KR20080008440A - Cetp 억제제의 약제학적 조성물 - Google Patents
Cetp 억제제의 약제학적 조성물 Download PDFInfo
- Publication number
- KR20080008440A KR20080008440A KR1020087000175A KR20087000175A KR20080008440A KR 20080008440 A KR20080008440 A KR 20080008440A KR 1020087000175 A KR1020087000175 A KR 1020087000175A KR 20087000175 A KR20087000175 A KR 20087000175A KR 20080008440 A KR20080008440 A KR 20080008440A
- Authority
- KR
- South Korea
- Prior art keywords
- phenyl
- group
- isopentylcyclohexanecarbonylamino
- substituted
- transfer protein
- 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.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 79
- 239000003112 inhibitor Substances 0.000 title abstract description 4
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims abstract description 157
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims abstract description 116
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 claims abstract description 86
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 claims abstract description 86
- 239000000654 additive Substances 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 35
- 230000000996 additive effect Effects 0.000 claims abstract description 34
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 17
- -1 stereoisomers Chemical class 0.000 claims description 431
- 150000001875 compounds Chemical class 0.000 claims description 142
- 230000000694 effects Effects 0.000 claims description 82
- 235000013305 food Nutrition 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 238000011282 treatment Methods 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 40
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- 230000036470 plasma concentration Effects 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 26
- 241000124008 Mammalia Species 0.000 claims description 23
- 125000002252 acyl group Chemical group 0.000 claims description 23
- YZQLWPMZQVHJED-UHFFFAOYSA-N 2-methylpropanethioic acid S-[2-[[[1-(2-ethylbutyl)cyclohexyl]-oxomethyl]amino]phenyl] ester Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CC(CC)CC)CCCCC1 YZQLWPMZQVHJED-UHFFFAOYSA-N 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 14
- 229960000913 crospovidone Drugs 0.000 claims description 14
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 14
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 14
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 8
- 208000029078 coronary artery disease Diseases 0.000 claims description 8
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- FFAADXOKPZHULO-UHFFFAOYSA-N 2-methylpropanethioic s-acid Chemical compound CC(C)C(S)=O FFAADXOKPZHULO-UHFFFAOYSA-N 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 206010021024 Hypolipidaemia Diseases 0.000 claims description 5
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 5
- 239000013078 crystal Substances 0.000 claims description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 5
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 208000029498 hypoalphalipoproteinemia Diseases 0.000 claims description 4
- 238000002203 pretreatment Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 3
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 3
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 239000002158 endotoxin Substances 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 208000037804 stenosis Diseases 0.000 claims description 3
- 230000036262 stenosis Effects 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- OVRLABAFXJPIMU-UHFFFAOYSA-N 1-(2-ethylbutyl)-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CC(CC)CC)CCCCC1 OVRLABAFXJPIMU-UHFFFAOYSA-N 0.000 claims description 2
