ES2731773T3 - Inhibidores de la histona desmetilasa - Google Patents

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Publication number

ES2731773T3

ES2731773T3 ES14767499T ES14767499T ES2731773T3 ES 2731773 T3 ES2731773 T3 ES 2731773T3 ES 14767499 T ES14767499 T ES 14767499T ES 14767499 T ES14767499 T ES 14767499T ES 2731773 T3 ES2731773 T3 ES 2731773T3

Authority

ES

Spain

Prior art keywords

pyridine

imidazol

carboxylic acid

ethyl

methyl

Prior art date

2013-03-14

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.)

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• 108010074870 Histone Demethylases Proteins 0.000 title description 19
• 102000008157 Histone Demethylases Human genes 0.000 title description 19
• 239000003112 inhibitor Substances 0.000 title description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 411
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 121
• 239000001257 hydrogen Substances 0.000 claims abstract description 108
• 125000003118 aryl group Chemical group 0.000 claims abstract description 86
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 65
• 125000006833 (C1-C5) alkylene group Chemical group 0.000 claims abstract description 62
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 55
• 150000003839 salts Chemical class 0.000 claims abstract description 48
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 41
• 150000002367 halogens Chemical group 0.000 claims abstract description 41
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
• 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 21
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims abstract description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
• 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 14
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 13
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
• 239000001301 oxygen Chemical group 0.000 claims abstract description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 10
• 229910052717 sulfur Chemical group 0.000 claims abstract description 10
• 239000011593 sulfur Chemical group 0.000 claims abstract description 10
• 125000006574 non-aromatic ring group Chemical group 0.000 claims abstract description 3
• -1 C 1 -C 5 alkyl Chemical group 0.000 claims description 389
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 282
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 claims description 194
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 90
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 81
• 239000002253 acid Substances 0.000 claims description 77
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 75
• 125000000623 heterocyclic group Chemical group 0.000 claims description 53
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 43
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 31
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
• 125000003070 2-(2-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 17
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
• 238000011282 treatment Methods 0.000 claims description 13
• 201000011510 cancer Diseases 0.000 claims description 10
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 6
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000000301 2-(3-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• VCGWROPGXPEYJD-UHFFFAOYSA-N 2-(5-bromo-1-methylimidazol-4-yl)pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1Br VCGWROPGXPEYJD-UHFFFAOYSA-N 0.000 claims description 2
• IOCMNXRIFNSUHI-UHFFFAOYSA-N 2-[1-methyl-5-[3-(methylcarbamoyl)phenyl]imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CNC(=O)C1=CC=CC(C=2N(C=NC=2C=2N=CC=C(C=2)C(O)=O)C)=C1 IOCMNXRIFNSUHI-UHFFFAOYSA-N 0.000 claims description 2
• IEUSSUSUNMFYEH-UHFFFAOYSA-N 2-[5-(3-fluorophenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=CC(F)=C1 IEUSSUSUNMFYEH-UHFFFAOYSA-N 0.000 claims description 2
• MDRIPRQWTFFXTF-UHFFFAOYSA-N 2-[5-(4-tert-butylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(C(C)(C)C)C=C1 MDRIPRQWTFFXTF-UHFFFAOYSA-N 0.000 claims description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
• CZNQEGMRCQUBDL-UHFFFAOYSA-N methyl 2-[5-(4-cyclopropylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C2=C(N(C)C=N2)C=2C=CC(=CC=2)C2CC2)=C1 CZNQEGMRCQUBDL-UHFFFAOYSA-N 0.000 claims description 2
• GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 17
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 7
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical group [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 5
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 2
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 2
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
• VUAXHMVRKOTJKP-UHFFFAOYSA-M 2,2-dimethylbutanoate Chemical compound CCC(C)(C)C([O-])=O VUAXHMVRKOTJKP-UHFFFAOYSA-M 0.000 claims 1
• CZNFQLDDPKKPMX-UHFFFAOYSA-N 2-(1-methylimidazol-4-yl)pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1 CZNFQLDDPKKPMX-UHFFFAOYSA-N 0.000 claims 1
• HRUSUMNASSGDCN-UHFFFAOYSA-N 2-[1-(2-pyrrolidin-1-ylethyl)imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C=2N=CN(CCN3CCCC3)C=2)=C1 HRUSUMNASSGDCN-UHFFFAOYSA-N 0.000 claims 1
• GUHGGLPTVJEQIO-UHFFFAOYSA-N 2-[1-[2-(n-methylanilino)ethyl]imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C=1C=CC=CC=1N(C)CCN(C=1)C=NC=1C1=CC(C(O)=O)=CC=N1 GUHGGLPTVJEQIO-UHFFFAOYSA-N 0.000 claims 1
• RRBCZBSZMNUAFC-UHFFFAOYSA-N 2-[1-[[2-(2-methylpropoxy)phenyl]methyl]imidazol-4-yl]-4-(2h-tetrazol-5-yl)pyridine Chemical compound CC(C)COC1=CC=CC=C1CN1C=C(C=2N=CC=C(C=2)C2=NNN=N2)N=C1 RRBCZBSZMNUAFC-UHFFFAOYSA-N 0.000 claims 1
• ZQVGHRRKWOITDJ-UHFFFAOYSA-N 2-[1-methyl-5-(4-pyrazol-1-ylphenyl)imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C(C=C1)=CC=C1N1C=CC=N1 ZQVGHRRKWOITDJ-UHFFFAOYSA-N 0.000 claims 1
• RYHMPYHFLUZIAQ-UHFFFAOYSA-N 2-[1-methyl-5-(4-pyrrolidin-1-ylphenyl)imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C(C=C1)=CC=C1N1CCCC1 RYHMPYHFLUZIAQ-UHFFFAOYSA-N 0.000 claims 1
• OTBZGJHFGXDSHF-UHFFFAOYSA-N 2-[1-methyl-5-[4-(trifluoromethoxy)phenyl]imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(OC(F)(F)F)C=C1 OTBZGJHFGXDSHF-UHFFFAOYSA-N 0.000 claims 1
• SDMVZUWEFWRXCR-UHFFFAOYSA-N 2-[1-methyl-5-[4-[1-(trifluoromethyl)cyclopropyl]phenyl]imidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C(C=C1)=CC=C1C1(C(F)(F)F)CC1 SDMVZUWEFWRXCR-UHFFFAOYSA-N 0.000 claims 1
• HWLLTDBRLRZLGC-UHFFFAOYSA-N 2-[5-(2-butoxy-4-fluorophenyl)-1-methylimidazol-4-yl]-4-(2h-tetrazol-5-yl)pyridine Chemical compound CCCCOC1=CC(F)=CC=C1C1=C(C=2N=CC=C(C=2)C2=NNN=N2)N=CN1C HWLLTDBRLRZLGC-UHFFFAOYSA-N 0.000 claims 1
• WHDIGPINEOYMPY-UHFFFAOYSA-N 2-[5-(3-chlorophenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=CC(Cl)=C1 WHDIGPINEOYMPY-UHFFFAOYSA-N 0.000 claims 1
• KHSDTLGQWSEUAQ-UHFFFAOYSA-N 2-[5-(3-hydroxy-4-methylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C1=C(O)C(C)=CC=C1C1=C(C=2N=CC=C(C=2)C(O)=O)N=CN1C KHSDTLGQWSEUAQ-UHFFFAOYSA-N 0.000 claims 1
• IJXQPIKMXWVJMM-UHFFFAOYSA-N 2-[5-(4-chloro-3-fluorophenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(Cl)C(F)=C1 IJXQPIKMXWVJMM-UHFFFAOYSA-N 0.000 claims 1
• WDNVDHFDAHTYMI-UHFFFAOYSA-N 2-[5-(4-chloro-3-methoxyphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C1=C(Cl)C(OC)=CC(C=2N(C=NC=2C=2N=CC=C(C=2)C(O)=O)C)=C1 WDNVDHFDAHTYMI-UHFFFAOYSA-N 0.000 claims 1
• UQVSSWJZBFXFEN-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(Cl)C=C1 UQVSSWJZBFXFEN-UHFFFAOYSA-N 0.000 claims 1
• UWUTURLDMHWALT-UHFFFAOYSA-N 2-[5-(4-cyclopropylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C(C=C1)=CC=C1C1CC1 UWUTURLDMHWALT-UHFFFAOYSA-N 0.000 claims 1
• YIYGVYOANZWNAL-UHFFFAOYSA-N 2-[5-(4-ethylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C1=CC(CC)=CC=C1C1=C(C=2N=CC=C(C=2)C(O)=O)N=CN1C YIYGVYOANZWNAL-UHFFFAOYSA-N 0.000 claims 1
• JHTVAONQTGIKOP-UHFFFAOYSA-N 2-[5-(4-ethynylphenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(C#C)C=C1 JHTVAONQTGIKOP-UHFFFAOYSA-N 0.000 claims 1
• OFVALDKDZDUPRW-UHFFFAOYSA-N 2-[5-(4-fluoro-3-phenylmethoxyphenyl)-1-methylimidazol-4-yl]-4-(2h-tetrazol-5-yl)pyridine Chemical compound CN1C=NC(C=2N=CC=C(C=2)C2=NNN=N2)=C1C(C=1)=CC=C(F)C=1OCC1=CC=CC=C1 OFVALDKDZDUPRW-UHFFFAOYSA-N 0.000 claims 1
• YPXMBUYRTBIECY-UHFFFAOYSA-N 2-[5-(4-fluorophenyl)-1-(2,2,2-trifluoroethyl)imidazol-4-yl]-4-(2h-tetrazol-5-yl)pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2N=CC=C(C=2)C2=NNN=N2)N=CN1CC(F)(F)F YPXMBUYRTBIECY-UHFFFAOYSA-N 0.000 claims 1
• ONKWECDQZPASOC-UHFFFAOYSA-N 2-[5-(4-fluorophenyl)-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(F)C=C1 ONKWECDQZPASOC-UHFFFAOYSA-N 0.000 claims 1
