JP2016501241A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2016501241A5 JP2016501241A5 JP2015545771A JP2015545771A JP2016501241A5 JP 2016501241 A5 JP2016501241 A5 JP 2016501241A5 JP 2015545771 A JP2015545771 A JP 2015545771A JP 2015545771 A JP2015545771 A JP 2015545771A JP 2016501241 A5 JP2016501241 A5 JP 2016501241A5
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- benzimidazole
- carbazol
- carboxylic acid
- alkyl
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- VTAXFHATHOHPMA-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 VTAXFHATHOHPMA-UHFFFAOYSA-N 0.000 claims description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 23
- 229910052799 carbon Inorganic materials 0.000 claims 15
- 229910052731 fluorine Inorganic materials 0.000 claims 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 12
- 229910052801 chlorine Inorganic materials 0.000 claims 11
- 125000000217 alkyl group Chemical group 0.000 claims 9
- 239000003112 inhibitor Substances 0.000 claims 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 5
- 229920000858 Cyclodextrin Polymers 0.000 claims 5
- -1 N, N- dimethylamino Chemical group 0.000 claims 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims 5
- 239000012453 solvate Substances 0.000 claims 5
- 238000011282 treatment Methods 0.000 claims 5
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 239000005557 antagonist Substances 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 208000031169 hemorrhagic disease Diseases 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims 3
- 208000005171 Dysmenorrhea Diseases 0.000 claims 3
- 206010013935 Dysmenorrhoea Diseases 0.000 claims 3
- 201000009273 Endometriosis Diseases 0.000 claims 3
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 201000010260 leiomyoma Diseases 0.000 claims 3
- 208000030761 polycystic kidney disease Diseases 0.000 claims 3
- 201000007954 uterine fibroid Diseases 0.000 claims 3
- 208000032843 Hemorrhage Diseases 0.000 claims 2
- 102000003964 Histone deacetylase Human genes 0.000 claims 2
- 108090000353 Histone deacetylase Proteins 0.000 claims 2
- 101000579300 Homo sapiens Prostaglandin F2-alpha receptor Proteins 0.000 claims 2
- 108091007960 PI3Ks Proteins 0.000 claims 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 102100028248 Prostaglandin F2-alpha receptor Human genes 0.000 claims 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- 230000000740 bleeding effect Effects 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 229940111134 coxibs Drugs 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims 2
- 102000015694 estrogen receptors Human genes 0.000 claims 2
- 108010038795 estrogen receptors Proteins 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 239000002379 progesterone receptor modulator Substances 0.000 claims 2
- 238000011321 prophylaxis Methods 0.000 claims 2
- 239000000849 selective androgen receptor modulator Substances 0.000 claims 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 claims 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 2
- 229920002554 vinyl polymer Polymers 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- RYUKCSMZZCGEIR-UHFFFAOYSA-N 1-(2-cyclopropyl-2-hydroxyethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC(O)C1CC1 RYUKCSMZZCGEIR-UHFFFAOYSA-N 0.000 claims 1
- WFHPTQLOIAKZQP-UHFFFAOYSA-N 1-(2-cyclopropylethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CCC1CC1 WFHPTQLOIAKZQP-UHFFFAOYSA-N 0.000 claims 1
- LGCHPYLRKINXIJ-UHFFFAOYSA-N 1-(2-methoxyethyl)-2-(9-prop-2-enylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C1=CC=C2C3=CC(C=4N(C5=CC=C(C=C5N=4)C(O)=O)CCOC)=CC=C3N(CC=C)C2=C1 LGCHPYLRKINXIJ-UHFFFAOYSA-N 0.000 claims 1
- PTPUMBAQYIXOIX-UHFFFAOYSA-N 1-(2-methoxyethyl)-2-(9-prop-2-ynylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound COCCN1C(=NC2=C1C=CC(=C2)C(=O)O)C=2C=CC=1N(C3=CC=CC=C3C1C2)CC#C PTPUMBAQYIXOIX-UHFFFAOYSA-N 0.000 claims 1
- PEWXSYIXHHFVSI-UHFFFAOYSA-N 1-(2-methoxyethyl)-2-(9-propylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CCC)=NC2=C1 PEWXSYIXHHFVSI-UHFFFAOYSA-N 0.000 claims 1
- LVSATUIUXPKXFR-UHFFFAOYSA-N 1-(2-methoxyethyl)-2-[9-(2-methoxyethyl)carbazol-3-yl]benzimidazole-5-carboxylic acid Chemical compound C1=CC=C2C3=CC(C=4N(C5=CC=C(C=C5N=4)C(O)=O)CCOC)=CC=C3N(CCOC)C2=C1 LVSATUIUXPKXFR-UHFFFAOYSA-N 0.000 claims 1
