JPWO2019182924A5 - - Google Patents
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- Publication number
- JPWO2019182924A5 JPWO2019182924A5 JP2020550114A JP2020550114A JPWO2019182924A5 JP WO2019182924 A5 JPWO2019182924 A5 JP WO2019182924A5 JP 2020550114 A JP2020550114 A JP 2020550114A JP 2020550114 A JP2020550114 A JP 2020550114A JP WO2019182924 A5 JPWO2019182924 A5 JP WO2019182924A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- pyrrolo
- amino
- azaspiro
- pyrimidin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 dehydrogen Chemical class 0.000 claims 112
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 24
- 125000000217 alkyl group Chemical group 0.000 claims 14
- 150000001875 compounds Chemical class 0.000 claims 13
- 125000001072 heteroaryl group Chemical group 0.000 claims 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims 11
- 125000003118 aryl group Chemical group 0.000 claims 10
- 235000019000 fluorine Nutrition 0.000 claims 10
- 125000000623 heterocyclic group Chemical group 0.000 claims 10
- 125000003342 alkenyl group Chemical group 0.000 claims 9
- 125000000304 alkynyl group Chemical group 0.000 claims 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 6
- 229910052731 fluorine Inorganic materials 0.000 claims 6
- 239000011737 fluorine Substances 0.000 claims 6
- 125000004104 aryloxy group Chemical group 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 150000002367 halogens Chemical class 0.000 claims 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000004414 alkyl thio group Chemical group 0.000 claims 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 4
- YCQNXZAQYYNQTH-UHFFFAOYSA-N 2-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CC1=NC=C2C=CNC2=N1 YCQNXZAQYYNQTH-UHFFFAOYSA-N 0.000 claims 3
- 125000004946 alkenylalkyl group Chemical group 0.000 claims 3
- 125000005038 alkynylalkyl group Chemical group 0.000 claims 3
- 125000005605 benzo group Chemical group 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- KDOUHIDUYPIERE-UHFFFAOYSA-N (1-methylpyrazol-3-yl)-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]methanone Chemical compound CN(C1CC2(CN(C2)C(=O)C2=NN(C=C2)C)C1)C=1C2=C(N=CN=1)NC=C2 KDOUHIDUYPIERE-UHFFFAOYSA-N 0.000 claims 1
- PWXMZODMDSDALW-UHFFFAOYSA-N (2-chloro-4-ethynylphenyl)-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]methanone Chemical compound ClC1=C(C=CC(=C1)C#C)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C PWXMZODMDSDALW-UHFFFAOYSA-N 0.000 claims 1
- VTSWOGVBFUOALQ-UHFFFAOYSA-N (3-chloro-4-ethynylphenyl)-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]methanone Chemical compound ClC=1C=C(C=CC=1C#C)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C VTSWOGVBFUOALQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- NWQMLXUIWUYHSD-UHFFFAOYSA-N 1-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]-3-methylsulfonylpropan-1-one Chemical compound CN(C1CC2(C1)CN(C2)C(=O)CCS(C)(=O)=O)C1=NC=NC2=C1C=CN2 NWQMLXUIWUYHSD-UHFFFAOYSA-N 0.000 claims 1
- BYISEBGOLCFZQT-UHFFFAOYSA-N 1-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]cyclopropane-1-carbonitrile Chemical compound CN(C1CC2(CN(C2)C(=O)C2(CC2)C#N)C1)C=1C2=C(N=CN=1)NC=C2 BYISEBGOLCFZQT-UHFFFAOYSA-N 0.000 claims 1
- PZIDCZRIHGNHPD-UHFFFAOYSA-N 1-methylbenzimidazole-5-carbaldehyde Chemical compound O=CC1=CC=C2N(C)C=NC2=C1 PZIDCZRIHGNHPD-UHFFFAOYSA-N 0.000 claims 1
- ZHIJLYUJVZKCDE-UHFFFAOYSA-N 2,2,2-trifluoroethyl 9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxylate Chemical compound CN(C1CCC2(CCN(CC2)C(=O)OCC(F)(F)F)CC1)C=1C2=C(N=CN=1)NC=C2 ZHIJLYUJVZKCDE-UHFFFAOYSA-N 0.000 claims 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- VWKRQZISFUNTGH-UHFFFAOYSA-N 2,3-dichloro-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound ClC1=C(C#N)C=CC(=C1Cl)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C VWKRQZISFUNTGH-UHFFFAOYSA-N 0.000 claims 1
- JPRZCHJAVZPIMR-UHFFFAOYSA-N 2,3-difluoro-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1F)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C JPRZCHJAVZPIMR-UHFFFAOYSA-N 0.000 claims 1
- IPSDQRYFGZNDAI-UHFFFAOYSA-N 2,3-difluoro-5-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC1=C(C#N)C=C(C=C1F)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C IPSDQRYFGZNDAI-UHFFFAOYSA-N 0.000 claims 1
- LZTVLJMNGXVCJP-UHFFFAOYSA-N 2,5-difluoro-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC1=C(C#N)C=C(C(=C1)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C)F LZTVLJMNGXVCJP-UHFFFAOYSA-N 0.000 claims 1