• PZUPDEOZRJAYNQ-UHFFFAOYSA-N 2-[5-[2-(cyclopropylmethoxy)-4,5-difluorophenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC(F)=C(F)C=C1OCC1CC1 PZUPDEOZRJAYNQ-UHFFFAOYSA-N 0.000 claims 1
• CDCAKPHONNAIQI-UHFFFAOYSA-N 2-[5-[2-(cyclopropylmethoxy)-4-fluorophenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(F)C=C1OCC1CC1 CDCAKPHONNAIQI-UHFFFAOYSA-N 0.000 claims 1
• CLOYPTYRSHJGFE-UHFFFAOYSA-N 2-[5-[2-(cyclopropylmethoxy)-5-methylphenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C=1C(C(O)=O)=CC=NC=1C=1N=CN(C)C=1C1=CC(C)=CC=C1OCC1CC1 CLOYPTYRSHJGFE-UHFFFAOYSA-N 0.000 claims 1
• ZBFLZYQTWARVNO-UHFFFAOYSA-N 2-[5-[2-(cyclopropylmethoxy)-6-fluorophenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=C(F)C=CC=C1OCC1CC1 ZBFLZYQTWARVNO-UHFFFAOYSA-N 0.000 claims 1
• IGZZKOJEHRREEV-UHFFFAOYSA-N 2-[5-[4-[1-(methoxymethyl)cyclopropyl]phenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound C=1C=C(C=2N(C=NC=2C=2N=CC=C(C=2)C(O)=O)C)C=CC=1C1(COC)CC1 IGZZKOJEHRREEV-UHFFFAOYSA-N 0.000 claims 1
• GOMLARFYKWXBIU-UHFFFAOYSA-N 2-[5-[4-chloro-2-(trifluoromethyl)phenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(Cl)C=C1C(F)(F)F GOMLARFYKWXBIU-UHFFFAOYSA-N 0.000 claims 1
• JBWWGJIWGUVEJH-UHFFFAOYSA-N 2-[5-[4-chloro-3-(trifluoromethyl)phenyl]-1-methylimidazol-4-yl]pyridine-4-carboxylic acid Chemical compound CN1C=NC(C=2N=CC=C(C=2)C(O)=O)=C1C1=CC=C(Cl)C(C(F)(F)F)=C1 JBWWGJIWGUVEJH-UHFFFAOYSA-N 0.000 claims 1
• 101100322888 Escherichia coli (strain K12) metL gene Proteins 0.000 claims 1
• 101100485158 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) wzzE gene Proteins 0.000 claims 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims 1
• 101150089110 metN gene Proteins 0.000 claims 1
• PZSMLEAMFUVDGG-UHFFFAOYSA-N methyl 2-[1-(2-pyrrolidin-1-ylethyl)imidazol-4-yl]pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C=2N=CN(CCN3CCCC3)C=2)=C1 PZSMLEAMFUVDGG-UHFFFAOYSA-N 0.000 claims 1
• QLURSABJFDGSCH-UHFFFAOYSA-N methyl 2-[1-[2-[benzyl(methyl)amino]ethyl]imidazol-4-yl]pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C=2N=CN(CCN(C)CC=3C=CC=CC=3)C=2)=C1 QLURSABJFDGSCH-UHFFFAOYSA-N 0.000 claims 1
• AXLZMGLGGIGAOX-UHFFFAOYSA-N n-benzyl-2-fluoro-5-[3-methyl-5-[4-(2h-tetrazol-5-yl)pyridin-2-yl]imidazol-4-yl]benzamide Chemical compound CN1C=NC(C=2N=CC=C(C=2)C2=NNN=N2)=C1C(C=1)=CC=C(F)C=1C(=O)NCC1=CC=CC=C1 AXLZMGLGGIGAOX-UHFFFAOYSA-N 0.000 claims 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
• 229950010765 pivalate Drugs 0.000 claims 1
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract description 42
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 33
• 125000005843 halogen group Chemical group 0.000 abstract description 11
• 238000002360 preparation method Methods 0.000 description 320
• 238000000034 method Methods 0.000 description 273
• GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 97
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 88
• 125000000217 alkyl group Chemical group 0.000 description 85
• 150000002431 hydrogen Chemical class 0.000 description 75
• 125000002947 alkylene group Chemical group 0.000 description 55
• 239000000243 solution Substances 0.000 description 47
• 150000002825 nitriles Chemical class 0.000 description 45
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 42
• 239000000203 mixture Substances 0.000 description 41
• 125000003710 aryl alkyl group Chemical group 0.000 description 39
• 125000004452 carbocyclyl group Chemical group 0.000 description 39
• 125000005884 carbocyclylalkyl group Chemical group 0.000 description 34
• TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 30
• 150000003254 radicals Chemical class 0.000 description 30
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
• 239000007787 solid Substances 0.000 description 28
• 238000006243 chemical reaction Methods 0.000 description 27
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 27
• 108090000623 proteins and genes Proteins 0.000 description 26
• 108010033040 Histones Proteins 0.000 description 25
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 25
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 230000008569 process Effects 0.000 description 22
• 239000011541 reaction mixture Substances 0.000 description 22
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