- UACXWYYXMSEMKI-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(5-ethylpyrido[4,3-b]indol-8-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=NC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 UACXWYYXMSEMKI-UHFFFAOYSA-N 0.000 claims 1
- NCSKSDRTTUYJAG-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethyl-1-methylpyrido[3,4-b]indol-3-yl)benzimidazole-5-carboxylic acid Chemical compound N=1C(C)=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 NCSKSDRTTUYJAG-UHFFFAOYSA-N 0.000 claims 1
- QEAYAWUXJAJQPY-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethyl-6-methoxycarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=C(OC)C=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 QEAYAWUXJAJQPY-UHFFFAOYSA-N 0.000 claims 1
- PZSWYLZSYHZFSY-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-4-fluorobenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=C(F)C(C(O)=O)=CC=C2N1CC1CC1 PZSWYLZSYHZFSY-UHFFFAOYSA-N 0.000 claims 1
- PBDYTDWNLUIEIC-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-4-methoxybenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=C(OC)C(C(O)=O)=CC=C2N1CC1CC1 PBDYTDWNLUIEIC-UHFFFAOYSA-N 0.000 claims 1
- QIXPAFKZHMAPQO-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=C(C)C(C(O)=O)=CC=C2N1CC1CC1 QIXPAFKZHMAPQO-UHFFFAOYSA-N 0.000 claims 1
- JYMMCQLLFAFGHN-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-6-fluorobenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=C(F)C=C2N1CC1CC1 JYMMCQLLFAFGHN-UHFFFAOYSA-N 0.000 claims 1
- OODXJBKGDCRQEA-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-6-methoxybenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=C(OC)C=C2N1CC1CC1 OODXJBKGDCRQEA-UHFFFAOYSA-N 0.000 claims 1
- BWQPVQKMQJNGJD-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)-6-methylbenzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=C(C)C=C2N1CC1CC1 BWQPVQKMQJNGJD-UHFFFAOYSA-N 0.000 claims 1
- FDCJBNUENMJJOW-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 FDCJBNUENMJJOW-UHFFFAOYSA-N 0.000 claims 1
- HJJMKXDMBDVSML-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylpyrido[2,3-b]indol-3-yl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound C1(CC1)CN1C(=NC2=C1C=CC(=C2C)C(=O)O)C2=CC1=C(N(C3=CC=CC=C13)CC)N=C2 HJJMKXDMBDVSML-UHFFFAOYSA-N 0.000 claims 1
- PEMKEFCIURPVDU-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylpyrido[2,3-b]indol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1N=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 PEMKEFCIURPVDU-UHFFFAOYSA-N 0.000 claims 1
- OQQWRHPJHVJCQL-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylpyrido[2,3-b]indol-6-yl)benzimidazole-5-carboxylic acid Chemical compound C1=C2C3=CC=CN=C3N(CC)C2=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 OQQWRHPJHVJCQL-UHFFFAOYSA-N 0.000 claims 1
- KHSJFGUPDOZGHZ-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylpyrido[3,4-b]indol-6-yl)benzimidazole-5-carboxylic acid Chemical compound C1=C2C3=CC=NC=C3N(CC)C2=CC=C1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 KHSJFGUPDOZGHZ-UHFFFAOYSA-N 0.000 claims 1
- QXAVQTCMAFPTHI-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-methylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(C)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 QXAVQTCMAFPTHI-UHFFFAOYSA-N 0.000 claims 1
- JNBHAYIJLOISKK-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-prop-2-enylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC=C)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1CC1CC1 JNBHAYIJLOISKK-UHFFFAOYSA-N 0.000 claims 1
- CQLAEMXFJFUNRC-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-propylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CCC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 CQLAEMXFJFUNRC-UHFFFAOYSA-N 0.000 claims 1
- QRGFXCGIAKNBLR-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-[9-(2-methoxyethyl)carbazol-3-yl]benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CCOC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 QRGFXCGIAKNBLR-UHFFFAOYSA-N 0.000 claims 1
- ANNBMWKEZQOIED-UHFFFAOYSA-N 1-[(2,2-dimethylcyclopropyl)methyl]-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound CC1(C(C1)CN1C(=NC2=C1C=CC(=C2)C(=O)O)C=2C=CC=1N(C3=CC=CC=C3C1C2)CC)C ANNBMWKEZQOIED-UHFFFAOYSA-N 0.000 claims 1
