EA031655B1 - Бензимидазол-2-амины в качестве ингибиторов midhi - Google Patents

Info

Publication number

EA031655B1

EA031655B1 EA201691590A EA201691590A EA031655B1 EA 031655 B1 EA031655 B1 EA 031655B1 EA 201691590 A EA201691590 A EA 201691590A EA 201691590 A EA201691590 A EA 201691590A EA 031655 B1 EA031655 B1 EA 031655B1

Authority

EA

Eurasian Patent Office

Prior art keywords

amino

phenyl

trimethylcyclohexyl

methyl

benzimidazol

Prior art date

2014-02-11

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• 239000003112 inhibitor Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 382
• 238000000034 method Methods 0.000 claims abstract description 127
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 201000010099 disease Diseases 0.000 claims abstract description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• 238000011282 treatment Methods 0.000 claims abstract description 9
• 238000004519 manufacturing process Methods 0.000 claims abstract description 7
• -1 3,3,5,5-tetramethylcyclohexyl Chemical group 0.000 claims description 432
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 393
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 337
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 276
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 188
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 179
• 239000000203 mixture Substances 0.000 claims description 142
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 121
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 118
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 110
• 150000003839 salts Chemical class 0.000 claims description 76
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 65
• 125000000217 alkyl group Chemical group 0.000 claims description 60
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 58
• 125000001424 substituent group Chemical group 0.000 claims description 51
• 125000005843 halogen group Chemical group 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 42
• 239000001257 hydrogen Substances 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 40
• 150000002367 halogens Chemical class 0.000 claims description 40
• 125000001072 heteroaryl group Chemical group 0.000 claims description 40
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 40
• 235000019260 propionic acid Nutrition 0.000 claims description 39
• 125000003118 aryl group Chemical group 0.000 claims description 38
• 235000011054 acetic acid Nutrition 0.000 claims description 36
• 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 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 29
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 28
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 22
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 125000001188 haloalkyl group Chemical group 0.000 claims description 20
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 19
• 125000004076 pyridyl group Chemical group 0.000 claims description 19
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 18
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 18
• 229910052731 fluorine Inorganic materials 0.000 claims description 16
• SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 15
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 108010075869 Isocitrate Dehydrogenase Proteins 0.000 claims description 10
• 102000012011 Isocitrate Dehydrogenase Human genes 0.000 claims description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 9
