CA2823935A1 - Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof - Google Patents
Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof Download PDFInfo
- Publication number
- CA2823935A1 CA2823935A1 CA2823935A CA2823935A CA2823935A1 CA 2823935 A1 CA2823935 A1 CA 2823935A1 CA 2823935 A CA2823935 A CA 2823935A CA 2823935 A CA2823935 A CA 2823935A CA 2823935 A1 CA2823935 A1 CA 2823935A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrrolo
- pyrimidin
- methyl
- octane
- diazaspiro
- 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.)
- Abandoned
Links
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract description 3
- RNFIBTDXEXGJBV-UHFFFAOYSA-N piperazine;sulfamide Chemical class NS(N)(=O)=O.C1CNCCN1 RNFIBTDXEXGJBV-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 329
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 201000010099 disease Diseases 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 14
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 11
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 11
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 11
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 11
- 230000001363 autoimmune Effects 0.000 claims abstract description 10
- 239000012453 solvate Substances 0.000 claims abstract description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 9
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 9
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 9
- 206010012689 Diabetic retinopathy 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
- 241001303601 Rosacea Species 0.000 claims abstract description 9
- 208000024799 Thyroid disease Diseases 0.000 claims abstract description 9
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 9
- 208000006673 asthma Diseases 0.000 claims abstract description 9
- 208000030533 eye disease Diseases 0.000 claims abstract description 9
- 208000032839 leukemia Diseases 0.000 claims abstract description 9
- 206010025135 lupus erythematosus Diseases 0.000 claims abstract description 9
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 9
- 201000004700 rosacea Diseases 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
- 150000004677 hydrates Chemical class 0.000 claims abstract description 5
- 229940002612 prodrug Drugs 0.000 claims abstract description 5
- 239000000651 prodrug Substances 0.000 claims abstract description 5
- 229940124530 sulfonamide Drugs 0.000 claims description 351
- -1 cyano, hydroxy Chemical group 0.000 claims description 250
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 146
- 125000000623 heterocyclic group Chemical group 0.000 claims description 122
- UIEQYZNDSLCTMK-UHFFFAOYSA-N octane-4-sulfonic acid Chemical compound CCCCC(S(O)(=O)=O)CCC UIEQYZNDSLCTMK-UHFFFAOYSA-N 0.000 claims description 111
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 108
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 76
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 239000001257 hydrogen Substances 0.000 claims description 68
- 125000003118 aryl group Chemical group 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 59
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 51
- 125000004043 oxo group Chemical group O=* 0.000 claims description 51
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims description 45
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 44
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 42
- 150000002367 halogens Chemical group 0.000 claims description 40
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 40
- 150000002431 hydrogen Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 30
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 18
- 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
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 16
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 13
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 13
- 238000011321 prophylaxis Methods 0.000 claims description 13
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 claims description 12
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 11
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 11
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 125000002393 azetidinyl group Chemical group 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 210000000987 immune system Anatomy 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 9
- 108091000080 Phosphotransferase Proteins 0.000 claims description 9
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 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 9
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
- 102000020233 phosphotransferase Human genes 0.000 claims description 9