- INKBUBAEIMNSIG-UHFFFAOYSA-N 1-(2-methylpropyl)-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CC(C)C)CCCCC1 INKBUBAEIMNSIG-UHFFFAOYSA-N 0.000 claims description 2
- WSDMOYWCWHLBPX-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(2-sulfanylphenyl)cyclopentane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCC1 WSDMOYWCWHLBPX-UHFFFAOYSA-N 0.000 claims description 2
- QSHCOFDJVJBWJU-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(4-methyl-2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=C(C)C=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 QSHCOFDJVJBWJU-UHFFFAOYSA-N 0.000 claims description 2
- ZUBAYESAZFWZPL-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(5-methyl-2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C(C)=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 ZUBAYESAZFWZPL-UHFFFAOYSA-N 0.000 claims description 2
- RPOWLQXTRJDTQA-UHFFFAOYSA-N 1-butyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCCC)CCCCC1 RPOWLQXTRJDTQA-UHFFFAOYSA-N 0.000 claims description 2
- HNJZDNMUVSELCB-UHFFFAOYSA-N 1-ethyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CC)CCCCC1 HNJZDNMUVSELCB-UHFFFAOYSA-N 0.000 claims description 2
- LRWUYINHKRXNQH-UHFFFAOYSA-N 1-methyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(C)CCCCC1 LRWUYINHKRXNQH-UHFFFAOYSA-N 0.000 claims description 2
- YOTSORLUOLPCCV-UHFFFAOYSA-N 1-propan-2-yl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(C(C)C)CCCCC1 YOTSORLUOLPCCV-UHFFFAOYSA-N 0.000 claims description 2
- GIBQUYMCEXFBRU-UHFFFAOYSA-N 1-propyl-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC)CCCCC1 GIBQUYMCEXFBRU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- ZYSULIBJXPPZRD-UHFFFAOYSA-N 6-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl]sulfanyl-6-oxohexanoic acid Chemical compound C=1C=CC=C(SC(=O)CCCCC(O)=O)C=1NC(=O)C1(CCC(C)C)CCCCC1 ZYSULIBJXPPZRD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- LRXMNFMNMFWCOJ-UHFFFAOYSA-N methyl [2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl]sulfanylformate Chemical compound COC(=O)SC1=CC=CC=C1NC(=O)C1(CCC(C)C)CCCCC1 LRXMNFMNMFWCOJ-UHFFFAOYSA-N 0.000 claims description 2
- GHSLUZCHSFWKRE-UHFFFAOYSA-N n-(4,5-dichloro-2-sulfanylphenyl)-1-(3-methylbutyl)cyclohexane-1-carboxamide Chemical compound C=1C(Cl)=C(Cl)C=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 GHSLUZCHSFWKRE-UHFFFAOYSA-N 0.000 claims description 2
- LHNSUEDKNSIQML-UHFFFAOYSA-N n-(4,5-dichloro-2-sulfanylphenyl)-1-(3-methylbutyl)cyclopentane-1-carboxamide Chemical compound C=1C(Cl)=C(Cl)C=C(S)C=1NC(=O)C1(CCC(C)C)CCCC1 LHNSUEDKNSIQML-UHFFFAOYSA-N 0.000 claims description 2
- WBCRBXAFIQXPJQ-UHFFFAOYSA-N s-[2-[(1-methylcyclohexanecarbonyl)amino]phenyl] 2,2-dimethylpropanethioate Chemical compound CC(C)(C)C(=O)SC1=CC=CC=C1NC(=O)C1(C)CCCCC1 WBCRBXAFIQXPJQ-UHFFFAOYSA-N 0.000 claims description 2
- CUFAKTNZJHSRMF-UHFFFAOYSA-N s-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 1-acetylpiperidine-4-carbothioate Chemical compound C=1C=CC=C(SC(=O)C2CCN(CC2)C(C)=O)C=1NC(=O)C1(CC(CC)CC)CCCCC1 CUFAKTNZJHSRMF-UHFFFAOYSA-N 0.000 claims description 2
- MJLUTSZKWAWVAY-UHFFFAOYSA-N s-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CC(CC)CC)CCCCC1 MJLUTSZKWAWVAY-UHFFFAOYSA-N 0.000 claims description 2
- CVANHIYHWIDBGC-UHFFFAOYSA-N s-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-(4-chlorophenoxy)ethanethioate Chemical compound C=1C=CC=C(SC(=O)COC=2C=CC(Cl)=CC=2)C=1NC(=O)C1(CC(CC)CC)CCCCC1 CVANHIYHWIDBGC-UHFFFAOYSA-N 0.000 claims description 2
- AFVJGCXNVCMGBC-UHFFFAOYSA-N s-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methoxyethanethioate Chemical compound C=1C=CC=C(SC(=O)COC)C=1NC(=O)C1(CC(CC)CC)CCCCC1 AFVJGCXNVCMGBC-UHFFFAOYSA-N 0.000 claims description 2