- ACULBGOBNAAIPK-KRWDZBQOSA-N 1-[(2s)-2,3-dihydroxypropyl]-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C[C@H](O)CO)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 ACULBGOBNAAIPK-KRWDZBQOSA-N 0.000 claims 1
- DISXHZOECNRANJ-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCN(C)C)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 DISXHZOECNRANJ-UHFFFAOYSA-N 0.000 claims 1
- 102100037426 17-beta-hydroxysteroid dehydrogenase type 1 Human genes 0.000 claims 1
- KRBRKVFRAUTGNF-UHFFFAOYSA-N 2-(5-ethylpyrido[3,2-b]indol-2-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3N=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 KRBRKVFRAUTGNF-UHFFFAOYSA-N 0.000 claims 1
- PNGKCFGAJWAWGO-UHFFFAOYSA-N 2-(6-chloro-9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC(Cl)=CC=C5N(C4=CC=3)CC)=NC2=C1C PNGKCFGAJWAWGO-UHFFFAOYSA-N 0.000 claims 1
- BXQVRCKNIKOYII-UHFFFAOYSA-N 2-(8-chloro-9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C3=CC=C4N(C5=C(Cl)C=CC=C5C4=C3)CC)=NC2=C1C BXQVRCKNIKOYII-UHFFFAOYSA-N 0.000 claims 1
- GLUVBPUPVTVFNT-UHFFFAOYSA-N 2-(9-ethyl-5-fluorocarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C3=CC=C4N(C5=CC=CC(F)=C5C4=C3)CC)=NC2=C1 GLUVBPUPVTVFNT-UHFFFAOYSA-N 0.000 claims 1
- VUICOLWEYUZJBO-UHFFFAOYSA-N 2-(9-ethyl-6-methoxycarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC(OC)=CC=C5N(C4=CC=3)CC)=NC2=C1 VUICOLWEYUZJBO-UHFFFAOYSA-N 0.000 claims 1
- FHXIZAPGGULPIK-UHFFFAOYSA-N 2-(9-ethyl-6-methylcarbazol-3-yl)-1-(2-methoxyethyl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC(C)=CC=C5N(C4=CC=3)CC)=NC2=C1C FHXIZAPGGULPIK-UHFFFAOYSA-N 0.000 claims 1
- YPARQYYRYUEBHJ-UHFFFAOYSA-N 2-(9-ethyl-7-fluorocarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C3=CC=C4N(C5=CC(F)=CC=C5C4=C3)CC)=NC2=C1 YPARQYYRYUEBHJ-UHFFFAOYSA-N 0.000 claims 1
- ZCGHJEMCRFWOER-UHFFFAOYSA-N 2-(9-ethyl-8-fluorocarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C3=CC=C4N(C5=C(F)C=CC=C5C4=C3)CC)=NC2=C1 ZCGHJEMCRFWOER-UHFFFAOYSA-N 0.000 claims 1
- ODXHWQWXZOXFPX-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-hydroxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCO)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 ODXHWQWXZOXFPX-UHFFFAOYSA-N 0.000 claims 1
- UYIJGNNZVACBMR-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)-4-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1C UYIJGNNZVACBMR-UHFFFAOYSA-N 0.000 claims 1
- OHCPIAVGSMNZKZ-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)-6-methylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=C(C)C=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 OHCPIAVGSMNZKZ-UHFFFAOYSA-N 0.000 claims 1
- XEQKPBUOQQCDKC-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 XEQKPBUOQQCDKC-UHFFFAOYSA-N 0.000 claims 1
- UNRDYSLYFZTCQW-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-methylsulfonylethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCS(C)(=O)=O)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 UNRDYSLYFZTCQW-UHFFFAOYSA-N 0.000 claims 1
- QRFDPXOPOVIWMQ-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-morpholin-4-ylethyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CCN1CCOCC1 QRFDPXOPOVIWMQ-UHFFFAOYSA-N 0.000 claims 1
- FUGKHYQCNCZXOW-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(2-pyrrolidin-1-ylethyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CCN1CCCC1 FUGKHYQCNCZXOW-UHFFFAOYSA-N 0.000 claims 1
- CQUUTXQVFFFFMQ-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(3-methoxypropyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 CQUUTXQVFFFFMQ-UHFFFAOYSA-N 0.000 claims 1
- XNIZGEFJXNDHLS-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(oxolan-2-ylmethyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CCCO1 XNIZGEFJXNDHLS-UHFFFAOYSA-N 0.000 claims 1
- FYZHEYINKISOSE-GOSISDBHSA-N 2-(9-ethylcarbazol-3-yl)-1-[(2r)-2-hydroxy-3-methoxypropyl]benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C[C@@H](O)COC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 FYZHEYINKISOSE-GOSISDBHSA-N 0.000 claims 1
- FYZHEYINKISOSE-SFHVURJKSA-N 2-(9-ethylcarbazol-3-yl)-1-[(2s)-2-hydroxy-3-methoxypropyl]benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C[C@H](O)COC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 FYZHEYINKISOSE-SFHVURJKSA-N 0.000 claims 1
