CA2471566A1 - Combinaison d'inhibiteurs de mtp ou d'inhibiteurs de secretions apob avec des fibrates en vue d'une utilisation comme medicament - Google Patents
Combinaison d'inhibiteurs de mtp ou d'inhibiteurs de secretions apob avec des fibrates en vue d'une utilisation comme medicament Download PDFInfo
- Publication number
- CA2471566A1 CA2471566A1 CA002471566A CA2471566A CA2471566A1 CA 2471566 A1 CA2471566 A1 CA 2471566A1 CA 002471566 A CA002471566 A CA 002471566A CA 2471566 A CA2471566 A CA 2471566A CA 2471566 A1 CA2471566 A1 CA 2471566A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alkyl
- phenyl
- carbonyl
- atom
- 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 claims abstract description 105
- 229940125753 fibrate Drugs 0.000 title claims abstract description 75
- 239000003814 drug Substances 0.000 title description 14
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims abstract description 118
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- -1 trifluoromethoxy, amino Chemical group 0.000 claims description 387
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 215
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 211
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 193
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 177
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 137
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 131
- 239000000460 chlorine Substances 0.000 claims description 128
- 229910052801 chlorine Inorganic materials 0.000 claims description 128
- 229910052731 fluorine Inorganic materials 0.000 claims description 124
- 239000011737 fluorine Substances 0.000 claims description 124
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 121
- 229910052757 nitrogen Inorganic materials 0.000 claims description 119
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 117
- 239000001301 oxygen Substances 0.000 claims description 117
- 229910052760 oxygen Inorganic materials 0.000 claims description 117
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 115
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 114
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 101
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims description 88
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 81
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 74
- 229910052799 carbon Inorganic materials 0.000 claims description 74
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 73
- 125000001072 heteroaryl group Chemical group 0.000 claims description 69
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 69
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 67
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 60
- 125000005549 heteroarylene group Chemical group 0.000 claims description 53
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 52
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 50
- 150000001721 carbon Chemical group 0.000 claims description 50
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 49
- 150000001875 compounds Chemical class 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 46
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 42
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical group N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 36
- 125000005842 heteroatom Chemical group 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 28
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 27
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 25
- 238000001727 in vivo Methods 0.000 claims description 24
- 150000002632 lipids Chemical class 0.000 claims description 24
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 24
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 23
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 20
- 229960002297 fenofibrate Drugs 0.000 claims description 20
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 20
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 20
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 20
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 19
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 19
- 125000002619 bicyclic group Chemical group 0.000 claims description 18
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 18
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- 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 claims description 16
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 16
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 claims description 13
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 12
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 12
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229960000516 bezafibrate Drugs 0.000 claims description 12
- 230000004962 physiological condition Effects 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 125000001246 bromo group Chemical group Br* 0.000 claims description 11
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 10
- 230000002829 reductive effect Effects 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims description 9
- MBBCVAKAJPKAKM-UHFFFAOYSA-N lomitapide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCC1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 MBBCVAKAJPKAKM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000005551 pyridylene group Chemical group 0.000 claims description 8
- 125000005576 pyrimidinylene group Chemical group 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 6
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 229960003627 gemfibrozil Drugs 0.000 claims description 6
- 231100000304 hepatotoxicity Toxicity 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 230000007056 liver toxicity Effects 0.000 claims description 6
- BHDHITBPLUIJBZ-UHFFFAOYSA-N n-[[4-(3-azaspiro[5.5]undecan-3-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)N2CCC3(CCCCC3)CC2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 BHDHITBPLUIJBZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 5
- MOOOIKCMFCEZGR-UHFFFAOYSA-N 1-methyl-n-[[4-(4-propylpiperidin-1-yl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1CC(CCC)CCN1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C MOOOIKCMFCEZGR-UHFFFAOYSA-N 0.000 claims description 5
- KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 229960002174 ciprofibrate Drugs 0.000 claims description 5
- KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 claims description 5
- 229960001214 clofibrate Drugs 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- TWAXWRDFNJFVFM-UHFFFAOYSA-N n-[[4-(1,4-dioxaspiro[4.5]decan-8-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C2CCC3(CC2)OCCO3)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 TWAXWRDFNJFVFM-UHFFFAOYSA-N 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- WHDPPODAZUHMFE-UHFFFAOYSA-N 1-methyl-n-[3-(4-phenylphenyl)prop-2-ynyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC#CC=2C=CC(=CC=2)C=2C=CC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 WHDPPODAZUHMFE-UHFFFAOYSA-N 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
