CA2767079A1 - Heterocyclic compounds as jak receptor and protein tyrosine kinase inhibitors - Google Patents

Info

Publication number

CA2767079A1

CA2767079A1 CA2767079A CA2767079A CA2767079A1 CA 2767079 A1 CA2767079 A1 CA 2767079A1 CA 2767079 A CA2767079 A CA 2767079A CA 2767079 A CA2767079 A CA 2767079A CA 2767079 A1 CA2767079 A1 CA 2767079A1

Authority

CA

Canada

Prior art keywords

pyrrolo

pyrimidin

diaza

oct

spiro

Prior art date

2009-07-08

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract description 3
• 102000005962 receptors Human genes 0.000 title description 10
• 150000002391 heterocyclic compounds Chemical class 0.000 title description 4
• 108091008598 receptor tyrosine kinases Proteins 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
• 201000010099 disease Diseases 0.000 claims abstract description 15
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
• 201000011510 cancer Diseases 0.000 claims abstract description 12
• 150000003839 salts Chemical class 0.000 claims abstract description 11
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 10
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 9
• 102000042838 JAK family Human genes 0.000 claims abstract description 9
• 108091082332 JAK family Proteins 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
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 9
• 239000012453 solvate Substances 0.000 claims abstract description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 7
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 7
• 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 7
• 241001303601 Rosacea Species 0.000 claims abstract description 7
• 208000024799 Thyroid disease Diseases 0.000 claims abstract description 7
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 7
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 7
• 208000006673 asthma Diseases 0.000 claims abstract description 7
• 230000001363 autoimmune Effects 0.000 claims abstract description 7
• 208000030533 eye 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
• 201000004700 rosacea Diseases 0.000 claims abstract description 7
• 150000004677 hydrates Chemical class 0.000 claims abstract description 3
• -1 cyano, hydroxy Chemical group 0.000 claims description 171
• 229910052739 hydrogen Inorganic materials 0.000 claims description 78
• 239000001257 hydrogen Substances 0.000 claims description 71
• 125000000623 heterocyclic group Chemical group 0.000 claims description 69
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 63
• 125000000217 alkyl group Chemical group 0.000 claims description 61
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 61
• 229910052736 halogen Inorganic materials 0.000 claims description 46
• 150000002367 halogens Chemical group 0.000 claims description 46
• 125000004432 carbon atom Chemical group C* 0.000 claims description 41
• 239000000203 mixture Substances 0.000 claims description 40
• 125000001072 heteroaryl group Chemical group 0.000 claims description 39
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 38
• 125000003342 alkenyl group Chemical group 0.000 claims description 37
• 238000000034 method Methods 0.000 claims description 34
• 125000000304 alkynyl group Chemical group 0.000 claims description 33
• 125000003118 aryl group Chemical group 0.000 claims description 33
• 125000004043 oxo group Chemical group O=* 0.000 claims description 32
• 150000002431 hydrogen Chemical group 0.000 claims description 31
• 238000011282 treatment Methods 0.000 claims description 29
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 23
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 125000004104 aryloxy group Chemical group 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 20
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
• 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
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 17
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
• 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 claims description 15