- VTALIBBCVSUPQG-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-[2-(trifluoromethoxy)ethyl]benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC(F)(F)F)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 VTALIBBCVSUPQG-UHFFFAOYSA-N 0.000 claims 1
- BAKDAGPTIWBXRP-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-prop-2-enylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CC=C)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 BAKDAGPTIWBXRP-UHFFFAOYSA-N 0.000 claims 1
- MHEQDBAVFQXCOV-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-propan-2-ylbenzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(C(C)C)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 MHEQDBAVFQXCOV-UHFFFAOYSA-N 0.000 claims 1
- DUFQDZCZLLVKQR-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-4-fluoro-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1F DUFQDZCZLLVKQR-UHFFFAOYSA-N 0.000 claims 1
- GGLRAOVFLKWYNU-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-6-fluoro-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=C(F)C=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 GGLRAOVFLKWYNU-UHFFFAOYSA-N 0.000 claims 1
- GIVBBEZUIKZZLH-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-6-methoxy-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=C(OC)C=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 GIVBBEZUIKZZLH-UHFFFAOYSA-N 0.000 claims 1
- WQVQCZLVBSEMRD-UHFFFAOYSA-N 2-[9-(cyclobutylmethyl)carbazol-3-yl]-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound N=1C2=CC(C(O)=O)=CC=C2N(CCOC)C=1C(C=C1C2=CC=CC=C22)=CC=C1N2CC1CCC1 WQVQCZLVBSEMRD-UHFFFAOYSA-N 0.000 claims 1
- URXPFHBOWBEBKM-UHFFFAOYSA-N 2-[9-(cyclobutylmethyl)carbazol-3-yl]-1-(cyclopropylmethyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC3CCC3)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(=O)O)=CC=C2N1CC1CC1 URXPFHBOWBEBKM-UHFFFAOYSA-N 0.000 claims 1
- BXTKOAWVQSCZBQ-UHFFFAOYSA-N 2-[9-(cyclopropylmethyl)carbazol-3-yl]-1-(2-methoxyethyl)benzimidazole-5-carboxylic acid Chemical compound N=1C2=CC(C(O)=O)=CC=C2N(CCOC)C=1C(C=C1C2=CC=CC=C22)=CC=C1N2CC1CC1 BXTKOAWVQSCZBQ-UHFFFAOYSA-N 0.000 claims 1
- 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 claims 1
- LIXQIYVELKPRDC-UHFFFAOYSA-N 4-chloro-1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=C(Cl)C(C(O)=O)=CC=C2N1CC1CC1 LIXQIYVELKPRDC-UHFFFAOYSA-N 0.000 claims 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 claims 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- 229940122815 Aromatase inhibitor Drugs 0.000 claims 1
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 claims 1
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 claims 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 claims 1
- 101000919849 Homo sapiens Cytochrome c oxidase subunit 1 Proteins 0.000 claims 1
- 101000605122 Homo sapiens Prostaglandin G/H synthase 1 Proteins 0.000 claims 1
- 229940127374 Hydroxylase Activators Drugs 0.000 claims 1
- 206010021143 Hypoxia Diseases 0.000 claims 1
- 101710146020 Kinin-1 Proteins 0.000 claims 1
- 102000013599 Kisspeptins Human genes 0.000 claims 1
- 108010012048 Kisspeptins Proteins 0.000 claims 1
- 101150018665 MAPK3 gene Proteins 0.000 claims 1
- 101150100676 Map2k1 gene Proteins 0.000 claims 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 claims 1
- 102000004079 Prolyl Hydroxylases Human genes 0.000 claims 1
- 108010043005 Prolyl Hydroxylases Proteins 0.000 claims 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims 1
- 108091008611 Protein Kinase B Proteins 0.000 claims 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 claims 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims 1
- 108010087999 Steryl-Sulfatase Proteins 0.000 claims 1
- 102100038021 Steryl-sulfatase Human genes 0.000 claims 1
- 102000005262 Sulfatase Human genes 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 101150045355 akt1 gene Proteins 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 239000003098 androgen Substances 0.000 claims 1
- 229940030486 androgens Drugs 0.000 claims 1
- 239000003418 antiprogestin Substances 0.000 claims 1
- 239000003886 aromatase inhibitor Substances 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 208000034158 bleeding Diseases 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- AZGOQNLLQXSKFN-UHFFFAOYSA-N ethyl 1-(2-methoxyethyl)-2-[9-(2-methoxyethyl)carbazol-3-yl]benzimidazole-5-carboxylate Chemical compound C1=CC=C2C3=CC(C=4N(CCOC)C5=CC=C(C=C5N=4)C(=O)OCC)=CC=C3N(CCOC)C2=C1 AZGOQNLLQXSKFN-UHFFFAOYSA-N 0.000 claims 1
