CA2745445A1 - Inhibitors of diacylglycerol aclytransferase - Google Patents
Inhibitors of diacylglycerol aclytransferase Download PDFInfo
- 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
- 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
- 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
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-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
- 125000003545 alkoxy group Chemical group 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229910052731 fluorine Inorganic materials 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- AFSHUZFNMVJNKX-LLWMBOQKSA-N 1,2-dioleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCC\C=C/CCCCCCCC AFSHUZFNMVJNKX-LLWMBOQKSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- HVEITWPHFPYBBQ-UHFFFAOYSA-N 2-phenyl-n-(4-piperidin-4-ylphenyl)-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide Chemical compound FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C1CCNCC1 HVEITWPHFPYBBQ-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 150000003626 triacylglycerols Chemical class 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 239000013024 dilution buffer Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- JXCDVJXPSHIHLP-UHFFFAOYSA-N ethyl 1-(4-aminophenyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC=C(N)C=C1 JXCDVJXPSHIHLP-UHFFFAOYSA-N 0.000 description 6
- UBBBDEXMDQPVMM-UHFFFAOYSA-N ethyl 1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 UBBBDEXMDQPVMM-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000011535 reaction buffer Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- DNPQOTDNTIJFQX-UHFFFAOYSA-N 1-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 DNPQOTDNTIJFQX-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- JHRDEHLFNLLCQS-UHFFFAOYSA-N n'-hydroxy-2-methylpropanimidamide Chemical compound CC(C)C(N)=NO JHRDEHLFNLLCQS-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 238000004808 supercritical fluid chromatography Methods 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- BTYRKSJMTZKPQO-UHFFFAOYSA-N 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 BTYRKSJMTZKPQO-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- VUTWFCGTRPCOLN-UHFFFAOYSA-N 6-[4-(4-fluorophenyl)piperazin-1-yl]pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCN(C=2C=CC(F)=CC=2)CC1 VUTWFCGTRPCOLN-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000010931 ester hydrolysis Methods 0.000 description 4
- DYEIOUCEYOYBPG-UHFFFAOYSA-N ethyl 1-(4-nitrophenyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC=C([N+]([O-])=O)C=C1 DYEIOUCEYOYBPG-UHFFFAOYSA-N 0.000 description 4
- XRMXFGXBZLNOAX-UHFFFAOYSA-N ethyl 1-(5-aminopyridin-2-yl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC=C(N)C=N1 XRMXFGXBZLNOAX-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- YRLQFRXDWBFGMK-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(N)C=C1 YRLQFRXDWBFGMK-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 3
- DSGKXGDSENGAHB-UHFFFAOYSA-N 1-(5-aminopyridin-2-yl)-4-phenylpiperidin-4-ol Chemical compound N1=CC(N)=CC=C1N1CCC(O)(C=2C=CC=CC=2)CC1 DSGKXGDSENGAHB-UHFFFAOYSA-N 0.000 description 3
- OXRVFOCLSMIASH-UHFFFAOYSA-N 1-[5-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 OXRVFOCLSMIASH-UHFFFAOYSA-N 0.000 description 3
- GTRIGSBTSTWUEE-UHFFFAOYSA-N 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyrimidin-2-yl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C(N=C1)=NC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 GTRIGSBTSTWUEE-UHFFFAOYSA-N 0.000 description 3
- AUYRCXFCCKSUKX-UHFFFAOYSA-N 1-phenyl-3-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound N1=C(C(F)(F)F)C(C(=O)O)=CN1C1=CC=CC=C1 AUYRCXFCCKSUKX-UHFFFAOYSA-N 0.000 description 3
- ZYYCJQBBKYFZIA-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-(trifluoromethyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C(F)(F)F)=C(C(=O)O)N=C1C1=CC=CC=C1Cl ZYYCJQBBKYFZIA-UHFFFAOYSA-N 0.000 description 3