- DJLMIXIBPMWLNC-UHFFFAOYSA-N n-[2-(2-acetamidoethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C=1C=C2CN(CCNC(=O)C)CCC2=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DJLMIXIBPMWLNC-UHFFFAOYSA-N 0.000 claims description 4
- LMFSUGDANQYZSG-UHFFFAOYSA-N n-[[4-(4-hydroxyphenyl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(O)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 LMFSUGDANQYZSG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 3
- 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 claims description 3
- PMXMADULYZHDGE-NRFANRHFSA-N n-[(2s)-2-(methanesulfonamido)-2,3-dihydro-1h-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=CC=CC(C(=O)NC=2C=C3C[C@H](CC3=CC=2)NS(C)(=O)=O)=C1C1=CC=C(C(F)(F)F)C=C1 PMXMADULYZHDGE-NRFANRHFSA-N 0.000 claims description 3
- WNDIAFXQKOHFLV-UHFFFAOYSA-N n-[2-(1h-1,2,4-triazol-5-ylmethyl)-3,4-dihydro-1h-isoquinolin-6-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CN(CC2=NNC=N2)CC2)C2=C1 WNDIAFXQKOHFLV-UHFFFAOYSA-N 0.000 claims description 3
- GSTMUBGCBOCOJN-UHFFFAOYSA-N n-[2-(dimethylcarbamoylamino)-2,3-dihydro-1h-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=C2CC(NC(=O)N(C)C)CC2=CC=C1NC(=O)C1=CC=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 GSTMUBGCBOCOJN-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- VXMOVUCQJPCZAT-UHFFFAOYSA-N 1-methyl-n-[3-(4-propan-2-ylphenyl)prop-2-ynyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1C#CCNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C VXMOVUCQJPCZAT-UHFFFAOYSA-N 0.000 claims description 2
- OHHJKEWYFFIELZ-UHFFFAOYSA-N 1-methyl-n-[[4-(4-methylphenyl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C OHHJKEWYFFIELZ-UHFFFAOYSA-N 0.000 claims description 2
- FWXBHUDVFMLMCQ-UHFFFAOYSA-N 1-methyl-n-[[4-(6-methylpyridazin-3-yl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound N1=NC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C FWXBHUDVFMLMCQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- RZQQXRVPPOOCQR-UHFFFAOYSA-N 2,3-dihydro-1,3,4-oxadiazole Chemical compound C1NN=CO1 RZQQXRVPPOOCQR-UHFFFAOYSA-N 0.000 claims description 2
- VKRGLHLCUMMXHA-UHFFFAOYSA-N 2,3-dihydro-1,3,4-thiadiazole Chemical group C1NN=CS1 VKRGLHLCUMMXHA-UHFFFAOYSA-N 0.000 claims description 2
- KIMRCJZMVARVSU-UHFFFAOYSA-N 2-cyclopentyl-2-[4-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n-(2-hydroxy-1-phenylethyl)acetamide Chemical compound C12=NC(C)=CC(C)=C2C2=CC=CC=C2N1CC(C=C1)=CC=C1C(C(=O)NC(CO)C=1C=CC=CC=1)C1CCCC1 KIMRCJZMVARVSU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- JSICOZLLLJJMTJ-HXUWFJFHSA-N 5-fluoro-n-[(2r)-2-(methanesulfonamido)-2,3-dihydro-1h-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C([C@H](CC1=C2)NS(=O)(=O)C)C1=CC=C2NC(=O)C1=CC(F)=CC=C1C1=CC=C(C(F)(F)F)C=C1 JSICOZLLLJJMTJ-HXUWFJFHSA-N 0.000 claims description 2
- VFJKBUFDAVLEQJ-UHFFFAOYSA-N 9-[4-[4-(2-phenylacetyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CC1=CC=CC=C1 VFJKBUFDAVLEQJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- JKHYOWBRQRJSTQ-OAQYLSRUSA-N methyl n-[(2r)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1h-inden-2-yl]carbamate Chemical compound C([C@H](CC1=C2)NC(=O)OC)C1=CC=C2NC(=O)C1=CC=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 JKHYOWBRQRJSTQ-OAQYLSRUSA-N 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- IUWGZPNDYBPGKC-UHFFFAOYSA-N n-[[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)N2CCC3(CC2)OCCO3)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IUWGZPNDYBPGKC-UHFFFAOYSA-N 0.000 claims description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000005557 thiazolylene group Chemical group 0.000 claims description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 51
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 28
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 15
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 9
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
- 125000006560 (C1-C5)alkylcarbonylamino group Chemical group 0.000 claims 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- 235000010290 biphenyl Nutrition 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- DQMVITUDHVGNTK-UHFFFAOYSA-N 1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-n-[3-[4-(trifluoromethyl)phenyl]prop-2-ynyl]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC#CC=2C=CC(=CC=2)C(F)(F)F)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DQMVITUDHVGNTK-UHFFFAOYSA-N 0.000 claims 1
- JSICOZLLLJJMTJ-FQEVSTJZSA-N 5-fluoro-n-[(2s)-2-(methanesulfonamido)-2,3-dihydro-1h-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C([C@@H](CC1=C2)NS(=O)(=O)C)C1=CC=C2NC(=O)C1=CC(F)=CC=C1C1=CC=C(C(F)(F)F)C=C1 JSICOZLLLJJMTJ-FQEVSTJZSA-N 0.000 claims 1
- JEMZBZYBGXMZBG-UHFFFAOYSA-N 9-[4-[4-(2-phenylbutanoyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C1CN(CCCCC2(C(=O)NCC(F)(F)F)C3=CC=CC=C3C3=CC=CC=C32)CCN1C(=O)C(CC)C1=CC=CC=C1 JEMZBZYBGXMZBG-UHFFFAOYSA-N 0.000 claims 1
- KUCDXVBAISIQPD-UHFFFAOYSA-N 9-[4-[4-(3-phenylpropanoyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CCC1=CC=CC=C1 KUCDXVBAISIQPD-UHFFFAOYSA-N 0.000 claims 1
- RKMCPGFKBFAYBP-UHFFFAOYSA-N 9-[4-[4-(4-phenylbutanoyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CCCC1=CC=CC=C1 RKMCPGFKBFAYBP-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- JKHYOWBRQRJSTQ-NRFANRHFSA-N methyl n-[(2s)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1h-inden-2-yl]carbamate Chemical compound C([C@@H](CC1=C2)NC(=O)OC)C1=CC=C2NC(=O)C1=CC=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 JKHYOWBRQRJSTQ-NRFANRHFSA-N 0.000 claims 1
- BDTAPNUWYMHQBH-UHFFFAOYSA-N n-(2,2,2-trifluoroethyl)-9-[4-[4-[2-[4-(trifluoromethyl)phenyl]acetyl]piperazin-1-yl]butyl]fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)CC1=CC=C(C(F)(F)F)C=C1 BDTAPNUWYMHQBH-UHFFFAOYSA-N 0.000 claims 1
- 125000005564 oxazolylene group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 319
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 245
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 165
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 99
- 239000000741 silica gel Substances 0.000 description 97
- 229910002027 silica gel Inorganic materials 0.000 description 97
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 89
- 238000001819 mass spectrum Methods 0.000 description 83
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 58
- 239000012317 TBTU Substances 0.000 description 50
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 50
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 230000000694 effects Effects 0.000 description 33
- 210000004185 liver Anatomy 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000011734 sodium Substances 0.000 description 30
