JP2012512252A - ジアシルグリセロールアシルトランスフェラーゼの阻害剤 - Google Patents

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Publication number

JP2012512252A

JP2012512252A JP2011542339A JP2011542339A JP2012512252A JP 2012512252 A JP2012512252 A JP 2012512252A JP 2011542339 A JP2011542339 A JP 2011542339A JP 2011542339 A JP2011542339 A JP 2011542339A JP 2012512252 A JP2012512252 A JP 2012512252A

Authority

JP

Japan

Prior art keywords

phenyl

trifluoromethyl

carboxylic acid

oxazole

piperidine

Prior art date

2008-12-17

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.)

Withdrawn

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• 239000003112 inhibitor Substances 0.000 title abstract description 8
• 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 title abstract description 5
• 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 title abstract description 5
• 150000001408 amides Chemical class 0.000 claims abstract description 14
• -1 alkyl oxadiazole Chemical compound 0.000 claims description 136
• 150000001875 compounds Chemical class 0.000 claims description 87
• PYCFLCQAJFEELT-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C(F)(F)F)=C(C(=O)O)N=C1C1=CC=CC=C1 PYCFLCQAJFEELT-UHFFFAOYSA-N 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 49
• 229910052799 carbon Inorganic materials 0.000 claims description 31
• 125000000217 alkyl group Chemical group 0.000 claims description 29
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 239000005711 Benzoic acid Substances 0.000 claims description 17
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 125000005907 alkyl ester group Chemical group 0.000 claims description 15
• 238000000034 method Methods 0.000 claims description 14
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
• SDSDAIQLQREBIR-UHFFFAOYSA-N 1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound N1=C(C(F)(F)F)C(C(=O)O)=CN1C1=CC=CC=N1 SDSDAIQLQREBIR-UHFFFAOYSA-N 0.000 claims description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• TVEAZHOLMPKUGM-UHFFFAOYSA-N 2-piperidinobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCCCC1 TVEAZHOLMPKUGM-UHFFFAOYSA-N 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• PFFPTUQGAMYZNZ-UHFFFAOYSA-N 2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C(F)(F)F)=C(C(=O)O)N=C1C1=CC=CC=C1OC(F)(F)F PFFPTUQGAMYZNZ-UHFFFAOYSA-N 0.000 claims description 7
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
• FUYFSLADZIFBCQ-UHFFFAOYSA-N 2-phenyl-n-[6-(4-pyrimidin-2-ylpiperazin-1-yl)pyridin-3-yl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCN1C1=NC=CC=N1 FUYFSLADZIFBCQ-UHFFFAOYSA-N 0.000 claims description 6
• FAVATDBDOUESNH-UHFFFAOYSA-N 3-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2CCC(CC2)C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=C1 FAVATDBDOUESNH-UHFFFAOYSA-N 0.000 claims description 5
• DLNNSFUQXKGREA-UHFFFAOYSA-N 4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 DLNNSFUQXKGREA-UHFFFAOYSA-N 0.000 claims description 5
• BNJMIAOVJXCRCF-UHFFFAOYSA-N 4-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperazin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCN(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 BNJMIAOVJXCRCF-UHFFFAOYSA-N 0.000 claims description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
• HJVZMZHBCNRXCD-UHFFFAOYSA-N 2-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperazin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCN(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 HJVZMZHBCNRXCD-UHFFFAOYSA-N 0.000 claims description 4
• ZFUJGWSHPNBAAF-UHFFFAOYSA-N 2-phenyl-n-[4-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CC(C)C1=NOC(C2CCN(CC2)C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=N1 ZFUJGWSHPNBAAF-UHFFFAOYSA-N 0.000 claims description 4
• SQUFJMKDTYFVQO-UHFFFAOYSA-N 2-phenyl-n-[6-(4-phenylpiperazin-1-yl)pyridin-3-yl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCN1C1=CC=CC=C1 SQUFJMKDTYFVQO-UHFFFAOYSA-N 0.000 claims description 4