- CCSJXVJLCREWRO-UHFFFAOYSA-N s-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] ethanethioate Chemical compound C=1C=CC=C(SC(C)=O)C=1NC(=O)C1(CC(CC)CC)CCCCC1 CCSJXVJLCREWRO-UHFFFAOYSA-N 0.000 claims description 2
- AVHJWJNTHBRPPL-UHFFFAOYSA-N s-[2-[[1-(2-methylpropyl)cyclohexanecarbonyl]amino]phenyl] 2-(4-chlorophenoxy)ethanethioate Chemical compound C=1C=CC=C(SC(=O)COC=2C=CC(Cl)=CC=2)C=1NC(=O)C1(CC(C)C)CCCCC1 AVHJWJNTHBRPPL-UHFFFAOYSA-N 0.000 claims description 2
- ZSWAVFZBRNIUBU-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]-4-(trifluoromethyl)phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(C(F)(F)F)=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 ZSWAVFZBRNIUBU-UHFFFAOYSA-N 0.000 claims description 2
- LJSAHYCOQKCCQZ-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]-4-nitrophenyl] 2,2-dimethylpropanethioate Chemical compound C=1C([N+]([O-])=O)=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 LJSAHYCOQKCCQZ-UHFFFAOYSA-N 0.000 claims description 2
- WIDPRMXSHTWZFE-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 WIDPRMXSHTWZFE-UHFFFAOYSA-N 0.000 claims description 2
- FXIULSQKMBPEOI-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-(4-chlorophenoxy)ethanethioate Chemical compound C=1C=CC=C(SC(=O)COC=2C=CC(Cl)=CC=2)C=1NC(=O)C1(CCC(C)C)CCCCC1 FXIULSQKMBPEOI-UHFFFAOYSA-N 0.000 claims description 2
- HYSIQIZWVLUQLT-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-acetamido-3-phenylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(CC=2C=CC=CC=2)NC(C)=O)C=1NC(=O)C1(CCC(C)C)CCCCC1 HYSIQIZWVLUQLT-UHFFFAOYSA-N 0.000 claims description 2
- OTMSDUWIKWKOJA-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-acetamido-5-amino-5-oxopentanethioate Chemical compound C=1C=CC=C(SC(=O)C(CCC(N)=O)NC(C)=O)C=1NC(=O)C1(CCC(C)C)CCCCC1 OTMSDUWIKWKOJA-UHFFFAOYSA-N 0.000 claims description 2
- SSAIZJDBBXDECD-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-chloroethanethioate Chemical compound C=1C=CC=C(SC(=O)CCl)C=1NC(=O)C1(CCC(C)C)CCCCC1 SSAIZJDBBXDECD-UHFFFAOYSA-N 0.000 claims description 2
- MXLMXGUKFHEMNV-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-hydroxy-2-methylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(C)(C)O)C=1NC(=O)C1(CCC(C)C)CCCCC1 MXLMXGUKFHEMNV-UHFFFAOYSA-N 0.000 claims description 2
- CVPUOEPURYNJKD-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methoxyethanethioate Chemical compound COCC(=O)SC1=CC=CC=C1NC(=O)C1(CCC(C)C)CCCCC1 CVPUOEPURYNJKD-UHFFFAOYSA-N 0.000 claims description 2
- XHVJBTXLUDEYRF-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 XHVJBTXLUDEYRF-UHFFFAOYSA-N 0.000 claims description 2
- FRZSEBDDONUPPE-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-phenoxyethanethioate Chemical compound C=1C=CC=C(SC(=O)COC=2C=CC=CC=2)C=1NC(=O)C1(CCC(C)C)CCCCC1 FRZSEBDDONUPPE-UHFFFAOYSA-N 0.000 claims description 2
- PAUVZWIHHQXRET-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] benzenecarbothioate Chemical compound C=1C=CC=C(SC(=O)C=2C=CC=CC=2)C=1NC(=O)C1(CCC(C)C)CCCCC1 PAUVZWIHHQXRET-UHFFFAOYSA-N 0.000 claims description 2
- OYMZRBRXYBINJS-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] cyclohexanecarbothioate Chemical compound C=1C=CC=C(SC(=O)C2CCCCC2)C=1NC(=O)C1(CCC(C)C)CCCCC1 OYMZRBRXYBINJS-UHFFFAOYSA-N 0.000 claims description 2
- UEQKYAQEIJRSJL-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] cyclopropanecarbothioate Chemical compound C=1C=CC=C(SC(=O)C2CC2)C=1NC(=O)C1(CCC(C)C)CCCCC1 UEQKYAQEIJRSJL-UHFFFAOYSA-N 0.000 claims description 2
- JDXPRSNPJGKLDY-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] ethanethioate Chemical compound C=1C=CC=C(SC(C)=O)C=1NC(=O)C1(CCC(C)C)CCCCC1 JDXPRSNPJGKLDY-UHFFFAOYSA-N 0.000 claims description 2