- 210000002381 plasma Anatomy 0.000 description 29
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- QEANUFFAGJXAQS-UHFFFAOYSA-N 1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxylic acid Chemical compound C1=C(C(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QEANUFFAGJXAQS-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 150000003626 triacylglycerols Chemical class 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 235000012000 cholesterol Nutrition 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 16
- 239000013543 active substance Substances 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- NSETWVJZUWGCKE-UHFFFAOYSA-N propylphosphonic acid Chemical compound CCCP(O)(O)=O NSETWVJZUWGCKE-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- QCCOKDZZAOFYLR-UHFFFAOYSA-N 1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxylic acid Chemical compound N1=C(C(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 QCCOKDZZAOFYLR-UHFFFAOYSA-N 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 239000000126 substance Substances 0.000 description 13
- 102000004895 Lipoproteins Human genes 0.000 description 12
- 108090001030 Lipoproteins Proteins 0.000 description 12
- 102000012141 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 10
- 108010082126 Alanine transaminase Proteins 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 235000014113 dietary fatty acids Nutrition 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- 239000000194 fatty acid Substances 0.000 description 10
- 229930195729 fatty acid Natural products 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- 101000950981 Bacillus subtilis (strain 168) Catabolic NAD-specific glutamate dehydrogenase RocG Proteins 0.000 description 9
- 102000016901 Glutamate dehydrogenase Human genes 0.000 description 9
- 239000008187 granular material Substances 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 8
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 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 8
- 101150102415 Apob gene Proteins 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- CNRGPVGAMUVYJG-UHFFFAOYSA-N [4-(4-methylphenyl)phenyl]methanamine Chemical compound C1=CC(C)=CC=C1C1=CC=C(CN)C=C1 CNRGPVGAMUVYJG-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 235000021588 free fatty acids Nutrition 0.000 description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 102000015779 HDL Lipoproteins Human genes 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 6
- 239000008108 microcrystalline cellulose Substances 0.000 description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 5
- 108010010234 HDL Lipoproteins Proteins 0.000 description 5
- 206010019708 Hepatic steatosis Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 229960001021 lactose monohydrate Drugs 0.000 description 5
- 230000037356 lipid metabolism Effects 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 239000001117 sulphuric acid Substances 0.000 description 5
- 235000011149 sulphuric acid Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- RLOQBKJCOAXOLR-UHFFFAOYSA-N 1h-pyrrole-2-carboxamide Chemical compound NC(=O)C1=CC=CN1 RLOQBKJCOAXOLR-UHFFFAOYSA-N 0.000 description 4
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 101710095342 Apolipoprotein B Proteins 0.000 description 4
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- CIUUQFSJSPLLEB-UHFFFAOYSA-N [4-(3-methyl-5-phenylpyrazol-1-yl)phenyl]methanamine Chemical compound C=1C=C(CN)C=CC=1N1N=C(C)C=C1C1=CC=CC=C1 CIUUQFSJSPLLEB-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 4
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 4
- 230000005779 cell damage Effects 0.000 description 4
- 208000037887 cell injury Diseases 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000012024 dehydrating agents Substances 0.000 description 4
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229940063823 fenofibrate 100 mg Drugs 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 239000005051 trimethylchlorosilane Substances 0.000 description 4
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
- RMSPOVPGDBDYKH-UHFFFAOYSA-N (4-phenylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1C1=CC=CC=C1 RMSPOVPGDBDYKH-UHFFFAOYSA-N 0.000 description 3
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 3
- FICORAQFRBIKTA-UHFFFAOYSA-N 1-methyl-3-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxylic acid Chemical compound CN1C=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1C(O)=O FICORAQFRBIKTA-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- 108090000340 Transaminases Proteins 0.000 description 3
- 102000003929 Transaminases Human genes 0.000 description 3
- LMJMOASAJTYHLC-UHFFFAOYSA-N [4-(6-methylpyridazin-3-yl)phenyl]methanamine Chemical compound N1=NC(C)=CC=C1C1=CC=C(CN)C=C1 LMJMOASAJTYHLC-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 230000000923 atherogenic effect Effects 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000005229 liver cell Anatomy 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000007863 steatosis Effects 0.000 description 3
- 231100000240 steatosis hepatitis Toxicity 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- AMNXBQPRODZJQR-DITALETJSA-N (2s)-2-cyclopentyl-2-[3-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n-[(1r)-2-hydroxy-1-phenylethyl]acetamide Chemical compound C1([C@@H](C=2C=CC=C(C=2)CN2C3=CC=CC=C3C3=C(C)C=C(N=C32)C)C(=O)N[C@@H](CO)C=2C=CC=CC=2)CCCC1 AMNXBQPRODZJQR-DITALETJSA-N 0.000 description 2
- WROBJEHXMLQDQP-UHFFFAOYSA-N (4-piperidin-1-ylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1N1CCCCC1 WROBJEHXMLQDQP-UHFFFAOYSA-N 0.000 description 2
- ILJYDQMZEQMUBB-UHFFFAOYSA-N (4-pyridin-4-ylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1C1=CC=NC=C1 ILJYDQMZEQMUBB-UHFFFAOYSA-N 0.000 description 2
- NTCBUXIQMLORSI-GIDUJCDVSA-N (e)-1-[4-(4-bromophenyl)phenyl]-3-phenylprop-2-en-1-one Chemical compound C1=CC(Br)=CC=C1C1=CC=C(C(=O)\C=C\C=2C=CC=CC=2)C=C1 NTCBUXIQMLORSI-GIDUJCDVSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- UWYMNIUBSZXPST-UHFFFAOYSA-N 1-methyl-n-[(4-pyridin-3-ylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=NC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 UWYMNIUBSZXPST-UHFFFAOYSA-N 0.000 description 2
- YORDFRRSVVUJIV-UHFFFAOYSA-N 1-methyl-n-[(4-pyridin-4-ylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CN=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 YORDFRRSVVUJIV-UHFFFAOYSA-N 0.000 description 2
- FLJBIGAZJFDVTC-UHFFFAOYSA-N 1-methylpyrrole-2-carboxamide Chemical compound CN1C=CC=C1C(N)=O FLJBIGAZJFDVTC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DSSBZTBUZTYHNJ-UHFFFAOYSA-N 2-[(2-phenylbenzoyl)amino]-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(NC(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 DSSBZTBUZTYHNJ-UHFFFAOYSA-N 0.000 description 2