• CFEGXHNBQVTVKM-UHFFFAOYSA-N 3-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperazin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(N2CCN(CC2)C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=C1 CFEGXHNBQVTVKM-UHFFFAOYSA-N 0.000 claims description 4
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• NYBJNMCQXDPCBM-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-n-[6-[4-[2-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-yl]-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCN1C1=CC=CC=C1C(F)(F)F NYBJNMCQXDPCBM-UHFFFAOYSA-N 0.000 claims description 3
• YKQYRBWQTCQQKC-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-n-[6-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-yl]-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 YKQYRBWQTCQQKC-UHFFFAOYSA-N 0.000 claims description 3
• KPUNYFDILYXQRE-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-n-[6-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-yl]-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCN1C1=CC=C(C(F)(F)F)C=C1 KPUNYFDILYXQRE-UHFFFAOYSA-N 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
• UZLFMMXJPRIDRZ-UHFFFAOYSA-N ethyl 4-[4-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperazin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCN(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 UZLFMMXJPRIDRZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 239000001257 hydrogen Chemical group 0.000 claims description 3
• 229910052739 hydrogen Chemical group 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• IRSVYBIJXNKBRG-UHFFFAOYSA-N n-[6-[4-(2-methoxyphenyl)piperazin-1-yl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound COC1=CC=CC=C1N1CCN(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 IRSVYBIJXNKBRG-UHFFFAOYSA-N 0.000 claims description 3
• BHYRDXWTCLJNDQ-UHFFFAOYSA-N n-[6-[4-(3-methoxyphenyl)piperazin-1-yl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=C1 BHYRDXWTCLJNDQ-UHFFFAOYSA-N 0.000 claims description 3
• VJVRORHYESEGSV-UHFFFAOYSA-N n-[6-[4-(4-methoxyphenyl)piperazin-1-yl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 VJVRORHYESEGSV-UHFFFAOYSA-N 0.000 claims description 3
• BQXSMDFVQCAVID-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-n-[6-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]pyridin-3-yl]-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=N1)=CC=C1N(CC1)CCC1C1=CC=CC(C(F)(F)F)=C1 BQXSMDFVQCAVID-UHFFFAOYSA-N 0.000 claims description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• YSSGWMIUYKMVDU-QFIPXVFZSA-N 4-[(3s)-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]pyrrolidin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1C[C@@H](OC=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 YSSGWMIUYKMVDU-QFIPXVFZSA-N 0.000 claims description 2
• PJGWDEIXVQQGHQ-UHFFFAOYSA-N 4-[4-[4-[(5-ethyl-2-phenyl-1,3-oxazole-4-carbonyl)amino]phenyl]piperidin-1-yl]benzoic acid Chemical compound CCC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C1=CC=C(C(O)=O)C=C1 PJGWDEIXVQQGHQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• PZLZNPDGRCCEHL-UHFFFAOYSA-N 6-[4-[4-[(4-phenylthiophene-2-carbonyl)amino]phenyl]piperidin-1-yl]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1N1CCC(C=2C=CC(NC(=O)C=3SC=C(C=3)C=3C=CC=CC=3)=CC=2)CC1 PZLZNPDGRCCEHL-UHFFFAOYSA-N 0.000 claims description 2
• JTRIRWFHXCNJRC-UHFFFAOYSA-N 6-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-1-yl]pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 JTRIRWFHXCNJRC-UHFFFAOYSA-N 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
• FCNWTYAGSIIHRL-UHFFFAOYSA-N ethyl 4-[4-[5-[[1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carbonyl]amino]pyridin-2-yl]piperazin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCN(C=2N=CC(NC(=O)C=3C(=NN(C=3)C=3N=CC=CC=3)C(F)(F)F)=CC=2)CC1 FCNWTYAGSIIHRL-UHFFFAOYSA-N 0.000 claims description 2
