PT2928884T - Derivados inovadores de benzimidazole como antagonistas de ep4 - Google Patents

Info

Publication number

PT2928884T

PT2928884T PT137986840T PT13798684T PT2928884T PT 2928884 T PT2928884 T PT 2928884T PT 137986840 T PT137986840 T PT 137986840T PT 13798684 T PT13798684 T PT 13798684T PT 2928884 T PT2928884 T PT 2928884T

Authority

PT

Portugal

Prior art keywords

ethyl

benzimidazole

carboxylic acid

carbazol

carbazole

Prior art date

2012-12-06

Links

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• Global Dossier
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• 239000005557 antagonist Substances 0.000 title claims description 27
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title description 2
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 284
• -1 (N, N-dimethylamino) -methyl Chemical group 0.000 claims description 177
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 70
• 238000011282 treatment Methods 0.000 claims description 64
• 229910052739 hydrogen Inorganic materials 0.000 claims description 59
• 201000009273 Endometriosis Diseases 0.000 claims description 54
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
• 229910052731 fluorine Inorganic materials 0.000 claims description 37
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 36
• 201000010099 disease Diseases 0.000 claims description 36
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
• 206010028980 Neoplasm Diseases 0.000 claims description 32
• 238000000034 method Methods 0.000 claims description 31
• 229910052799 carbon Inorganic materials 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 29
• 229910052801 chlorine Inorganic materials 0.000 claims description 27
• 239000003112 inhibitor Substances 0.000 claims description 26
• 201000011510 cancer Diseases 0.000 claims description 23
• 239000003814 drug Substances 0.000 claims description 23
• 238000011321 prophylaxis Methods 0.000 claims description 23
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 22
• 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 description 21
• 208000002193 Pain Diseases 0.000 claims description 20
• 208000032843 Hemorrhage Diseases 0.000 claims description 19
• 230000000740 bleeding effect Effects 0.000 claims description 19
• 239000012453 solvate Substances 0.000 claims description 18
• 208000034158 bleeding Diseases 0.000 claims description 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 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 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
• 201000010260 leiomyoma Diseases 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 13
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 206010046798 Uterine leiomyoma Diseases 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• FDCJBNUENMJJOW-UHFFFAOYSA-N 1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical class C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1CC1 FDCJBNUENMJJOW-UHFFFAOYSA-N 0.000 claims description 10
• 239000000556 agonist Substances 0.000 claims description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 10
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class 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 description 10
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 9
• 208000035475 disorder Diseases 0.000 claims description 9
• 229940044551 receptor antagonist Drugs 0.000 claims description 9
• 239000002464 receptor antagonist Substances 0.000 claims description 9
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 8
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 208000005171 Dysmenorrhea Diseases 0.000 claims description 8
• 206010013935 Dysmenorrhoea Diseases 0.000 claims description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
• 239000013543 active substance Substances 0.000 claims description 8
• 208000032839 leukemia Diseases 0.000 claims description 8
• 239000000583 progesterone congener Substances 0.000 claims description 8
• 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 description 7
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
• 102000015694 estrogen receptors Human genes 0.000 claims description 7
• 108010038795 estrogen receptors Proteins 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 208000030761 polycystic kidney disease Diseases 0.000 claims description 7
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 6
• 208000031169 hemorrhagic disease Diseases 0.000 claims description 6
• 239000000333 selective estrogen receptor modulator Substances 0.000 claims description 6
• 229940095743 selective estrogen receptor modulator Drugs 0.000 claims description 6
• 108091007960 PI3Ks Proteins 0.000 claims description 5
• 206010046788 Uterine haemorrhage Diseases 0.000 claims description 5
• 210000000481 breast Anatomy 0.000 claims description 5
• 230000001788 irregular Effects 0.000 claims description 5
• 210000004072 lung Anatomy 0.000 claims description 5
• 239000002379 progesterone receptor modulator Substances 0.000 claims description 5
• 210000002307 prostate Anatomy 0.000 claims description 5
• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 5
• 210000003491 skin Anatomy 0.000 claims description 5
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
• 229920002554 vinyl polymer Polymers 0.000 claims description 5
• DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 claims description 4
• JXIMJWLDISCDNL-UHFFFAOYSA-N 1-(1,4-dioxan-2-ylmethyl)-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=C2N1CC1COCCO1 JXIMJWLDISCDNL-UHFFFAOYSA-N 0.000 claims description 4
• 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 description 4
• 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 description 4
• 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 description 4
• 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 description 4
• 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 description 4
• 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 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 239000003098 androgen Substances 0.000 claims description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
• 230000005923 long-lasting effect Effects 0.000 claims description 4
• 230000007774 longterm Effects 0.000 claims description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
• 231100000252 nontoxic Toxicity 0.000 claims description 4
• 230000003000 nontoxic effect Effects 0.000 claims description 4
• 201000007954 uterine fibroid Diseases 0.000 claims description 4
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• JDOSJWHLPMCIKO-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-1-(oxetan-3-ylmethyl)benzimidazole-5-carboxylic acid Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1C1=NC2=CC(C(O)=O)=CC=C2N1CC1COC1 JDOSJWHLPMCIKO-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• ZCZGFBPJNHIDKO-UHFFFAOYSA-N 2-(9-ethylcarbazol-3-yl)-3h-benzimidazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC(C=3C=C4C5=CC=CC=C5N(C4=CC=3)CC)=NC2=C1 ZCZGFBPJNHIDKO-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 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 description 3
• 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 description 3
• LIXQIYVELKPRDC-UHFFFAOYSA-N 4-chloro-1-(cyclopropylmethyl)-2-(9-ethylcarbazol-3-yl)benzimidazole-5-carboxylic acid Chemical class 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 description 3
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 3
• 102000003964 Histone deacetylase Human genes 0.000 claims description 3
• 108090000353 Histone deacetylase Proteins 0.000 claims description 3
• 229940127374 Hydroxylase Activators Drugs 0.000 claims description 3
• 102000004079 Prolyl Hydroxylases Human genes 0.000 claims description 3
• 108010043005 Prolyl Hydroxylases Proteins 0.000 claims description 3
• 229940030486 androgens Drugs 0.000 claims description 3
• 239000003886 aromatase inhibitor Substances 0.000 claims description 3
• 229940046844 aromatase inhibitors Drugs 0.000 claims description 3
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 claims description 3
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims description 3
• 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 description 3
• 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 description 3
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