- UKTOUQCHJZMXFX-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl chloride Chemical compound ClC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 UKTOUQCHJZMXFX-UHFFFAOYSA-N 0.000 description 3
- GLUGOKFZOVXKIB-NTISSMGPSA-N 2-phenyl-n-[4-[(3s)-pyrrolidin-3-yl]oxyphenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carboxamide;hydrochloride Chemical compound Cl.FC(F)(F)C=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1O[C@H]1CCNC1 GLUGOKFZOVXKIB-NTISSMGPSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- RIXSPNNCCXWOCO-UHFFFAOYSA-N 4-phenyl-n-(4-piperidin-4-ylphenyl)thiophene-2-carboxamide Chemical compound C=1C(C=2C=CC=CC=2)=CSC=1C(=O)NC(C=C1)=CC=C1C1CCNCC1 RIXSPNNCCXWOCO-UHFFFAOYSA-N 0.000 description 3
- XMNCTHGNUJJFAD-UHFFFAOYSA-N 5-ethyl-2-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(CC)OC(C=2C=CC=CC=2)=N1 XMNCTHGNUJJFAD-UHFFFAOYSA-N 0.000 description 3
- YDBRIJXCVXHDMO-UHFFFAOYSA-N 5-ethyl-2-phenyl-n-(4-piperidin-4-ylphenyl)-1,3-oxazole-4-carboxamide Chemical compound CCC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C1CCNCC1 YDBRIJXCVXHDMO-UHFFFAOYSA-N 0.000 description 3
- YZWRGKBTNPWPNZ-UHFFFAOYSA-N 5-methyl-2-phenyl-n-(4-piperidin-4-ylphenyl)-1,3-oxazole-4-carboxamide Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C1CCNCC1 YZWRGKBTNPWPNZ-UHFFFAOYSA-N 0.000 description 3
- WNYRUKPZNBDMMK-UHFFFAOYSA-N 6-(4-phenylpiperazin-1-yl)pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCN(C=2C=CC=CC=2)CC1 WNYRUKPZNBDMMK-UHFFFAOYSA-N 0.000 description 3
- KJXCUVXXNXPFCC-UHFFFAOYSA-N 6-(4-phenylpiperidin-1-yl)pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCC(C=2C=CC=CC=2)CC1 KJXCUVXXNXPFCC-UHFFFAOYSA-N 0.000 description 3
- JCTWFAZLZQFBPZ-UHFFFAOYSA-N 6-[4-(2-methoxyphenyl)piperazin-1-yl]pyridin-3-amine Chemical compound COC1=CC=CC=C1N1CCN(C=2N=CC(N)=CC=2)CC1 JCTWFAZLZQFBPZ-UHFFFAOYSA-N 0.000 description 3
- KBMXGYYDORMLEG-UHFFFAOYSA-N 6-[4-(3-methoxyphenyl)piperazin-1-yl]pyridin-3-amine Chemical compound COC1=CC=CC(N2CCN(CC2)C=2N=CC(N)=CC=2)=C1 KBMXGYYDORMLEG-UHFFFAOYSA-N 0.000 description 3
- CJAPRVNYYCRFKN-UHFFFAOYSA-N 6-[4-(4-methoxyphenyl)piperazin-1-yl]pyridin-3-amine Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2N=CC(N)=CC=2)CC1 CJAPRVNYYCRFKN-UHFFFAOYSA-N 0.000 description 3
- YBBIIHCEILUOSI-UHFFFAOYSA-N 6-[4-[2-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCN(C=2C(=CC=CC=2)C(F)(F)F)CC1 YBBIIHCEILUOSI-UHFFFAOYSA-N 0.000 description 3
- YNLQNHRSJYYZND-UHFFFAOYSA-N 6-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCN(C=2C=C(C=CC=2)C(F)(F)F)CC1 YNLQNHRSJYYZND-UHFFFAOYSA-N 0.000 description 3
- CTNLAOBVNABMQD-UHFFFAOYSA-N 6-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]pyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCN(C=2C=CC(=CC=2)C(F)(F)F)CC1 CTNLAOBVNABMQD-UHFFFAOYSA-N 0.000 description 3
- UJDLCTNVHJEBDG-UHFFFAOYSA-N 6-fluoropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(F)N=C1 UJDLCTNVHJEBDG-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102100035762 Diacylglycerol O-acyltransferase 2 Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000930020 Homo sapiens Diacylglycerol O-acyltransferase 2 Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000002393 azetidinyl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- UHSPRKUASDYQJN-UHFFFAOYSA-N ethyl 3-[4-(5-aminopyridin-2-yl)piperazin-1-yl]benzoate Chemical compound CCOC(=O)C1=CC=CC(N2CCN(CC2)C=2N=CC(N)=CC=2)=C1 UHSPRKUASDYQJN-UHFFFAOYSA-N 0.000 description 3
- FKIZYOYJFZEPBK-UHFFFAOYSA-N ethyl 4-[4-(5-aminopyridin-2-yl)piperazin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCN(C=2N=CC(N)=CC=2)CC1 FKIZYOYJFZEPBK-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- JUIVFVTWQWMVCM-UHFFFAOYSA-N methyl 1-(5-aminopyridin-2-yl)pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C1=CC=C(N)C=N1 JUIVFVTWQWMVCM-UHFFFAOYSA-N 0.000 description 3