• 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
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 13
• 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 13
• 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 13
• 125000005418 aryl aryl group Chemical group 0.000 claims description 12
• 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 12
• 238000011321 prophylaxis Methods 0.000 claims description 12
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 11
• 208000015181 infectious disease Diseases 0.000 claims description 11
• 230000002458 infectious effect Effects 0.000 claims description 11
• 108091000080 Phosphotransferase Proteins 0.000 claims description 10
• 125000004946 alkenylalkyl group Chemical group 0.000 claims description 10
• 125000005038 alkynylalkyl group Chemical group 0.000 claims description 10
• 125000005018 aryl alkenyl group Chemical group 0.000 claims description 10
• 125000005015 aryl alkynyl group Chemical group 0.000 claims description 10
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 10
• 125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 10
• 230000000694 effects Effects 0.000 claims description 10
• 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 10
• 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 10
• 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 10
• 210000000987 immune system Anatomy 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 102000020233 phosphotransferase Human genes 0.000 claims description 10
• 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 9
• 206010012601 diabetes mellitus Diseases 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical compound OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 7
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
• 206010039705 Scleritis Diseases 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
• 230000001684 chronic effect Effects 0.000 claims description 6
• CIIJBWFCTGDACO-UHFFFAOYSA-N methyl 4-[4-(4-cyanobutanoyl)-4,7-diazaspiro[2.5]octan-7-yl]-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2NC(C(=O)OC)=CC2=C1N(C1)CCN(C(=O)CCCC#N)C21CC2 CIIJBWFCTGDACO-UHFFFAOYSA-N 0.000 claims description 6
• HMNWKHBYIFIILU-UHFFFAOYSA-N n-(2-methylpropyl)-5-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]thiophene-3-sulfonamide Chemical compound CC(C)CNS(=O)(=O)C1=CSC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 HMNWKHBYIFIILU-UHFFFAOYSA-N 0.000 claims description 6
• 208000017520 skin disease Diseases 0.000 claims description 6
• 125000006655 (C3-C8) heteroaryl group Chemical group 0.000 claims description 5
• JHPJYTPUCSEZFG-UHFFFAOYSA-N [7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-(1,2,3,4-tetrahydronaphthalen-1-yl)methanone Chemical compound C1CCC2=CC=CC=C2C1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 JHPJYTPUCSEZFG-UHFFFAOYSA-N 0.000 claims description 5
• 230000001154 acute effect Effects 0.000 claims description 5
• 208000010668 atopic eczema Diseases 0.000 claims description 5
• 102000004169 proteins and genes Human genes 0.000 claims description 5
• 108090000623 proteins and genes Proteins 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 201000004624 Dermatitis Diseases 0.000 claims description 4
• 206010040799 Skin atrophy Diseases 0.000 claims description 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 230000032683 aging Effects 0.000 claims description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
• 230000002757 inflammatory effect Effects 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• FBOHBMDPMVKPSX-UHFFFAOYSA-N tert-butyl 3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 FBOHBMDPMVKPSX-UHFFFAOYSA-N 0.000 claims description 4
• LVQDPLRYZGWXCF-UHFFFAOYSA-N (2-methoxypyridin-3-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound COC1=NC=CC=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 LVQDPLRYZGWXCF-UHFFFAOYSA-N 0.000 claims description 3