- VFDVBQMLLPCXNP-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoyl chloride Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(Cl)=O VFDVBQMLLPCXNP-UHFFFAOYSA-N 0.000 description 2
- IWZKQBLIWDPTLH-UHFFFAOYSA-N 4-(3,4-dihydro-2h-quinolin-1-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1N1C2=CC=CC=C2CCC1 IWZKQBLIWDPTLH-UHFFFAOYSA-N 0.000 description 2
- CTHMMRWZQNYZMH-UHFFFAOYSA-N 4-(3-methyl-5-phenylpyrazol-1-yl)benzonitrile Chemical compound C=1C=C(C#N)C=CC=1N1N=C(C)C=C1C1=CC=CC=C1 CTHMMRWZQNYZMH-UHFFFAOYSA-N 0.000 description 2
- QVCDBOQTJPSXRP-UHFFFAOYSA-N 4-[4-(aminomethyl)phenyl]phenol Chemical compound C1=CC(CN)=CC=C1C1=CC=C(O)C=C1 QVCDBOQTJPSXRP-UHFFFAOYSA-N 0.000 description 2
- BTXUFGJYNVWESK-UHFFFAOYSA-N 5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 BTXUFGJYNVWESK-UHFFFAOYSA-N 0.000 description 2
- CZXHIQKQRQJZRA-UHFFFAOYSA-N 5-nitro-n-[(4-phenylphenyl)methyl]thiophene-2-carboxamide Chemical compound S1C([N+](=O)[O-])=CC=C1C(=O)NCC1=CC=C(C=2C=CC=CC=2)C=C1 CZXHIQKQRQJZRA-UHFFFAOYSA-N 0.000 description 2
- WAZOUGDYHDXOJK-UHFFFAOYSA-N 6-amino-n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]pyrimidine-4-carboxamide Chemical compound C1=NC(N)=CC(C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)=N1 WAZOUGDYHDXOJK-UHFFFAOYSA-N 0.000 description 2
- AVTQPDQNRBZJER-UHFFFAOYSA-N 6-chloro-n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]pyrimidine-4-carboxamide Chemical compound C1=NC(Cl)=CC(C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)=N1 AVTQPDQNRBZJER-UHFFFAOYSA-N 0.000 description 2
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 2
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 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 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- YODALNBFVXLPTG-UHFFFAOYSA-N [4-(1,4-dioxaspiro[4.5]decan-8-yl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1C1CCC2(OCCO2)CC1 YODALNBFVXLPTG-UHFFFAOYSA-N 0.000 description 2
- CWQGJPUHIYXPAZ-UHFFFAOYSA-N [4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1N1C2=CC=CC=C2CCC1 CWQGJPUHIYXPAZ-UHFFFAOYSA-N 0.000 description 2
- RVNFCJGQVWHMKN-UHFFFAOYSA-N [4-[4-(trifluoromethyl)phenyl]phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1C1=CC=C(C(F)(F)F)C=C1 RVNFCJGQVWHMKN-UHFFFAOYSA-N 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000007449 liver function test Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- VCRJLUOTCWCNEQ-UHFFFAOYSA-N methyl 1-methyl-4-[(2-morpholin-4-ylbenzoyl)amino]pyrrole-2-carboxylate Chemical compound CN1C(C(=O)OC)=CC(NC(=O)C=2C(=CC=CC=2)N2CCOCC2)=C1 VCRJLUOTCWCNEQ-UHFFFAOYSA-N 0.000 description 2
- QFRQBZJYJQDOLO-UHFFFAOYSA-N methyl 4-[4-[[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]methyl]phenyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C QFRQBZJYJQDOLO-UHFFFAOYSA-N 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- YLINWOGOTFSRFA-UHFFFAOYSA-N n-[(4-phenylphenyl)methyl]-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]thiophene-2-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC=CC=2)S1 YLINWOGOTFSRFA-UHFFFAOYSA-N 0.000 description 2
- LNIJTMGXVKXZQY-UHFFFAOYSA-N n-[4-(aminomethyl)phenyl]benzamide Chemical compound C1=CC(CN)=CC=C1NC(=O)C1=CC=CC=C1 LNIJTMGXVKXZQY-UHFFFAOYSA-N 0.000 description 2
- XEXPVOWYFHZQIQ-UHFFFAOYSA-N n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XEXPVOWYFHZQIQ-UHFFFAOYSA-N 0.000 description 2
- VFQOIZTVRQIYDX-UHFFFAOYSA-N n-[[4-(4-chlorophenyl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(Cl)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 VFQOIZTVRQIYDX-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000000291 postprandial effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229940117972 triolein Drugs 0.000 description 2
- 229940075966 (+)- menthol Drugs 0.000 description 1
- NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
- QOWBXWFYRXSBAS-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C(OC)=C1 QOWBXWFYRXSBAS-UHFFFAOYSA-N 0.000 description 1
- PMFCMLGAPHZRTE-UHFFFAOYSA-N (2-phenyl-1,3-thiazol-4-yl)methanamine Chemical compound NCC1=CSC(C=2C=CC=CC=2)=N1 PMFCMLGAPHZRTE-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WKHABRRJMGVELW-UHFFFAOYSA-N (3-phenylphenyl)methanamine Chemical compound NCC1=CC=CC(C=2C=CC=CC=2)=C1 WKHABRRJMGVELW-UHFFFAOYSA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- XRNVSPDQTPVECU-UHFFFAOYSA-N (4-bromophenyl)methanamine Chemical compound NCC1=CC=C(Br)C=C1 XRNVSPDQTPVECU-UHFFFAOYSA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- FIPZWVLCZIYEMW-UHFFFAOYSA-N (4-cyanophenoxy)boronic acid Chemical compound OB(O)OC1=CC=C(C#N)C=C1 FIPZWVLCZIYEMW-UHFFFAOYSA-N 0.000 description 1
- BXHXBVNRKRXSHM-UHFFFAOYSA-N (4-pyridin-2-ylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1C1=CC=CC=N1 BXHXBVNRKRXSHM-UHFFFAOYSA-N 0.000 description 1
- FUHDBJVMRRGFTR-UHFFFAOYSA-N (4-pyridin-3-ylphenyl)methanamine Chemical compound C1=CC(CN)=CC=C1C1=CC=CN=C1 FUHDBJVMRRGFTR-UHFFFAOYSA-N 0.000 description 1
- MPWSRGAWRAYBJK-UHFFFAOYSA-N (4-tert-butylphenyl)methanamine Chemical compound CC(C)(C)C1=CC=C(CN)C=C1 MPWSRGAWRAYBJK-UHFFFAOYSA-N 0.000 description 1
- DRCWOKJLSQUJPZ-DZGCQCFKSA-N (4ar,9as)-n-ethyl-1,4,9,9a-tetrahydrofluoren-4a-amine Chemical compound C1C2=CC=CC=C2[C@]2(NCC)[C@H]1CC=CC2 DRCWOKJLSQUJPZ-DZGCQCFKSA-N 0.000 description 1
- NSDZEDPPVWGLBQ-UHFFFAOYSA-N (5-phenyl-1,3,4-oxadiazol-2-yl)methanamine Chemical compound O1C(CN)=NN=C1C1=CC=CC=C1 NSDZEDPPVWGLBQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- PKJBWOWQJHHAHG-UHFFFAOYSA-N 1-bromo-4-phenylbenzene Chemical group C1=CC(Br)=CC=C1C1=CC=CC=C1 PKJBWOWQJHHAHG-UHFFFAOYSA-N 0.000 description 1
- ZMQWCLFBBZITPB-UHFFFAOYSA-N 1-ethyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxylic acid Chemical compound C1=C(C(O)=O)N(CC)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 ZMQWCLFBBZITPB-UHFFFAOYSA-N 0.000 description 1
- KCXBJYZRLNFMRG-UHFFFAOYSA-N 1-ethyl-n-[[4-(4-methylphenyl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(C)=CC=2)N(CC)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 KCXBJYZRLNFMRG-UHFFFAOYSA-N 0.000 description 1
- VWOXNMYHNUKBFO-UHFFFAOYSA-N 1-methyl-4-[(2-phenylbenzoyl)amino]pyrrole-2-carboxylic acid Chemical compound C1=C(C(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1 VWOXNMYHNUKBFO-UHFFFAOYSA-N 0.000 description 1
- NEMRHDDMDXVYMQ-UHFFFAOYSA-N 1-methyl-4-[[2-(4-methylphenyl)benzoyl]amino]-n-[[4-(4-methylphenyl)phenyl]methyl]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(C)=CC=2)=CN1C NEMRHDDMDXVYMQ-UHFFFAOYSA-N 0.000 description 1
- SKYVZNXFDYJUOE-UHFFFAOYSA-N 1-methyl-4-[[2-(4-methylphenyl)benzoyl]amino]pyrrole-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(=O)NC1=CN(C)C(C(O)=O)=C1 SKYVZNXFDYJUOE-UHFFFAOYSA-N 0.000 description 1
- XWLTZDOZNHUZOK-UHFFFAOYSA-N 1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-n-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(=CC=2)C(F)(F)F)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XWLTZDOZNHUZOK-UHFFFAOYSA-N 0.000 description 1