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
• 239000004471 Glycine Substances 0.000 claims description 8
• 239000000460 chlorine Substances 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
• NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
• RNMAUIMMNAHKQR-APWZRJJASA-N 3-[2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O)(F)F RNMAUIMMNAHKQR-APWZRJJASA-N 0.000 claims description 6
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 6
• 230000024932 T cell mediated immunity Effects 0.000 claims description 6
• 230000001413 cellular effect Effects 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 230000004083 survival effect Effects 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• LXLGZKRGTAWWOQ-UZLBHIALSA-N 3-[6-methyl-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CCC(=O)O LXLGZKRGTAWWOQ-UZLBHIALSA-N 0.000 claims description 4
• LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 230000010261 cell growth Effects 0.000 claims description 4
• 230000004663 cell proliferation Effects 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 230000028709 inflammatory response Effects 0.000 claims description 4
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 4
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 4
• 239000011593 sulfur Substances 0.000 claims description 4
• UAYCJDYGIDLXRD-XXBNENTESA-N 3-[2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O UAYCJDYGIDLXRD-XXBNENTESA-N 0.000 claims description 3
• DINSIIZPPDOBKB-OFNKIYASSA-N 4-[2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxybutanoic acid Chemical compound C(C)(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCCCC(=O)O DINSIIZPPDOBKB-OFNKIYASSA-N 0.000 claims description 3
• OJXRHXBBYSWYQU-MJGOQNOKSA-N 4-[2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxybutanoic acid Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCCCC(=O)O)(F)F OJXRHXBBYSWYQU-MJGOQNOKSA-N 0.000 claims description 3
• 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 3
• 208000009849 Female Genital Neoplasms Diseases 0.000 claims description 3
• 206010025323 Lymphomas Diseases 0.000 claims description 3
• 206010059282 Metastases to central nervous system Diseases 0.000 claims description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 3
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical class CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 210000000038 chest Anatomy 0.000 claims description 3
• 201000011523 endocrine gland cancer Diseases 0.000 claims description 3
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
• 210000003734 kidney Anatomy 0.000 claims description 3
• 208000032839 leukemia Diseases 0.000 claims description 3
• 208000037841 lung tumor Diseases 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 102200069690 rs121913500 Human genes 0.000 claims description 3
• 210000003932 urinary bladder Anatomy 0.000 claims description 3
• 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 2
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
• 239000005711 Benzoic acid Substances 0.000 claims description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
• 206010039491 Sarcoma Diseases 0.000 claims description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
• 235000010233 benzoic acid Nutrition 0.000 claims description 2
• 210000000481 breast Anatomy 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
• 230000002401 inhibitory effect Effects 0.000 claims description 2