- HWBRDPQUXXEYBF-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] n-phenylcarbamothioate Chemical compound C=1C=CC=C(SC(=O)NC=2C=CC=CC=2)C=1NC(=O)C1(CCC(C)C)CCCCC1 HWBRDPQUXXEYBF-UHFFFAOYSA-N 0.000 claims description 2
- ZWIFWJMAXNUTID-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] propanethioate Chemical compound CCC(=O)SC1=CC=CC=C1NC(=O)C1(CCC(C)C)CCCCC1 ZWIFWJMAXNUTID-UHFFFAOYSA-N 0.000 claims description 2
- IUOPLRYKLPOZOU-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] pyridine-3-carbothioate Chemical compound C=1C=CC=C(SC(=O)C=2C=NC=CC=2)C=1NC(=O)C1(CCC(C)C)CCCCC1 IUOPLRYKLPOZOU-UHFFFAOYSA-N 0.000 claims description 2
- XBYRAJQIWBCYTG-UHFFFAOYSA-N s-[2-[[1-(3-methylbutyl)cyclopentanecarbonyl]amino]phenyl] ethanethioate Chemical compound C=1C=CC=C(SC(C)=O)C=1NC(=O)C1(CCC(C)C)CCCC1 XBYRAJQIWBCYTG-UHFFFAOYSA-N 0.000 claims description 2
- JFCOHMGXJCIKPZ-UHFFFAOYSA-N s-[4,5-dichloro-2-[(1-cyclopropylcyclohexanecarbonyl)amino]phenyl] 2,2-dimethylpropanethioate Chemical compound CC(C)(C)C(=O)SC1=CC(Cl)=C(Cl)C=C1NC(=O)C1(C2CC2)CCCCC1 JFCOHMGXJCIKPZ-UHFFFAOYSA-N 0.000 claims description 2
- OLXQLAYHYKQVRD-UHFFFAOYSA-N s-[4,5-dichloro-2-[(1-pentylcyclohexanecarbonyl)amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCCCC)CCCCC1 OLXQLAYHYKQVRD-UHFFFAOYSA-N 0.000 claims description 2
- LRLVDOHJDUBITP-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(3-methylbutyl)cyclobutanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCC1 LRLVDOHJDUBITP-UHFFFAOYSA-N 0.000 claims description 2
- MPTSSPNHRTXQBL-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(3-methylbutyl)cycloheptanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCCC1 MPTSSPNHRTXQBL-UHFFFAOYSA-N 0.000 claims description 2
- LSJSNHMUBPMISY-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 LSJSNHMUBPMISY-UHFFFAOYSA-N 0.000 claims description 2
- BFYLHKTYMPKXHG-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(3-methylbutyl)cyclopentanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCC1 BFYLHKTYMPKXHG-UHFFFAOYSA-N 0.000 claims description 2
- NOPRLOFLORGLJY-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(cyclohexylmethyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound CC(C)(C)C(=O)SC1=CC(Cl)=C(Cl)C=C1NC(=O)C1(CC2CCCCC2)CCCCC1 NOPRLOFLORGLJY-UHFFFAOYSA-N 0.000 claims description 2
- MSFCBUDDVRTHPO-UHFFFAOYSA-N s-[4,5-dichloro-2-[[1-(cyclopropylmethyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound CC(C)(C)C(=O)SC1=CC(Cl)=C(Cl)C=C1NC(=O)C1(CC2CC2)CCCCC1 MSFCBUDDVRTHPO-UHFFFAOYSA-N 0.000 claims description 2
- IAJQFWNTMVVJFU-UHFFFAOYSA-N s-[4,5-difluoro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(F)=C(F)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 IAJQFWNTMVVJFU-UHFFFAOYSA-N 0.000 claims description 2
- TURBPAKUUPDMHO-UHFFFAOYSA-N s-[4-chloro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 TURBPAKUUPDMHO-UHFFFAOYSA-N 0.000 claims description 2
- GQAZVPMGDGAFBJ-UHFFFAOYSA-N s-[4-cyano-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(C#N)=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 GQAZVPMGDGAFBJ-UHFFFAOYSA-N 0.000 claims description 2
- XIKSVWQUCOSSBL-UHFFFAOYSA-N s-[4-methyl-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] ethanethioate Chemical compound C=1C(C)=CC=C(SC(C)=O)C=1NC(=O)C1(CCC(C)C)CCCCC1 XIKSVWQUCOSSBL-UHFFFAOYSA-N 0.000 claims description 2
- FEENFRZHDJHJGY-UHFFFAOYSA-N s-[5-fluoro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C=C(F)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 FEENFRZHDJHJGY-UHFFFAOYSA-N 0.000 claims description 2
- KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 claims 2