- 125000006413 ring segment Chemical group 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 230000002458 infectious effect Effects 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 208000017520 skin disease Diseases 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 7
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000002253 acid Substances 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
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical class COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 230000002757 inflammatory 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical compound OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 206010039705 Scleritis Diseases 0.000 claims description 4
- 206010040799 Skin atrophy Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 230000032683 aging 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
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 claims description 4
- RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003566 oxetanyl group Chemical group 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 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
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
- 230000002500 effect on skin Effects 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
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- GUMBNOITRNRLCS-UHFFFAOYSA-N n-methyl-2-phenoxyethanamine Chemical compound CNCCOC1=CC=CC=C1 GUMBNOITRNRLCS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 claims description 3
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 2
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- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 2
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- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
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- 208000003455 anaphylaxis Diseases 0.000 claims description 2
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- 150000003431 steroids Chemical class 0.000 claims description 2
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- 125000005843 halogen group Chemical group 0.000 claims 8
- 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 5
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000006532 (C3-C5) alkyl group Chemical group 0.000 claims 1
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 1
- 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 1
- PIDLOAOWCYMMHN-UHFFFAOYSA-N 1-[[7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]piperidine-3-carbonitrile Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N1CCCC(C#N)C1 PIDLOAOWCYMMHN-UHFFFAOYSA-N 0.000 claims 1
- LJNYZRGQGRKNRP-UHFFFAOYSA-N 1-[[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]piperidine-4-carbonitrile Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N1CCC(C#N)CC1 LJNYZRGQGRKNRP-UHFFFAOYSA-N 0.000 claims 1
- ZVHLOQRQRCTGEO-UHFFFAOYSA-N 2-(1,1-dioxothian-4-yl)-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)CC1CCS(=O)(=O)CC1 ZVHLOQRQRCTGEO-UHFFFAOYSA-N 0.000 claims 1
- FMBSAYNKWUSSNX-UHFFFAOYSA-N 2-(1,1-dioxothiolan-3-yl)-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)CC1CCS(=O)(=O)C1 FMBSAYNKWUSSNX-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- VVZYKTKWNPJKNW-UHFFFAOYSA-N 3,3,3-trifluoro-n-methyl-n-[[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]propanamide Chemical compound FC(F)(F)CC(=O)N(C)S(=O)(=O)N1CCN(C=2C=3C=CNC=3N=CN=2)CC11CC1 VVZYKTKWNPJKNW-UHFFFAOYSA-N 0.000 claims 1
- KVHKBPLCAITBRO-UHFFFAOYSA-N 3-(1,1-dioxothiolan-3-yl)-N-methyl-N-[[7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]propanamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C(=O)CCC1CCS(=O)(=O)C1 KVHKBPLCAITBRO-UHFFFAOYSA-N 0.000 claims 1
- OZKAPOUXJYTSAI-UHFFFAOYSA-N 3-cyclopentyl-n-methyl-n-[[7-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diazaspiro[2.5]octan-4-yl]sulfonyl]propanamide Chemical compound C1CN(C=2C=3C=CNC=3N=CN=2)CC2(CC2)N1S(=O)(=O)N(C)C(=O)CCC1CCCC1 OZKAPOUXJYTSAI-UHFFFAOYSA-N 0.000 claims 1
- OZLKUNKEBURGNH-UHFFFAOYSA-N 4-(2-phenylethylamino)butanenitrile Chemical compound N#CCCCNCCC1=CC=CC=C1 OZLKUNKEBURGNH-UHFFFAOYSA-N 0.000 claims 1
- 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 1
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- CMWWGIDJXSETJU-UHFFFAOYSA-N n-cyclopropyl-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)C1CC1 CMWWGIDJXSETJU-UHFFFAOYSA-N 0.000 claims 1
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US201161430670P | 2011-01-07 | 2011-01-07 | |
| US61/430,670 | 2011-01-07 | ||
| PCT/EP2012/050187 WO2012093169A1 (en) | 2011-01-07 | 2012-01-06 | Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof |
Publications (1)
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| CA2823935A1 true CA2823935A1 (en) | 2012-07-12 |
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| CA2823935A Abandoned CA2823935A1 (en) | 2011-01-07 | 2012-01-06 | Novel sulfamide piperazine derivatives as protein tyrosine kinase inhibitors and pharmaceutical use thereof |
