CA2930735A1 - Tetracyclic autotaxin inhibitors - Google Patents
Tetracyclic autotaxin inhibitors Download PDFInfo
- Publication number
- CA2930735A1 CA2930735A1 CA2930735A CA2930735A CA2930735A1 CA 2930735 A1 CA2930735 A1 CA 2930735A1 CA 2930735 A CA2930735 A CA 2930735A CA 2930735 A CA2930735 A CA 2930735A CA 2930735 A1 CA2930735 A1 CA 2930735A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- pyrido
- substituted
- imidazo
- unsubstituted
- 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
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- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 title abstract description 38
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 title abstract description 37
- 239000003112 inhibitor Substances 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 496
- 238000000034 method Methods 0.000 claims abstract description 84
- 239000003814 drug Substances 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims description 114
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 111
- -1 C1-C6deuteroalkyl Chemical group 0.000 claims description 106
- 229910052731 fluorine Inorganic materials 0.000 claims description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 83
- 239000012453 solvate Substances 0.000 claims description 79
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 74
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 64
- 235000019260 propionic acid Nutrition 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 49
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 44
- 241000124008 Mammalia Species 0.000 claims description 43
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000004429 atom Chemical group 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 229910052794 bromium Inorganic materials 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 20
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229940124597 therapeutic agent Drugs 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 15
- 206010016654 Fibrosis Diseases 0.000 claims description 14
- 230000004761 fibrosis Effects 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000004306 triazinyl group Chemical group 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 10
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 125000001425 triazolyl group Chemical group 0.000 claims description 10
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 6
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 6
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 6
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 5
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 5
- 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- IEZLOKTWFZIIDZ-IBGZPJMESA-N 4-[(15S)-8-[(6-methoxypyridin-3-yl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]butanoic acid Chemical compound COC1=CC=C(C=N1)CN1C2=C(C=3C=CC=CC1=3)C[C@@H]1N(C2)C(N(C1=O)CCCC(=O)O)=O IEZLOKTWFZIIDZ-IBGZPJMESA-N 0.000 claims description 4
- 229940122849 Autotaxin inhibitor Drugs 0.000 claims description 4
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- CBCZHAJOTDVBKD-HNNXBMFYSA-N 3-[(15S)-12,14-dioxo-8-[[2-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound O=C1N(C(N2CC=3N(C=4C=CC=CC=4C=3C[C@H]21)CC1=CN=C(S1)C(F)(F)F)=O)CCC(=O)O CBCZHAJOTDVBKD-HNNXBMFYSA-N 0.000 claims description 2
- BSTKPKFHNBHEGA-UHFFFAOYSA-N 8-[(4-fluorophenyl)methyl]-13-(2H-tetrazol-5-ylmethyl)-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione Chemical compound N=1NN=NC=1CN1C(N2CC=3N(C=4C=CC=CC=4C=3CC2C1=O)CC1=CC=C(C=C1)F)=O BSTKPKFHNBHEGA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
- FARUMNUOOCOIFR-UHFFFAOYSA-N 3-[8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(N(C2=O)CCC(=O)O)=O)C=C1 FARUMNUOOCOIFR-UHFFFAOYSA-N 0.000 claims 3