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 claims 1
- WJZIPMQUKSTHLV-UHFFFAOYSA-N 2-ethyldecanoic acid Chemical compound CCCCCCCCC(CC)C(O)=O WJZIPMQUKSTHLV-UHFFFAOYSA-N 0.000 claims 1
- ZKVWEDANSGSWPD-UHFFFAOYSA-N 2-fluoro-5-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC1=C(C#N)C=C(C=C1)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C ZKVWEDANSGSWPD-UHFFFAOYSA-N 0.000 claims 1
- OXQAFIPYGXVTEI-UHFFFAOYSA-N 2-methyl-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound CC1=C(C#N)C=CC(=C1)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C OXQAFIPYGXVTEI-UHFFFAOYSA-N 0.000 claims 1
- TVBKULHUOUDGIL-UHFFFAOYSA-N 3,5-difluoro-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C)F TVBKULHUOUDGIL-UHFFFAOYSA-N 0.000 claims 1
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 claims 1
- UYAIPRMOKFAMMH-UHFFFAOYSA-N 3-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]-3-oxopropanenitrile Chemical compound CN(C1CC2(CN(C2)C(CC#N)=O)C1)C=1C2=C(N=CN=1)NC=C2 UYAIPRMOKFAMMH-UHFFFAOYSA-N 0.000 claims 1
- YPBRWUQWYVFATN-UHFFFAOYSA-N 3-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound CN(C1CC2(CN(C2)C(=O)C=2C=C(C#N)C=CC=2)C1)C=1C2=C(N=CN=1)NC=C2 YPBRWUQWYVFATN-UHFFFAOYSA-N 0.000 claims 1
- NDUWLZCWAXNXLO-UHFFFAOYSA-N 3-[9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carbonyl]benzonitrile Chemical compound CN(C1CCC2(CCN(CC2)C(=O)C=2C=C(C#N)C=CC=2)CC1)C=1C2=C(N=CN=1)NC=C2 NDUWLZCWAXNXLO-UHFFFAOYSA-N 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- JFZIQIRABHLLKM-UHFFFAOYSA-N 3-fluoro-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C JFZIQIRABHLLKM-UHFFFAOYSA-N 0.000 claims 1
- GAUWBTAIXVUZLY-UHFFFAOYSA-N 3-fluoro-4-[9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carbonyl]benzonitrile Chemical compound FC=1C=C(C#N)C=CC=1C(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C GAUWBTAIXVUZLY-UHFFFAOYSA-N 0.000 claims 1
- RSVWDCQCHSMMND-UHFFFAOYSA-N 3-fluoro-5-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC=1C=C(C#N)C=C(C=1)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C RSVWDCQCHSMMND-UHFFFAOYSA-N 0.000 claims 1
- BSQKBHXYEKVKMN-UHFFFAOYSA-N 3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=CSC=1C=O BSQKBHXYEKVKMN-UHFFFAOYSA-N 0.000 claims 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims 1
- GEDPIBRYKFZQSE-UHFFFAOYSA-N 4,4,4-trifluoro-1-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]butan-1-one Chemical compound FC(CCC(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C)(F)F GEDPIBRYKFZQSE-UHFFFAOYSA-N 0.000 claims 1
- BLZMXOQDHLRLNE-UHFFFAOYSA-N 4-[2-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]-2-oxoethyl]benzonitrile Chemical compound CN(C1CC2(CN(C2)C(CC2=CC=C(C#N)C=C2)=O)C1)C=1C2=C(N=CN=1)NC=C2 BLZMXOQDHLRLNE-UHFFFAOYSA-N 0.000 claims 1
- DICQZGXPVOZSBT-UHFFFAOYSA-N 4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]-4-oxobutanenitrile Chemical compound CN(C1CC2(CN(C2)C(CCC#N)=O)C1)C=1C2=C(N=CN=1)NC=C2 DICQZGXPVOZSBT-UHFFFAOYSA-N 0.000 claims 1
- JMMCTEYNTCZHTP-UHFFFAOYSA-N 4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzenesulfonamide Chemical compound CN(C1CC2(CN(C2)C(=O)C2=CC=C(C=C2)S(=O)(=O)N)C1)C=1C2=C(N=CN=1)NC=C2 JMMCTEYNTCZHTP-UHFFFAOYSA-N 0.000 claims 1
- OKEQLCCGZRYWNG-UHFFFAOYSA-N 4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]cyclohexan-1-one Chemical compound CN(C1CC2(CN(C2)C(=O)C2CCC(CC2)=O)C1)C=1C2=C(N=CN=1)NC=C2 OKEQLCCGZRYWNG-UHFFFAOYSA-N 0.000 claims 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims 1
- GORVKYKEYCQOMR-UHFFFAOYSA-N 5-fluoro-2-methyl-4-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carbonyl]benzonitrile Chemical compound FC=1C(=CC(=C(C#N)C=1)C)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C GORVKYKEYCQOMR-UHFFFAOYSA-N 0.000 claims 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- RCSIOFWAUFWXMM-UHFFFAOYSA-N N-(2-ethylsulfonyl-2-azaspiro[3.3]heptan-6-yl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C(C)S(=O)(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C RCSIOFWAUFWXMM-UHFFFAOYSA-N 0.000 claims 1
- WXXYIUCRGXQTIQ-UHFFFAOYSA-N N-(3-methoxyphenyl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound COC=1C=C(C=CC=1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C WXXYIUCRGXQTIQ-UHFFFAOYSA-N 0.000 claims 1
- DCVLNAFSEGHRSD-UHFFFAOYSA-N N-(4-cyanophenyl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound C(#N)C1=CC=C(C=C1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C DCVLNAFSEGHRSD-UHFFFAOYSA-N 0.000 claims 1
