen, cyano, hydroxyl, amino, carboxy, aminocarbonyl, aryl, heteroaryl, (aryl)C1-C6 linear or branched chain alkyl, (heteroaryl)C1-C6 linear or branched chain alkyl, (heterocyclic)C1-C6 linear or branched chain alkyl, (C1-C6 linear or branched chain alkyl)aryl, (C1-C6 linear or branched chain alkyl)heteroaryl, (C1-C6 linear or branched chain alkyl heterocyclic, (C1-C6 linear or branched chain alkoxyl)carbonyl, (C1-C6 linear or branched chain alkyl)amino-carbonylamino, or (C1-C6 linear or branched chain alkyl)aminocarbonyl; R4 is selected from hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C1-C6 linear or branched chain perfluoroalkyl, aryl, and alkylaryl; X is selected from —NH— and —CRaRb—, where (a) Ra and Rb are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, (aryl)C1-C6 linear or branched chain alkyl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, (heteroaryl)C1-C6 linear or branched chain alkyl, (heterocyclic)C1-C6 linear or branched chain alkyl, or (b) Ra and Rb together form a chain comprising —(CRcRd)j—, where Rc and Rd are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, halo, CN, CF3, hydroxyl, CONH2, or SO2CH3; Y is -A-R5, where A is a bond, —(CH2)k— or —(CD2)k— and R5 is C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, or —NRa′Rb′, or is an unsaturated, 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, nitrogen, and sulfur, wherein said alkyl, C3-C6 cycloalkyl, aryl, or monocyclic or bicyclic ring structure is further optionally substituted with one or more substituents selected from the group consisting of deuterium, halo, C1-C6 linear or branched chain alkyl, CN, hydroxyl, CF3, —ORe, —NReRf, —S(O)pRe and C3-C6 cycloalkyl, where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo, CN, hydroxyl, CONH2, and SO2CH3, where (a) Ra′ and Rb′ are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, C3-C6 cycloalkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, or (C1-C6 linear or branched chain alkyl heteroaryl, where said alkyl and cycloalkyl may be optionally substituted with one or more Rc′, or (b) Ra′ and Rb′ together form a chain comprising —(CRc′Rd′)j—, where Rc′ and Rd′ are independently hydrogen, deuterium C1-C6 linear or branched chain alkyl, aryl, (C1-C6 linear or branched chain alkyl)aryl, heteroaryl, (C1-C6 linear or branched chain alkyl)heteroaryl, halo, CN, hydroxyl, CF3, CONH2, —ORe, —NReRf, or —S(O)pRe; where Re and Rf are independently hydrogen, deuterium, C1-C6 linear or branched chain alkyl, or C3-C6 cycloalkyl, where said alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo, CN, hydroxyl, CF3, and CONH2; j is 2, 3, 4 or 5; k is 1, 2; 3, or 4; p is 0, 1 or 2; and, n is 1 or 2, said compound being 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-cyclopropyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-methanesulfonamide; N-{cis-3-[(butylsulfonyl)methyl]cyclobutyl}-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine; 1-cyclopropyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-azetidine-3-sulfonamide; 3-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-azetidine-1-sulfonamide; (1R,5S)—N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-6-oxa-3-azabicyclo[3.1.1]heptane-3-sulfonamide; (3R)-3-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-pyrrolidine-1-sulfonamide; (3S)-3-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-pyrrolidine-1-sulfonamide; N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-1-(oxetan-3-yl)methane-sulfonamide; 1-(3,3-difluorocyclobutyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methane-sulfonamide; trans-3-(cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-cyclobutyl}cyclo-butanesulfonamide; cis-3-(cyanomethyl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-cyclobutyl}cyclobutane-sulfonamide; N-[cis-3-({[(3,3-difluorocyclobutyl)methyl]sulfonyl}methyl)cyclobutyl]-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine; (1S,5S)-1-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-3-azabicyclo[3.1.0]hexane-3-sulfonamide; (1R,5R)-1-cyano-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-3-azabicyclo[3.1.0]hexane-3-sulfonamide; (3R)-1-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}meth-yl)sulfonyl]pyrrolidine-3-carbonitrile; 1-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]-4-(trifluoromethyl)piperidin-4-ol; N-(cis-3-{[(4,4-difluoropiperidin-1-yl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine; (3S)-1-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}meth-yl)sulfonyl]pyrrolidine-3-carbonitrile; N-(cis-3-{[(3-chloro-4-fluorophenyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine; N-(cis-3-{[(2-cyclopropylethyl)sulfonyl]methyl}cyclobutyl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine; N-methyl-N-[cis-3-({[1-(propan-2-yl)pyrrolidin-3-yl]sulfonyl}methyl)cyclobutyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine; 3,3-difluoro-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclobutane-sulfonamide; 1-[3-(cyanomethyl)oxetan-3-yl]-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-methanesulfonamide; cis-3-(cyanomethyl)-3-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-cyclobutanesulfonamide; trans-3-(cyanomethyl)-3-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}cyclobutanesulfonamide; N-(2-cyanoethyl)-N-methyl-N′-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}sulfuric diamide; N-{(1S,3R)-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclopentyl}propane-1-sulfonamide; 3-(2-hydroxypropan-2-yl)-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}benzene-sulfonamide; N-(cyclopropylmethyl)-N′-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}sulfuric diamide; N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-4-(1H-pyrazol-3-yl)piperidine-1-sulfonamide; 2-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-sulfonamide; N-cyclopropyl-1-{trans-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methane-sulfonamide; 2-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]pyridine-4-carbonitrile; (1S,3S)-3-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methylysulfonyl]cyclopentanecarbonitrile; (1R,3R)-3-[({cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methyl)sulfonyl]cyclopentanecarbonitrile; 1-cyclopropyl-N-{trans-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}methane sulfonamide; 3-cyano-N-{trans-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}pyrrolidine-1-sulfonamide; N-methyl-N-{trans-3-[(propylsulfonyl)methyl]cyclobutyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine; and, 2-methyl-N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}-1,3-thiazole-5-sulfonamide; or, a pharmaceutically acceptable salt thereof. |
