JP2013533868A - タンパク質チロシンキナーゼ阻害剤としての新規ホモピペラジン誘導体およびそれらの医薬使用 - Google Patents

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Publication number

JP2013533868A

JP2013533868A JP2013517018A JP2013517018A JP2013533868A JP 2013533868 A JP2013533868 A JP 2013533868A JP 2013517018 A JP2013517018 A JP 2013517018A JP 2013517018 A JP2013517018 A JP 2013517018A JP 2013533868 A JP2013533868 A JP 2013533868A

Authority

JP

Japan

Prior art keywords

diazaspiro

pyrrolo

pyrimidin

nonan

methanone

Prior art date

2010-07-09

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.)

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• 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract 2
• 150000004050 homopiperazines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 207
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 150000003839 salts Chemical class 0.000 claims abstract description 12
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 10
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 9
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 9
• 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 9
• 201000011510 cancer Diseases 0.000 claims abstract description 9
• 239000012453 solvate Substances 0.000 claims abstract description 9
• 102000042838 JAK family Human genes 0.000 claims abstract description 8
• 108091082332 JAK family Proteins 0.000 claims abstract description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
• 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 7
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 7
• 208000006673 asthma Diseases 0.000 claims abstract description 7
• 208000010928 autoimmune thyroid disease Diseases 0.000 claims abstract description 7
• 208000032839 leukemia Diseases 0.000 claims abstract description 7
• 206010025135 lupus erythematosus Diseases 0.000 claims abstract description 7
• 208000002780 macular degeneration Diseases 0.000 claims abstract description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 7
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 6
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 6
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 6
• 208000022873 Ocular disease Diseases 0.000 claims abstract 3
• -1 cyano, hydroxy Chemical group 0.000 claims description 307
• 125000000217 alkyl group Chemical group 0.000 claims description 105
• 125000000623 heterocyclic group Chemical group 0.000 claims description 91
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 71
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 68
• 125000003118 aryl group Chemical group 0.000 claims description 58
• 125000004043 oxo group Chemical group O=* 0.000 claims description 54
• 229910052736 halogen Inorganic materials 0.000 claims description 53
• 150000002367 halogens Chemical class 0.000 claims description 53
• 125000001072 heteroaryl group Chemical group 0.000 claims description 50
• 239000001257 hydrogen Substances 0.000 claims description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims description 46
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 42
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 35
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 34
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 33
• 150000002431 hydrogen Chemical class 0.000 claims description 32
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
• 125000003342 alkenyl group Chemical group 0.000 claims description 25
• 238000000034 method Methods 0.000 claims description 24
• 125000000304 alkynyl group Chemical group 0.000 claims description 21
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 21
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 19
• 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 17
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 17
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 17
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 17
• 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims description 15
• 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 15
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 15
• 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 230000002265 prevention Effects 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 208000015181 infectious disease Diseases 0.000 claims description 11
• 230000002458 infectious effect Effects 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 10
• 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 10
• 125000005324 aryloxy alkyloxy group Chemical group 0.000 claims description 10
• 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 10
• 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 10
• 210000000987 immune system Anatomy 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000004946 alkenylalkyl group Chemical group 0.000 claims description 9