- 102100037637 Cholesteryl ester transfer protein Human genes 0.000 claims 2
- 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 claims 2
- 208000028867 ischemia Diseases 0.000 claims 2
- 230000004952 protein activity Effects 0.000 claims 2
- OBWOWYBSZTURFB-UHFFFAOYSA-N 1-(3-methylbutyl)-n-(2-sulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(S)C=1NC(=O)C1(CCC(C)C)CCCCC1 OBWOWYBSZTURFB-UHFFFAOYSA-N 0.000 claims 1
- BEZLZUVKRNXSDY-UHFFFAOYSA-N 1-methyl-n-(2-phenylsulfanylcarbonylsulfanylphenyl)cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(SC(=O)SC=2C=CC=CC=2)C=1NC(=O)C1(C)CCCCC1 BEZLZUVKRNXSDY-UHFFFAOYSA-N 0.000 claims 1
- JHSXHKMJBWOMRU-UHFFFAOYSA-N 2,2-dimethylpropanethioic s-acid Chemical compound CC(C)(C)C(S)=O JHSXHKMJBWOMRU-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 230000008676 import Effects 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- MJGXFBMXAVDVQR-UHFFFAOYSA-N s-[2-[[1-(2-methylpropyl)cyclohexanecarbonyl]amino]phenyl] 1-acetylpiperidine-4-carbothioate Chemical compound C=1C=CC=C(SC(=O)C2CCN(CC2)C(C)=O)C=1NC(=O)C1(CC(C)C)CCCCC1 MJGXFBMXAVDVQR-UHFFFAOYSA-N 0.000 claims 1
- ZKLYDYIGXBYRKG-UHFFFAOYSA-N s-[2-[[1-(2-methylpropyl)cyclohexanecarbonyl]amino]phenyl] 2-methylpropanethioate Chemical compound C=1C=CC=C(SC(=O)C(C)C)C=1NC(=O)C1(CC(C)C)CCCCC1 ZKLYDYIGXBYRKG-UHFFFAOYSA-N 0.000 claims 1
- QRUWEPAFXQSBDS-UHFFFAOYSA-N s-[4-fluoro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(F)=CC=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 QRUWEPAFXQSBDS-UHFFFAOYSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 description 33
- 108010023302 HDL Cholesterol Proteins 0.000 description 27
- 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 22
- 239000000902 placebo Substances 0.000 description 20
- 229940068196 placebo Drugs 0.000 description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
- 239000003814 drug Substances 0.000 description 18
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 15
- 239000000460 chlorine Substances 0.000 description 15
- 229910052801 chlorine Inorganic materials 0.000 description 15
- 229910052731 fluorine Inorganic materials 0.000 description 15
- 239000011737 fluorine Substances 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 14
- 125000003710 aryl alkyl group Chemical group 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 235000021152 breakfast Nutrition 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 10
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 10
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 9
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 7
- 108010010234 HDL Lipoproteins Proteins 0.000 description 7
- 102000015779 HDL Lipoproteins Human genes 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000000454 talc Substances 0.000 description 6
- 229910052623 talc Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 208000007502 anemia Diseases 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 5
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- 150000003573 thiols Chemical class 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 4
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 4
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 230000009246 food effect Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 239000011812 mixed powder Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- 229920002554 vinyl polymer Polymers 0.000 description 4