- IDHQIVCHWLXHEJ-UHFFFAOYSA-N N-(5-fluoro-1,3-thiazol-2-yl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound FC1=CN=C(S1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C IDHQIVCHWLXHEJ-UHFFFAOYSA-N 0.000 claims 1
- MWFZEGBBWGJGPE-UHFFFAOYSA-N N-(5-methoxypyrazin-2-yl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound COC=1N=CC(=NC=1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C MWFZEGBBWGJGPE-UHFFFAOYSA-N 0.000 claims 1
- HALYKECWLOUIFT-UHFFFAOYSA-N N-(5-methoxypyridin-2-yl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound COC=1C=CC(=NC=1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C HALYKECWLOUIFT-UHFFFAOYSA-N 0.000 claims 1
- PSCQQIWXFNPLPN-UHFFFAOYSA-N N-(5-methylpyrazin-2-yl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound CN(C1CCC2(CCN(CC2)C(=O)NC2=NC=C(N=C2)C)CC1)C=1C2=C(N=CN=1)NC=C2 PSCQQIWXFNPLPN-UHFFFAOYSA-N 0.000 claims 1
- LBGAWZULJFMLJK-UHFFFAOYSA-N N-(6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-methyl-3-propylsulfonyl-3-azaspiro[5.5]undecan-9-amine Chemical compound N1=CN=C(C2=C1NCC2)N(C1CCC2(CCN(CC2)S(=O)(=O)CCC)CC1)C LBGAWZULJFMLJK-UHFFFAOYSA-N 0.000 claims 1
- SBJVNDZLFROZPP-UHFFFAOYSA-N N-(6-methoxypyridin-2-yl)-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound COC1=CC=CC(=N1)NC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C SBJVNDZLFROZPP-UHFFFAOYSA-N 0.000 claims 1
- FGFBDNHPJMDHEB-UHFFFAOYSA-N N-methyl-9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxamide Chemical compound CNC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C FGFBDNHPJMDHEB-UHFFFAOYSA-N 0.000 claims 1
- JXRUFSJHYPIPGT-UHFFFAOYSA-N [4-(1-methylpyrazol-3-yl)phenyl]-[6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]methanone Chemical compound CN1N=C(C=C1)C1=CC=C(C=C1)C(=O)N1CC2(C1)CC(C2)N(C=1C2=C(N=CN=1)NC=C2)C JXRUFSJHYPIPGT-UHFFFAOYSA-N 0.000 claims 1
- XZLVYKRCLBOZJX-UHFFFAOYSA-N [6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptan-2-yl]-pyrazin-2-ylmethanone Chemical compound CN(C1CC2(CN(C2)C(=O)C2=NC=CN=C2)C1)C=1C2=C(N=CN=1)NC=C2 XZLVYKRCLBOZJX-UHFFFAOYSA-N 0.000 claims 1
- 150000001345 alkine derivatives Chemical class 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
- 239000000739 antihistaminic agent Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 125000005018 aryl alkenyl group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000005015 aryl alkynyl group Chemical group 0.000 claims 1
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 1
- 229940046731 calcineurin inhibitors Drugs 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims 1
- FJMRXECXSJRKNH-UHFFFAOYSA-N ethyl 6-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-2-azaspiro[3.3]heptane-2-carboxylate Chemical compound CN(C1CC2(CN(C2)C(=O)OCC)C1)C=1C2=C(N=CN=1)NC=C2 FJMRXECXSJRKNH-UHFFFAOYSA-N 0.000 claims 1
- IEZLVROUSQUEJE-UHFFFAOYSA-N ethyl 9-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-3-azaspiro[5.5]undecane-3-carboxylate Chemical compound C(C)OC(=O)N1CCC2(CC1)CCC(CC2)N(C=1C2=C(N=CN=1)NC=C2)C IEZLVROUSQUEJE-UHFFFAOYSA-N 0.000 claims 1
- 125000004404 heteroalkyl group Chemical group 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 125000005312 heteroarylalkynyl group Chemical group 0.000 claims 1
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims 1
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims 1
- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 208000026278 immune system disease Diseases 0.000 claims 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims 1
- 229960000681 leflunomide Drugs 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 150000002825 nitriles Chemical class 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
Claims (14)
A、B、C、及び、Dは、独立してN又はC-R5であり、Eは、Nであり、
R5は、水素、重水素、ハロゲン、ヒドロキシ、アミノ、ニトロ、CN、-SO2NH2、-SONH 2 、-NHOH、-CONH2、-OR5a、-N(R5a)2、-SR5a、アルキル、シクロアルキル、アルコキシ、アルキルチオ、アルキルスルホニル、ヘテロシクリル、アリール、ヘテロアリール、-CF3、-CF2H、-OCF3、-OCF2H、1~5個のフッ素で置換されているC1~6アルキル、1~5個のフッ素で置換されているC3~6シクロアルキル、1~5個のフッ素で置換されているC1~4アルコキシ、1~5個のフッ素で置換されているC1~4アルキルチオ、1~5個のフッ素で置換されているC1~4アルキルスルホニル、カルボキシ、C1~4アルキルオキシカルボニル、及びC1~4アルキルカルボニルからなる群から選択され、
R5aは、アルキル、シクロアルキル、アルコキシ、アルキルチオ、アルキルスルホニル、ヘテロシクリル、アリール、ヘテロアリール、-CF3、-CF2H、-OCF3、-OCF2H、1~5個のフッ素で置換されているC1~6アルキル、1~5個のフッ素で置換されているC3~6シクロアルキル、1~5個のフッ素で置換されているC1~4アルコキシ、1~5個のフッ素で置換されているC1~4アルキルチオ、1~5個のフッ素で置換されているC1~4アルキルスルホニル、カルボキシ、C1~4アルキルオキシカルボニル及びC1~4アルキルカルボニルからなる群から選択され、