- SHGGEBPXRZLUOY-UHFFFAOYSA-N methyl 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 SHGGEBPXRZLUOY-UHFFFAOYSA-N 0.000 description 3
- KCCKSVFVFQJTDB-UHFFFAOYSA-N methyl 2-[4-(5-aminopyridin-2-yl)piperazin-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC=C1N1CCN(C=2N=CC(N)=CC=2)CC1 KCCKSVFVFQJTDB-UHFFFAOYSA-N 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- BFJJYXUCGYOXDM-UHFFFAOYSA-N tert-butyl 4-bromobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(Br)C=C1 BFJJYXUCGYOXDM-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- WIIJTJYZWJVTSA-UHFFFAOYSA-N 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]pyrrolidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 WIIJTJYZWJVTSA-UHFFFAOYSA-N 0.000 description 2
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- GVHWTQYNZUNGIA-UHFFFAOYSA-N 2-[(2-chlorobenzoyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1Cl GVHWTQYNZUNGIA-UHFFFAOYSA-N 0.000 description 2
- HODRSYBSOZPUFX-UHFFFAOYSA-N 2-[4-(5-nitropyridin-2-yl)piperazin-1-yl]pyrimidine Chemical compound N1=CC([N+](=O)[O-])=CC=C1N1CCN(C=2N=CC=CN=2)CC1 HODRSYBSOZPUFX-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 2
- PTTYGIWPBPJHAM-UHFFFAOYSA-N 5-nitro-2-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]pyridine Chemical group N1=CC([N+](=O)[O-])=CC=C1N1CCC(C=2C=C(C=CC=2)C(F)(F)F)CC1 PTTYGIWPBPJHAM-UHFFFAOYSA-N 0.000 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 description 2
- 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 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- 241001137307 Cyprinodon variegatus Species 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 101000927974 Homo sapiens Diacylglycerol O-acyltransferase 1 Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229910008066 SnC12 Inorganic materials 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001298 alcohols Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 2
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 2
- 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000006350 alkyl thio alkyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000004103 aminoalkyl group Chemical group 0.000 description 2
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 description 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 125000004069 aziridinyl group Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 2
- CKYOENXBJPTZAM-UHFFFAOYSA-N benzyl 2-benzamido-3-oxopentanoate Chemical compound C=1C=CC=CC=1COC(=O)C(C(=O)CC)NC(=O)C1=CC=CC=C1 CKYOENXBJPTZAM-UHFFFAOYSA-N 0.000 description 2
- DPTOYMYPUUQKMU-UHFFFAOYSA-N benzyl 5-ethyl-2-phenyl-1,3-oxazole-4-carboxylate Chemical compound CCC=1OC(C=2C=CC=CC=2)=NC=1C(=O)OCC1=CC=CC=C1 DPTOYMYPUUQKMU-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 235000013877 carbamide Nutrition 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000004623 carbolinyl group Chemical group 0.000 description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003596 drug target Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000004146 energy storage Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- JNIIQKJYBLQUKR-UHFFFAOYSA-N ethyl 1-(5-aminopyrimidin-2-yl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=NC=C(N)C=N1 JNIIQKJYBLQUKR-UHFFFAOYSA-N 0.000 description 2
- DDZVQOOCVSHDKD-UHFFFAOYSA-N ethyl 1-[5-[[2-[2-(trifluoromethoxy)phenyl]-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C(=CC=CC=2)OC(F)(F)F)=N1 DDZVQOOCVSHDKD-UHFFFAOYSA-N 0.000 description 2
- UWOBZMIWGZDMNO-UHFFFAOYSA-N ethyl 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]piperidin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1NCC(NC(=O)C2=C(OC(=N2)C=2C=CC=CC=2)C(F)(F)F)CC1 UWOBZMIWGZDMNO-UHFFFAOYSA-N 0.000 description 2
- HISVXNZWBUIRCT-UHFFFAOYSA-N ethyl 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyridin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(N=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 HISVXNZWBUIRCT-UHFFFAOYSA-N 0.000 description 2