- OSLKOIUZUTVPBZ-UHFFFAOYSA-N 8-[(4-fluorophenyl)methyl]-16,16-dimethyl-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C(C2N(C3)C(NC2=O)=O)(C)C)C=C1 OSLKOIUZUTVPBZ-UHFFFAOYSA-N 0.000 claims 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 2
- QUCKSDQHANYGTD-OAHLLOKOSA-N (15R)-8-[(4-fluorophenyl)methyl]-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@H]2N(C3)C(OC2)=O)C=C1 QUCKSDQHANYGTD-OAHLLOKOSA-N 0.000 claims 1
- YCUBOPJCXGLAFU-KRWDZBQOSA-N (15S)-5-chloro-8-[(4-fluorophenyl)methyl]-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2(7),3,5-tetraene-12,14-dione Chemical compound ClC=1C=CC=2C3=C(N(C=2C=1)CC1=CC=C(C=C1)F)CN1[C@@H](C3)C(NC1=O)=O YCUBOPJCXGLAFU-KRWDZBQOSA-N 0.000 claims 1
- OZNFVRJBRPRKSF-KRWDZBQOSA-N (15S)-8-[(4-fluorophenyl)methyl]-12-sulfanylidene-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-14-one Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(NC2=O)=S)C=C1 OZNFVRJBRPRKSF-KRWDZBQOSA-N 0.000 claims 1
- QUCKSDQHANYGTD-HNNXBMFYSA-N (15S)-8-[(4-fluorophenyl)methyl]-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(OC2)=O)C=C1 QUCKSDQHANYGTD-HNNXBMFYSA-N 0.000 claims 1
- LRGAZQBFSHLAGN-KRWDZBQOSA-N (15S)-8-[(4-fluorophenyl)methyl]-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraene-12,14-dione Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(NC2=O)=O)C=C1 LRGAZQBFSHLAGN-KRWDZBQOSA-N 0.000 claims 1
- 125000006747 (C2-C10) heterocycloalkyl group Chemical group 0.000 claims 1
- JGNBYLIDGMPJKK-FQEVSTJZSA-N 1-[[(15S)-8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CC2(CC2)C(=O)O)=O)C=C1 JGNBYLIDGMPJKK-FQEVSTJZSA-N 0.000 claims 1
- AILJKGFWQVGMIU-IBGZPJMESA-N 1-[[(15S)-8-[(6-methoxypyridin-3-yl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]methyl]cyclopropane-1-carboxylic acid Chemical compound COC1=CC=C(C=N1)CN1C2=C(C=3C=CC=CC1=3)C[C@@H]1N(C2)C(N(C1=O)CC1(CC1)C(=O)O)=O AILJKGFWQVGMIU-IBGZPJMESA-N 0.000 claims 1
- QSSSGTOAFDQKBM-UHFFFAOYSA-N 17-[(4-fluorophenyl)methyl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(CNC2=O)=O)C=C1 QSSSGTOAFDQKBM-UHFFFAOYSA-N 0.000 claims 1
- FNKZZXFELALFPW-UHFFFAOYSA-N 2-[17-[(4-fluorophenyl)methyl]-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]acetic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(CN(C2=O)CC(=O)O)=O)C=C1 FNKZZXFELALFPW-UHFFFAOYSA-N 0.000 claims 1
- YLYVSXXLTPESAN-UHFFFAOYSA-N 2-[8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]acetic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(N(C2=O)CC(=O)O)=O)C=C1 YLYVSXXLTPESAN-UHFFFAOYSA-N 0.000 claims 1
- GXZWVFLJEBVHCS-UHFFFAOYSA-N 2-[8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]acetonitrile Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(N(C2=O)CC#N)=O)C=C1 GXZWVFLJEBVHCS-UHFFFAOYSA-N 0.000 claims 1
- SDHPKFWVGUIUEZ-UHFFFAOYSA-N 2-[8-[(4-fluorophenyl)methyl]-12-oxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]acetic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(N(C2)CC(=O)O)=O)C=C1 SDHPKFWVGUIUEZ-UHFFFAOYSA-N 0.000 claims 1
- ORJRDRRVHIIGCS-IBGZPJMESA-N 3-[(15S)-8-[(2,4-dichlorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound ClC1=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CCC(=O)O)=O)C=CC(=C1)Cl ORJRDRRVHIIGCS-IBGZPJMESA-N 0.000 claims 1
- TUJUCRXIHYHJBE-IBGZPJMESA-N 3-[(15S)-8-[(2,4-difluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CCC(=O)O)=O)C=CC(=C1)F TUJUCRXIHYHJBE-IBGZPJMESA-N 0.000 claims 1
- VMFDSXXYAIDCRK-IBGZPJMESA-N 3-[(15S)-8-[(4-chloro-2-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound ClC1=CC(=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CCC(=O)O)=O)C=C1)F VMFDSXXYAIDCRK-IBGZPJMESA-N 0.000 claims 1
- ZLHOPMRBMUIHIW-FQEVSTJZSA-N 3-[(15S)-8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]-2,2-dimethylpropanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CC(C(=O)O)(C)C)=O)C=C1 ZLHOPMRBMUIHIW-FQEVSTJZSA-N 0.000 claims 1