- METGUEUINHCSAY-UHFFFAOYSA-N ethyl 1-[2-(dimethylamino)ethyl]-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylate Chemical compound C1=CC=C2C3=CC(C=4N(CCN(C)C)C5=CC=C(C=C5N=4)C(=O)OCC)=CC=C3N(CC)C2=C1 METGUEUINHCSAY-UHFFFAOYSA-N 0.000 claims 1
- JOUIHPVQCQZDQC-UHFFFAOYSA-N ethyl 2-(9-ethylcarbazol-3-yl)-1-(2-pyrrolidin-1-ylethyl)benzimidazole-5-carboxylate Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(=O)OCC)=CC=C2N1CCN1CCCC1 JOUIHPVQCQZDQC-UHFFFAOYSA-N 0.000 claims 1
- FLDOWCQVTOMQEU-UHFFFAOYSA-N ethyl 2-(9-ethylcarbazol-3-yl)-1-(3-methoxypropyl)benzimidazole-5-carboxylate Chemical compound C1=CC=C2C3=CC(C=4N(CCCOC)C5=CC=C(C=C5N=4)C(=O)OCC)=CC=C3N(CC)C2=C1 FLDOWCQVTOMQEU-UHFFFAOYSA-N 0.000 claims 1
- GNQHCGMAMYAYOJ-UHFFFAOYSA-N ethyl 2-(9-ethylcarbazol-3-yl)-1-(oxetan-3-ylmethyl)benzimidazole-5-carboxylate Chemical compound C(C)N1C2=CC=CC=C2C=2C=C(C=CC12)C1=NC2=C(N1CC1COC1)C=CC(=C2)C(=O)OCC GNQHCGMAMYAYOJ-UHFFFAOYSA-N 0.000 claims 1
- PMMJUEFCMGVBQK-UHFFFAOYSA-N ethyl 2-(9-ethylcarbazol-3-yl)-1-propan-2-ylbenzimidazole-5-carboxylate Chemical compound C1=CC=C2C3=CC(C=4N(C(C)C)C5=CC=C(C=C5N=4)C(=O)OCC)=CC=C3N(CC)C2=C1 PMMJUEFCMGVBQK-UHFFFAOYSA-N 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 210000000936 intestine Anatomy 0.000 claims 1
- 230000001788 irregular Effects 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- HIJRXRGAZYBOEJ-UHFFFAOYSA-N methyl 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylate Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(=O)OC)=CC=C2N1CC1CC1 HIJRXRGAZYBOEJ-UHFFFAOYSA-N 0.000 claims 1
- LYNJDOGZYHQGFN-UHFFFAOYSA-N methyl 1-ethyl-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylate Chemical compound C1=CC=C2C3=CC(C=4N(C5=CC=C(C=C5N=4)C(=O)OC)CC)=CC=C3N(CC)C2=C1 LYNJDOGZYHQGFN-UHFFFAOYSA-N 0.000 claims 1
- HNKQOIMXIKNLQZ-UHFFFAOYSA-N methyl 2-(9-ethylcarbazol-3-yl)-1-(2-methoxyethyl)benzimidazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2N(CCOC)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 HNKQOIMXIKNLQZ-UHFFFAOYSA-N 0.000 claims 1
- MMZFRHDNEKNLQA-UHFFFAOYSA-N methyl 2-(9-ethylcarbazol-3-yl)-1-prop-2-enylbenzimidazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2N(CC=C)C(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 MMZFRHDNEKNLQA-UHFFFAOYSA-N 0.000 claims 1
- SEHFIEWPIZNUQB-UHFFFAOYSA-N methyl 4-chloro-1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylate Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=C(Cl)C(C(=O)OC)=CC=C2N1CC1CC1 SEHFIEWPIZNUQB-UHFFFAOYSA-N 0.000 claims 1
- 239000003226 mitogen Substances 0.000 claims 1
- 210000002569 neuron Anatomy 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 229940127234 oral contraceptive Drugs 0.000 claims 1
- 239000003539 oral contraceptive agent Substances 0.000 claims 1
- 125000003566 oxetanyl group Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 229960005489 paracetamol Drugs 0.000 claims 1
- 230000002085 persistent effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 102000020233 phosphotransferase Human genes 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000000583 progesterone congener Substances 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 210000003491 skin Anatomy 0.000 claims 1
- 108060007951 sulfatase Proteins 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- CICNHFQGJQVXKR-UHFFFAOYSA-N O1C(CC1)CN1C(=NC2=C1C=C(C(=C2)C(=O)O)OC)C=2C=CC=1N(C3=CC=CC=C3C1C2)CC Chemical compound O1C(CC1)CN1C(=NC2=C1C=C(C(=C2)C(=O)O)OC)C=2C=CC=1N(C3=CC=CC=C3C1C2)CC CICNHFQGJQVXKR-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- MKYVLQPHUCCQLZ-UHFFFAOYSA-N ethyl 2-(9-ethylcarbazol-3-yl)-1-methylbenzimidazole-5-carboxylate Chemical compound C(C)N1C2=CC=CC=C2C=2C=C(C=CC1=2)C1=NC2=C(N1C)C=CC(=C2)C(=O)OCC MKYVLQPHUCCQLZ-UHFFFAOYSA-N 0.000 description 1
- FWPHMYMCQHSZHC-UHFFFAOYSA-N methyl 2-(9-ethylcarbazol-3-yl)-3h-benzimidazole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=C2NC(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 FWPHMYMCQHSZHC-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12195849.0 | 2012-12-06 | ||
| EP12195849 | 2012-12-06 | ||
| PCT/EP2013/075309 WO2014086739A1 (de) | 2012-12-06 | 2013-12-03 | Neuartige benzimidazolderivate als ep4-antagonisten |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016501241A JP2016501241A (ja) | 2016-01-18 |