- RNOJREZLCGQMPX-UHFFFAOYSA-N ethyl 1-phenyl-3-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound N1=C(C(F)(F)F)C(C(=O)OCC)=CN1C1=CC=CC=C1 RNOJREZLCGQMPX-UHFFFAOYSA-N 0.000 description 2
- VYXIHSAEOXPAEY-UHFFFAOYSA-N ethyl 5-(trifluoromethyl)-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1C(F)(F)F VYXIHSAEOXPAEY-UHFFFAOYSA-N 0.000 description 2
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000003106 haloaryl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 description 2
- 125000002636 imidazolinyl group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 2
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 2
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- IMSQUKXCGIMIJO-UHFFFAOYSA-N methyl 1-(5-nitropyridin-2-yl)pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OC)CCN1C1=CC=C([N+]([O-])=O)C=N1 IMSQUKXCGIMIJO-UHFFFAOYSA-N 0.000 description 2
- NVWHFQJYAXGYIN-UHFFFAOYSA-N methyl 2-[(2-chlorobenzoyl)amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1Cl NVWHFQJYAXGYIN-UHFFFAOYSA-N 0.000 description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000004999 nitroaryl group Chemical group 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003457 sulfones Chemical group 0.000 description 2
- 150000003462 sulfoxides Chemical group 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- RYWQNZFJMSYAED-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-aminophenoxy)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C(N)C=C1 RYWQNZFJMSYAED-ZDUSSCGKSA-N 0.000 description 2
- YPNHSMCBGQTTKH-IBGZPJMESA-N tert-butyl (3s)-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 YPNHSMCBGQTTKH-IBGZPJMESA-N 0.000 description 2
- IGPBZYKGFXJMOG-VWLOTQADSA-N tert-butyl 4-[(3s)-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenoxy]pyrrolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=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 IGPBZYKGFXJMOG-VWLOTQADSA-N 0.000 description 2
- NIDGOBZYDGALIM-UHFFFAOYSA-N tert-butyl 4-[4-[(5-ethyl-2-phenyl-1,3-oxazole-4-carbonyl)amino]phenyl]piperidine-1-carboxylate Chemical compound CCC=1OC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1)=CC=C1C1CCN(C(=O)OC(C)(C)C)CC1 NIDGOBZYDGALIM-UHFFFAOYSA-N 0.000 description 2
- LRHUGTSLXWLTHB-UHFFFAOYSA-N tert-butyl 4-[4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1N1CCC(C=2C=CC(NC(=O)C3=C(OC(=N3)C=3C=CC=CC=3)C(F)(F)F)=CC=2)CC1 LRHUGTSLXWLTHB-UHFFFAOYSA-N 0.000 description 2
- NCPLWAPMXWQLCI-UHFFFAOYSA-N tert-butyl 4-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(C=C1)=CC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 NCPLWAPMXWQLCI-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 150000003568 thioethers Chemical group 0.000 description 2
- 150000003573 thiols Chemical group 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- UNEQFVVZNSHYBR-UHFFFAOYSA-N 1,3-oxazole-2,4-dicarboxamide Chemical class NC(=O)C1=COC(C(N)=O)=N1 UNEQFVVZNSHYBR-UHFFFAOYSA-N 0.000 description 1
- JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical class OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical compound C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 1
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 1
- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 1
- PZIBVWUXWNYTNL-UHFFFAOYSA-N 1-(3-methoxyphenyl)piperazine Chemical compound COC1=CC=CC(N2CCNCC2)=C1 PZIBVWUXWNYTNL-UHFFFAOYSA-N 0.000 description 1
- IBQMAPSJLHRQPE-UHFFFAOYSA-N 1-(4-(trifluoromethyl)phenyl)piperazine Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CCNCC1 IBQMAPSJLHRQPE-UHFFFAOYSA-N 0.000 description 1
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 1
- VWYOMBOCTBBKKQ-UHFFFAOYSA-N 1-(5-aminopyridin-2-yl)-4-[3-(trifluoromethyl)phenyl]piperidin-4-ol Chemical compound N1=CC(N)=CC=C1N1CCC(O)(C=2C=C(C=CC=2)C(F)(F)F)CC1 VWYOMBOCTBBKKQ-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- VZUBMIDXJRGARE-UHFFFAOYSA-N 1-[2-(trifluoromethyl)phenyl]piperazine Chemical compound FC(F)(F)C1=CC=CC=C1N1CCNCC1 VZUBMIDXJRGARE-UHFFFAOYSA-N 0.000 description 1