• ZYLZQIMSYNAILC-UHFFFAOYSA-N 2-piperazin-1-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCNCC1 ZYLZQIMSYNAILC-UHFFFAOYSA-N 0.000 claims 4
• ASMNZIPDDLMPLY-UHFFFAOYSA-N piperidine;pyridine-2-carboxylic acid Chemical compound C1CCNCC1.OC(=O)C1=CC=CC=N1 ASMNZIPDDLMPLY-UHFFFAOYSA-N 0.000 claims 3
• RVFVPPONXUZVTJ-UHFFFAOYSA-N piperazine;pyrimidine Chemical compound C1CNCCN1.C1=CN=CN=C1 RVFVPPONXUZVTJ-UHFFFAOYSA-N 0.000 claims 2
• BIDJDZNQEXQRQK-UHFFFAOYSA-N 2-phenyl-n-[2-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyrimidin-5-yl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CC(C)C1=NOC(C2CCN(CC2)C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CN=2)=N1 BIDJDZNQEXQRQK-UHFFFAOYSA-N 0.000 claims 1
• JZTAYPMFFRPCGR-UHFFFAOYSA-N 2-phenyl-n-[6-[3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)pyrrolidin-1-yl]pyridin-3-yl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CC(C)C1=NOC(C2CN(CC2)C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=N1 JZTAYPMFFRPCGR-UHFFFAOYSA-N 0.000 claims 1
• YSSGWMIUYKMVDU-UHFFFAOYSA-N 4-[3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]pyrrolidin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CC(OC=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 YSSGWMIUYKMVDU-UHFFFAOYSA-N 0.000 claims 1
• GCGZHOKMJIEQDC-UHFFFAOYSA-N 4-cyclopropyloxadiazole;piperidine Chemical compound C1CCNCC1.C1CC1C1=CON=N1 GCGZHOKMJIEQDC-UHFFFAOYSA-N 0.000 claims 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
• YSKBWIRXFWWGIJ-UHFFFAOYSA-N n-[6-[4-(4-fluorophenyl)piperazin-1-yl]pyridin-3-yl]-1-pyridin-2-yl-3-(trifluoromethyl)pyrazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1N1CCN(C=2N=CC(NC(=O)C=3C(=NN(C=3)C=3N=CC=CC=3)C(F)(F)F)=CC=2)CC1 YSKBWIRXFWWGIJ-UHFFFAOYSA-N 0.000 claims 1
• DFWAKSFJIHBKMB-UHFFFAOYSA-N n-[6-[4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(O)(C=2C=C(C=CC=2)C(F)(F)F)CCN1C(N=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 DFWAKSFJIHBKMB-UHFFFAOYSA-N 0.000 claims 1
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 abstract description 5
• 201000010099 disease Diseases 0.000 abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
• 235000020824 obesity Nutrition 0.000 abstract description 5
• 208000001145 Metabolic Syndrome Diseases 0.000 abstract description 4
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 4
• 238000002360 preparation method Methods 0.000 description 129
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 124
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
• 239000000203 mixture Substances 0.000 description 68
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 56
• 235000019439 ethyl acetate Nutrition 0.000 description 43
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 39
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 33
• 239000007787 solid Substances 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• 239000002904 solvent Substances 0.000 description 30
• 239000000243 solution Substances 0.000 description 28
• 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 24
• 108050004099 Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000002253 acid Substances 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 20
• GTZBKUZUOZNIOK-UHFFFAOYSA-N 6-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCC(C=2C=C(C=CC=2)C(F)(F)F)CC1 GTZBKUZUOZNIOK-UHFFFAOYSA-N 0.000 description 19
• BAZVFQBTJPBRTJ-UHFFFAOYSA-N 2-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1 BAZVFQBTJPBRTJ-UHFFFAOYSA-N 0.000 description 18
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 238000005984 hydrogenation reaction Methods 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 239000000463 material Substances 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• 125000003545 alkoxy group Chemical group 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
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