- HPIOSDRWDOFUSB-UHFFFAOYSA-N 1-methyl-n-(pyridin-3-ylmethyl)-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=NC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 HPIOSDRWDOFUSB-UHFFFAOYSA-N 0.000 description 1
- KTJVZVPRSMXMQK-UHFFFAOYSA-N 1-methyl-n-[(2-phenyl-1,3-thiazol-4-yl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2N=C(SC=2)C=2C=CC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 KTJVZVPRSMXMQK-UHFFFAOYSA-N 0.000 description 1
- OAOISBOGMXVTGN-UHFFFAOYSA-N 1-methyl-n-[(4-phenylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 OAOISBOGMXVTGN-UHFFFAOYSA-N 0.000 description 1
- MCFNYZJAESAXSS-UHFFFAOYSA-N 1-methyl-n-[(4-pyridin-2-ylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2N=CC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 MCFNYZJAESAXSS-UHFFFAOYSA-N 0.000 description 1
- BDSYFMLEZLSBDX-UHFFFAOYSA-N 1-methyl-n-[(4-pyridin-4-ylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CN=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 BDSYFMLEZLSBDX-UHFFFAOYSA-N 0.000 description 1
- AUHXPYNYPMXDNB-UHFFFAOYSA-N 1-methyl-n-[3-(4-methylphenyl)prop-2-ynyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C#CCNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C AUHXPYNYPMXDNB-UHFFFAOYSA-N 0.000 description 1
- OMLFYLYPSNVLGC-UHFFFAOYSA-N 1-methyl-n-[3-(4-methylphenyl)propyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1CCCNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C OMLFYLYPSNVLGC-UHFFFAOYSA-N 0.000 description 1
- YNSLVVWKSGFBSP-UHFFFAOYSA-N 1-methyl-n-[[4-(2-methylphenyl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound CC1=CC=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C YNSLVVWKSGFBSP-UHFFFAOYSA-N 0.000 description 1
- KRZUXUWHFCHBPK-UHFFFAOYSA-N 1-methyl-n-[[4-(3-methyl-5-phenylpyrazol-1-yl)phenyl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C=1C=C(CNC(=O)C=2N(C=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=2)C)C=CC=1N1N=C(C)C=C1C1=CC=CC=C1 KRZUXUWHFCHBPK-UHFFFAOYSA-N 0.000 description 1
- MKEHUYKVDUSCCH-UHFFFAOYSA-N 1-methyl-n-[[4-(4-methylphenyl)phenyl]methyl]-4-[(2-morpholin-4-ylbenzoyl)amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)N2CCOCC2)=CN1C MKEHUYKVDUSCCH-UHFFFAOYSA-N 0.000 description 1
- FOZZEIFQSZXJFD-UHFFFAOYSA-N 1-methyl-n-[[4-(4-methylphenyl)phenyl]methyl]-4-[(2-phenylbenzoyl)amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=CN1C FOZZEIFQSZXJFD-UHFFFAOYSA-N 0.000 description 1
- VWPNAPJPVDRHBC-UHFFFAOYSA-N 1-methyl-n-[[6-(4-methylphenyl)pyridin-3-yl]methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=CC(C)=CC=C1C(N=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C VWPNAPJPVDRHBC-UHFFFAOYSA-N 0.000 description 1
- UIKPUVLIJJJXNA-UHFFFAOYSA-N 1-methylimidazole-2-carboxamide Chemical compound CN1C=CN=C1C(N)=O UIKPUVLIJJJXNA-UHFFFAOYSA-N 0.000 description 1
- CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 1
- DTMCOYOYXVFCKJ-UHFFFAOYSA-N 2,2,4,6-tetramethyl-1h-quinoline Chemical compound C1=C(C)C=C2C(C)=CC(C)(C)NC2=C1 DTMCOYOYXVFCKJ-UHFFFAOYSA-N 0.000 description 1
- LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
- VNCNZEBRKSWUPK-UHFFFAOYSA-N 2-[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]acetic acid Chemical compound C1=C(C(=O)NCC(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 VNCNZEBRKSWUPK-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- YQKHVPRKUHIAAA-UHFFFAOYSA-N 2-cyclopentyl-2-[4-[(2,4-dimethylpyrido[2,3-b]indol-9-yl)methyl]phenyl]-n'-phenylacetohydrazide Chemical compound C12=NC(C)=CC(C)=C2C2=CC=CC=C2N1CC(C=C1)=CC=C1C(C(=O)NNC=1C=CC=CC=1)C1CCCC1 YQKHVPRKUHIAAA-UHFFFAOYSA-N 0.000 description 1
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- XUBUJTVBAXQIKG-UHFFFAOYSA-N 2-morpholin-4-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCOCC1 XUBUJTVBAXQIKG-UHFFFAOYSA-N 0.000 description 1
- ILYSAKHOYBPSPC-UHFFFAOYSA-N 2-phenylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1 ILYSAKHOYBPSPC-UHFFFAOYSA-N 0.000 description 1
- QZEGAMBZENMETP-UHFFFAOYSA-N 3-(4-methylphenyl)prop-2-yn-1-amine Chemical compound CC1=CC=C(C#CCN)C=C1 QZEGAMBZENMETP-UHFFFAOYSA-N 0.000 description 1
- RRCFNQVGLSDEHT-UHFFFAOYSA-N 3-(4-phenylphenyl)prop-2-yn-1-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(C#CCN)=CC=C1C1=CC=CC=C1 RRCFNQVGLSDEHT-UHFFFAOYSA-N 0.000 description 1
- CBTUCPSWKXOWDG-UHFFFAOYSA-N 3-(4-propan-2-ylphenyl)prop-2-yn-1-amine Chemical compound CC(C)C1=CC=C(C#CCN)C=C1 CBTUCPSWKXOWDG-UHFFFAOYSA-N 0.000 description 1
- JXEMKSBRONNHEI-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]prop-2-yn-1-amine Chemical compound NCC#CC1=CC=C(C(F)(F)F)C=C1 JXEMKSBRONNHEI-UHFFFAOYSA-N 0.000 description 1
- BKDZTJNNXCNSCK-UHFFFAOYSA-N 3-aminothiophene-2-carboxamide Chemical compound NC(=O)C=1SC=CC=1N BKDZTJNNXCNSCK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- PRORLQAJNJMGAR-UHFFFAOYSA-N 3-chloro-6-methylpyridazine Chemical compound CC1=CC=C(Cl)N=N1 PRORLQAJNJMGAR-UHFFFAOYSA-N 0.000 description 1
- XWCGPHUZEGMFAI-UHFFFAOYSA-N 3-chloro-n-methyl-5-(trifluoromethyl)pyridin-2-amine Chemical compound CNC1=NC=C(C(F)(F)F)C=C1Cl XWCGPHUZEGMFAI-UHFFFAOYSA-N 0.000 description 1
- 102100029103 3-ketoacyl-CoA thiolase Human genes 0.000 description 1
- YIVHOQIKHMTVRG-UHFFFAOYSA-N 3-methyl-1h-pyrrole-2-carboxylic acid Chemical compound CC=1C=CNC=1C(O)=O YIVHOQIKHMTVRG-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FHPWMMHBXITIKG-UHFFFAOYSA-N 4-(6-methylpyridazin-3-yl)benzonitrile Chemical compound N1=NC(C)=CC=C1C1=CC=C(C#N)C=C1 FHPWMMHBXITIKG-UHFFFAOYSA-N 0.000 description 1
- KHPYOWZTQXAIAB-UHFFFAOYSA-N 4-(aminomethyl)-n-cyclohexyl-n-methylbenzamide Chemical compound C=1C=C(CN)C=CC=1C(=O)N(C)C1CCCCC1 KHPYOWZTQXAIAB-UHFFFAOYSA-N 0.000 description 1
- LHYJIWDAOGVEBH-UHFFFAOYSA-N 4-(aminomethyl)-n-phenylbenzamide Chemical compound C1=CC(CN)=CC=C1C(=O)NC1=CC=CC=C1 LHYJIWDAOGVEBH-UHFFFAOYSA-N 0.000 description 1
- NISQFVUXQOBVLN-UHFFFAOYSA-N 4-[4-[[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]methyl]phenyl]benzoic acid Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(=CC=2)C(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 NISQFVUXQOBVLN-UHFFFAOYSA-N 0.000 description 1
- BLJRHWHFKZOOBZ-UHFFFAOYSA-N 4-[[2-(4-fluorophenyl)benzoyl]amino]-1-methylpyrrole-2-carboxylic acid Chemical compound C1=C(C(O)=O)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(F)C=C1 BLJRHWHFKZOOBZ-UHFFFAOYSA-N 0.000 description 1
- JRMWNRYWJINSJM-UHFFFAOYSA-N 4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-1h-pyrrole-2-carboxylic acid Chemical compound N1C(C(=O)O)=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 JRMWNRYWJINSJM-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- DZUUSHCOMPROCJ-UHFFFAOYSA-N 4-hydrazinylbenzonitrile Chemical compound NNC1=CC=C(C#N)C=C1 DZUUSHCOMPROCJ-UHFFFAOYSA-N 0.000 description 1
- XMRMFVAFZGSNRX-UHFFFAOYSA-N 5-methyl-1h-imidazole-2-carboxamide Chemical compound CC1=CNC(C(N)=O)=N1 XMRMFVAFZGSNRX-UHFFFAOYSA-N 0.000 description 1