• SCIBQICCVMELLP-UHFFFAOYSA-N (3-methyl-4-methylsulfonylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C1=C(S(C)(=O)=O)C(C)=CC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 SCIBQICCVMELLP-UHFFFAOYSA-N 0.000 claims description 3
• DWNDGRNTOKWLMA-UHFFFAOYSA-N (3-methylsulfonylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound CS(=O)(=O)C1=CC=CC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 DWNDGRNTOKWLMA-UHFFFAOYSA-N 0.000 claims description 3
• MZYJPIIHIMBCGC-UHFFFAOYSA-N (3-phenylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 MZYJPIIHIMBCGC-UHFFFAOYSA-N 0.000 claims description 3
• WDIODPMMEWTVCE-UHFFFAOYSA-N (4-cyclopentylsulfonylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C=C(S(=O)(=O)C2CCCC2)C=CC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 WDIODPMMEWTVCE-UHFFFAOYSA-N 0.000 claims description 3
• PLFGLRCMSDYPOV-UHFFFAOYSA-N (4-fluoro-3-methylsulfonylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C1=C(F)C(S(=O)(=O)C)=CC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 PLFGLRCMSDYPOV-UHFFFAOYSA-N 0.000 claims description 3
• DHEHVNZIUYKLJA-UHFFFAOYSA-N (4-methylthiophen-2-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound CC1=CSC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 DHEHVNZIUYKLJA-UHFFFAOYSA-N 0.000 claims description 3
• WYLBYEUHBWQDRU-UHFFFAOYSA-N (4-phenylphenyl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 WYLBYEUHBWQDRU-UHFFFAOYSA-N 0.000 claims description 3
• YSQKHPCRMRWYLK-UHFFFAOYSA-N (4-propan-2-ylsulfonylphenyl)-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound C1=CC(S(=O)(=O)C(C)C)=CC=C1C(=O)N1C2CCC1CN(C=1C=3C=CNC=3N=CN=1)C2 YSQKHPCRMRWYLK-UHFFFAOYSA-N 0.000 claims description 3
• BPPSREOIVHBZJC-UHFFFAOYSA-N (5-fluoro-1h-indol-2-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 BPPSREOIVHBZJC-UHFFFAOYSA-N 0.000 claims description 3
• AJKRNQMEGXEFDL-UHFFFAOYSA-N (5-fluoro-3-methyl-1h-indol-2-yl)-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound N1C2=CC=C(F)C=C2C(C)=C1C(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 AJKRNQMEGXEFDL-UHFFFAOYSA-N 0.000 claims description 3
• KSHJKLUTKFAUTR-UHFFFAOYSA-N (5-fluoro-3-methyl-1h-indol-2-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound N1C2=CC=C(F)C=C2C(C)=C1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 KSHJKLUTKFAUTR-UHFFFAOYSA-N 0.000 claims description 3
• XREQWEOPAPCJDD-UHFFFAOYSA-N (5-methoxythiophen-3-yl)-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound S1C(OC)=CC(C(=O)N2C3CCC2CN(C3)C=2C=3C=CNC=3N=CN=2)=C1 XREQWEOPAPCJDD-UHFFFAOYSA-N 0.000 claims description 3
• WWBDYUMDRUHJKW-UHFFFAOYSA-N (5-methyl-1h-indol-2-yl)-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound C=1C2=CC(C)=CC=C2NC=1C(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 WWBDYUMDRUHJKW-UHFFFAOYSA-N 0.000 claims description 3
• LZKWYUSTYHCVSM-UHFFFAOYSA-N (5-methylsulfonyl-1h-indol-2-yl)-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound C=1C2=CC(S(=O)(=O)C)=CC=C2NC=1C(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 LZKWYUSTYHCVSM-UHFFFAOYSA-N 0.000 claims description 3
• ZJZHDWXWCKOIBQ-UHFFFAOYSA-N (6-methylpyrazin-2-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound CC1=CN=CC(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=N1 ZJZHDWXWCKOIBQ-UHFFFAOYSA-N 0.000 claims description 3
• NXKRGYWZHKHJTC-UHFFFAOYSA-N (7-fluoro-1h-indol-2-yl)-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound N1C=2C(F)=CC=CC=2C=C1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 NXKRGYWZHKHJTC-UHFFFAOYSA-N 0.000 claims description 3
• YKXBYRBNIALWPU-UHFFFAOYSA-N 1-[2-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]pyrrolidin-1-yl]ethanone Chemical compound CC(=O)N1CCCC1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 YKXBYRBNIALWPU-UHFFFAOYSA-N 0.000 claims description 3
• ACZXHFVAOBKJLQ-UHFFFAOYSA-N 1-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-[4-(trifluoromethyl)phenyl]ethanone Chemical compound C1=CC(C(F)(F)F)=CC=C1CC(=O)N1C2CCC1CN(C=1C=3C=CNC=3N=CN=1)C2 ACZXHFVAOBKJLQ-UHFFFAOYSA-N 0.000 claims description 3