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 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 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052789 astatine Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 125000005936 piperidyl group Chemical group 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000004886 process control Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 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 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 2
- 125000006065 1,3-dimethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006025 1-methyl-1-butenyl group Chemical group 0.000 description 2
- 125000006048 1-methyl-2-pentenyl group Chemical group 0.000 description 2
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000006023 1-pentenyl group Chemical group 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000020937 fasting conditions Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000009477 glass transition Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([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 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- XCFKYPVNRYNNEM-UHFFFAOYSA-N 1-acetylpiperidine-4-carbothioic s-acid Chemical compound CC(=O)N1CCC(C(S)=O)CC1 XCFKYPVNRYNNEM-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- 125000003764 2,4-dimethylpentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- ZBJJDYGJCNTNTH-UHFFFAOYSA-N Betahistine mesilate Chemical group CS(O)(=O)=O.CS(O)(=O)=O.CNCCC1=CC=CC=N1 ZBJJDYGJCNTNTH-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 241000854711 Shinkai Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000000872 buffer Substances 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
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000000078 claw Anatomy 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000026758 coronary atherosclerosis Diseases 0.000 description 1
- XWCWNUSFQVJNDI-UHFFFAOYSA-N cyclohex-3-en-1-ylbenzene Chemical compound C1C=CCCC1C1=CC=CC=C1 XWCWNUSFQVJNDI-UHFFFAOYSA-N 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000002704 decyl 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])* 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Chemical group C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003745 glyceroyl group Chemical group C(C(O)CO)(=O)* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000005842 heteroatom Chemical group 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
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- 208000026621 hypolipoproteinemia Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([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
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 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 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- ITEBOTJVVWYIQA-UHFFFAOYSA-N s-[4,5-dichloro-2-[(1-propan-2-ylcyclohexanecarbonyl)amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C(Cl)=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(C(C)C)CCCCC1 ITEBOTJVVWYIQA-UHFFFAOYSA-N 0.000 description 1
- PPLIUJAXWQFCOC-UHFFFAOYSA-N s-[5-chloro-2-[[1-(3-methylbutyl)cyclohexanecarbonyl]amino]phenyl] 2,2-dimethylpropanethioate Chemical compound C=1C=C(Cl)C=C(SC(=O)C(C)(C)C)C=1NC(=O)C1(CCC(C)C)CCCCC1 PPLIUJAXWQFCOC-UHFFFAOYSA-N 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 235000021055 solid food Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 229940033134 talc Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000005425 toluyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/82—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/265—Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45529303P | 2003-03-17 | 2003-03-17 | |
| US60/455,293 | 2003-03-17 | ||
| US46052103P | 2003-04-04 | 2003-04-04 | |
| US60/460,521 | 2003-04-04 | ||
| US47720203P | 2003-06-10 | 2003-06-10 | |