- BYEANWQDRDXPPA-UHFFFAOYSA-N 5-nitrothiophene-2-carbonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)S1 BYEANWQDRDXPPA-UHFFFAOYSA-N 0.000 description 1
- FAJZIXITZFFSPC-UHFFFAOYSA-N 6-chloropyrimidine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC(Cl)=NC=N1 FAJZIXITZFFSPC-UHFFFAOYSA-N 0.000 description 1
- PCOWNQCLFYEXLR-UHFFFAOYSA-N 9-[4-[2,5-dimethyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound CC1=CC=C2N(CCCCC3(C(=O)NCC(F)(F)F)C4=CC=CC=C4C4=CC=CC=C43)C(C)=NC2=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 PCOWNQCLFYEXLR-UHFFFAOYSA-N 0.000 description 1
- CPCJMQXTYXVRGO-UHFFFAOYSA-N 9-[4-[4-(2-oxo-2-phenylacetyl)piperazin-1-yl]butyl]-n-(2,2,2-trifluoroethyl)fluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(C(=O)NCC(F)(F)F)CCCCN(CC1)CCN1C(=O)C(=O)C1=CC=CC=C1 CPCJMQXTYXVRGO-UHFFFAOYSA-N 0.000 description 1
- NMLCQSAJFUXACX-UHFFFAOYSA-N 9h-fluorene-9-carboxamide Chemical compound C1=CC=C2C(C(=O)N)C3=CC=CC=C3C2=C1 NMLCQSAJFUXACX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010003902 Acetyl-CoA C-acyltransferase Proteins 0.000 description 1
- 108010001058 Acyl-CoA Dehydrogenase Proteins 0.000 description 1
- 102000002735 Acyl-CoA Dehydrogenase Human genes 0.000 description 1
- 102000004539 Acyl-CoA Oxidase Human genes 0.000 description 1
- 108020001558 Acyl-CoA oxidase Proteins 0.000 description 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
- 102000009081 Apolipoprotein A-II Human genes 0.000 description 1
- 108010087614 Apolipoprotein A-II Proteins 0.000 description 1
- 108010056301 Apolipoprotein C-III Proteins 0.000 description 1
- 102000018616 Apolipoproteins B Human genes 0.000 description 1
- 108010027006 Apolipoproteins B Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091007403 Cholesterol transporters Proteins 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- 102000005870 Coenzyme A Ligases Human genes 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699662 Cricetomys gambianus Species 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000030914 Fatty Acid-Binding Human genes 0.000 description 1
- KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010019837 Hepatocellular injury Diseases 0.000 description 1
- 101001008429 Homo sapiens Nucleobindin-2 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 108010011449 Long-chain-fatty-acid-CoA ligase Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 102100027441 Nucleobindin-2 Human genes 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000016227 Protein disulphide isomerases Human genes 0.000 description 1
- 108050004742 Protein disulphide isomerases Proteins 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108091005487 SCARB1 Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- JXWIVYXYPMEIQF-UHFFFAOYSA-N [4-(2-methylphenyl)phenyl]methanamine Chemical compound CC1=CC=CC=C1C1=CC=C(CN)C=C1 JXWIVYXYPMEIQF-UHFFFAOYSA-N 0.000 description 1
- KIOZCTLKIJUQOD-UHFFFAOYSA-N [4-(3,4-dihydro-1h-isoquinolin-2-yl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1N1CC2=CC=CC=C2CC1 KIOZCTLKIJUQOD-UHFFFAOYSA-N 0.000 description 1
- FWSCINFUBQNPJM-UHFFFAOYSA-N [4-(thiadiazol-4-yl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1C1=CSN=N1 FWSCINFUBQNPJM-UHFFFAOYSA-N 0.000 description 1
- TUBHMWZGDZGNEZ-UHFFFAOYSA-N [6-(4-methylphenyl)pyridin-3-yl]methanamine Chemical compound C1=CC(C)=CC=C1C1=CC=C(CN)C=N1 TUBHMWZGDZGNEZ-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N acetic acid;palladium Chemical compound [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FCCCRBDJBTVFSJ-UHFFFAOYSA-N butanehydrazide Chemical compound CCCC(=O)NN FCCCRBDJBTVFSJ-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- YRMUHWOOLNBYDS-UHFFFAOYSA-N ethyl 2-[(2-phenylbenzoyl)amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 YRMUHWOOLNBYDS-UHFFFAOYSA-N 0.000 description 1
- BIHHBTVQFPVSTE-UHFFFAOYSA-N ethyl 2-bromobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1Br BIHHBTVQFPVSTE-UHFFFAOYSA-N 0.000 description 1
- UIVDSGDHUXOYDW-UHFFFAOYSA-N ethyl 2-morpholin-4-ylbenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N1CCOCC1 UIVDSGDHUXOYDW-UHFFFAOYSA-N 0.000 description 1
- 108091022862 fatty acid binding Proteins 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229950005809 implitapide Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 229960003566 lomitapide Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- OIAOINKYBIOBOI-UHFFFAOYSA-N methyl 2-[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]acetate Chemical compound CN1C(C(=O)NCC(=O)OC)=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 OIAOINKYBIOBOI-UHFFFAOYSA-N 0.000 description 1
- CJLCKOWGYSFWIK-UHFFFAOYSA-N methyl 2-ethyl-5-[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]-2-phenylpentanoate Chemical compound C=1C=CC=CC=1C(CC)(C(=O)OC)CCCNC(=O)C(N(C=1)C)=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 CJLCKOWGYSFWIK-UHFFFAOYSA-N 0.000 description 1
- WSQLDWJXFBEGNO-UHFFFAOYSA-N methyl 3-[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]propanoate Chemical compound CN1C(C(=O)NCCC(=O)OC)=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WSQLDWJXFBEGNO-UHFFFAOYSA-N 0.000 description 1
- DXQCQLJXMICOKQ-UHFFFAOYSA-N methyl 4-amino-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(N)=CN1C DXQCQLJXMICOKQ-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- CAHCQGPUTIORJU-UHFFFAOYSA-N n,1-dimethyl-n-[(4-phenylphenyl)methyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C=1C(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN(C)C=1C(=O)N(C)CC(C=C1)=CC=C1C1=CC=CC=C1 CAHCQGPUTIORJU-UHFFFAOYSA-N 0.000 description 1
- FQIYOTXGMOTBEP-UHFFFAOYSA-N n-[(4-benzamidophenyl)methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(NC(=O)C=3C=CC=CC=3)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 FQIYOTXGMOTBEP-UHFFFAOYSA-N 0.000 description 1
- JGZSIYKSSDCNGU-UHFFFAOYSA-N n-[(4-benzamidophenyl)methyl]-2-[(2-phenylbenzoyl)amino]-1,3-thiazole-4-carboxamide Chemical compound C=1SC(NC(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=NC=1C(=O)NCC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 JGZSIYKSSDCNGU-UHFFFAOYSA-N 0.000 description 1
- UFDBANLDKNLWBC-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(Br)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 UFDBANLDKNLWBC-UHFFFAOYSA-N 0.000 description 1
- HAVMEIVNWWJQHI-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(Cl)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 HAVMEIVNWWJQHI-UHFFFAOYSA-N 0.000 description 1
- IOQRHESNCXOMAC-UHFFFAOYSA-N n-[4-(aminomethyl)phenyl]pyrimidine-4-carboxamide Chemical compound C1=CC(CN)=CC=C1NC(=O)C1=CC=NC=N1 IOQRHESNCXOMAC-UHFFFAOYSA-N 0.000 description 1
- JBDGYEPEPXCOFH-UHFFFAOYSA-N n-[4-[[[1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carbonyl]amino]methyl]phenyl]pyrimidine-4-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(NC(=O)C=3N=CN=CC=3)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 JBDGYEPEPXCOFH-UHFFFAOYSA-N 0.000 description 1
