CA2471566A1 - Combination of mtp inhibitors or apob-secretion inhibitors with fibrates for use as pharmaceuticals - Google Patents
Combination of mtp inhibitors or apob-secretion inhibitors with fibrates for use as pharmaceuticals 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
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- 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
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- 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
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- 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
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
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- 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
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 230000002195 synergetic effect Effects 0.000 description 1
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- 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
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- 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
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- 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
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- 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
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- 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)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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 (de) | 2002-01-10 | 2003-01-07 | KOMBINATION VON MTP INHIBITOREN ODER apoB-SEKRETIONS-INHIBITOREN MIT FIBRATEN ZUR VERWENDUNG ALS ARZNEIMITTEL |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2471566A1 true CA2471566A1 (en) | 2003-07-17 |
Family
ID=26010911
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002471566A Abandoned CA2471566A1 (en) | 2002-01-10 | 2003-01-07 | Combination of mtp inhibitors or apob-secretion inhibitors with fibrates for use as pharmaceuticals |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP1465613A2 (de) |
JP (1) | JP2005525309A (de) |
AR (1) | AR038178A1 (de) |
AU (1) | AU2003205570A1 (de) |
CA (1) | CA2471566A1 (de) |
PE (1) | PE20030924A1 (de) |
TW (1) | TW200402292A (de) |
UY (1) | UY27610A1 (de) |
WO (1) | WO2003057205A2 (de) |
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 |
---|---|---|---|---|
EP1578725A1 (de) * | 2002-12-20 | 2005-09-28 | Pfizer Products Inc. | Inhibitoren des microsomalen trigylceridtransferproteins |
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 |
UA97348C2 (en) * | 2005-07-29 | 2012-02-10 | 4Сц Аг | HETEROCYCLIC NF-kB INHIBITORS |
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 |
CN102548986A (zh) | 2009-06-05 | 2012-07-04 | 链接医药公司 | 氨基吡咯烷酮衍生物及其用途 |
CN111065383A (zh) | 2017-07-11 | 2020-04-24 | 沃泰克斯药物股份有限公司 | 用作钠通道调节剂的羧酰胺 |
EP3762368B1 (de) | 2018-03-08 | 2022-01-26 | Incyte Corporation | Aminopyrazindiolverbindungen als pi3k-y-hemmer |
US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
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 (en) * | 1999-11-10 | 2005-08-02 | Pfizer Products Inc. | 7-¬(4'-trifluoromethyl-biphenyl-2-carbonyl)amino|-quinoline-3-carboxylic acid amides, and methods of inhibiting the secretion of apolipoprotein 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 AU AU2003205570A patent/AU2003205570A1/en not_active Abandoned
- 2003-01-07 WO PCT/EP2003/000057 patent/WO2003057205A2/de active Application Filing
- 2003-01-07 JP JP2003557563A patent/JP2005525309A/ja active Pending
- 2003-01-07 EP EP03702391A patent/EP1465613A2/de not_active Ceased
- 2003-01-07 UY UY27610A patent/UY27610A1/es not_active Application Discontinuation
- 2003-01-07 CA CA002471566A patent/CA2471566A1/en not_active Abandoned
- 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 (de) | 2004-10-13 |
AU2003205570A8 (en) | 2003-07-24 |
WO2003057205A3 (de) | 2004-04-01 |
PE20030924A1 (es) | 2003-12-17 |
AR038178A1 (es) | 2005-01-05 |
TW200402292A (en) | 2004-02-16 |
UY27610A1 (es) | 2003-08-29 |
WO2003057205A2 (de) | 2003-07-17 |
AU2003205570A1 (en) | 2003-07-24 |
JP2005525309A (ja) | 2005-08-25 |
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