CA2745445A1 - Inhibitors of diacylglycerol aclytransferase - Google Patents

Info

Publication number

CA2745445A1

CA2745445A1 CA2745445A CA2745445A CA2745445A1 CA 2745445 A1 CA2745445 A1 CA 2745445A1 CA 2745445 A CA2745445 A CA 2745445A CA 2745445 A CA2745445 A CA 2745445A CA 2745445 A1 CA2745445 A1 CA 2745445A1

Authority

CA

Canada

Prior art keywords

phenyl

trifluoromethyl

compound

oxazole

carboxylic acid

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000003112 inhibitor Substances 0.000 title abstract description 10
• 150000001982 diacylglycerols Chemical class 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims description 128
• -1 alkyl oxadiazole Chemical compound 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 29
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 22
• 239000005711 Benzoic acid Substances 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 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 15
• 125000005907 alkyl ester group Chemical group 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 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
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 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 6
• 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 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
• 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
• 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 4
• 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 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
• 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 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
• 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 4
• 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 4
• 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 description 4
• 229910052717 sulfur Inorganic materials 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
• 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 3
• 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 description 3
• IIUFGAGBJXFLME-UHFFFAOYSA-N 2-phenyl-n-[6-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyridin-3-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)=CC=2)=N1 IIUFGAGBJXFLME-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• 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 3
• 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 3
• GFUVLROCUYVNQQ-UHFFFAOYSA-N 6-[4-[4-[(5-methyl-2-phenyl-1,3-oxazole-4-carbonyl)amino]phenyl]piperidin-1-yl]pyridine-3-carboxylic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C(CC1)CCN1C1=CC=C(C(O)=O)C=N1 GFUVLROCUYVNQQ-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
• BTIWOZSAEHPEML-UHFFFAOYSA-N n-[6-(4-hydroxy-4-phenylpiperidin-1-yl)pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1C(N=C1)=CC=C1NC(=O)C(=C(O1)C(F)(F)F)N=C1C1=CC=CC=C1 BTIWOZSAEHPEML-UHFFFAOYSA-N 0.000 claims description 3
• LGZFXCRVMWCAQW-UHFFFAOYSA-N n-[6-[4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyridin-3-yl]-2-phenyl-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)CCC1C(ON=1)=NC=1C1CC1 LGZFXCRVMWCAQW-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
• DKQNBUORDQCUJZ-UHFFFAOYSA-N n-[6-[4-(3-methyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyridin-3-yl]-2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound CC1=NOC(C2CCN(CC2)C=2N=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)=N1 DKQNBUORDQCUJZ-UHFFFAOYSA-N 0.000 claims description 3
• DHJPZAUYABQNGF-UHFFFAOYSA-N n-[6-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyridin-3-yl]-2-[2-(trifluoromethoxy)phenyl]-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)OC(F)(F)F)C(F)(F)F)=CC=2)=N1 DHJPZAUYABQNGF-UHFFFAOYSA-N 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-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
• TVEAZHOLMPKUGM-UHFFFAOYSA-N 2-piperidinobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCCCC1 TVEAZHOLMPKUGM-UHFFFAOYSA-N 0.000 claims 7
• ZYLZQIMSYNAILC-UHFFFAOYSA-N 2-piperazin-1-ylbenzoic acid Chemical group OC(=O)C1=CC=CC=C1N1CCNCC1 ZYLZQIMSYNAILC-UHFFFAOYSA-N 0.000 claims 4
• 125000004356 hydroxy functional group Chemical group O* 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 4
• NWPXZRJKYWWFCY-UHFFFAOYSA-N 1-pyridin-2-yl-3-(trifluoromethyl)-n-[6-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]pyridin-3-yl]pyrazole-4-carboxamide Chemical compound FC(F)(F)C1=NN(C=2N=CC=CC=2)C=C1C(=O)NC(C=N1)=CC=C1N(CC1)CCC1C1=CC=CC(C(F)(F)F)=C1 NWPXZRJKYWWFCY-UHFFFAOYSA-N 0.000 claims 2
• QEVBROSTPFOFBB-UHFFFAOYSA-N 2-phenyl-n-[6-(4-phenylpiperidin-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)CCC1C1=CC=CC=C1 QEVBROSTPFOFBB-UHFFFAOYSA-N 0.000 claims 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 2
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• 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 2
• 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 2
• RVFVPPONXUZVTJ-UHFFFAOYSA-N piperazine;pyrimidine Chemical compound C1CNCCN1.C1=CN=CN=C1 RVFVPPONXUZVTJ-UHFFFAOYSA-N 0.000 claims 2
• 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
• 208000008589 Obesity Diseases 0.000 abstract description 5
• 150000001408 amides Chemical class 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
• 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 abstract description 4
• 208000001145 Metabolic Syndrome Diseases 0.000 abstract description 4
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 4
• 201000010099 disease Diseases 0.000 abstract description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 4
• 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 abstract description 3
• 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
• 239000000203 mixture Substances 0.000 description 73
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
• 238000000034 method Methods 0.000 description 65
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 60
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
• 235000019439 ethyl acetate Nutrition 0.000 description 43
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
• 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 description 36
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
• 239000007787 solid Substances 0.000 description 33
• 239000000243 solution Substances 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• 239000002904 solvent Substances 0.000 description 30
• 102100036869 Diacylglycerol O-acyltransferase 1 Human genes 0.000 description 27
• 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 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• 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 22
• 108050004099 Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• 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
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
• 238000005984 hydrogenation reaction Methods 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
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