- MFKCLEOOYFXUGZ-UHFFFAOYSA-N 1-pyridin-2-yl-2h-pyridine-4-carboxylic acid Chemical compound C1=CC(C(=O)O)=CCN1C1=CC=CC=N1 MFKCLEOOYFXUGZ-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- KSHPWYXAJJCUMJ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzoyl chloride Chemical compound FC(F)(F)OC1=CC=CC=C1C(Cl)=O KSHPWYXAJJCUMJ-UHFFFAOYSA-N 0.000 description 1
- QBTNPRFNDWGCRW-UHFFFAOYSA-N 2-[(2-chlorobenzoyl)amino]-4,4,4-trifluoro-3,3-dihydroxybutanoic acid Chemical compound FC(F)(F)C(O)(O)C(C(=O)O)NC(=O)C1=CC=CC=C1Cl QBTNPRFNDWGCRW-UHFFFAOYSA-N 0.000 description 1
- DPRAYRYQQAXQPE-UHFFFAOYSA-N 2-bromohexadecanoic acid Chemical compound CCCCCCCCCCCCCCC(Br)C(O)=O DPRAYRYQQAXQPE-UHFFFAOYSA-N 0.000 description 1
- GTGTXZRPJHDASG-UHFFFAOYSA-N 2-bromooctanoic acid Chemical compound CCCCCCC(Br)C(O)=O GTGTXZRPJHDASG-UHFFFAOYSA-N 0.000 description 1
- OFCBNMYNAHUDGE-UHFFFAOYSA-N 2-chloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1 OFCBNMYNAHUDGE-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- MPYMDEVGWBOXLN-UHFFFAOYSA-N 2h-pyrimido[4,5-e]oxazin-3-amine Chemical class C1=NC=C2ONC(N)=CC2=N1 MPYMDEVGWBOXLN-UHFFFAOYSA-N 0.000 description 1
- STAWYILKMSIACI-UHFFFAOYSA-N 3,3-dihydroxybutanoic acid Chemical compound CC(O)(O)CC(O)=O STAWYILKMSIACI-UHFFFAOYSA-N 0.000 description 1
- JNRLEMMIVRBKJE-UHFFFAOYSA-N 4,4'-Methylenebis(N,N-dimethylaniline) Chemical compound C1=CC(N(C)C)=CC=C1CC1=CC=C(N(C)C)C=C1 JNRLEMMIVRBKJE-UHFFFAOYSA-N 0.000 description 1
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
- ILKPZCKFWLTEBQ-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidin-4-ol Chemical compound C=1C=CC(C(F)(F)F)=CC=1C1(O)CCNCC1 ILKPZCKFWLTEBQ-UHFFFAOYSA-N 0.000 description 1
- IPKSNWXGEIHOMR-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidine Chemical compound FC(F)(F)C1=CC=CC(C2CCNCC2)=C1 IPKSNWXGEIHOMR-UHFFFAOYSA-N 0.000 description 1
- OGZONGZRKSIERU-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C2CCNCC2)=C1 OGZONGZRKSIERU-UHFFFAOYSA-N 0.000 description 1
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 1
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 1
- VHKMTORCXXPIFI-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NNC=1C(F)(F)F VHKMTORCXXPIFI-UHFFFAOYSA-N 0.000 description 1
- YABCPNYCFFUVNM-UHFFFAOYSA-N 5-methyl-2-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=C(C)OC(C=2C=CC=CC=2)=N1 YABCPNYCFFUVNM-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 101001074429 Bacillus subtilis (strain 168) Polyketide biosynthesis acyltransferase homolog PksD Proteins 0.000 description 1
- 101000936617 Bacillus velezensis (strain DSM 23117 / BGSC 10A6 / FZB42) Polyketide biosynthesis acyltransferase homolog BaeD Proteins 0.000 description 1
- OGBVRMYSNSKIEF-UHFFFAOYSA-N Benzylphosphonic acid Chemical class OP(O)(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- UXDDRFCJKNROTO-UHFFFAOYSA-N Glycerol 1,2-diacetate Chemical compound CC(=O)OCC(CO)OC(C)=O UXDDRFCJKNROTO-UHFFFAOYSA-N 0.000 description 1
- 241001562081 Ikeda Species 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- YKGCBLWILMDSAV-GOSISDBHSA-N Isoxanthohumol Natural products O(C)c1c2C(=O)C[C@H](c3ccc(O)cc3)Oc2c(C/C=C(\C)/C)c(O)c1 YKGCBLWILMDSAV-GOSISDBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- 101100499143 Mus musculus Dgat1 gene Proteins 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000035871 PIK3CA-related overgrowth syndrome Diseases 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 229930183118 Tanshinone Natural products 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- HYWVELCSGZINQW-ZWKOTPCHSA-N ac1l4j9n Chemical compound CN([C@@H]1[C@H](O)C2=C(C3=C11)C=CC=C2OC)CCC1=CC1=C3OCO1 HYWVELCSGZINQW-ZWKOTPCHSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 159000000013 aluminium salts Chemical class 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KFNIDRLZPBRDNJ-UHFFFAOYSA-N benzyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1COC(=O)CN=C(C=1C=CC=CC=1)C1=CC=CC=C1 KFNIDRLZPBRDNJ-UHFFFAOYSA-N 0.000 description 1