• 125000005038 alkynylalkyl group Chemical group 0.000 claims description 9
• 150000001408 amides Chemical class 0.000 claims description 9
• 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 9
• 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 230000000694 effects Effects 0.000 claims description 9
• 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 9
• 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 201000004624 Dermatitis Diseases 0.000 claims description 7
• 125000004104 aryloxy group Chemical group 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 208000030533 eye disease Diseases 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 208000017520 skin disease Diseases 0.000 claims description 7
• DNLYKIBLZSHIRI-UHFFFAOYSA-N (5-methyl-1h-pyrazol-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1N=C(C)C=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 DNLYKIBLZSHIRI-UHFFFAOYSA-N 0.000 claims description 6
• HIAZHBYRJBITLA-UHFFFAOYSA-N 1h-imidazol-5-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound C=1NC=NC=1C(=O)N(C1)CCN(C=2C=3C=CNC=3N=CN=2)CC21CC2 HIAZHBYRJBITLA-UHFFFAOYSA-N 0.000 claims description 6
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 6
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
• 125000002837 carbocyclic group Chemical group 0.000 claims description 6
• 230000001684 chronic effect Effects 0.000 claims description 6
• 206010023332 keratitis Diseases 0.000 claims description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 238000002560 therapeutic procedure Methods 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• ZKZWUNHNOIHYGY-UHFFFAOYSA-N 1h-imidazol-5-yl-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C=1NC=NC=1C(=O)N1CCCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 ZKZWUNHNOIHYGY-UHFFFAOYSA-N 0.000 claims description 5
• 208000010668 atopic eczema Diseases 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• VIJCSROECFZLKA-UHFFFAOYSA-N (5-methyl-1h-pyrazol-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound N1N=C(C)C=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 VIJCSROECFZLKA-UHFFFAOYSA-N 0.000 claims description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
• 206010040799 Skin atrophy Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• DAQRPXKNDPOIKK-UHFFFAOYSA-N n-(2-cyanoethyl)-n-methyl-5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonane-8-carboxamide Chemical compound C1N(C(=O)N(CCC#N)C)CCN(C=2C=3C=CNC=3N=CN=2)CC21CC2 DAQRPXKNDPOIKK-UHFFFAOYSA-N 0.000 claims description 4
• 125000002971 oxazolyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 230000009759 skin aging Effects 0.000 claims description 4
• IDVKHQGJCUQGDA-UHFFFAOYSA-N (2,5-dimethylpyrazol-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CN1N=C(C)C=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 IDVKHQGJCUQGDA-UHFFFAOYSA-N 0.000 claims description 3
• AMUAFMVUIRXNNS-UHFFFAOYSA-N (2-methoxypyridin-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound COC1=NC=CC=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 AMUAFMVUIRXNNS-UHFFFAOYSA-N 0.000 claims description 3
• CZLBVCVCIKFBAJ-UHFFFAOYSA-N (2-methylpyridin-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CC1=NC=CC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 CZLBVCVCIKFBAJ-UHFFFAOYSA-N 0.000 claims description 3
• MLBGYNJQRALAPI-UHFFFAOYSA-N (3,5-dimethoxyphenyl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound COC1=CC(OC)=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 MLBGYNJQRALAPI-UHFFFAOYSA-N 0.000 claims description 3
• GZBVZGCHDBQKDP-UHFFFAOYSA-N (3-chlorophenyl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound ClC1=CC=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 GZBVZGCHDBQKDP-UHFFFAOYSA-N 0.000 claims description 3
• CKPWLXQDULJNMK-UHFFFAOYSA-N (3-chlorophenyl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound ClC1=CC=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1 CKPWLXQDULJNMK-UHFFFAOYSA-N 0.000 claims description 3
• SQWISDWIVXFEKR-UHFFFAOYSA-N (3-ethyl-4,5-dihydro-1,2-oxazol-5-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C1C(CC)=NOC1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 SQWISDWIVXFEKR-UHFFFAOYSA-N 0.000 claims description 3
• SPAAIIIEXZELRQ-UHFFFAOYSA-N (3-methyl-1,2-oxazol-4-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CC1=NOC=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 SPAAIIIEXZELRQ-UHFFFAOYSA-N 0.000 claims description 3
• CPYRGZVNRRNJIU-UHFFFAOYSA-N (3-methyl-1,2-oxazol-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CC1=NOC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 CPYRGZVNRRNJIU-UHFFFAOYSA-N 0.000 claims description 3