- SAHKIBJYOAHPGH-UHFFFAOYSA-N n-[[4-(1,4-dioxaspiro[4.5]decan-8-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)C2CCC3(CC2)OCCO3)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 SAHKIBJYOAHPGH-UHFFFAOYSA-N 0.000 description 1
- OCAVFDCXFPFVRX-UHFFFAOYSA-N n-[[4-(3,4-dihydro-1h-isoquinolin-2-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)N2CC3=CC=CC=C3CC2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 OCAVFDCXFPFVRX-UHFFFAOYSA-N 0.000 description 1
- XPFOSFWADUNBQJ-UHFFFAOYSA-N n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 XPFOSFWADUNBQJ-UHFFFAOYSA-N 0.000 description 1
- BYIVSPVLAIOKIE-UHFFFAOYSA-N n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]-6-[(2,3-dimethoxyphenyl)methylamino]pyrimidine-4-carboxamide Chemical compound COC1=CC=CC(CNC=2N=CN=C(C=2)C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)=C1OC BYIVSPVLAIOKIE-UHFFFAOYSA-N 0.000 description 1
- VZDPIZNQWVITTB-UHFFFAOYSA-N n-[[4-(3,4-dihydro-2h-quinolin-1-yl)phenyl]methyl]-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrimidine-4-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC(C(=O)NCC=2C=CC(=CC=2)N2C3=CC=CC=C3CCC2)=NC=N1 VZDPIZNQWVITTB-UHFFFAOYSA-N 0.000 description 1
- PJHFEZBBHSTPOW-UHFFFAOYSA-N n-[[4-(3-methyl-5-phenylpyrazol-1-yl)phenyl]methyl]-2-[(2-phenylbenzoyl)amino]-1,3-thiazole-4-carboxamide Chemical compound C=1C=C(CNC(=O)C=2N=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC=CC=3)SC=2)C=CC=1N1N=C(C)C=C1C1=CC=CC=C1 PJHFEZBBHSTPOW-UHFFFAOYSA-N 0.000 description 1
- PHOFKJCJDOFNGO-UHFFFAOYSA-N n-[[4-(3-methyl-5-phenylpyrazol-1-yl)phenyl]methyl]-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyridine-3-carboxamide Chemical compound C=1C=C(CNC(=O)C=2C=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=NC=2)C=CC=1N1N=C(C)C=C1C1=CC=CC=C1 PHOFKJCJDOFNGO-UHFFFAOYSA-N 0.000 description 1
- OIGOQOHEEOZAJN-UHFFFAOYSA-N n-[[4-(4-chlorophenyl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(Cl)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 OIGOQOHEEOZAJN-UHFFFAOYSA-N 0.000 description 1
- AMELMMHEARKTQB-UHFFFAOYSA-N n-[[4-(4-hydroxyphenyl)phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]imidazole-2-carboxamide Chemical compound N1=C(C(=O)NCC=2C=CC(=CC=2)C=2C=CC(O)=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 AMELMMHEARKTQB-UHFFFAOYSA-N 0.000 description 1
- COLREVSQFZIPON-UHFFFAOYSA-N n-[[4-(4-methylphenyl)phenyl]methyl]-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyridine-3-carboxamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CN=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 COLREVSQFZIPON-UHFFFAOYSA-N 0.000 description 1
- CVTNWHTXPINYDE-UHFFFAOYSA-N n-[[4-(phenylcarbamoyl)phenyl]methyl]-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyridine-3-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CN=CC(C(=O)NCC=2C=CC(=CC=2)C(=O)NC=2C=CC=CC=2)=C1 CVTNWHTXPINYDE-UHFFFAOYSA-N 0.000 description 1
- JXHVLZRBOXBQTO-UHFFFAOYSA-N n-[[4-[5-(dimethylamino)pyridin-2-yl]phenyl]methyl]-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound N1=CC(N(C)C)=CC=C1C(C=C1)=CC=C1CNC(=O)C1=CC(NC(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=CN1C JXHVLZRBOXBQTO-UHFFFAOYSA-N 0.000 description 1
- DHJGFKQMUOFEQT-UHFFFAOYSA-N n-benzyl-1-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyrrole-2-carboxamide Chemical compound C1=C(C(=O)NCC=2C=CC=CC=2)N(C)C=C1NC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 DHJGFKQMUOFEQT-UHFFFAOYSA-N 0.000 description 1
- GZUHCAWQWUONPS-UHFFFAOYSA-N n-methyl-1-(4-phenylphenyl)methanamine Chemical compound C1=CC(CNC)=CC=C1C1=CC=CC=C1 GZUHCAWQWUONPS-UHFFFAOYSA-N 0.000 description 1
- 125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- JKNKNWJNCOJPLI-UHFFFAOYSA-N o-phthalaldehydic acid Chemical compound C1=CC=C2C(O)OC(=O)C2=C1 JKNKNWJNCOJPLI-UHFFFAOYSA-N 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
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 230000000858 peroxisomal effect Effects 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- AKCRNFFTGXBONI-UHFFFAOYSA-N torin 1 Chemical compound C1CN(C(=O)CC)CCN1C1=CC=C(N2C(C=CC3=C2C2=CC(=CC=C2N=C3)C=2C=C3C=CC=CC3=NC=2)=O)C=C1C(F)(F)F AKCRNFFTGXBONI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- KYBJXENQEZJILU-UHFFFAOYSA-N zolamine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=NC=CS1 KYBJXENQEZJILU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
L'invention concerne d'une part, l'utilisation de fibrates en vue de réduire la toxicité hépatique des inhibiteurs de MTP et, d'autre part, des compositions pharmaceutiques renfermant un inhibiteur de MTP et un fibrate.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2002100633 DE10200633A1 (de) | 2002-01-10 | 2002-01-10 | Kombination von MTP Inhibitoren oder apoB-Sekretions-Inhibitoren mit Fibraten zur Verwendung als Arzneimittel |
DE10200633.4 | 2002-01-10 | ||
DE10256184.2 | 2002-12-02 | ||
DE10256184A DE10256184A1 (de) | 2002-12-02 | 2002-12-02 | Kombination von MTP Inhibitoren oder apoB-Sekretions-Inhibitoren mit Fibraten zur Verwendung als Arzneimittel |
PCT/EP2003/000057 WO2003057205A2 (fr) | 2002-01-10 | 2003-01-07 | Combinaison d'inhibiteurs de mtp ou d'inhibiteurs de secretions apob avec des fibrates en vue d'une utilisation comme medicament |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2471566A1 true CA2471566A1 (fr) | 2003-07-17 |
Family
ID=26010911
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002471566A Abandoned CA2471566A1 (fr) | 2002-01-10 | 2003-01-07 | Combinaison d'inhibiteurs de mtp ou d'inhibiteurs de secretions apob avec des fibrates en vue d'une utilisation comme medicament |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1465613A2 (fr) |
JP (1) | JP2005525309A (fr) |
AR (1) | AR038178A1 (fr) |
AU (1) | AU2003205570A1 (fr) |
CA (1) | CA2471566A1 (fr) |
PE (1) | PE20030924A1 (fr) |
TW (1) | TW200402292A (fr) |
UY (1) | UY27610A1 (fr) |
WO (1) | WO2003057205A2 (fr) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7648998B2 (en) | 2003-12-22 | 2010-01-19 | K.U. Leuven Research & Development | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
US7737162B2 (en) | 2002-07-03 | 2010-06-15 | Gilead Sciences, Inc. | Viral inhibitors |
US7754720B2 (en) | 2006-07-07 | 2010-07-13 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US7795276B2 (en) | 2004-12-21 | 2010-09-14 | Gilead Sciences, Inc. | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
US8106054B2 (en) | 2007-07-06 | 2012-01-31 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
US9556177B2 (en) | 2007-06-29 | 2017-01-31 | Millennium Pharmaceuticals, Inc. | Substituted 1,3-thiazoles as synthetic intermediates for preparation of Raf kinase inhibitors |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2505604A1 (fr) * | 2002-12-20 | 2004-07-08 | Pfizer Products Inc. | Inhibiteurs de proteine microsomale de transfert de triglyceride |