R2、R3、及びR4は、独立して出現ごとに、水素、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキルアルキル、シクロアルキルアルケニル、シクロアルキルアルキニル、シクロアルケニルアルキル、シクロアルケニルアルケニル、シクロアルケニルアルキニル、ヘテロシクリル、ヘテロシクリルアルキル、ヘテロシクリルアルケニル、ヘテロシクリルアルキニル、アリール、アリールアルキル、アリールアルケニル、アリールアルキニル、アリールシクロアルキル、アリールオキシアルキル、アリールオキシシクロアルキル、ヘテロアリール、ヘテロアリールアルキル,ヘテロアリールアルケニル、ヘテロアリールアルキニル、ヘテロアリールシクロアルキル、ヘテロアリールオキシアルキル、及びヘテロアリールオキシシクロアルキル(それらのいずれかは、任意に1つ以上のR2aで置換されていてもよい)からなる群から選択され、
R2aは、ハロゲン、シアノ、ヒドロキシ、オキソ、-NH2、-SO2NH2、-SONH2、-CONH2、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、ヘテロシクリル、R2bO-L-、R2bS-L-、(R2b)2N-L-、R2b-C(=O)L-、R2b-C(=O)-L-、(R2b)2N-C(=O)-L-、R2b-C(=O)N(R2b)-L-、R2bO-C(=O)N(R2b)-L-、(R2b)2NC(=O)N(R2b)-L-、R2b-C(=O)O-L-、R2bO-C(=O)O-L-、(R2b)2N-C(=O)O-L-、R2bO-S(=O)2-L-、(R2b)2N-S(=O)2-L-、R2b-S(=O)2N(R2b)-L-、R2b-S(=O)2N(R2b)-L-、(R2b)2N-S(=O)2N(R2b)-L-、R2bS(=O)2O-L-、R2b-S(=O)2O-L-、(R2b)N-S(=O)2O-L-、アリール-、アリールオキシ-、ヘテロアリール、及びヘテロアリールオキシからなる群から選択され、
R2bは、独立して出現ごとに、アルキル、アルケニル、アルキニル、シクロアルキル、ヘテロシクリル、アリール、及びヘテロアリールからなる群から選択され、
R1は、水素、アルキル、ヘテロアルキル、アリール、アリールオキシ、ヘテロアリール、又はヘテロアリールオキシ(これらは、任意に1つ以上のR1aで置換されてもよい)であり,ここでいずれか2個のR1aは、それらが結合する環原子と共に、シクロアルキル又はヘテロ環を形成し、2個のR1aは同じC原子に結合するか又は2個の非隣接C原子に結合し、
R1aは、独立して出現ごとに、ハロゲン、シアノ、ヒドロキシ、オキソ、-NH2、-SO2NH2、-SONH2、-CONH2、アルキル、アルケニル、アルキニル、アルケニルアルキル、アルキニルアルキル、シクロアルキル、シクロアルケニル、シクロアルキルアルキル、シクロアルキルアルケニル、ヘテロシクリル、R1bO-L-、R1bS-L-、(R1b)2N-L-、R1b-C(=O)L-、R1b-C(=O)-L-、(R1b)2N-C(=O)-L-,R1b-C(=O)N(R1b)-L-、R1bO-C(=O)N(R1b)-L-、(R1b)2NC(=O)N(R1b)-L-、R1b-C(=O)O-L-、R1bO-C(=O)O-L-、(R1b)2N-C(=O)O-L-、R1bO-S(=O)2-L-、(R1b)2N-S(=O)2-L-、R1b-S(=O)2N(R1b)-L-、R1b-S(=O)2N(R1b)-L-、(R1b)2N-S(=O)2N(R1b)-L-、R1bS(=O)2O-L-、R1b-S(=O)2O-L-、(R1b)N-S(=O)2O-L-、アリール、アリールオキシ、ヘテロアリール、及びヘテロアリールオキシからなる群から選択され、
R1bは、独立して出現ごとに、アルキル、アルケニル、アルキニル、シクロアルキル、ヘテロシクリル、アリール、及びヘテロアリールからなる群から選択され、
Lは共有結合であるか、又はLは独立して出現ごとに、アルキル、シクロアルキル、アルキルシクロアルキル及びシクロアルキルからなる群から選択され、及び、
Xは共有結合であるか、又はXは-C(=O)-、-S(=O)-、-S(=O)2-、-C(=O)O-、-C(=O)NH-、-S(=O)NH-、-S(=O)2NH-からなる群から選択される。)の化合物、若しくは、それらの薬学的に許容可能な塩、プロドラッグ、水和物、又は、溶媒和物。 General formula (I)
A, B, C, and D are independently N or CR 5 , and E is N.
R 5 is hydrogen, dehydrogen, halogen, hydroxy, amino, nitro, CN, -SO 2 NH 2 , -SONH 2 , -NHOH, -CONH 2 , -OR 5a , -N (R 5a ) 2 , -SR. 5a , alkyl, cycloalkyl, alkoxy, alkylthio, alkylsulfonyl, heterocyclyl, aryl, heteroaryl, -CF 3 , -CF 2 H, -OCF 3 , -OCF 2 H, substituted with 1-5 fluorines C 1-6 alkyl substituted with 1-5 fluorine C 3-6 cycloalkyl substituted with 1-5 fluorine C 1-4 alkoxy substituted with 1-5 fluorine Selected from the group consisting of C 1-4 alkylthios, C 1-4 alkylsulfonyls substituted with 1-5 fluorines, carboxy, C1-4 alkyloxycarbonyls, and C1-4 alkylcarbonyls.
R 5a is substituted with alkyl, cycloalkyl, alkoxy, alkylthio, alkylsulfonyl, heterocyclyl, aryl, heteroaryl, -CF 3 , -CF 2 H, -OCF 3 , -OCF 2 H, 1-5 fluorines. C 1-6 alkyl substituted with 1-5 fluorine C 3-6 cycloalkyl substituted with 1-5 fluorine C 1-4 alkoxy substituted with 1-5 fluorine Selected from the group consisting of substituted C 1-4 alkylthios substituted with 1-5 fluorines C 1-4 alkylsulfonyls, carboxys, C 1-4 alkyloxycarbonyls and C1-4 alkylcarbonyls ,
R 2 , R 3 , and R 4 independently appear on each appearance as hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenylalkyl, cycloalkenyl. Alkenyl, cycloalkenyl alkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylcycloalkyl, aryloxyalkyl, aryloxycycloalkyl, heteroaryl, heteroarylalkyl, heteroaryl Select from the group consisting of alkenyl, heteroarylalkynyl, heteroarylcycloalkyl, heteroaryloxyalkyl, and heteroaryloxycycloalkyl, any of which may optionally be substituted with one or more R 2a . Being done
R 2a is halogen, cyano, hydroxy, oxo, -NH 2 , -SO 2 NH 2 , -SONH 2 , -CONH 2 , alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, R 2b OL-. , R 2b SL-, (R 2b ) 2N-L-, R 2b -C (= O) L-, R 2b -C (= O) -L-, (R 2b ) 2N - C (= O) -L-, R 2b -C (= O) N (R 2b ) -L-, R 2b OC (= O) N (R 2b ) -L-, (R 2b ) 2 NC (= O) ) N (R 2b ) -L-, R 2b -C (= O) OL-, R 2b OC (= O) OL-, (R 2b ) 2 N-C (= O) O -L-, R 2b OS (= O) 2 -L-, (R 2b ) 2 N-S (= O) 2 -L-, R 2b -S (= O) 2 N (R 2b )- L-, R 2b -S (= O) 2 N (R 2b ) -L-, (R 2b ) 2 N-S (= O) 2 N (R 2b ) -L-, R 2b S (= O) 2OL- , R 2b -S ( = O) 2OL- , (R 2b ) NS (= O) 2OL-, aryl-, aryloxy-, heteroaryl, and heteroaryl Selected from the group consisting of oxy,
R 2b is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl with each appearance.
R 1 is hydrogen, alkyl, heteroalkyl, aryl, aryloxy, heteroaryl, or heteroaryloxy, which may optionally be substituted with one or more R1a , where any 2 The R 1a form a cycloalkyl or heterocycle with the ring atom to which they are attached, and the two R 1a are attached to the same C atom or to two non-adjacent C atoms.