• HZCASOOJBJYHQL-UHFFFAOYSA-N (3-methylimidazol-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CN1C=NC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 HZCASOOJBJYHQL-UHFFFAOYSA-N 0.000 claims description 3
• GJDMLYCUSJVERE-UHFFFAOYSA-N (3-methylpyrazin-2-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CC1=NC=CN=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 GJDMLYCUSJVERE-UHFFFAOYSA-N 0.000 claims description 3
• QOYZGVMSDVXFLE-UHFFFAOYSA-N (3-methylpyridin-4-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CC1=CN=CC=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 QOYZGVMSDVXFLE-UHFFFAOYSA-N 0.000 claims description 3
• URSLSNQGIZMBSX-UHFFFAOYSA-N (3-methylpyridin-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CC1=CN=CC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 URSLSNQGIZMBSX-UHFFFAOYSA-N 0.000 claims description 3
• CWEMDCYMQJBEIZ-UHFFFAOYSA-N (4-amino-1,2,5-oxadiazol-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound NC1=NON=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 CWEMDCYMQJBEIZ-UHFFFAOYSA-N 0.000 claims description 3
• FUYSRNWXOSZVMS-UHFFFAOYSA-N (4-chlorophenyl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 FUYSRNWXOSZVMS-UHFFFAOYSA-N 0.000 claims description 3
• MKNYWGXTYRTGPU-UHFFFAOYSA-N (4-chlorophenyl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 MKNYWGXTYRTGPU-UHFFFAOYSA-N 0.000 claims description 3
• UAPZYDKCISXBMD-UHFFFAOYSA-N (4-fluorophenyl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 UAPZYDKCISXBMD-UHFFFAOYSA-N 0.000 claims description 3
• UKYVCXCVEOAAPZ-UHFFFAOYSA-N (4-methyl-1,3-oxazol-5-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1=COC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1C UKYVCXCVEOAAPZ-UHFFFAOYSA-N 0.000 claims description 3
• NFOADZYWXJCNPU-UHFFFAOYSA-N (4-methylpyridin-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CC1=CC=NC=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 NFOADZYWXJCNPU-UHFFFAOYSA-N 0.000 claims description 3
• UOIFQHVXTCWLIZ-UHFFFAOYSA-N (4-methylpyridin-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CC1=CC=NC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 UOIFQHVXTCWLIZ-UHFFFAOYSA-N 0.000 claims description 3
• GADMYKNGDQCNQJ-UHFFFAOYSA-N (4-methylthiadiazol-5-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound N1=NSC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1C GADMYKNGDQCNQJ-UHFFFAOYSA-N 0.000 claims description 3
• YPDWYVPPLASDMY-UHFFFAOYSA-N (4-methylthiadiazol-5-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1=NSC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1C YPDWYVPPLASDMY-UHFFFAOYSA-N 0.000 claims description 3
• AFVLIVYQEFQFNS-UHFFFAOYSA-N (5-methyl-1,2-oxazol-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound O1C(C)=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=N1 AFVLIVYQEFQFNS-UHFFFAOYSA-N 0.000 claims description 3
• MKJLTHSGTKCEFT-UHFFFAOYSA-N (5-methyl-1,2-oxazol-4-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound O1N=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1C MKJLTHSGTKCEFT-UHFFFAOYSA-N 0.000 claims description 3
• JAHIKQHAYSKNEB-UHFFFAOYSA-N (5-methyl-1,2-oxazol-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound O1N=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1C JAHIKQHAYSKNEB-UHFFFAOYSA-N 0.000 claims description 3
• VIZKLZUPUCRISP-UHFFFAOYSA-N (5-methyl-1,2-thiazol-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound S1N=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1C VIZKLZUPUCRISP-UHFFFAOYSA-N 0.000 claims description 3
• YUVRQNUTVZLDCG-UHFFFAOYSA-N (5-methyl-1,3,4-oxadiazol-2-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound O1C(C)=NN=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 YUVRQNUTVZLDCG-UHFFFAOYSA-N 0.000 claims description 3
• FLFJBXFMMOXOMS-UHFFFAOYSA-N (5-methyl-1,3-thiazol-2-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound S1C(C)=CN=C1C(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 FLFJBXFMMOXOMS-UHFFFAOYSA-N 0.000 claims description 3
• VCCRPPGFLCLCBR-UHFFFAOYSA-N (5-methyl-1h-1,2,4-triazol-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1C(C)=NN=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 VCCRPPGFLCLCBR-UHFFFAOYSA-N 0.000 claims description 3
• NQHGJYINHULTFT-UHFFFAOYSA-N (5-methyl-1h-pyrazol-4-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1N=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1C NQHGJYINHULTFT-UHFFFAOYSA-N 0.000 claims description 3
• FTKXKIZVGDKCKA-UHFFFAOYSA-N (5-methylpyrazin-2-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C1=NC(C)=CN=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 FTKXKIZVGDKCKA-UHFFFAOYSA-N 0.000 claims description 3
• ZJYUSYKZJXRKQX-UHFFFAOYSA-N (6-methylpyrazin-2-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CC1=CN=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=N1 ZJYUSYKZJXRKQX-UHFFFAOYSA-N 0.000 claims description 3