• PFXZQMUXSPHNKR-UHFFFAOYSA-N 1-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-2-thiophen-2-ylethanone Chemical compound C1N(C=2C=3C=CNC=3N=CN=2)CC2CCC1N2C(=O)CC1=CC=CS1 PFXZQMUXSPHNKR-UHFFFAOYSA-N 0.000 claims description 3
• WFQGKZYDLOQVSL-UHFFFAOYSA-N 1-[4-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl]thiophen-2-yl]ethanone Chemical compound S1C(C(=O)C)=CC(C(=O)N2C3CCC2CN(C3)C=2C=3C=CNC=3N=CN=2)=C1 WFQGKZYDLOQVSL-UHFFFAOYSA-N 0.000 claims description 3
• SQMUOKMUTSHVBQ-UHFFFAOYSA-N 1-[7-(2-amino-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-2-[4-(trifluoromethyl)phenyl]ethanone Chemical compound C=12C=CNC2=NC(N)=NC=1N(CC12CC2)CCN1C(=O)CC1=CC=C(C(F)(F)F)C=C1 SQMUOKMUTSHVBQ-UHFFFAOYSA-N 0.000 claims description 3
• OFUMLJHOHOPOTE-UHFFFAOYSA-N 1-[7-(2-amino-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]cyclopropane-1-carbonitrile Chemical compound C=12C=CNC2=NC(N)=NC=1N(CC12CC2)CCN1C(=O)C1(C#N)CC1 OFUMLJHOHOPOTE-UHFFFAOYSA-N 0.000 claims description 3
• ZXNIZFBAOORZOY-UHFFFAOYSA-N 1-[7-(5-chloro-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-2-(4-fluorophenyl)ethanone Chemical compound C1=CC(F)=CC=C1CC(=O)N1C2(CC2)CN(C=2C=3C(Cl)=CNC=3N=CN=2)CC1 ZXNIZFBAOORZOY-UHFFFAOYSA-N 0.000 claims description 3
• YTZJOWVNDIADIO-UHFFFAOYSA-N 1-[7-(5-chloro-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-2-[4-(trifluoromethyl)phenyl]ethanone Chemical compound C1=CC(C(F)(F)F)=CC=C1CC(=O)N1C2(CC2)CN(C=2C=3C(Cl)=CNC=3N=CN=2)CC1 YTZJOWVNDIADIO-UHFFFAOYSA-N 0.000 claims description 3
• JBQIXTBMDUTVQV-UHFFFAOYSA-N 1-benzothiophen-3-yl-[7-(1h-pyrrolo[2,3-b]pyridin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1SC2=CC=CC=C2C=1C(=O)N1CCN(C=2C=3C=CNC=3N=CC=2)CC11CC1 JBQIXTBMDUTVQV-UHFFFAOYSA-N 0.000 claims description 3
• CUMUYNPOFLYAPJ-UHFFFAOYSA-N 1-benzothiophen-5-yl-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C=C2SC=CC2=CC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 CUMUYNPOFLYAPJ-UHFFFAOYSA-N 0.000 claims description 3
• KYHPYJDZIRVFAB-UHFFFAOYSA-N 1-methyl-5-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]pyrrole-2-sulfonamide Chemical compound C1=C(S(N)(=O)=O)N(C)C(C(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 KYHPYJDZIRVFAB-UHFFFAOYSA-N 0.000 claims description 3
• PPBIDSCTDFFIEV-UHFFFAOYSA-N 1-methyl-5-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]pyrrole-3-sulfonamide Chemical compound CN1C=C(S(N)(=O)=O)C=C1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 PPBIDSCTDFFIEV-UHFFFAOYSA-N 0.000 claims description 3
• ULORBKOAGWKZAZ-UHFFFAOYSA-N 1h-indol-2-yl-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound C1=CC=C2NC(C(N3C4CCC3CN(C4)C=3C=4C=CNC=4N=CN=3)=O)=CC2=C1 ULORBKOAGWKZAZ-UHFFFAOYSA-N 0.000 claims description 3
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• YWSJSYAWMCUKKP-UHFFFAOYSA-N 2-(3-methylsulfonylphenyl)-1-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]ethanone Chemical compound CS(=O)(=O)C1=CC=CC(CC(=O)N2C3(CC3)CN(CC2)C=2C=3C=CNC=3N=CN=2)=C1 YWSJSYAWMCUKKP-UHFFFAOYSA-N 0.000 claims description 3
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• PKULRBYJKHTWQT-UHFFFAOYSA-N 1-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]propan-1-one Chemical compound CCC(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 PKULRBYJKHTWQT-UHFFFAOYSA-N 0.000 claims description 2
• GLPAYBDUCFFDAO-UHFFFAOYSA-N 1-[4-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 GLPAYBDUCFFDAO-UHFFFAOYSA-N 0.000 claims description 2
• QKRXHSMOQCBERI-UHFFFAOYSA-N 1-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl]cyclopropane-1-carbonitrile Chemical compound C1C(N(C2)C=3C=4C=CNC=4N=CN=3)CC2N1C(=O)C1(C#N)CC1 QKRXHSMOQCBERI-UHFFFAOYSA-N 0.000 claims description 2
• RWVFDZNYSPLVKS-UHFFFAOYSA-N 1-[7-(1h-pyrrolo[2,3-b]pyridin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]cyclopropane-1-carbonitrile Chemical compound C1CC1(C#N)C(=O)N1CCN(C=2C=3C=CNC=3N=CC=2)CC11CC1 RWVFDZNYSPLVKS-UHFFFAOYSA-N 0.000 claims description 2
