TW201309703A - 作為蛋白質酪胺酸激酶抑制劑之新穎磺醯胺哌□衍生物及其醫藥用途 - Google Patents

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Publication number

TW201309703A

TW201309703A TW101100842A TW101100842A TW201309703A TW 201309703 A TW201309703 A TW 201309703A TW 101100842 A TW101100842 A TW 101100842A TW 101100842 A TW101100842 A TW 101100842A TW 201309703 A TW201309703 A TW 201309703A

Authority

TW

Taiwan

Prior art keywords

methyl

octane

pyrrolo

pyrimidin

diazaspiro

Prior art date

2011-01-07

Links

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• Global Dossier
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• 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract 2
• RNFIBTDXEXGJBV-UHFFFAOYSA-N piperazine;sulfamide Chemical class NS(N)(=O)=O.C1CNCCN1 RNFIBTDXEXGJBV-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 323
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
• 201000010099 disease Diseases 0.000 claims abstract description 14
• 150000003839 salts Chemical class 0.000 claims abstract description 14
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
• 201000011510 cancer Diseases 0.000 claims abstract description 13
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 11
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 10
• 102000042838 JAK family Human genes 0.000 claims abstract description 10
• 108091082332 JAK family Proteins 0.000 claims abstract description 10
• 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 10
• 208000030533 eye disease Diseases 0.000 claims abstract description 10
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 10
• 239000012453 solvate Substances 0.000 claims abstract description 10
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 8
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 8
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 8
• 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 8
• 241001303601 Rosacea Species 0.000 claims abstract description 8
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 8
• 208000006673 asthma Diseases 0.000 claims abstract description 8
• 208000032839 leukemia Diseases 0.000 claims abstract description 8
• 206010025135 lupus erythematosus Diseases 0.000 claims abstract description 8
• 208000002780 macular degeneration Diseases 0.000 claims abstract description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 8
• 201000004700 rosacea Diseases 0.000 claims abstract description 8
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 7
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
• 229940002612 prodrug Drugs 0.000 claims abstract description 5
• 239000000651 prodrug Substances 0.000 claims abstract description 5
• -1 cyano, hydroxyl Chemical group 0.000 claims description 304
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 196
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 178
• 229940124530 sulfonamide Drugs 0.000 claims description 178
• 125000000623 heterocyclic group Chemical group 0.000 claims description 114
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 69
• 239000001257 hydrogen Substances 0.000 claims description 68
• 229910052739 hydrogen Inorganic materials 0.000 claims description 68
• 125000000217 alkyl group Chemical group 0.000 claims description 63
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 59
• 239000000203 mixture Substances 0.000 claims description 55
• 125000003118 aryl group Chemical group 0.000 claims description 53
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 49
• 229910052736 halogen Inorganic materials 0.000 claims description 47
• 150000002367 halogens Chemical class 0.000 claims description 47
• 125000004432 carbon atom Chemical group C* 0.000 claims description 45
• JALJYLNIVJITOC-UHFFFAOYSA-N 7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonic acid Chemical compound OS(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 JALJYLNIVJITOC-UHFFFAOYSA-N 0.000 claims description 43
• 125000001072 heteroaryl group Chemical group 0.000 claims description 43
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 41
• 150000002431 hydrogen Chemical class 0.000 claims description 36
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 33
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
• 238000011282 treatment Methods 0.000 claims description 30
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 25
• UIEQYZNDSLCTMK-UHFFFAOYSA-N octane-4-sulfonic acid Chemical compound CCCCC(S(O)(=O)=O)CCC UIEQYZNDSLCTMK-UHFFFAOYSA-N 0.000 claims description 23
• 125000000304 alkynyl group Chemical group 0.000 claims description 21
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 20
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 20
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 19
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 19
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 19
• QWOKKHXWFDAJCZ-UHFFFAOYSA-N octane-1-sulfonamide Chemical compound CCCCCCCCS(N)(=O)=O QWOKKHXWFDAJCZ-UHFFFAOYSA-N 0.000 claims description 19
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 18
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
• 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 16
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
• 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 claims description 14
• 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 14
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 14
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
• 230000002265 prevention Effects 0.000 claims description 14
• 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims description 12
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 10
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 10
• 125000002393 azetidinyl group Chemical group 0.000 claims description 10
• 239000000460 chlorine Substances 0.000 claims description 10
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 239000002253 acid Substances 0.000 claims description 9
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 9
• 210000000987 immune system Anatomy 0.000 claims description 9
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 8
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• 125000002837 carbocyclic group Chemical group 0.000 claims description 8