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| EP (1) | EP2661436B1 (enExample) |
| JP (1) | JP2014501772A (enExample) |
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| TW (1) | TW201309703A (enExample) |
| WO (1) | WO2012093169A1 (enExample) |
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| EP3145512B1 (en) * | 2014-05-19 | 2019-07-17 | Jiangsu Hengrui Medicine Co., Ltd. | Substituted ethynyl heterobicyclic compounds as tyrosine kinase inhibitors |
| CN106661031B (zh) | 2014-06-24 | 2019-07-23 | 大鹏药品工业株式会社 | 吡咯并嘧啶化合物或其盐、含有其的药物组合物及应用 |
| CN110291090A (zh) * | 2017-01-20 | 2019-09-27 | 利奥制药有限公司 | 作为新型jak激酶抑制剂的双环胺 |
| US10799507B2 (en) | 2017-02-03 | 2020-10-13 | Leo Pharma A/S | 5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-5-azaspiro[2.5]octane-8-carboxylic acid derivatives as novel JAK kinase inhibitors |
| CN108822048A (zh) * | 2018-07-23 | 2018-11-16 | 上海昌肽生物科技有限公司 | 4-(4-乙基-4,7二氮杂螺环[3,3]辛基)-2-硝基苯胺的合成工艺 |
| CN116730927A (zh) * | 2023-03-21 | 2023-09-12 | 广州佳途科技股份有限公司 | 一种新型高效合成4,7-二氮杂螺[2.5]辛烷盐酸盐的方法 |
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| AU3951899A (en) * | 1998-06-19 | 2000-01-05 | Pfizer Products Inc. | Pyrrolo(2,3-d)pyrimidine compounds |
| PA8474101A1 (es) * | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| OA12118A (en) * | 1999-12-10 | 2006-05-04 | Pfizer Prod Inc | PyrroloÄ2,3-dÜpyrimidine compounds. |
| WO2003022214A2 (en) * | 2001-09-06 | 2003-03-20 | Millennium Pharmaceuticals, Inc. | Piperazine and homopiperazine compounds |
| AU2003284142A1 (en) * | 2002-10-15 | 2004-05-04 | Synta Pharmaceuticals Corp | Aromatic bicyclic heterocyles to modulate 1L-12 production |
| SE0301372D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Novel compounds |
| AU2004293026B2 (en) | 2003-11-21 | 2012-01-19 | Array Biopharma Inc. | AKT protein kinase inhibitors |
| CA2545192A1 (en) * | 2003-11-25 | 2005-06-09 | Pfizer Products Inc. | Method of treatment of atherosclerosis |
| RU2006120956A (ru) | 2003-12-17 | 2008-01-27 | Пфайзер Продактс Инк. (Us) | Пирроло{2, 3-d}пиримидиновые соединения для лечения отторжения трансплантата |
| TWI380816B (zh) | 2004-04-13 | 2013-01-01 | Synta Pharmaceuticals Corp | 抑制介白素-１２（ｉｌ-１２）生成之二鹽抑制劑 |
| AR054416A1 (es) * | 2004-12-22 | 2007-06-27 | Incyte Corp | Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas. |
| US8633205B2 (en) * | 2005-02-03 | 2014-01-21 | Vertex Pharmaceuticals Incorporated | Substituted pyrrolo[2,3-d]pyrimidines as inhibitors of protein kinases |
| US7423043B2 (en) | 2005-02-18 | 2008-09-09 | Lexicon Pharmaceuticals, Inc. | 4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine compounds |
| JP2008545660A (ja) * | 2005-05-20 | 2008-12-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼ阻害剤として有用なピロロピリジン化合物 |
| CN102127078A (zh) * | 2005-07-14 | 2011-07-20 | 安斯泰来制药株式会社 | Janus激酶3的杂环类抑制剂 |
| HRP20120786T1 (hr) | 2006-02-02 | 2012-11-30 | Millennium Pharmaceuticals, Inc. | Inhibitori aktivirajuä†eg enzima e1 |
| GB0604944D0 (en) * | 2006-03-11 | 2006-04-19 | Vernalis R&D Ltd | Pyrrolopyrimidine compounds |
| CA2645343A1 (en) | 2006-03-11 | 2007-09-20 | Vernalis (R&D) Limited | Pyrrolopyrimidine derivatives used as hsp90 inhibitors |
| JP2009532475A (ja) | 2006-04-05 | 2009-09-10 | バーテックス ファーマシューティカルズ インコーポレイテッド | ヤヌスキナーゼの阻害剤として有用なデアザプリン |
| AU2008240188A1 (en) * | 2007-04-13 | 2008-10-23 | Supergen, Inc. | Axl kinase inhibitors useful for the treatment of cancer or hyperproliferative disorders |
| ES2557931T3 (es) * | 2007-08-08 | 2016-01-29 | Lexicon Pharmaceuticals, Inc. | (7H-Pirrolo[2,3-d]pirimidin-4-il)-piperazinas como inhibidores de cinasas para el tratamiento de cáncer e inflamación |
| JP5690823B2 (ja) * | 2009-07-08 | 2015-03-25 | レオ ファーマ アクティーゼルスカブ | Ｊａｋ受容体およびタンパク質チロシンキナーゼ阻害薬としての複素環化合物 |
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- 2012-01-06 MX MX2013007792A patent/MX2013007792A/es not_active Application Discontinuation
- 2012-01-06 WO PCT/EP2012/050187 patent/WO2012093169A1/en not_active Ceased
- 2012-01-06 CA CA2823935A patent/CA2823935A1/en not_active Abandoned
- 2012-01-06 RU RU2013136906/04A patent/RU2013136906A/ru not_active Application Discontinuation
- 2012-01-09 TW TW101100842A patent/TW201309703A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2012204843A1 (en) | 2013-05-02 |
| JP2014501772A (ja) | 2014-01-23 |
| US20130345194A1 (en) | 2013-12-26 |
| BR112013017184A2 (pt) | 2016-09-20 |
| EP2661436A1 (en) | 2013-11-13 |
| WO2012093169A1 (en) | 2012-07-12 |
| TW201309703A (zh) | 2013-03-01 |
| MX2013007792A (es) | 2013-07-30 |
| RU2013136906A (ru) | 2015-02-20 |
| CN103298817A (zh) | 2013-09-11 |
| EP2661436B1 (en) | 2016-04-13 |
| US9233964B2 (en) | 2016-01-12 |
| KR20140058402A (ko) | 2014-05-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20160106 |