R 1a is an independent each appearance of halogen, cyano, hydroxy, oxo, -NH 2 , -SO 2 NH 2 , -SONH 2 , -CONH 2 , alkyl, alkenyl, alkynyl, alkenylalkyl, alkynylalkyl, cyclo. Alkyne, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, R 1b OL-, R 1b S-L-, (R 1b ) 2 N-L-, R 1b -C (= O) L-, R 1b -C (= O) -L-, (R 1b ) 2 N-C (= O) -L-, R 1b -C (= O) N (R 1b ) -L-, R 1b OC (= O) N (R 1b ) -L-, (R 1b ) 2 NC (= O) N (R 1b ) -L-, R 1b -C (= O) OL-, R 1b OC (= O) OL-, (R 1b) 2 NC (= O) OL-, R 1b OS (= O) 2-L-, (R 1b ) 2 NS ( = O) 2 -L-, R 1b -S (= O) 2 N (R 1b ) -L-, R 1b -S (= O) 2 N (R 1b ) -L-, (R 1b ) 2 N- S (= O) 2 N (R 1b ) -L-, R 1b S (= O) 2 OL-, R 1b -S (= O) 2 OL-, (R 1b ) NS ( = O) 2 Select from the group consisting of OL-, aryl, aryloxy, heteroaryl, and heteroaryloxy.
R 1b is independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl with each appearance.
L is a covalent bond, or L is independently selected from the group consisting of alkyl, cycloalkyl, alkylcycloalkyl and cycloalkyl with each appearance, and
X is a covalent bond, or X is -C (= O)-, -S (= O)-, -S (= O) 2- , -C (= O) O-, -C (= O) ) NH-, -S (= O) NH-, -S (= O) 2 NH- is selected from the group. ), Or their pharmaceutically acceptable salts, prodrugs, hydrates, or solvates.
R1aは、独立して出現ごとに、ハロゲン、シアノ、ヒドロキシ、-NH2、-SO2NH2、-SONH2、-CONH2、アルキル、アルケニル、アルキニル、アルケニルアルキル、アルキニルアルキル、シクロアルキル、シクロアルケニル、シクロアルキルアルキル、シクロアルキルアルケニル、ヘテロシクリル、アリール、アリールオキシ、ヘテロアリール、及びヘテロアリールオキシからなる群から選択される。)である、請求項1から5のいずれか1項に記載の一般式(I)の化合物。 R 1 is
R 1a is an independent, each appearance of halogen, cyano, hydroxy, -NH 2 , -SO 2 NH 2 , -SONH 2 , -CONH 2 , alkyl, alkenyl, alkynyl, alkenylalkyl, alkynylalkyl, cycloalkyl, It is selected from the group consisting of cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, heterocyclyl, aryl, aryloxy, heteroaryl, and heteroaryloxy. ), The compound of the general formula (I) according to any one of claims 1 to 5 .
R1aは、独立して出現ごとに、ハロゲン、シアノ、ヒドロキシ、-NH2、-SO2NH2、-SONH2、-CONH2、アルキル、アルケニル、アルキニル、アルケニルアルキル-、アルキニルアルキル-、シクロアルキル、シクロアルケニル、シクロアルキルアルキル、シクロアルキルアルケニル、ヘテロシクリル、アリール-、アリールオキシ-、ヘテロアリール、及びヘテロアリールオキシからなる群から選択される。)である、請求項1から5のいずれか1項に記載の一般式(I)の化合物。 R 1 is
R1a independently appeared on each appearance as halogen, cyano, hydroxy, -NH 2 , -SO 2 NH 2 , -SONH 2 , -CONH 2 , alkyl, alkenyl, alkynyl, alkenylalkyl-, alkynylalkyl-, cycloalkyl. , Cycloalkenyl, Cycloalkylalkyl, Cycloalkylalkenyl, Heterocyclyl, Aryl-, Aryloxy-, Heteroaryl, and Heteroaryloxy. ), The compound of the general formula (I) according to any one of claims 1 to 5 .
(3-フルオロ-4-プロプ-1-イニル-フェニル)-{6-[-[(メチル-d3)-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-2-アザ-スピロ[3.3]ヘプト-2-イル}-メタノン、2,3-ジフルオロ-4-{6-[(メチル-d3)-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-2-アザ-スピロ[3.3]ヘプタン-2-カルボニル}-ベンゾニトリル、[4-(1-メチル-1H-ピラゾール-3-イル)-フェニル]-{6-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-2-アザ-スピロ[3.3]ヘプト-2-イル}-メタノン、(1-シクロプロピル-1H-ピラゾール-4-イル)-{6-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-2-アザ-スピロ[3.3]ヘプト-2-イル}-メタノン、2,6-ジフルオロ-3-{6-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-2-アザ-スピロ[3.3]ヘプタン-2-カルボニル}-ベンゾニトリル、N-(3-メトキシ-1,2,4-チアジアゾール-5-イル)-6-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-2-アザスピロ[3.3]ヘプタン-2-カルボキサミド、4-(6-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-2-アザスピロ[3.3]ヘプタン-2-カルボニル)ベンゼンスルホンアミド、1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-エタノン、(3-エタンスルホニル-3-アザ-スピロ[5.5]ウンデカ-9-イル)-メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミン、2-ヒドロキシ-1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-エタノン、1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-プロパン-1-オン、メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-[3-(2,2,2-トリフルオロ-エチル)-3-アザ-スピロ[5.5]ウンデカ-9-イル]-アミン、{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-ピリジン-3-イル-メタノン、4-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-4-オキソ-ブチロニトリル、4-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボニル}-シクロヘキサノン、{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-(3-トリフルオロメチル-フェニル)-メタノン、3-フルオロ-4-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボニル}-ベンゾニトリル、4-(2-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-2-オキソ-エチル)-ベンゾニトリル、2-フルオロ-4-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボニル}-ベンゾニトリル、{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-ピラジン-2-イル-メタノン、1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボニル}-シクロプロパンカルボニトリル、(6-メチル-ピラジン-2-イル)-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-メタノン、4,4,4-トリフルオロ-1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-ブタン-1-オン、ベンゾ[b]チオフェン-3-イル-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-メタノン、2-(1H-インドール-3-イル)-1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-エタノン、{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-(3-メチル-チオフェン-2-イル)-メタノン、(1H-インドール-2-イル)-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-メタノン、2-メチルアミノ-1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-エタノン、シクロプロピル-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-メタノン、1-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-ブタン-1-オン、{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-(3-トリフルオロメトキシ-フェニル)-メタノン、3-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボニル}-ベンゾニトリル、9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカン-3-カルボン酸エチルエステル、メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-[3-(2,2,2-トリフルオロ-エタンスルホニル)-3-アザ-スピロ[5.5]ウンデカ-9-イル]-アミン、3-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-3-オキソ-プロピオニトリル、ベンゾ[b]チオフェン-2-イル-{9-[メチル-(7H-ピロロ[2,3-d]ピリミジン-4-イル)-アミノ]-3-アザ-スピロ[5.5]ウンデカ-3-イル}-メタノン、tert-ブチル9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキシレート、2-メトキシ-1-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)エタン-1-オン、1-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-フェノキシエタン-1-オン、2,2,2-トリフルオロエチル9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキシレート、N-(3-メトキシ-1,2,4-チアジアゾール-5-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-N-(2,2,2-トリフルオロエチル)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-メチル-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N,N-ジエチル-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-スルホンアミド、4-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボニル)ベンゼンスルホンアミド、3-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-3-オキソプロパン-1-スルホンアミド、3-フルオロ-5-(2-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-オキソエトキシ)ベンゾニトリル、4-(2-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-オキソエトキシ)ベンゾニトリル、3-(2-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-オキソエトキシ)ベンゾニトリル、2-フルオロ-4-(2-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-オキソエトキシ)ベンゾニトリル、2,3-ジフルオロ-4-(2-(9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-イル)-2-オキソエトキシ)ベンゾニトリル、N-(4-メトキシフェニル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、