• ILUPOJFBTMSWDL-UHFFFAOYSA-N 1-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-2-thiophen-2-ylethane-1,2-dione Chemical compound C=1C=CSC=1C(=O)C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 ILUPOJFBTMSWDL-UHFFFAOYSA-N 0.000 claims description 2
• QHDSGXBLTQLBMG-UHFFFAOYSA-N 1-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]cyclopropane-1-carbonitrile Chemical compound C1CC1(C#N)C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 QHDSGXBLTQLBMG-UHFFFAOYSA-N 0.000 claims description 2
• XOLWZNJDNMLVKA-UHFFFAOYSA-N 1-benzothiophen-2-yl-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1C2=CC=CC=C2SC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 XOLWZNJDNMLVKA-UHFFFAOYSA-N 0.000 claims description 2
• WIAGMDDCANYFEO-UHFFFAOYSA-N 1-benzothiophen-3-yl-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone Chemical compound C1=CC=C2C(C(N3C4CCC3CN(C4)C=3C=4C=CNC=4N=CN=3)=O)=CSC2=C1 WIAGMDDCANYFEO-UHFFFAOYSA-N 0.000 claims description 2
• AVRWEMLZWWIVRU-UHFFFAOYSA-N 1-benzothiophen-3-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C1=CC=C2C(C(N3C4CC(N(C4)C=4C=5C=CNC=5N=CN=4)C3)=O)=CSC2=C1 AVRWEMLZWWIVRU-UHFFFAOYSA-N 0.000 claims description 2
• IVBMADFNLXNLMZ-UHFFFAOYSA-N 1-benzothiophen-3-yl-[7-(5-methoxy-1h-pyrrolo[2,3-b]pyridin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound COC1=CN=C2NC=CC2=C1N(C1)CCN(C(=O)C=2C3=CC=CC=C3SC=2)C21CC2 IVBMADFNLXNLMZ-UHFFFAOYSA-N 0.000 claims description 2
• HWWXXDLPCRRZLN-UHFFFAOYSA-N 1H-indol-4-yl-[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methanone [3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]-quinoxalin-2-ylmethanone Chemical compound N1=CN=C(C2=C1NC=C2)N2CC1CCC(C2)N1C(=O)C1=NC2=CC=CC=C2N=C1.N1C=CC2=C(C=CC=C12)C(=O)N1C2CN(CC1CC2)C=2C1=C(N=CN2)NC=C1 HWWXXDLPCRRZLN-UHFFFAOYSA-N 0.000 claims description 2
• VSGPPSNTYUYOAY-UHFFFAOYSA-N 1H-indol-4-yl-[7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone [7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-[3-(trifluoromethoxy)phenyl]methanone Chemical compound N1=CN=C(C2=C1NC=C2)N2CCN(C1(CC1)C2)C(=O)C2=CC(=CC=C2)OC(F)(F)F.N2C=CC1=C(C=CC=C21)C(=O)N2C1(CC1)CN(CC2)C=2C1=C(N=CN2)NC=C1 VSGPPSNTYUYOAY-UHFFFAOYSA-N 0.000 claims description 2
• BPRXXJQULVXYFZ-UHFFFAOYSA-N 1h-indol-2-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C1=CC=C2NC(C(N3C4CC(N(C4)C=4C=5C=CNC=5N=CN=4)C3)=O)=CC2=C1 BPRXXJQULVXYFZ-UHFFFAOYSA-N 0.000 claims description 2
• DRQRMYIBVAGIAW-UHFFFAOYSA-N 1h-indol-3-yl-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]methanone Chemical compound C=1NC2=CC=CC=C2C=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 DRQRMYIBVAGIAW-UHFFFAOYSA-N 0.000 claims description 2
• GGCOOJSYTZHKJB-UHFFFAOYSA-N 1h-indol-4-yl-[5-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone Chemical compound C1C(N(C2)C=3C=4C=CNC=4N=CN=3)CC2N1C(=O)C1=CC=CC2=C1C=CN2 GGCOOJSYTZHKJB-UHFFFAOYSA-N 0.000 claims description 2
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• FIFMUWXYUNGFBO-UHFFFAOYSA-N 2-[3-[2-[7-(2-amino-7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]-2-oxoethyl]phenyl]acetonitrile Chemical compound C=12C=CNC2=NC(N)=NC=1N(CC12CC2)CCN1C(=O)CC1=CC=CC(CC#N)=C1 FIFMUWXYUNGFBO-UHFFFAOYSA-N 0.000 claims description 2
• RDUAXXQXHDEVJJ-UHFFFAOYSA-N 2-[3-[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-carbonyl]phenoxy]acetonitrile Chemical compound C=1C=CC(OCC#N)=CC=1C(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 RDUAXXQXHDEVJJ-UHFFFAOYSA-N 0.000 claims description 2
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• ZZZAAIYKVSOIDZ-UHFFFAOYSA-N 2-[4-[3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carbonyl]phenyl]acetonitrile Chemical compound C1N(C=2C=3C=CNC=3N=CN=2)CC2CCC1N2C(=O)C1=CC=C(CC#N)C=C1 ZZZAAIYKVSOIDZ-UHFFFAOYSA-N 0.000 claims description 2
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• VRDLAAFEFFOQQK-UHFFFAOYSA-N 2-methoxyethyl 3-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound COCCOC(=O)N1C(C2)CCC1CN2C1=NC=NC2=C1C=CN2 VRDLAAFEFFOQQK-UHFFFAOYSA-N 0.000 claims description 2
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