• 230000000694 effects Effects 0.000 claims description 8
• 239000011737 fluorine Substances 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 208000015181 infectious disease Diseases 0.000 claims description 8
• 230000002458 infectious effect Effects 0.000 claims description 8
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 208000017520 skin disease Diseases 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 claims description 7
• 208000002249 Diabetes Complications Diseases 0.000 claims description 7
• 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
• 125000004043 oxo group Chemical group O=* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
• 206010012655 Diabetic complications Diseases 0.000 claims description 6
• 125000004104 aryloxy group Chemical group 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 6
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
• 230000002757 inflammatory effect Effects 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 6
• OEXDCSYVQCRQNO-UHFFFAOYSA-N 7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound NS(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 OEXDCSYVQCRQNO-UHFFFAOYSA-N 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 208000010928 autoimmune thyroid disease Diseases 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
• NHRCAZVIQFZGRF-QGZVFWFLSA-N n-[[(2r)-1-(3-cyanopropanoyl)pyrrolidin-2-yl]methyl]-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C[C@H]1CCCN1C(=O)CCC#N NHRCAZVIQFZGRF-QGZVFWFLSA-N 0.000 claims description 5
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• 201000004624 Dermatitis Diseases 0.000 claims description 4
• 206010020751 Hypersensitivity Diseases 0.000 claims description 4
• 206010061218 Inflammation Diseases 0.000 claims description 4
• 206010040799 Skin atrophy Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
• 208000010668 atopic eczema Diseases 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 claims description 4
• 230000004054 inflammatory process Effects 0.000 claims description 4
• 206010023332 keratitis Diseases 0.000 claims description 4
• YOCSHVIPBWMION-UHFFFAOYSA-N n-(cyclobutylmethyl)-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CC1CCC1 YOCSHVIPBWMION-UHFFFAOYSA-N 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 125000006532 (C3-C5) alkyl group Chemical group 0.000 claims description 3
• UPBPAKISEVOITE-MSXFZWOLSA-N (NZ)-N-[(4-methoxyphenyl)methylidene]-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1=CC(OC)=CC=C1\C=N/S(=O)(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 UPBPAKISEVOITE-MSXFZWOLSA-N 0.000 claims description 3
• DRXAZKROKYSBAZ-UHFFFAOYSA-N 2-cyclopentyl-n-methyl-n-[[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]acetamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C(=O)CC1CCCC1 DRXAZKROKYSBAZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
• PODDKJDNQSSKHD-UHFFFAOYSA-N 4-(4-piperidin-1-ylsulfonyl-4,7-diazaspiro[2.5]octan-7-yl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N1CCCCC1 PODDKJDNQSSKHD-UHFFFAOYSA-N 0.000 claims description 3
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
• ULRRKTYCONSYMA-HNNXBMFYSA-N N-[[(2S)-4,4-difluoro-1-(3-hydroxypropanoyl)pyrrolidin-2-yl]methyl]-N-methyl-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C[C@@H]1CC(F)(F)CN1C(=O)CCO ULRRKTYCONSYMA-HNNXBMFYSA-N 0.000 claims description 3
• BBKNDPZTJPDRKJ-UHFFFAOYSA-N N-[[1-(3-cyanopropanoyl)piperidin-4-yl]methyl]-N-methyl-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CC1CCN(C(=O)CCC#N)CC1 BBKNDPZTJPDRKJ-UHFFFAOYSA-N 0.000 claims description 3
• VUELUIFCCDJRAJ-UHFFFAOYSA-N N-[[2-(2,2-difluoroethyl)-1,5-dihydropyrazol-5-yl]methyl]-N-methyl-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CC1NN(CC(F)F)C=C1 VUELUIFCCDJRAJ-UHFFFAOYSA-N 0.000 claims description 3
• 230000037429 base substitution Effects 0.000 claims description 3
• 239000004202 carbamide Substances 0.000 claims description 3
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• MOTFWHWYWQVXRV-UHFFFAOYSA-N n-(2-hydroxyethyl)-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound OCCN(C)S(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 MOTFWHWYWQVXRV-UHFFFAOYSA-N 0.000 claims description 3
• YEXDARNQPFGTOB-UHFFFAOYSA-N n-(2-hydroxyethyl)-n-propan-2-yl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound OCCN(C(C)C)S(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 YEXDARNQPFGTOB-UHFFFAOYSA-N 0.000 claims description 3
• IOJSBENOGFHMSY-UHFFFAOYSA-N n-(cyanomethyl)-n-propan-2-yl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound N#CCN(C(C)C)S(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 IOJSBENOGFHMSY-UHFFFAOYSA-N 0.000 claims description 3
• SPMXMUUWHSTVNZ-UHFFFAOYSA-N n-[(3,3-difluorocyclobutyl)methyl]-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CC1CC(F)(F)C1 SPMXMUUWHSTVNZ-UHFFFAOYSA-N 0.000 claims description 3
• AXCRXYDVQZNBOX-UHFFFAOYSA-N n-[(4,4-difluorocyclohexyl)methyl]-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CC1CCC(F)(F)CC1 AXCRXYDVQZNBOX-UHFFFAOYSA-N 0.000 claims description 3
• JBQQYFNYVHVADI-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1=CC(OC)=CC=C1CNS(=O)(=O)N1C2(CC2)CN(C=2C=3C=CNC=3N=CN=2)CC1 JBQQYFNYVHVADI-UHFFFAOYSA-N 0.000 claims description 3
• UHLWUOGTPVXWQG-INIZCTEOSA-N n-[[(2s)-1-(3-cyanopropanoyl)-4,4-difluoropyrrolidin-2-yl]methyl]-n-methyl-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C[C@@H]1CC(F)(F)CN1C(=O)CCC#N UHLWUOGTPVXWQG-INIZCTEOSA-N 0.000 claims description 3
• ZXVPQAYRROPSID-UHFFFAOYSA-N n-cyclobutyl-n-(2-hydroxyethyl)-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(CCO)C1CCC1 ZXVPQAYRROPSID-UHFFFAOYSA-N 0.000 claims description 3
• XQLOPSDMRSFQOL-UHFFFAOYSA-N n-cyclobutyl-n-(2-morpholin-4-ylethyl)-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C1CCC1)CCN1CCOCC1 XQLOPSDMRSFQOL-UHFFFAOYSA-N 0.000 claims description 3
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• OPZXZFJPENFDEN-UHFFFAOYSA-N n-methyl-n-(2-pyrazol-1-ylethyl)-7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octane-4-sulfonamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)CCN1C=CC=N1 OPZXZFJPENFDEN-UHFFFAOYSA-N 0.000 claims description 3
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