- VZESHIJLKYKJAP-FQEVSTJZSA-N 3-[(15S)-8-[(4-fluorophenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]-N-methylsulfonylpropanamide Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CCC(=O)NS(=O)(=O)C)=O)C=C1 VZESHIJLKYKJAP-FQEVSTJZSA-N 0.000 claims 1
- VTWXWGOVENLUAT-IBGZPJMESA-N 3-[(15S)-8-[(4-fluorophenyl)methyl]-12-oxo-14-sulfanylidene-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=S)CCC(=O)O)=O)C=C1 VTWXWGOVENLUAT-IBGZPJMESA-N 0.000 claims 1
- XJYAVHBLBATKGO-FQEVSTJZSA-N 3-[(15S)-8-[(4-methoxyphenyl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound COC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)C[C@@H]2N(C3)C(N(C2=O)CCC(=O)O)=O)C=C1 XJYAVHBLBATKGO-FQEVSTJZSA-N 0.000 claims 1
- UQBQGMVQMFLLNZ-KRWDZBQOSA-N 3-[(15S)-8-[(6-chloropyridin-3-yl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound ClC1=CC=C(C=N1)CN1C2=C(C=3C=CC=CC1=3)C[C@@H]1N(C2)C(N(C1=O)CCC(=O)O)=O UQBQGMVQMFLLNZ-KRWDZBQOSA-N 0.000 claims 1
- PYWWVCQEMKEUMW-KRWDZBQOSA-N 3-[(15S)-8-[(6-fluoropyridin-3-yl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=CC=C(C=N1)CN1C2=C(C=3C=CC=CC1=3)C[C@@H]1N(C2)C(N(C1=O)CCC(=O)O)=O PYWWVCQEMKEUMW-KRWDZBQOSA-N 0.000 claims 1
- OOBJTDBLYKSTAP-SFHVURJKSA-N 3-[(15S)-8-[(6-methoxypyridin-3-yl)methyl]-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)CN1C2=C(C=3C=CC=CC1=3)C[C@@H]1N(C2)C(N(C1=O)CCC(=O)O)=O OOBJTDBLYKSTAP-SFHVURJKSA-N 0.000 claims 1
- YNBBJATXDCHGEQ-UHFFFAOYSA-N 3-[17-[(4-fluorophenyl)methyl]-4,7-dioxo-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraen-6-yl]propanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(CN(C2=O)CCC(=O)O)=O)C=C1 YNBBJATXDCHGEQ-UHFFFAOYSA-N 0.000 claims 1
- NXQVLUUSRAPKEC-UHFFFAOYSA-N 3-[8-[(4-fluorophenyl)methyl]-12-oxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2N(C3)C(N(C2)CCC(=O)O)=O)C=C1 NXQVLUUSRAPKEC-UHFFFAOYSA-N 0.000 claims 1
- SLUVFDFGMLBFKX-UHFFFAOYSA-N 3-[8-[(4-fluorophenyl)methyl]-15-methyl-12,14-dioxo-8,11,13-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-13-yl]propanoic acid Chemical compound FC1=CC=C(CN2C3=C(C=4C=CC=CC2=4)CC2(N(C3)C(N(C2=O)CCC(=O)O)=O)C)C=C1 SLUVFDFGMLBFKX-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
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- C—CHEMISTRY; METALLURGY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
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Landscapes
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
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| PCT/US2014/066705 WO2015077502A1 (en) | 2013-11-22 | 2014-11-20 | Tetracyclic autotaxin inhibitors |
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| US9951026B2 (en) | 2013-09-17 | 2018-04-24 | Pharmakea, Inc. | Heterocyclic vinyl autotaxin inhibitor compounds |
| EP3049405A4 (en) | 2013-09-26 | 2017-03-08 | Pharmakea Inc. | Autotaxin inhibitor compounds |
| HRP20210957T1 (hr) | 2013-11-22 | 2021-09-17 | Sabre Therapeutics Llc | Spojevi inhibitori autotaksina |
| US9926318B2 (en) | 2013-11-22 | 2018-03-27 | Pharmakea, Inc. | Tetracyclic autotaxin inhibitors |
| EP4026549A1 (en) | 2015-05-27 | 2022-07-13 | Sabre Therapeutics LLC | Autotaxin inhibitors and uses thereof |
| US10730878B2 (en) * | 2015-07-11 | 2020-08-04 | Advenchen Pharmaceuticals, LLC | Fused quinoline compounds as PI3K/mTOR inhibitors |
| CN105021735B (zh) * | 2015-07-21 | 2017-09-19 | 中国科学院西北高原生物研究所 | 白刺种子或其提取物中ss和rsMTCA的检测方法 |
| US20250002505A1 (en) * | 2021-10-05 | 2025-01-02 | Turning Point Therapeutics, Inc. | Synthesis of macroyclic compounds |
| CN119591596B (zh) * | 2024-12-04 | 2025-10-17 | 沈阳药科大学 | 4,5-二氢-3H-吡咯并[2,3-c]喹啉-4-酮衍生物及其应用 |
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| US6890933B1 (en) | 2000-02-24 | 2005-05-10 | President And Fellows Of Harvard College | Kinesin inhibitors |
| ATE332903T1 (de) | 2000-10-03 | 2006-08-15 | Lilly Icos Llc | Kondensierte pyridoindolderivate |