JP2007008816A (ja) * | 2003-10-15 | 2007-01-18 | Ube Ind Ltd | 新規イソキノリン誘導体 |
US20060241073A1 (en) * | 2005-04-20 | 2006-10-26 | Wanders Ronaldus J A | Means and methods for counteracting fatty acid accumulation |
KR20080031038A (ko) * | 2005-07-29 | 2008-04-07 | 4에스체 악티엔게젤샤프트 | 신규의 헤테로환 NF-κB 억제제 |
JP5642922B2 (ja) * | 2007-04-24 | 2014-12-17 | サントリーホールディングス株式会社 | 複数の肝障害マーカーを指標とする肝障害の評価方法 |
WO2010141932A1 (fr) | 2009-06-05 | 2010-12-09 | Link Medicine Corporation | Dérivés d'aminopyrrolidinone et utilisations de ceux-ci |
JP7277431B2 (ja) | 2017-07-11 | 2023-05-19 | バーテックス ファーマシューティカルズ インコーポレイテッド | ナトリウムチャネルのモジュレーターとしてのカルボキサミド |
KR20200142508A (ko) | 2018-03-08 | 2020-12-22 | 인사이트 코포레이션 | PI3K-γ 저해제로서의 아미노피라진 다이올 화합물 |
WO2020010003A1 (fr) | 2018-07-02 | 2020-01-09 | Incyte Corporation | DÉRIVÉS D'AMINOPYRAZINE UTILISÉS EN TANT QU'INHIBITEURS DE PI3K-γ |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5883109A (en) * | 1996-07-24 | 1999-03-16 | Bristol-Myers Squibb Company | Method for lowering serum lipid levels employing an MTP inhibitor in combination with another cholesterol lowering drug |
CA2325358C (fr) * | 1999-11-10 | 2005-08-02 | Pfizer Products Inc. | Amides de l'acide 7-¬(4'-trifluoromethylbiphenyl-2-carbonyl)amino|-quinoleine-3-carboxylique et methodes pour inhiber la secretion d'apolipoproteine b |
DE10033337A1 (de) * | 2000-07-08 | 2002-01-17 | Boehringer Ingelheim Pharma | Biphenylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
DE10132686A1 (de) * | 2001-07-05 | 2003-01-16 | Boehringer Ingelheim Pharma | Heteroarylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
-
2003
- 2003-01-07 CA CA002471566A patent/CA2471566A1/fr not_active Abandoned
- 2003-01-07 UY UY27610A patent/UY27610A1/es not_active Application Discontinuation
- 2003-01-07 EP EP03702391A patent/EP1465613A2/fr not_active Ceased
- 2003-01-07 AU AU2003205570A patent/AU2003205570A1/en not_active Abandoned
- 2003-01-07 WO PCT/EP2003/000057 patent/WO2003057205A2/fr active Application Filing
- 2003-01-07 JP JP2003557563A patent/JP2005525309A/ja active Pending
- 2003-01-08 TW TW092100321A patent/TW200402292A/zh unknown
- 2003-01-09 PE PE2003000036A patent/PE20030924A1/es not_active Application Discontinuation
- 2003-01-10 AR ARP030100056A patent/AR038178A1/es not_active Withdrawn
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7737162B2 (en) | 2002-07-03 | 2010-06-15 | Gilead Sciences, Inc. | Viral inhibitors |
US8779141B2 (en) | 2002-07-03 | 2014-07-15 | Gilead Sciences, Inc. | Viral inhibitors |
US7648998B2 (en) | 2003-12-22 | 2010-01-19 | K.U. Leuven Research & Development | Imidazo 4,5-c pyridine compounds and methods of antiviral treatment |
US8329727B2 (en) | 2003-12-22 | 2012-12-11 | Gilead Sciences, Inc. | Imidazo[4,5-c]pyridine compounds and methods of antiviral treatment |
US7795276B2 (en) | 2004-12-21 | 2010-09-14 | Gilead Sciences, Inc. | Imiadazo[4,5-c] pyridine compound and method of antiviral treatment |
US7754720B2 (en) | 2006-07-07 | 2010-07-13 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US7956184B2 (en) | 2006-07-07 | 2011-06-07 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US8569487B2 (en) | 2006-07-07 | 2013-10-29 | Gilead Sciences, Inc. | Pyridazine compound and use thereof |
US9556177B2 (en) | 2007-06-29 | 2017-01-31 | Millennium Pharmaceuticals, Inc. | Substituted 1,3-thiazoles as synthetic intermediates for preparation of Raf kinase inhibitors |
US9920048B2 (en) | 2007-06-29 | 2018-03-20 | Millennium Pharmaceuticals, Inc. | Substituted pyrimidines for inhibiting Raf kinase activity |
US8106054B2 (en) | 2007-07-06 | 2012-01-31 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
US8569488B2 (en) | 2007-07-06 | 2013-10-29 | Gilead Sciences, Inc. | Crystalline pyridazine compound |
Also Published As
Publication number | Publication date |
---|---|
EP1465613A2 (fr) | 2004-10-13 |
WO2003057205A2 (fr) | 2003-07-17 |
AU2003205570A8 (en) | 2003-07-24 |
WO2003057205A3 (fr) | 2004-04-01 |
TW200402292A (en) | 2004-02-16 |
PE20030924A1 (es) | 2003-12-17 |
UY27610A1 (es) | 2003-08-29 |
AU2003205570A1 (en) | 2003-07-24 |
JP2005525309A (ja) | 2005-08-25 |
AR038178A1 (es) | 2005-01-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1368028B1 (fr) | Composes de benzimidazole modulateurs de l'ige et inhibiteurs de la proliferation cellulaire | |
TW410156B (en) | Methods of inhibiting physiological conditions associated with an excess of neuropeptide Y with raloxifene and the derivatives thereof | |
CA2471566A1 (fr) | Combinaison d'inhibiteurs de mtp ou d'inhibiteurs de secretions apob avec des fibrates en vue d'une utilisation comme medicament | |
KR20070099527A (ko) | 유기 화합물의 조합물 | |
WO2004011427A2 (fr) | Benzanilides substitues utilises en tant que modulateurs du recepteur ccr5 | |
KR20080012304A (ko) | 피라졸 화합물 및 이들 피라졸 화합물을 포함하여이루어지는 당뇨병 치료약 | |
EA002365B1 (ru) | Комбинация ингибитора альдозоредуктазы и ингибитора гликогенфосфорилазы | |
EP0710479B1 (fr) | Utilisation d'un agoniste de la sérotonine en combinaison avec un antagoniste du récepteur de la tachykinine pour la fabrication d'un médicament pour la prévention ou le traitement de la migraine | |
US7566728B2 (en) | Remedy for sleep disturbance | |
WO2005097103A2 (fr) | Traitement du diabete et du syndrome metabolique au moyen d'inhibiteurs de la cathepsine b | |
KR20070038503A (ko) | 신규 헤테로시클릭 카르복시산 아미드 유도체 | |
WO2004091610A1 (fr) | Derives d'imidazole destines au traitement de troubles allergiques et hyperproliferatifs | |
WO2004010942A2 (fr) | Composes heterocycliques substitues utilises comme modulateurs du recepteur ccr5 | |
EP0747049A1 (fr) | Utilisation d'antagonistes de la tachykinine en combinaison avec des agonistes de la sérotonine ou avec des inhibiteurs de réabsorption de sérotonine pour la fabrication d'un médicament pour le traitement de la rhinite allergique | |
TW200946118A (en) | Soluble epoxide hydrolase inhibitors | |
US20030162788A1 (en) | Combination of MTP inhibitors or apoB-secretion inhibitors with fibrates for use as pharmaceuticals | |
US6759425B2 (en) | Benzimidazole compounds for modulating IgE and inhibiting cellular proliferation | |
EP1371646B1 (fr) | Compose alicyclique a substitution aryle et composition medicale contenant ce compose | |
EA010893B1 (ru) | Новые производные бензоилмочевины | |
EP0747055A2 (fr) | Utilisation d'antagonistes du récepteur de tachykinine pour le traitement du rhume et de la rhinite allergique | |
KR20060130619A (ko) | 유기 화합물의 조합물 | |
US20030073836A1 (en) | Heteroarylcarboxylic acid amides, the preparation thereof and their use as pharmaceutical compositions | |
AU2005222399A1 (en) | Ion channel modulators | |
RU2646475C2 (ru) | Лечение диабета I и II типа | |
US20040171659A1 (en) | Methods for treating diabetes |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Dead |