N-(3-メトキシフェニル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(4-シアノフェニル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(3-シアノフェニル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(6-シアノピリジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(6-メトキシピリジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-シアノピリジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-N-(5-メチルチアゾール-2-イル)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-N-(1-メチル-1H-ピラゾール-3-イル)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-N-(5-メチルピラジン-2-イル)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-メトキシピラジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-メトキシピリジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-フルオロチアゾール-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-クロロチアゾール-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、N-(5-シアノチアゾール-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-N-(チアゾール-2-イル)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミド、及びN-(5-メトキシチアゾロ[5,4-b]ピリジン-2-イル)-9-(メチル(7H-ピロロ[2,3-d]ピリミジン-4-イル)アミノ)-3-アザスピロ[5.5]ウンデカン-3-カルボキサミドからなる群から選択される、請求項1に記載の一般式(I)の化合物。 The compound is 2-fluoro-4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzo. Nitrile, 3- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) -3-oxopropanenitrile, 2-Hydroxy-1- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) etanone, 1-( 6- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) Etanone, 1- (6- (Methyl (7H-) Pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) propan-1-one, N- (2- (ethylsulfonyl) -2-azaspiro [3.3] Heptane-6-yl) -N-methyl-7H-pyrrolo [2,3-d] pyrimidine-4-amine, methyl 6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-) 4-yl) amino) -2-azaspiro [3.3] heptane-2-carboxylate, ethyl 6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carboxylate, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl ) (Ppyridine-3-yl) methanone, 4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl ) -4-oxobutanenitrile, 3- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzo Nitrile, 4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) cyclohexanone, (6- (methyl) (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) (3- (trifluoromethyl) phenyl) methanone, 3-fluoro- 4- (6- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-Azaspiro [3.3] heptane-2-carbonyl) benzonitrile, 4- (2- (6-(methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2- Azaspiro [3.3] heptane-2-yl) -2-oxoethyl) benzonitrile , ( 6-(methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3] .3] Heptane-2-yl) (3- (trifluoromethoxy) phenyl) metanone, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [ 3.3] Heptane-2-yl) (pyrazine-2-yl) methanone, 1-(6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [ 3.3] Heptane-2-carbonyl) cyclopropanecarbonitrile, benzo [b] thiophen-2-yl (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2 -Azaspiro [3.3] heptane-2-yl) metanone, 4,4,4-trifluoro-1- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-Azaspiro [3.3] heptane-2-yl) butane-1-one, benzo [b] thiophen-3-yl (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-) Il) Amino) -2-azaspiro [3.3] heptane-2-yl) methanone, 2- (1H-indole-3-yl) -1- (6- (methyl (7H-pyrrolo [2,3-d]) ] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) ethenone, (4-methoxyphenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-) 4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (4-chlorophenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl)) Amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (4-ethynylphenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino)- 2-Azaspiro [3.3] heptane-2-yl) metanone, (4-fluorophenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] Heptane-2-yl) Metanone, (6- (Methyl (7H-Pyrimoli] 2,3-d] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) (3-methylthiophen-2-yl) methanone, (6- (methyl (7H-pyrrolo) [2,3-d] Pyrimidine-4-yl) Amino) -2-azaspiro [3.3] Heptane-2-yl) (6-Methylpyrazine-2-yl) Metanone, (1H-Indol-2-yl) ) (6- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (6- (methyl (7H-) Pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) (4- (trifluoromethyl) phenyl) metanone, (5-chloropyridine-2) -Il) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, N- (3-chlorophenyl) ) -6- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carboxamide, 2-methyl-4- (6-( Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzonitrile, 5- (6- (methyl (7H-pyrrolo [7H-pyrrolo [] 2,3-d] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) picorinonitrile, 2-chloro-4- (6- (methyl (7H-pyrrolo [2]) , 3-d] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzonitrile, 3-chloro-4- (6- (methyl (7H-pyrrolo [2,3]) -D] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzonitrile, (4-iodophenyl) (6- (methyl (7H-pyrrolo [2,3-d]) ] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (4-cyclopropylphenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin) -4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (4-ethynyl-3-methylphenyl) (6- (methyl (7H-pyrrolo [2,3-d]] Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2- Il) methanone, (4-ethynyl-2-fluorophenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2 -Il) methanone, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) (4- (prop-) 1-in-1-yl) phenyl) methanone, (2-chloro-4-ethynylphenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] Heptane-2-yl) methanone, 3-methyl-4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3. 