| JP2016501241A5 true JP2016501241A5 (https=) | 2017-12-14 |
| JP6367822B2 JP6367822B2 (ja) | 2018-08-01 |
Family
ID=47325927
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015545771A Active JP6367822B2 (ja) | 2012-12-06 | 2013-12-03 | Ｅｐ４アンタゴニストとしての新規ベンゾイミダゾール誘導体 |
Country Status (40)
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| US8633178B2 (en) | 2011-11-23 | 2014-01-21 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
| US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
| US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
| US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
| US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| EP2961747B1 (en) | 2013-02-27 | 2017-11-15 | Bristol-Myers Squibb Company | Carbazole compounds useful as bromodomain inhibitors |
| US9492460B2 (en) * | 2013-02-27 | 2016-11-15 | Bristol-Myers Squibb Company | Carbazole compounds useful as bromodomain inhibitors |
| JP2016534984A (ja) | 2013-10-01 | 2016-11-10 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | アフィニティークロマトグラフィーのためおよび治療薬の半減期の延長のための化合物 |
| TW201607943A (zh) | 2013-12-19 | 2016-03-01 | 拜耳製藥公司 | 作為ｅｐ４配體之新穎苯并咪唑衍生物 |
| US9458156B2 (en) | 2014-12-23 | 2016-10-04 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
| KR102457145B1 (ko) * | 2013-12-24 | 2022-10-19 | 브리스톨-마이어스 스큅 컴퍼니 | 항암제로서의 트리시클릭 화합물 |
| EP3145489A1 (en) | 2014-05-22 | 2017-03-29 | TherapeuticsMD, Inc. | Natural combination hormone replacement formulations and therapies |
| CN104326937B (zh) * | 2014-09-03 | 2016-08-24 | 天津市肿瘤研究所 | 抗肿瘤化合物及其医药用途 |
| TWI735416B (zh) | 2014-10-06 | 2021-08-11 | 美商維泰克斯製藥公司 | 囊腫纖維化症跨膜傳導調節蛋白之調節劑 |
| US9725449B2 (en) | 2015-05-12 | 2017-08-08 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
| US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| ES2946970T3 (es) | 2016-03-31 | 2023-07-28 | Vertex Pharma | Regulador de conductancia transmembrana de moduladores de fibrosis quística |
| WO2017173071A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
| WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
| SI3519401T1 (sl) | 2016-09-30 | 2022-01-31 | Vertex Pharmaceuticals Incorporated | Modulator regulatorja transmembranske prevodnosti pri cistični fibrozi, farmacevtski sestavki, postopki zdravljenja in proces za izdelavo modulatorja |
| CN110267948B (zh) | 2016-12-09 | 2023-12-08 | 弗特克斯药品有限公司 | 囊性纤维化跨膜传导调控剂的调节剂、药物组合物、治疗方法和制备所述调节剂的方法 |
| WO2018162562A1 (en) * | 2017-03-10 | 2018-09-13 | Bayer Pharma Aktiengesellschaft | Use of an ep4 antagonist for the treatment of inflammatory pain |
| US11839613B2 (en) | 2017-05-18 | 2023-12-12 | Idorsia Pharmaceuticals Ltd | Pyrimidine derivatives as PGE2 receptor modulators |
| KR102612140B1 (ko) | 2017-05-18 | 2023-12-08 | 이도르시아 파마슈티컬스 리미티드 | 피리미딘 유도체 |
| TWI768043B (zh) | 2017-05-18 | 2022-06-21 | 瑞士商愛杜西亞製藥有限公司 | N-取代吲哚衍生物 |
| PE20191814A1 (es) | 2017-05-18 | 2019-12-27 | Idorsia Pharmaceuticals Ltd | Derivados de pirimidina como moduladores del receptor de pge2 |
| TW201900179A (zh) | 2017-05-18 | 2019-01-01 | 瑞士商愛杜西亞製藥有限公司 | 作為pge2受體調節劑之苯并呋喃及苯并噻吩衍生物 |
| AU2018279646B2 (en) | 2017-06-08 | 2023-04-06 | Vertex Pharmaceuticals Incorporated | Methods of treatment for cystic fibrosis |
| MA49631A (fr) | 2017-07-17 | 2020-05-27 | Vertex Pharma | Méthodes de traitement de la fibrose kystique |
| TWI799435B (zh) | 2017-08-02 | 2023-04-21 | 美商維泰克斯製藥公司 | 製備化合物之製程 |
| WO2019038156A1 (en) | 2017-08-22 | 2019-02-28 | Bayer Pharma Aktiengesellschaft | USE OF AN EP4 ANTAGONIST FOR THE TREATMENT OF ARTHRITIS |
| US10654829B2 (en) | 2017-10-19 | 2020-05-19 | Vertex Pharmaceuticals Incorporated | Crystalline forms and compositions of CFTR modulators |
| KR102716244B1 (ko) | 2017-12-08 | 2024-10-14 | 버텍스 파마슈티칼스 인코포레이티드 | 낭포성 섬유증 막횡단 전도 조절자의 조정제의 제조 방법 |
| TWI810243B (zh) | 2018-02-05 | 2023-08-01 | 美商維泰克斯製藥公司 | 用於治療囊腫纖化症之醫藥組合物 |
| EP3774825A1 (en) | 2018-04-13 | 2021-02-17 | Vertex Pharmaceuticals Incorporated | Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator |
| US20210300921A1 (en) * | 2018-07-11 | 2021-09-30 | Arrys Therapeutics, Inc. | Ep4 inhibitors and synthesis thereof |
| CN113527206B (zh) * | 2020-04-17 | 2022-12-30 | 上海中泽医药科技有限公司 | 一种苯并氮杂环类化合物、其制备方法及用途 |