• 230000035755 proliferation Effects 0.000 claims description 2
• 208000023958 prostate neoplasm Diseases 0.000 claims description 2
• 230000004222 uncontrolled growth Effects 0.000 claims description 2
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 14
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 3
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 3
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 3
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 3
• LDTUJXQAJHFZTM-UTKZUKDTSA-N 2-[6-fluoro-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O LDTUJXQAJHFZTM-UTKZUKDTSA-N 0.000 claims 2
• JVAIZCSWEWGEEW-XLIONFOSSA-N 2-[6-fluoro-2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O JVAIZCSWEWGEEW-XLIONFOSSA-N 0.000 claims 2
• GEYCTRMDTQZHRU-NQIIRXRSSA-N 2-[6-methoxy-2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O GEYCTRMDTQZHRU-NQIIRXRSSA-N 0.000 claims 2
• SVGIEKTYEVCEOB-JPYJTQIMSA-N 2-[6-methyl-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O SVGIEKTYEVCEOB-JPYJTQIMSA-N 0.000 claims 2
• LBPZQTVIJVMPFD-GCJKJVERSA-N 2-[6-methyl-2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O LBPZQTVIJVMPFD-GCJKJVERSA-N 0.000 claims 2
• AYBJXJLBRDNWBW-KNQAVFIVSA-N 3-[2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O AYBJXJLBRDNWBW-KNQAVFIVSA-N 0.000 claims 2
• RNMAUIMMNAHKQR-QFBILLFUSA-N 3-[2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O)(F)F RNMAUIMMNAHKQR-QFBILLFUSA-N 0.000 claims 2
• IDYSQSOMMVJYJP-KNQAVFIVSA-N 3-[6-methoxy-2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=C(C(=C2)CCC(=O)O)OC IDYSQSOMMVJYJP-KNQAVFIVSA-N 0.000 claims 2
• ACYIYUMICDTELC-APWZRJJASA-N 2-[2-(4-cyanoanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxyacetic acid Chemical compound C(#N)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCC(=O)O ACYIYUMICDTELC-APWZRJJASA-N 0.000 claims 1
• GFMCQUKGINIVSW-UHFFFAOYSA-N 2-[2-(4-propan-2-ylanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]acetic acid Chemical compound CC(C)C1=CC=C(NC2=NC3=C(C=CC(CC(O)=O)=C3)N2C2CC(C)(C)CC(C)(C)C2)C=C1 GFMCQUKGINIVSW-UHFFFAOYSA-N 0.000 claims 1
• RBDPRDBWQJOHTD-PGRDOPGGSA-N 2-[2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CC(=O)O RBDPRDBWQJOHTD-PGRDOPGGSA-N 0.000 claims 1
• RBDPRDBWQJOHTD-GCJKJVERSA-N 2-[2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CC(=O)O RBDPRDBWQJOHTD-GCJKJVERSA-N 0.000 claims 1
• KYYZDJFEWZGSAN-UHFFFAOYSA-N 2-[2-(4-propan-2-yloxyanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]acetic acid Chemical compound CC(C)OC1=CC=C(C=C1)NC1=NC2=C(N1C1CC(CC(C1)(C)C)(C)C)C=CC(=C2)CC(=O)O KYYZDJFEWZGSAN-UHFFFAOYSA-N 0.000 claims 1
• PWIWVXULADEBKS-GHTZIAJQSA-N 2-[2-(4-propan-2-yloxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CC(=O)O PWIWVXULADEBKS-GHTZIAJQSA-N 0.000 claims 1
• PWIWVXULADEBKS-NQIIRXRSSA-N 2-[2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CC(=O)O PWIWVXULADEBKS-NQIIRXRSSA-N 0.000 claims 1
• DLJQAEILEDAEPE-QUCCMNQESA-N 2-[2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxyacetic acid Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCC(=O)O DLJQAEILEDAEPE-QUCCMNQESA-N 0.000 claims 1
• RMFIERQLLAPUDQ-MAUKXSAKSA-N 2-[2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CC(=O)O)(F)F RMFIERQLLAPUDQ-MAUKXSAKSA-N 0.000 claims 1
• RMFIERQLLAPUDQ-QAPCUYQASA-N 2-[2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC(OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)CC(=O)O)(F)F RMFIERQLLAPUDQ-QAPCUYQASA-N 0.000 claims 1