- XYGZMXAJRUUADZ-UHFFFAOYSA-N benzyl 2-amino-3-oxopentanoate Chemical compound CCC(=O)C(N)C(=O)OCC1=CC=CC=C1 XYGZMXAJRUUADZ-UHFFFAOYSA-N 0.000 description 1
- DUNIQVJFYQVEAZ-UHFFFAOYSA-N benzyl 2-amino-3-oxopentanoate;hydrochloride Chemical compound Cl.CCC(=O)C(N)C(=O)OCC1=CC=CC=C1 DUNIQVJFYQVEAZ-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 150000001789 chalcones Chemical class 0.000 description 1
- 235000005513 chalcones Nutrition 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229930191753 cochlioquinone Natural products 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011340 continuous therapy Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- FUSADYLVRMROPL-UHFFFAOYSA-N demethylxanthohumol Natural products CC(C)=CCC1=C(O)C=C(O)C(C(=O)C=CC=2C=CC(O)=CC=2)=C1O FUSADYLVRMROPL-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000003374 diacylglycerol group Chemical group 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- MRIZUWLPEUPULM-UHFFFAOYSA-N ethyl 1-(5-nitropyridin-2-yl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC=C([N+]([O-])=O)C=N1 MRIZUWLPEUPULM-UHFFFAOYSA-N 0.000 description 1
- NDVBUBASVLSDAV-UHFFFAOYSA-N ethyl 1-(5-nitropyrimidin-2-yl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=NC=C([N+]([O-])=O)C=N1 NDVBUBASVLSDAV-UHFFFAOYSA-N 0.000 description 1
- FQDCKQVXCGWLSX-UHFFFAOYSA-N ethyl 1-[5-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]amino]pyrimidin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(N=C1)=NC=C1NC(=O)C1=C(C(F)(F)F)OC(C=2C=CC=CC=2)=N1 FQDCKQVXCGWLSX-UHFFFAOYSA-N 0.000 description 1
- MFHSHQIHYPPRMQ-UHFFFAOYSA-N ethyl 3-piperazin-1-ylbenzoate Chemical compound CCOC(=O)C1=CC=CC(N2CCNCC2)=C1 MFHSHQIHYPPRMQ-UHFFFAOYSA-N 0.000 description 1
- OQEHTFFLOHTFSB-UHFFFAOYSA-N ethyl 4-piperazin-1-ylbenzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCNCC1 OQEHTFFLOHTFSB-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002185 fatty acyl-CoAs Chemical class 0.000 description 1
- 150000002190 fatty acyls Chemical group 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- XGNPSKXFPSPTDE-UHFFFAOYSA-N methyl 2-piperazin-1-ylbenzoate Chemical compound COC(=O)C1=CC=CC=C1N1CCNCC1 XGNPSKXFPSPTDE-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- VVWWZOKQKXPVIV-UHFFFAOYSA-N methyl pyrrolidine-3-carboxylate Chemical compound COC(=O)C1CCNC1 VVWWZOKQKXPVIV-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
- FVZJIAUYFDQQKJ-DQEYMECFSA-N n-[4-[(4as,10br)-8,9-dimethoxy-2-methyl-3,4,4a,10b-tetrahydro-1h-benzo[c][1,6]naphthyridin-6-yl]phenyl]-4-methylbenzenesulfonamide Chemical compound N([C@H]1CCN(C)C[C@H]1C=1C=C(C(=CC=11)OC)OC)=C1C(C=C1)=CC=C1NS(=O)(=O)C1=CC=C(C)C=C1 FVZJIAUYFDQQKJ-DQEYMECFSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- MNBKLUUYKPBKDU-BBECNAHFSA-N palmitoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MNBKLUUYKPBKDU-BBECNAHFSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- MRDGZSKYFPGAKP-UHFFFAOYSA-N para-methoxyphenylpiperazine Chemical compound C1=CC(OC)=CC=C1N1CCNCC1 MRDGZSKYFPGAKP-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001197 polyacetylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229930008679 prenylflavonoid Natural products 0.000 description 1
- 150000007951 prenylflavonoids Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 1
- OWKPZEQIOUPYPN-UHFFFAOYSA-N pyrrolo[1,2-b]pyridazine Chemical class N1=CC=CC2=C=C[CH]N21 OWKPZEQIOUPYPN-UHFFFAOYSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- SGQPXIZHVCLLRP-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-nitrophenoxy)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 SGQPXIZHVCLLRP-ZDUSSCGKSA-N 0.000 description 1