| EP4146648A1 (en) * | 2020-05-04 | 2023-03-15 | Otsuka Pharmaceutical Co., Ltd. | Iap antagonist compounds and intermediates and methods for synthesizing the same |
| US20230390303A1 (en) | 2020-11-13 | 2023-12-07 | Ono Pharmaceutical Co., Ltd. | Cancer treatment by combination of ep4 antagonist and immune checkpoint inhibitor |
| US12016847B2 (en) | 2021-03-12 | 2024-06-25 | Bristol-Myers Squibb Company | Methods of treating prostate cancer |
| KR102708701B1 (ko) * | 2021-12-27 | 2024-09-24 | 에이치케이이노엔 주식회사 | 벤즈이미다졸 유도체의 제조방법 |
| CN116789646B (zh) * | 2023-07-12 | 2025-07-08 | 广西医科大学 | 咔唑-苯并咪唑偶联类化合物及其应用 |
| WO2025135108A1 (ja) * | 2023-12-22 | 2025-06-26 | Ａｇｃ株式会社 | 新規なｅｐ４アンタゴニスト |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ514403A (en) | 1999-12-27 | 2002-10-25 | Japan Tobacco Inc | Fused-ring compounds and use thereof as drugs |
| KR100913910B1 (ko) | 2000-01-18 | 2009-08-26 | 바이엘 쉐링 파마 악티엔게젤샤프트 | 호르몬 보충 요법용 드로스피렌온 |
| HN2001000224A (es) | 2000-10-19 | 2002-06-13 | Pfizer | Compuestos de imidazol condensado con arilo o heteroarilo como agentes anti - inflamatorios y analgesicos. |
| AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
| CN100579518C (zh) | 2002-04-12 | 2010-01-13 | 美国辉瑞有限公司 | Ep4受体配体在制备治疗il-6相关疾病的药物中的应用 |
| CA2492305A1 (en) * | 2002-07-31 | 2004-02-05 | Euro-Celtique S.A. | Aryl substituted benzimidazoles and their use as sodium channel blockers |
| AU2002951247A0 (en) | 2002-09-06 | 2002-09-19 | Alchemia Limited | Compounds that interact with kinases |
| EA009871B1 (ru) | 2002-11-15 | 2008-04-28 | Тиботек Фармасьютикалз Лтд. | Замещённые индолпиридиниевые соединения в качестве противоинфекционного средства |
| US6949564B2 (en) | 2002-12-18 | 2005-09-27 | Pfizer Inc. | NPY-5 antagonists |
| DE602004013938D1 (de) | 2003-01-29 | 2008-07-03 | Asterand Uk Ltd | Hemmstoffe des ep4-rezeptors |
| EP1613618A2 (en) | 2003-04-03 | 2006-01-11 | Neurosearch A/S | BENZIMIDAZOLE DERIVATIVES AND THEIR USE FOR MODULATING THE GABA- sb A /sb RECEPTOR COMPLEX |
| TW200512147A (en) | 2003-07-25 | 2005-04-01 | Black Clawson Converting Machinery Inc | Method and apparatus for splicing webs |
| KR100747401B1 (ko) | 2003-09-03 | 2007-08-08 | 화이자 인코포레이티드 | 프로스타글란딘 ｅ2 길항제로서의 페닐 또는 피리딜 아미드 화합물 |
| WO2005102389A2 (en) | 2004-04-20 | 2005-11-03 | Pfizer Products Inc. | Combinations comprising alpha-2-delta ligands and ep4 receptor antagonists |
| JP2008504233A (ja) | 2004-04-23 | 2008-02-14 | パラテック ファーマシューティカルズ インコーポレイテッド | 転写因子調節化合物およびその使用法 |
| JP4054369B2 (ja) | 2004-05-04 | 2008-02-27 | ファイザー株式会社 | オルト置換アリールまたはヘテロアリールアミド化合物 |
| CN101142185A (zh) * | 2005-01-19 | 2008-03-12 | 比奥里波克斯公司 | 用于炎症治疗的吲哚 |
| ES2392192T3 (es) | 2006-04-24 | 2012-12-05 | Merck Canada Inc. | Derivados de indol amida como antagonistas del receptor EP4 |
| US7732447B2 (en) * | 2006-06-22 | 2010-06-08 | Cephalon, Inc. | Fused [d]pyridazin-7-ones |
| GB0614066D0 (en) * | 2006-07-14 | 2006-08-23 | Glaxo Group Ltd | Compounds |
| FR2904318B1 (fr) * | 2006-07-27 | 2011-02-25 | Scras | Derives de pyrimidinone et leur utilisation comme medicament |
| US8969394B2 (en) | 2006-08-11 | 2015-03-03 | Merck Frosst Canada Ltd. | Thiophenecarboxamide derivatives as EP4 receptor ligands |
| CA2679175C (en) | 2007-02-26 | 2015-01-13 | Merck Frosst Canada Ltd. | Indole and indoline cyclopropyl amide derivatives as ep4 receptor antagonists |
| DE102007011105A1 (de) | 2007-03-02 | 2008-09-04 | Bayer Schering Pharma Aktiengesellschaft | Mineralcorticoid-Rezeptor-Antagonisten zur Behandlung von Endometriose |
| JP5408434B2 (ja) | 2007-07-03 | 2014-02-05 | アステラス製薬株式会社 | アミド化合物 |
| CN102026991A (zh) | 2007-08-09 | 2011-04-20 | 默沙东公司 | 制造噻吩甲酰胺衍生物的方法 |
| JP5536773B2 (ja) | 2008-08-14 | 2014-07-02 | ベータ・ファーマ・カナダ・インコーポレイテッド | Ｅｐ４受容体アンタゴニストとしてのヘテロ環式アミド誘導体 |
| US20100249125A1 (en) | 2009-03-31 | 2010-09-30 | The Texas A&M University System | Inhibition of prostglandin e2 receptors for the treatment of endometriosis |
| WO2010124097A2 (en) | 2009-04-22 | 2010-10-28 | Paratek Pharmaceuticals, Inc. | Transcription factor modulating compounds and methods of use thereof |
| US9457084B2 (en) | 2010-02-22 | 2016-10-04 | Raqualia Pharma Inc. | Use of EP4 receptor antagonists in the treatment of IL-23 mediated diseases |
| TW201607943A (zh) * | 2013-12-19 | 2016-03-01 | 拜耳製藥公司 | 作為ｅｐ４配體之新穎苯并咪唑衍生物 |
-
2013
- 2013-03-12 UA UAA201506493A patent/UA115576C2/uk unknown