• QQYRFFPVPWVDLU-UHFFFAOYSA-N 2-[6-fluoro-2-(4-propan-2-ylanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]acetic acid Chemical compound FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)C2CC(CC(C2)(C)C)(C)C)C1)CC(=O)O QQYRFFPVPWVDLU-UHFFFAOYSA-N 0.000 claims 1
• LDTUJXQAJHFZTM-LAUBAEHRSA-N 2-[6-fluoro-2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CC(=O)O LDTUJXQAJHFZTM-LAUBAEHRSA-N 0.000 claims 1
• LWYUOIJTRLWRLA-WMLDXEAASA-N 2-[6-fluoro-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical class FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CC(=O)O LWYUOIJTRLWRLA-WMLDXEAASA-N 0.000 claims 1
• LWYUOIJTRLWRLA-PBHICJAKSA-N 2-[6-fluoro-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound FC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O LWYUOIJTRLWRLA-PBHICJAKSA-N 0.000 claims 1
• AQKJCKXDYIBPFR-UHFFFAOYSA-N 2-[6-methoxy-1-(3,3,5,5-tetramethylcyclohexyl)-2-[4-(trifluoromethoxy)anilino]benzimidazol-5-yl]acetic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)C2CC(CC(C2)(C)C)(C)C)C1)CC(=O)O AQKJCKXDYIBPFR-UHFFFAOYSA-N 0.000 claims 1
• OLGPLGPOVKGOOE-PGRDOPGGSA-N 2-[6-methoxy-2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@H]2CC(C[C@H](C2)C)(C)C)C1)CC(=O)O OLGPLGPOVKGOOE-PGRDOPGGSA-N 0.000 claims 1
• OLGPLGPOVKGOOE-GCJKJVERSA-N 2-[6-methoxy-2-(4-propan-2-ylanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O OLGPLGPOVKGOOE-GCJKJVERSA-N 0.000 claims 1
• XFHJFTNABYBOGI-QAPCUYQASA-N 2-[6-methoxy-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O XFHJFTNABYBOGI-QAPCUYQASA-N 0.000 claims 1
• OSQZOHAKEDLCQF-UHFFFAOYSA-N 2-[6-methyl-2-(4-propan-2-ylanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)C2CC(CC(C2)(C)C)(C)C)C1)CC(=O)O OSQZOHAKEDLCQF-UHFFFAOYSA-N 0.000 claims 1
• MAVPXVJCUNQQQN-UHFFFAOYSA-N 2-[6-methyl-2-(4-propan-2-yloxyanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(C)C)C2CC(CC(C2)(C)C)(C)C)C1)CC(=O)O MAVPXVJCUNQQQN-UHFFFAOYSA-N 0.000 claims 1
• LBPZQTVIJVMPFD-PGRDOPGGSA-N 2-[6-methyl-2-(4-propan-2-yloxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(C)C)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CC(=O)O LBPZQTVIJVMPFD-PGRDOPGGSA-N 0.000 claims 1
• KUWULFLLHTWYQB-HNAYVOBHSA-N 2-[6-methyl-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CC(=O)O KUWULFLLHTWYQB-HNAYVOBHSA-N 0.000 claims 1
• KUWULFLLHTWYQB-BEFAXECRSA-N 2-[6-methyl-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]acetic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CC(=O)O KUWULFLLHTWYQB-BEFAXECRSA-N 0.000 claims 1
• VAHHCMLOSSLRAR-UHFFFAOYSA-N 3-[1-(3,3-dimethylcyclohexyl)-2-(4-propan-2-ylanilino)benzimidazol-5-yl]propanoic acid Chemical compound CC1(CC(CCC1)N1C(=NC2=C1C=CC(=C2)CCC(=O)O)NC2=CC=C(C=C2)C(C)C)C VAHHCMLOSSLRAR-UHFFFAOYSA-N 0.000 claims 1
• PHBJIBVCOYVKKV-UHFFFAOYSA-N 3-[1-(3,3-dimethylcyclohexyl)-2-(4-propan-2-yloxyanilino)benzimidazol-5-yl]propanoic acid Chemical compound CC1(CC(CCC1)N1C(=NC2=C1C=CC(=C2)CCC(=O)O)NC2=CC=C(C=C2)OC(C)C)C PHBJIBVCOYVKKV-UHFFFAOYSA-N 0.000 claims 1
• MDIKLUQTOPSIDZ-UHFFFAOYSA-N 3-[1-(3,3-dimethylcyclohexyl)-2-[4-(trifluoromethoxy)anilino]benzimidazol-5-yl]propanoic acid Chemical compound CC1(CC(CCC1)N1C(=NC2=C1C=CC(=C2)CCC(=O)O)NC2=CC=C(C=C2)OC(F)(F)F)C MDIKLUQTOPSIDZ-UHFFFAOYSA-N 0.000 claims 1
• IBEUHHFLADTBKZ-UHFFFAOYSA-N 3-[2-(4-propan-2-ylanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]propanoic acid Chemical compound CC(C)C1=CC=C(C=C1)NC1=NC2=C(N1C1CC(CC(C1)(C)C)(C)C)C=CC(=C2)CCC(=O)O IBEUHHFLADTBKZ-UHFFFAOYSA-N 0.000 claims 1