3] Heptane-2-carbonyl) benzonitrile, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) (1H-pyrazole-3-yl) metanone, (3-chloro-4-ethynylphenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [ 3.3] Heptane-2-yl) methanone, (4-ethynyl-3-fluorophenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl) metanone, (5-ethynylpyridine-2-yl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2- Azaspiro [3.3] heptane-2-yl) metanone, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2 -Il) (1-methyl-1H-benzo [d] imidazole-5-yl) methanone, (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] Heptane-2-yl) (1-methyl-1H-pyrazole-3-yl) methanone, 2,5-difluoro-4- (6- (methyl (7H-pyrrolo [2,3-d]) Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzonitrile, 2,6-difluoro-4- (6- (methyl (7H-pyrrolo [2,3-d]) Pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzoni Trill, 2,3-difluoro-4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) benzo Nitrile, 5-fluoro-2-methyl-4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl ) Benzonitrile, (2,3-difluorophenyl) (6- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -2-azaspiro [3.3] heptane-2-yl ) Metanone, 3,5-difluoro-4- (6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [3.3] heptane-2-carbonyl) Benzonitrile, 2-fluoro-5-{6- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -2-aza-spiro [3.3] heptane-2- Carbonyl} -benzonitrile, 3-fluoro-5-{6- [methyl- (7H-pyrrolo [2,3-d] pyrimidine-4-yl) -amino] -2-aza-spiro [3.3] heptane -2-carbonyl} -benzonitrile, 2,5-difluoro-4- {6- [methyl- (7H-pyrrolo [2,3-d] pyrimidine-4-yl) -amino] -2-aza-spiro [ 3.3] Heptane-2-carbonyl} -benzonitrile, 2,3-dichloro-4- {6- [methyl- (7H-pyrrolo [2,3-d] pyrimidine-4-yl) -amino] -2 -Aza-spiro [3.3] heptane-2-carbonyl} -benzonitrile, 2,3-difluoro-5- {6- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -Amino] -2-aza-spiro [3.3] heptane-2-carbonyl} -benzonitrile, 3,4-difluoro-5-{6- [methyl- (7H-pyrrolo [2,3-d] pyrimidine -4-yl) -amino] -2-aza-spiri [3.3] heptane-2-carbonyl} -benzonitrile, (4-ethynyl-3-fluoro-phenyl)-{6- [-[(methyl-) d 3 )-(7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -2-aza-spiro [3.3] hept-2-yl} -methanone, 2-fluoro-4- {6-[-[(Methyl-d 3 )-(7H-pyrrolo [2,3-d] pyrimidine-4-yl) -amino] -2-aza- Spiro [3.3] heptane-2-carbonyl} -benzonitrile,
(3-Fluoro-4-prop-1-inyl-phenyl)-{6-[-[(methyl-d 3 )-(7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino]- 2-aza-spiro [3.3] hept-2-yl} -methanone, 2,3-difluoro-4- {6-[(methyl-d 3 )-(7H-pyrrolo [2,3-d] pyrimidin) -4-yl) -amino] -2-aza-spiro [3.3] heptane-2-carbonyl} -benzonitrile, [4- (1-methyl-1H-pyrazole-3-yl) -phenyl]-{ 6- [Methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -2-aza-spiro [3.3] hept-2-yl} -methanone, (1-cyclopropyl) -1H-pyrazole-4-yl)-{6- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -2-aza-spiro [3.3] hept-2 -Il} -methanone, 2,6-difluoro-3- {6- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -2-aza-spiro [3.3] ] Heptane-2-carbonyl} -benzonitrile, N- (3-methoxy-1,2,4-thiadiazol-5-yl) -6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-) Il) amino) -2-azaspiro [3.3] heptane-2-carboxamide, 4-(6- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -2-azaspiro [ 3.3] Heptane-2-carbonyl) benzenesulfonamide, 1- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5] .5] Undeca-3-yl} -etanone, (3-ethanesulfonyl-3-aza-spiro [5.5] undeca-9-yl) -methyl- (7H-pyrrolo [2,3-d] pyrimidin- 4-yl) -amine, 2-hydroxy-1-{9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] Undeca-3-yl} -etanone, 1- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca- 3-Il} -Propane-1-one, Methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl)-[3- (2,2,2-trifluoro-ethyl) -3-aza -Spiro [5.5] c Ndec-9-yl] -amine, {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undec-3- Il} -pyridine-3-yl-methanone, 4-{9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] Undeca-3-yl} -4-oxo-butyronitrile, 4-{9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5. 5] Undecane-3-carbonyl} -cyclohexanone, {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca- 3-Il}-(3-trifluoromethyl-phenyl) -methanone, 3-fluoro-4-{9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino]- 3-aza-spiro [5.5] undecane-3-carbonyl} -benzonitrile, 4- (2- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino ] -3-aza-spiro [5.5] undeca-3-yl} -2-oxo-ethyl) -benzonitrile, 2 -fluoro-4- {9- [methyl- (7H-pyrrolo [2,3-] d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undecane-3-carbonyl} -benzonitrile, {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin) -4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -pyrazine-2-yl-methanone, 1- {9- [methyl- (7H-pyrrolo [2,3] -D] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undecane-3-carbonyl} -cyclopropanecarbonitrile, (6-methyl-pyrazin-2-yl)-{9- [Methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -methanone, 4,4,4-tri Fluoro-1- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undec-3-yl} -butane- 1-one, benzo [b] thiophen-3-yl- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] ] Undeca -3-Il} -methanone, 2- (1H-indole-3-yl) -1-{9- [methyl- (7H-pyrrolo [2,3-d] pyrimidine-4-yl) -amino] -3 -Aza-spiro [5.5] undeca-3-yl} -etanone, {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] Undeca-3-yl}-(3-methyl-thiophen-2-yl) -methanone, (1H-indole-2-yl)-{9- [methyl- (7H-pyrrolo [2,3] -D] Pyrimidine-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -methanone, 2 -methylamino-1- {9- [methyl- (7H-pyrrolo) [2,3-d] Pyrimidine-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -etanone , cyclopropyl- {9- [methyl- (7H-) Pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -methanone, 1- {9- [methyl- (7H-pyrrolo [7H-pyrrolo [7H-pyrrolo] 2,3-d] Pyrimidine-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -butane-1-one, {9- [methyl- (7H-pyrrolo [7H-pyrrolo] 2,3-d] Pyrimidine-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl}-(3-trifluoromethoxy-phenyl) -methanone, 3- {9- [Methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undecane-3-carbonyl} -benzonitrile, 9- [methyl- ( 7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undecane-3-carboxylic acid