- 2013-12-03 BR BR112015012555-7A patent/BR112015012555B1/pt active IP Right Grant
- 2013-12-03 CN CN201380063594.4A patent/CN104854098B/zh active Active
- 2013-12-03 MY MYPI2015701808A patent/MY175272A/en unknown
- 2013-12-03 AP AP2015008463A patent/AP3862A/en active
- 2013-12-03 LT LTEP13798684.0T patent/LT2928884T/lt unknown
- 2013-12-03 ME MEP-2017-181A patent/ME02950B/me unknown
- 2013-12-03 DK DK13798684.0T patent/DK2928884T3/en active
- 2013-12-03 WO PCT/EP2013/075309 patent/WO2014086739A1/de not_active Ceased
- 2013-12-03 US US14/649,896 patent/US9708311B2/en active Active
- 2013-12-03 PE PE2015000750A patent/PE20151065A1/es active IP Right Grant
- 2013-12-03 HR HRP20171200TT patent/HRP20171200T1/hr unknown
- 2013-12-03 EP EP13798684.0A patent/EP2928884B1/de active Active
- 2013-12-03 NZ NZ707825A patent/NZ707825A/en unknown
- 2013-12-03 CA CA2893630A patent/CA2893630C/en active Active
- 2013-12-03 PT PT137986840T patent/PT2928884T/pt unknown
- 2013-12-03 JP JP2015545771A patent/JP6367822B2/ja active Active
- 2013-12-03 MX MX2015007135A patent/MX2015007135A/es active IP Right Grant
- 2013-12-03 PL PL13798684T patent/PL2928884T3/pl unknown
- 2013-12-03 AU AU2013354226A patent/AU2013354226B2/en active Active
- 2013-12-03 SI SI201330742T patent/SI2928884T1/sl unknown
- 2013-12-03 EA EA201591087A patent/EA028830B1/ru not_active IP Right Cessation
- 2013-12-03 KR KR1020157017666A patent/KR20150092248A/ko not_active Abandoned
- 2013-12-03 RS RS20170790A patent/RS56121B1/sr unknown
- 2013-12-03 ES ES13798684.0T patent/ES2637738T3/es active Active
- 2013-12-03 MA MA38146A patent/MA38146B1/fr unknown
- 2013-12-04 JO JOP/2013/0349A patent/JO3431B1/ar active
- 2013-12-06 UY UY0001035177A patent/UY35177A/es unknown
- 2013-12-06 AR ARP130104542A patent/AR093840A1/es unknown
- 2013-12-06 TW TW102144979A patent/TWI613198B/zh not_active IP Right Cessation
-
2015
- 2015-05-27 IL IL239026A patent/IL239026A0/en active IP Right Grant
- 2015-06-04 CL CL2015001508A patent/CL2015001508A1/es unknown
- 2015-06-04 CU CU2015000056A patent/CU20150056A7/es unknown
- 2015-06-05 TN TNP2015000250A patent/TN2015000250A1/fr unknown
- 2015-06-05 EC ECIEPI201522555A patent/ECSP15022555A/es unknown
- 2015-06-05 CR CR20150296A patent/CR20150296A/es unknown
- 2015-06-05 GT GT201500138A patent/GT201500138A/es unknown
- 2015-06-05 PH PH12015501289A patent/PH12015501289B1/en unknown
- 2015-06-05 NI NI201500077A patent/NI201500077A/es unknown
-
2017
- 2017-08-10 CY CY20171100862T patent/CY1119200T1/el unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016501241A5 (https=) | ||
| HRP20171200T1 (hr) | Novi derivati benzimidazola kao antagonisti ep4 | |
| RU2660897C2 (ru) | Новые соединения в качестве ингибиторов гистондеацетилазы 6 и содержащие их фармацевтические композиции | |
| JP7193460B2 (ja) | Ｃｄｋ８調節およびその適応症のための化合物および方法 | |
| CN101384550B (zh) | 酰胺衍生物或其盐 | |
| JP3868814B2 (ja) | 抗ウイルスアザインドール誘導体 | |
| JP4727925B2 (ja) | 統合失調症およびうつ病等の疾患を処置するためのフェノキシピペリジン | |
| DK2800748T3 (en) | CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE AND APPLICATIONS THEREOF | |
| HUP0501016A2 (en) | (s)-4-amino-5-chloro-2-methoxy-n-{1-[1-(2-tetrahydrofurylcarbonyl)-4-piperidinylmethyl]-4-piperidinyl}benzamide, process for the preparation thereof pharmaceutical composition containing the same and intermediate therefor | |
| JP2020515546A (ja) | Ｍｄｍ２−ｐ５３相互作用のイソインドリノン阻害剤およびそれを作製するためのプロセス | |
| CN105814038A (zh) | 作为ep4配体的苯并咪唑衍生物 | |
| WO2021083328A1 (zh) | 多取代异吲哚啉类化合物、其制备方法、药物组合物及用途 | |
| JP2009040767A5 (https=) | ||
| WO2006115244A1 (ja) | ４－ブロモイソキノリン誘導体及びこれを含有する医薬 | |
| CN111303147A (zh) | 吡啶酮衍生物、其组合物及作为抗流感病毒药物的应用 | |
| CN102470132B (zh) | 二取代的[4-(5-氨基甲基-苯基)-哌啶-1-基]-1h-吲哚-3-基]-甲酮 | |
| JP2024535019A (ja) | ２－アリール又はヘテロアリール－３－オキソ－４－カルバミド－６－環状－ジヒドロピラジンアリール炭化水素受容体モジュレータ並びに疾患及び障害の治療におけるそれらの使用 | |
| CA2615209A1 (en) | Mc4r-ag0nists for the treatment of urinary tract dysfunction | |
| TW200924765A (en) | Piperidine derivative | |
| WO2010062221A1 (ru) | Замещенные 2-(5-гидpokcи-2-metил-1н-иhдoл-3-ил)уkcуchыe кислоты и их эфиры и их применение для лечения вирусных заболеваний | |
| US12428424B2 (en) | Estrogen receptor-modulating compounds | |
| JP2015514728A5 (https=) | ||
| CN112142817B (zh) | 一种抗抑郁甾体化合物 | |
| WO2006115245A1 (ja) | ４－エチニルイソキノリン誘導体及びこれを含有する医薬 | |
| CN101463019B (zh) | 含有芳基、芳甲基和哌嗪基的脒类化合物 |