• IAEWNUXNTNQGLH-UHFFFAOYSA-N (6-methylpyrazin-2-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound CC1=CN=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=N1 IAEWNUXNTNQGLH-UHFFFAOYSA-N 0.000 claims description 3
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 3
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• KAKXGIASPNGBOK-UHFFFAOYSA-N 1-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]-2-thiophen-2-ylethanone Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)CN1C(=O)CC1=CC=CS1 KAKXGIASPNGBOK-UHFFFAOYSA-N 0.000 claims description 3
• LXSLTLFBEUARIJ-UHFFFAOYSA-N 1-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.6]nonane-4-carbonyl]cyclopropane-1-carbonitrile Chemical compound C1CC1(C#N)C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CCC11CC1 LXSLTLFBEUARIJ-UHFFFAOYSA-N 0.000 claims description 3
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• JZAYAIHDMLAIJR-UHFFFAOYSA-N 1-benzothiophen-2-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound C=1C2=CC=CC=C2SC=1C(=O)N(C1)CCN(C=2C=3C=CNC=3N=CN=2)CC21CC2 JZAYAIHDMLAIJR-UHFFFAOYSA-N 0.000 claims description 3
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• KVXOVHTUZOWJSY-UHFFFAOYSA-N 1h-pyrazol-5-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound C1=CNN=C1C(=O)N(C1)CCN(C=2C=3C=CNC=3N=CN=2)CC21CC2 KVXOVHTUZOWJSY-UHFFFAOYSA-N 0.000 claims description 3
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• OZIAQZHJWQVSBA-UHFFFAOYSA-N 2-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]ethanone Chemical compound CC1=NOC(C)=C1CC(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 OZIAQZHJWQVSBA-UHFFFAOYSA-N 0.000 claims description 3
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• LBHYKFUVXUEBQC-UHFFFAOYSA-N 2-fluoro-4-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonane-8-carbonyl]benzonitrile Chemical compound C1=C(C#N)C(F)=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 LBHYKFUVXUEBQC-UHFFFAOYSA-N 0.000 claims description 3
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• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
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• ARRIGLQGDRKGFL-UHFFFAOYSA-N (4-propylthiophen-2-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound CCCC1=CSC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 ARRIGLQGDRKGFL-UHFFFAOYSA-N 0.000 claims description 2
• GHBSEPZTCBOPRV-UHFFFAOYSA-N (5-chloro-1h-1,2,4-triazol-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound N1C(Cl)=NC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=N1 GHBSEPZTCBOPRV-UHFFFAOYSA-N 0.000 claims description 2
• YUYUHOLHMDENDF-UHFFFAOYSA-N (5-chloro-1h-1,2,4-triazol-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound N1C(Cl)=NC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=N1 YUYUHOLHMDENDF-UHFFFAOYSA-N 0.000 claims description 2
• QNPUUVINTOITBB-UHFFFAOYSA-N (5-fluoropyridin-3-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound FC1=CN=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 QNPUUVINTOITBB-UHFFFAOYSA-N 0.000 claims description 2
• XLJZXACOKNMACD-UHFFFAOYSA-N (5-fluoropyridin-3-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound FC1=CN=CC(C(=O)N2C3(CC3)CN(CCC2)C=2C=3C=CNC=3N=CN=2)=C1 XLJZXACOKNMACD-UHFFFAOYSA-N 0.000 claims description 2
• CDSRJCPKPLSCQX-UHFFFAOYSA-N (5-methyl-1,3,4-oxadiazol-2-yl)-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound O1C(C)=NN=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CCC1 CDSRJCPKPLSCQX-UHFFFAOYSA-N 0.000 claims description 2
• DGALRVDETBRHJK-UHFFFAOYSA-N (5-methyl-1h-pyrazol-4-yl)-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound N1N=CC(C(=O)N2CC3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1C DGALRVDETBRHJK-UHFFFAOYSA-N 0.000 claims description 2
• DPSYUZJOMWRBDG-UHFFFAOYSA-N 1,2,5-oxadiazol-3-yl-[8-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,8-diazaspiro[2.6]nonan-4-yl]methanone Chemical compound C1=NON=C1C(=O)N1CCCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 DPSYUZJOMWRBDG-UHFFFAOYSA-N 0.000 claims description 2
• CKTFFKKQHTYERD-UHFFFAOYSA-N 1,2-oxazol-5-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]methanone Chemical compound C=1C=NOC=1C(=O)N(C1)CCN(C=2C=3C=CNC=3N=CN=2)CC21CC2 CKTFFKKQHTYERD-UHFFFAOYSA-N 0.000 claims description 2
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 2
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• YQYHIALRGBIGKX-UHFFFAOYSA-N 1-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-5,8-diazaspiro[2.6]nonan-8-yl]-2-[4-(trifluoromethyl)phenyl]ethanone Chemical compound C1=CC(C(F)(F)F)=CC=C1CC(=O)N1CC2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 YQYHIALRGBIGKX-UHFFFAOYSA-N 0.000 claims description 2
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