- NPVLZVSAZXTBSR-UHFFFAOYSA-N tert-butyl 3-bromobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC(Br)=C1 NPVLZVSAZXTBSR-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- ORXQGKIUCDPEAJ-YRNVUSSQSA-N xanthohumol Chemical compound COC1=CC(O)=C(CC=C(C)C)C(O)=C1C(=O)\C=C\C1=CC=C(O)C=C1 ORXQGKIUCDPEAJ-YRNVUSSQSA-N 0.000 description 1
- UVBDKJHYMQEAQV-UHFFFAOYSA-N xanthohumol Natural products OC1=C(CC=C(C)C)C(OC)=CC(OC)=C1C(=O)C=CC1=CC=C(O)C=C1 UVBDKJHYMQEAQV-UHFFFAOYSA-N 0.000 description 1
- 235000008209 xanthohumol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13815708P | 2008-12-17 | 2008-12-17 | |
| US61/138,157 | 2008-12-17 | ||
| PCT/US2009/068048 WO2010077861A1 (en) | 2008-12-17 | 2009-12-15 | Inhibitors of diacylglycerol aclytransferase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2745445A1 true CA2745445A1 (en) | 2010-07-08 |
Family
ID=42241316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2745445A Abandoned CA2745445A1 (en) | 2008-12-17 | 2009-12-15 | Inhibitors of diacylglycerol aclytransferase |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8211914B2 (enExample) |
| EP (1) | EP2378878A4 (enExample) |
| JP (1) | JP2012512252A (enExample) |
| CN (1) | CN102245024A (enExample) |
| AU (1) | AU2009333333A1 (enExample) |
| CA (1) | CA2745445A1 (enExample) |
| IL (1) | IL213164A0 (enExample) |
| WO (1) | WO2010077861A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8153644B2 (en) | 2007-05-22 | 2012-04-10 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8115011B2 (en) | 2007-05-22 | 2012-02-14 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8211884B2 (en) | 2008-08-06 | 2012-07-03 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8324385B2 (en) | 2008-10-30 | 2012-12-04 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| JP2012512252A (ja) | 2008-12-17 | 2012-05-31 | ブイアイエイ・ファーマシューティカルズ・インコーポレーテッド | 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 |
| TW201305140A (zh) * | 2011-06-17 | 2013-02-01 | Daiichi Sankyo Co Ltd | 新穎聯芳基醚衍生物 |
| US9527859B2 (en) | 2012-04-13 | 2016-12-27 | Mitsubishi Tanabe Pharma Corporation | Amidopyridine derivative and use thereof |
| MY195016A (en) | 2014-08-04 | 2023-01-03 | Nuevolution As | Optionally Fused Heterocyclyl-Substituted Derivatives of Pyrimidine Useful for The Treatment of Inflammatory, Metabolic, Oncologic and Autoimmune Diseases |
| AR109179A1 (es) | 2016-08-19 | 2018-11-07 | Pfizer | Inhibidores de diacilglicerol aciltransferasa 2 |
| AU2020405446A1 (en) | 2019-12-20 | 2022-05-26 | Nuevolution A/S | Compounds active towards nuclear receptors |
| BR112022012205A2 (pt) | 2019-12-20 | 2022-09-13 | Nuevolution As | Compostos ativos para receptores nucleares |
| JP7713954B2 (ja) | 2020-03-31 | 2025-07-28 | ヌエヴォリューション・アクティーゼルスカブ | 核内受容体に対して活性な化合物 |
| CA3174252A1 (en) | 2020-03-31 | 2021-10-07 | Nuevolution A/S | Compounds active towards nuclear receptors |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3250771A (en) * | 1962-12-17 | 1966-05-10 | Geigy Chem Corp | 5-monocarbocyclic aryl-n-lower alkyl-2-pyrrolidine carboxylic acid, esters, amides and derivatives thereof |
| DE2337461A1 (de) * | 1973-07-24 | 1975-02-06 | Boehringer Mannheim Gmbh | Neue indolderivate und verfahren zu deren herstellung |
| US4066654A (en) * | 1975-04-16 | 1978-01-03 | G. D. Searle & Co. | 1-triarylalkyl-4-phenyl-4-piperidine carboxylic acids and derivatives |
| US6495558B1 (en) * | 1999-01-22 | 2002-12-17 | Amgen Inc. | Kinase inhibitors |
| DE60017115T2 (de) | 1999-02-10 | 2005-12-08 | Mitsubishi Pharma Corp. | Amid-derivate und deren medizinische verwendung |
| US6756374B2 (en) * | 2001-01-22 | 2004-06-29 | Hoffmann-La Roche Inc. | Diaminothiazoles having antiproliferative activity |
| BR0212158A (pt) | 2001-08-31 | 2004-07-13 | Aventis Pharma Gmbh | Derivados de diarilcicloalquila, processos para a sua preparação e sua aplicação como ativadores de ppar |
| US7553867B2 (en) | 2002-09-06 | 2009-06-30 | Takeda Pharmaceutical Company Limited | Furan or thiophene derivative and medicinal use thereof |