ethyl ester, methyl- (7H-pyrrolo [2,3-yl) d] Pyrimidine-4-yl)-[3- (2,2,2-trifluoro-ethanesulfonyl) -3-aza-spiro [5.5] undec-9-yl] -amine, 3- {9- [Methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca-3-yl} -3-oxo-propionitrile, benzo [B] Thiophen-2-yl- {9- [methyl- (7H-pyrrolo [2,3-d] pyrimidin-4-yl) -amino] -3-aza-spiro [5.5] undeca-3- Il} -methanone, tert-butyl 9- (me Chill (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxylate, 2-methoxy-1- (9- (methyl (7H-) Pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-yl) ethane-1-one, 1- (9- (methyl (7H-pyrrolo [2]) , 3-d] Pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-yl) -2-phenoxyetane-1-one, 2,2,2-trifluoroethyl 9- ( Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxylate, N- (3-methoxy-1,2,4-thiaidazole) -5-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, 9- (methyl (7H) -Pyrrolo [2,3-d] pyrimidin-4-yl) amino) -N- (2,2,2-trifluoroethyl) -3-azaspiro [5.5] undecane-3-carboxamide, N-methyl- 9- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N, N-diethyl-9- (methyl (7H) -Pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-sulfonamide, 4- (9- (methyl (7H-pyrrolo [2,3-d)) ] Pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carbonyl) benzenesulfonamide, 3- (9- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-d]) Il) amino) -3-azaspiro [5.5] undecane-3-yl) -3-oxopropan-1-sulfonamide, 3-fluoro-5- (2- (9- (methyl (7H-pyrrolo [2]) , 3-d] Pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-yl) -2-oxoethoxy) benzonitrile, 4- (2- (9- (methyl (7H-) Pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-yl) -2-oxoethoxy) benzonitrile, 3- (2- (9- (methyl) (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-aza Spiro [5.5] undecane-3-yl) -2-oxoethoxy) benzonitrile, 2-fluoro-4- (2- (9- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-) Il) amino) -3-azaspiro [5.5] undecane-3-yl) -2-oxoethoxy) benzonitrile, 2,3-difluoro-4- (2- (9- (methyl (7H-pyrrolo [2]) , 3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-yl) -2-oxoethoxy) benzonitrile, N- (4-methoxyphenyl) -9- (methyl) (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide,
N- (3-methoxyphenyl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- ( 4-cyanophenyl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- (3-cyano) Phenyl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- (6-cyanopyridine-2) -Il) -9- (Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- (6-methoxypyridine- 2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- (5-cyanopyridine) -2-Il) -9- (Methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-Azaspiro [5.5] Undecane-3-carboxamide, 9- (Methyl (7H) -Pyrrolo [2,3-d] pyrimidin-4-yl) amino) -N- (5-methylthiazole-2-yl) -3-azaspiro [5.5] undecane-3-carboxamide, 9- (methyl (5-methyl) 7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -N- (1-methyl-1H-pyrazol-3-yl) -3-azaspiro [5.5] undecane-3-carboxamide, 9 -(Methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -N- (5-methylpyrazine-2-yl) -3-azaspiro [5.5] undecane-3-carboxamide, N- (5-methoxypyrazine-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide , N- (5-methoxypyridine-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3- Carboxamide, N- (5-fluorothiazole-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3 -Carboxamide, N- (5-Chlo) Rotiazole-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, N- (5-) Cyanothiazole-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -3-azaspiro [5.5] undecane-3-carboxamide, 9- (methyl) (7H-pyrrolo [2,3-d] pyrimidin-4-yl) amino) -N- (thiazole-2-yl) -3-azaspiro [5.5] undecane-3-carboxamide, and N- (5-) Methoxythiazolo [5,4-b] pyridine-2-yl) -9- (methyl (7H-pyrrolo [2,3-d] pyrimidine-4-yl) amino) -3-azaspiro [5.5] undecane The compound of the general formula (I) according to claim 1, selected from the group consisting of -3-carboxamide.
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US (1) | US11365188B2 (en) |
EP (1) | EP3768272A4 (en) |
JP (1) | JP7462951B2 (en) |
CN (1) | CN111936144B (en) |
AU (1) | AU2019237991A1 (en) |
CA (1) | CA3093706A1 (en) |
WO (1) | WO2019182924A1 (en) |
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KR20210019607A (en) | 2016-06-07 | 2021-02-22 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Novel heterocyclic derivatives useful as shp2 inhibitors |
WO2018172984A1 (en) | 2017-03-23 | 2018-09-27 | Jacobio Pharmaceuticals Co., Ltd. | Novel heterocyclic derivatives useful as shp2 inhibitors |
BR112021008742A2 (en) * | 2018-11-05 | 2021-08-10 | Avista Pharma Solutions, Inc. | chemical compounds |
WO2020154350A1 (en) | 2019-01-23 | 2020-07-30 | Theravance Biopharma R&D Ip, Llc | Imidazo[1,5-a]pyridine, 1,2,4-triazolo[4,3-a]pyridine and imidazo[1,5-a]pyrazine as jak inhibitors |
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DK2796460T3 (en) * | 2011-12-21 | 2018-08-27 | Jiangsu Hengrui Medicine Co | SEXUAL PYRROL HETEROARYL RING DERIVATIVES, METHOD OF PREPARATION AND MEDICAL APPLICATIONS THEREOF |
PT3077395T (en) * | 2013-12-05 | 2018-01-03 | Pfizer | Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl and pyrrolo[2,3-d]pyridinyl acrylamides |
CN106661039B (en) | 2014-02-28 | 2019-09-13 | 林伯士拉克许米公司 | 2 (TYK2) inhibitor of tyrosine protein matter kinases and its purposes |
ES2750655T3 (en) * | 2014-08-12 | 2020-03-26 | Pfizer | Pyrrolo [2,3-d] pyrimidine derivatives useful to inhibit Janus kinase |
CA2979425C (en) * | 2015-01-20 | 2020-04-14 | Wuxi Fortune Pharmaceutical Co., Ltd | Jak inhibitor |
WO2018169700A1 (en) * | 2017-03-14 | 2018-09-20 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
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2019
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- 2019-03-18 US US16/979,455 patent/US11365188B2/en active Active
- 2019-03-18 CN CN201980020463.5A patent/CN111936144B/en active Active
- 2019-03-18 AU AU2019237991A patent/AU2019237991A1/en active Pending
- 2019-03-18 CA CA3093706A patent/CA3093706A1/en active Pending
- 2019-03-18 EP EP19770607.0A patent/EP3768272A4/en active Pending
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