• UAYCJDYGIDLXRD-WMZHIEFXSA-N 3-[2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC(C)C1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O UAYCJDYGIDLXRD-WMZHIEFXSA-N 0.000 claims 1
• AYBJXJLBRDNWBW-SIKLNZKXSA-N 3-[2-(4-propan-2-yloxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=CC(=C2)CCC(=O)O AYBJXJLBRDNWBW-SIKLNZKXSA-N 0.000 claims 1
• GARRPMJMNOEDDE-UHFFFAOYSA-N 3-[4-fluoro-2-(4-propan-2-yloxyanilino)-1-(3,3,5,5-tetramethylcyclohexyl)benzimidazol-5-yl]propanoic acid Chemical compound FC1=C(C=CC=2N(C(=NC21)NC2=CC=C(C=C2)OC(C)C)C2CC(CC(C2)(C)C)(C)C)CCC(=O)O GARRPMJMNOEDDE-UHFFFAOYSA-N 0.000 claims 1
• LPPDJFQKLXOTAS-WMZHIEFXSA-N 3-[6-methoxy-2-(4-propan-2-ylanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(C)C)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CCC(=O)O LPPDJFQKLXOTAS-WMZHIEFXSA-N 0.000 claims 1
• IDYSQSOMMVJYJP-SIKLNZKXSA-N 3-[6-methoxy-2-(4-propan-2-yloxyanilino)-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@H]1CC(C[C@H](C1)C)(C)C)C=C(C(=C2)CCC(=O)O)OC IDYSQSOMMVJYJP-SIKLNZKXSA-N 0.000 claims 1
• RRIGKXHXERNTDY-QFBILLFUSA-N 3-[6-methoxy-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CCC(=O)O RRIGKXHXERNTDY-QFBILLFUSA-N 0.000 claims 1
• RRIGKXHXERNTDY-APWZRJJASA-N 3-[6-methoxy-2-[4-(trifluoromethoxy)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CCC(=O)O RRIGKXHXERNTDY-APWZRJJASA-N 0.000 claims 1
• GCGATJCXUINDSU-OXJNMPFZSA-N 3-[6-methoxy-2-[4-(trifluoromethyl)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CCC(=O)O GCGATJCXUINDSU-OXJNMPFZSA-N 0.000 claims 1
• GCGATJCXUINDSU-UZLBHIALSA-N 3-[6-methoxy-2-[4-(trifluoromethyl)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound COC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(F)(F)F)[C@@H]2CC(C[C@@H](C2)C)(C)C)C1)CCC(=O)O GCGATJCXUINDSU-UZLBHIALSA-N 0.000 claims 1
• LXLGZKRGTAWWOQ-OXJNMPFZSA-N 3-[6-methyl-2-[4-(trifluoromethoxy)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)OC(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C1)CCC(=O)O LXLGZKRGTAWWOQ-OXJNMPFZSA-N 0.000 claims 1
• WYBQNXIIWGGTOU-HRAATJIYSA-N 3-[6-methyl-2-[4-(trifluoromethyl)anilino]-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]propanoic acid Chemical compound CC=1C(=CC2=C(N(C(=N2)NC2=CC=C(C=C2)C(F)(F)F)[C@H]2CC(C[C@H](C2)C)(C)C)C=1)CCC(=O)O WYBQNXIIWGGTOU-HRAATJIYSA-N 0.000 claims 1
• MUUIXNXJXMWHQB-IRLDBZIGSA-N 4-[2-(4-propan-2-yloxyanilino)-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxybutanoic acid Chemical compound C(C)(C)OC1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCCCC(=O)O MUUIXNXJXMWHQB-IRLDBZIGSA-N 0.000 claims 1
• IJUSKGQPDMKWHF-XLIONFOSSA-N 4-[2-[4-(trifluoromethyl)anilino]-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-5-yl]oxybutanoic acid Chemical compound FC(C1=CC=C(C=C1)NC1=NC2=C(N1[C@@H]1CC(C[C@@H](C1)C)(C)C)C=CC(=C2)OCCCC(=O)O)(F)F IJUSKGQPDMKWHF-XLIONFOSSA-N 0.000 claims 1
• IUJCCIXEWIUFEB-OXJNMPFZSA-N 4-[[5-(2-carboxyethyl)-6-methoxy-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]benzimidazol-2-yl]amino]benzoic acid Chemical compound C(=O)(O)CCC1=CC2=C(N(C(=N2)NC2=CC=C(C(=O)O)C=C2)[C@H]2CC(C[C@H](C2)C)(C)C)C=C1OC IUJCCIXEWIUFEB-OXJNMPFZSA-N 0.000 claims 1
• IUJCCIXEWIUFEB-UZLBHIALSA-N 4-[[5-(2-carboxyethyl)-6-methoxy-1-[(1S,5S)-3,3,5-trimethylcyclohexyl]benzimidazol-2-yl]amino]benzoic acid Chemical compound C(=O)(O)CCC1=CC2=C(N(C(=N2)NC2=CC=C(C(=O)O)C=C2)[C@@H]2CC(C[C@@H](C2)C)(C)C)C=C1OC IUJCCIXEWIUFEB-UZLBHIALSA-N 0.000 claims 1
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