| US20060270634A1 (en) | 2005-05-06 | 2006-11-30 | Miller Duane D | Acetal phosphate-derived LPA mimics, PPARgamma activators, and autotaxin inhibitors |
| DE102007047737A1 (de) | 2007-10-05 | 2009-04-30 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
| US8268891B1 (en) | 2007-11-13 | 2012-09-18 | University Of Memphis Research Foundation | Autotaxin inhibitors |
| US8378100B2 (en) | 2008-01-09 | 2013-02-19 | University Of Virginia Patent Foundation | Phosphonate derivatives as autotaxin inhibitors |
| US20110110886A1 (en) | 2008-06-13 | 2011-05-12 | Yale University | Small molecule inhibitors of autotaxin and methods of use |
| WO2010040080A1 (en) | 2008-10-03 | 2010-04-08 | Abby Louise Parrill-Baker | Mechanism-based inactivators of autotaxin |
| DE102008059578A1 (de) | 2008-11-28 | 2010-06-10 | Merck Patent Gmbh | Benzo-Naphtyridin Verbindungen |
| CA2745041C (en) | 2008-12-01 | 2017-08-22 | Kai Schiemann | 2, 5-diamino-substituted pyrido [4, 3-d] pyrimidines as autotaxin inhibitors against cancer |
| KR20120027177A (ko) | 2009-04-02 | 2012-03-21 | 메르크 파텐트 게엠베하 | 오토탁신 저해제로서의 피페리딘 및 피라진 유도체 |
| AU2010230646B2 (en) | 2009-04-02 | 2015-11-26 | Merck Patent Gmbh | Heterocyclic compounds as autotaxin inhibitors |
| EA201101396A1 (ru) | 2009-04-02 | 2012-09-28 | Мерк Патент Гмбх | Ингибиторы аутотаксина |
| WO2011002918A1 (en) | 2009-06-30 | 2011-01-06 | The University Of Memphis Research Foundation | Novel diverse lead compound autotaxin inhibitors |
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-
2014
- 2014-11-20 US US15/036,370 patent/US9926318B2/en active Active
- 2014-11-20 AU AU2014352887A patent/AU2014352887A1/en not_active Abandoned
- 2014-11-20 BR BR112016010221A patent/BR112016010221A2/pt not_active Application Discontinuation
- 2014-11-20 KR KR1020167014492A patent/KR20160088878A/ko not_active Ceased
- 2014-11-20 CN CN201480063882.4A patent/CN105764903B/zh not_active Expired - Fee Related
- 2014-11-20 EP EP14863158.3A patent/EP3071569A4/en not_active Withdrawn
- 2014-11-20 JP JP2016533529A patent/JP2016537388A/ja active Pending
- 2014-11-20 EA EA201690880A patent/EA201690880A1/ru unknown
- 2014-11-20 MX MX2016006688A patent/MX2016006688A/es unknown
- 2014-11-20 WO PCT/US2014/066705 patent/WO2015077502A1/en not_active Ceased
- 2014-11-20 PE PE2016000667A patent/PE20160902A1/es not_active Application Discontinuation
- 2014-11-20 CA CA2930735A patent/CA2930735A1/en not_active Abandoned
- 2014-11-20 CR CR20160290A patent/CR20160290A/es unknown
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2016
- 2016-05-02 IL IL245389A patent/IL245389A0/en unknown
- 2016-05-10 PH PH12016500863A patent/PH12016500863A1/en unknown
- 2016-05-20 NI NI201600070A patent/NI201600070A/es unknown
- 2016-05-20 CL CL2016001232A patent/CL2016001232A1/es unknown
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2018
- 2018-02-08 US US15/892,142 patent/US20180162859A1/en not_active Abandoned
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|---|---|
| IL245389A0 (en) | 2016-06-30 |
| EP3071569A1 (en) | 2016-09-28 |
| PE20160902A1 (es) | 2016-09-04 |
| WO2015077502A1 (en) | 2015-05-28 |
| EA201690880A1 (ru) | 2016-12-30 |
| HK1226074B (zh) | 2017-09-22 |
| EP3071569A4 (en) | 2017-09-13 |
| CR20160290A (es) | 2016-09-28 |
| CN105764903A (zh) | 2016-07-13 |
| AU2014352887A1 (en) | 2016-06-09 |
| BR112016010221A2 (pt) | 2018-05-02 |
| MX2016006688A (es) | 2016-11-29 |
| KR20160088878A (ko) | 2016-07-26 |
| US20180162859A1 (en) | 2018-06-14 |
| JP2016537388A (ja) | 2016-12-01 |
| PH12016500863A1 (en) | 2016-07-18 |
| CL2016001232A1 (es) | 2017-02-03 |
| US9926318B2 (en) | 2018-03-27 |
| CN105764903B (zh) | 2018-09-18 |
| US20160264575A1 (en) | 2016-09-15 |
| NI201600070A (es) | 2016-09-21 |
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