| EP1562956A4 (en) * | 2002-11-22 | 2007-10-10 | Japan Tobacco Inc | HETEROCYCLES CONTAINING FUSED BICYCLIC NITROGEN |
| US7148246B2 (en) * | 2003-02-27 | 2006-12-12 | Sanofi-Aventis Deutschland Gmbh | Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals |
| DE10308353A1 (de) * | 2003-02-27 | 2004-12-02 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkylderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CN101115711A (zh) * | 2005-02-07 | 2008-01-30 | 霍夫曼-拉罗奇有限公司 | 二酰基甘油酰基转移酶(dgat)的抑制剂 |
| CA2610188A1 (en) | 2005-06-11 | 2006-12-21 | Astrazeneca Ab | Oxadiazole derivatives as dgat inhibitors |
| BRPI0619052A2 (pt) | 2005-11-28 | 2011-09-20 | Hoffmann La Roche | compostos, processo para a sua preparação, composições farmacêuticas que os compreendem, método para o tratamento terapêutico e/ou profilático de enfermidades que são moduladas por inibidores de diacilglicerol aciltransferase, e seu uso |
| CN101316844A (zh) * | 2005-11-28 | 2008-12-03 | 霍夫曼-拉罗奇有限公司 | 二酰甘油酰基转移酶(dgat)抑制剂 |
| US8058299B2 (en) * | 2007-05-22 | 2011-11-15 | Via Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8115011B2 (en) * | 2007-05-22 | 2012-02-14 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8153644B2 (en) * | 2007-05-22 | 2012-04-10 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US20090099201A1 (en) * | 2007-05-22 | 2009-04-16 | David Robert Bolin | Diacylglycerol Acyltransferase Inhibitors |
| EP2155687A1 (en) | 2007-05-22 | 2010-02-24 | Via Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US8211884B2 (en) | 2008-08-06 | 2012-07-03 | Madrigal Pharmaceuticals, Inc. | Diacylglycerol acyltransferase inhibitors |
| US20110224193A1 (en) * | 2008-11-19 | 2011-09-15 | Merck Sharp & Dohme Corp | Inhibitors of diacylglycerol acyltransferase |
| EP2367817A4 (en) | 2008-12-03 | 2012-05-09 | Via Pharmaceuticals Inc | INHIBITORS OF DIACYLGLYCEROL ACYLTRANSFERASE |
| JP2012512252A (ja) | 2008-12-17 | 2012-05-31 | ブイアイエイ・ファーマシューティカルズ・インコーポレーテッド | 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 |
-
2009
- 2009-12-15 JP JP2011542339A patent/JP2012512252A/ja not_active Withdrawn
- 2009-12-15 EP EP09836834A patent/EP2378878A4/en not_active Withdrawn
- 2009-12-15 CA CA2745445A patent/CA2745445A1/en not_active Abandoned
- 2009-12-15 CN CN2009801505265A patent/CN102245024A/zh active Pending
- 2009-12-15 WO PCT/US2009/068048 patent/WO2010077861A1/en not_active Ceased
- 2009-12-15 AU AU2009333333A patent/AU2009333333A1/en not_active Abandoned
- 2009-12-15 US US12/638,244 patent/US8211914B2/en not_active Expired - Fee Related
-
2011
- 2011-05-26 IL IL213164A patent/IL213164A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2378878A4 (en) | 2012-08-01 |
| EP2378878A1 (en) | 2011-10-26 |
| AU2009333333A1 (en) | 2011-06-30 |
| CN102245024A (zh) | 2011-11-16 |
| US8211914B2 (en) | 2012-07-03 |
| WO2010077861A1 (en) | 2010-07-08 |
| JP2012512252A (ja) | 2012-05-31 |
| US20100152445A1 (en) | 2010-06-17 |
| IL213164A0 (en) | 2011-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8211914B2 (en) | Inhibitors of diacylglycerol acyltransferase | |
| EP2350311B1 (en) | Diacylglycerol acyltransferase inhibitors | |
| US8058299B2 (en) | Diacylglycerol acyltransferase inhibitors | |
| US8124766B2 (en) | Inhibitors of diacylglycerol acyltransferase | |
| US8115011B2 (en) | Diacylglycerol acyltransferase inhibitors | |
| CA2630269C (en) | Inhibitors of diacyglycerol acyltransferase (dgat) | |
| CA2686951C (en) | Diacylglycerol acyltransferase inhibitors | |
| US8153644B2 (en) | Diacylglycerol acyltransferase inhibitors | |
| EP2197875A1 (en) | Diacylglycerol acyltransferase inhibitors | |
| US20090099201A1 (en) | Diacylglycerol Acyltransferase Inhibitors | |
| US8211884B2 (en) | Diacylglycerol acyltransferase inhibitors | |
| HK1163446A (en) | Inhibitors of diacylglycerol aclytransferase | |
| HK1162053A (en) | Diacylglycerol acyltransferase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20141216 |