| US60/477,202 | 2003-06-10 | ||
| US49364903P | 2003-08-08 | 2003-08-08 | |
| US60/493,649 | 2003-08-08 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057017449A Division KR100857759B1 (ko) | 2003-03-17 | 2004-03-17 | Cetp 억제제의 약제학적 조성물 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080008440A true KR20080008440A (ko) | 2008-01-23 |
Family
ID=33033290
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087000175A Withdrawn KR20080008440A (ko) | 2003-03-17 | 2004-03-17 | Cetp 억제제의 약제학적 조성물 |
| KR1020057017449A Expired - Lifetime KR100857759B1 (ko) | 2003-03-17 | 2004-03-17 | Cetp 억제제의 약제학적 조성물 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057017449A Expired - Lifetime KR100857759B1 (ko) | 2003-03-17 | 2004-03-17 | Cetp 억제제의 약제학적 조성물 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US20040225018A1 (https=) |
| EP (2) | EP2289507A1 (https=) |
| JP (2) | JP5546715B2 (https=) |
| KR (2) | KR20080008440A (https=) |
| AT (1) | ATE534381T1 (https=) |
| AU (1) | AU2004222434B2 (https=) |
| BR (1) | BRPI0408466B8 (https=) |
| CA (1) | CA2519432C (https=) |
| CO (1) | CO5640101A2 (https=) |
| CY (1) | CY1112324T1 (https=) |
| DK (1) | DK1603553T3 (https=) |
| ES (1) | ES2377121T3 (https=) |
| IL (1) | IL170749A (https=) |
| MX (1) | MXPA05009848A (https=) |
| NO (1) | NO336891B1 (https=) |
| NZ (1) | NZ542852A (https=) |
| PL (1) | PL1603553T3 (https=) |
| PT (1) | PT1603553E (https=) |
| SI (1) | SI1603553T1 (https=) |
| WO (1) | WO2004082593A2 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7312044B2 (en) | 2003-03-07 | 2007-12-25 | The Trustees Of Columbia University In The City Of New York | Type 1 ryanodine receptor-based methods |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7879840B2 (en) | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7393652B2 (en) | 2000-05-10 | 2008-07-01 | The Trustees Of Columbia University In The City Of New York | Methods for identifying a chemical compound that directly enhances binding of FKBP12.6 to PKA-phosphorylated type 2 ryanodine receptor (RyR2) |
| US7718644B2 (en) | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US7186735B2 (en) * | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
| US7544678B2 (en) | 2002-11-05 | 2009-06-09 | The Trustees Of Columbia University In The City Of New York | Anti-arrythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) |
| PT1603553E (pt) * | 2003-03-17 | 2012-02-03 | Japan Tobacco Inc | Composições farmacêuticas de inibidores de cetp |
| WO2004082675A1 (en) | 2003-03-17 | 2004-09-30 | Japan Tobacco Inc. | Method for increasing the oral bioavailability of s-[2- ([[1- (2-ethylbutyl) cyclohexyl] carbonyl] amino) phenyl] 2-methylpropanethioate |
| TWI494102B (zh) * | 2003-05-02 | 2015-08-01 | Japan Tobacco Inc | 包含s-〔2(〔〔1-(2-乙基丁基)環己基〕羰基〕胺基)苯基〕2-甲基丙烷硫酯及hmg輔酶a還原酶抑制劑之組合 |
| MXPA06003357A (es) * | 2003-09-26 | 2006-06-08 | Japan Tobacco Inc | Metodo para inhibir la produccion de lipoproteina remanente. |
| US8710045B2 (en) | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| DOP2005000123A (es) | 2004-07-02 | 2011-07-15 | Merck Sharp & Dohme | Inhibidores de cetp |
| WO2006098394A1 (ja) * | 2005-03-14 | 2006-09-21 | Japan Tobacco Inc. | 脂質吸収抑制方法および脂質吸収抑制剤 |
| US7704990B2 (en) | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| WO2007092642A2 (en) | 2006-02-09 | 2007-08-16 | Merck & Co., Inc. | Polymer formulations of cetp inhibitors |
| BRPI0922888A2 (pt) * | 2008-12-08 | 2019-09-24 | Hoffmann La Roche | administração combinada de fármaco |
| CN102293734A (zh) * | 2010-06-25 | 2011-12-28 | 江苏恒瑞医药股份有限公司 | 托伐普坦固体分散体及其制备方法 |
| CN103200935A (zh) * | 2010-11-04 | 2013-07-10 | 霍夫曼-拉罗奇有限公司 | 包含2-甲基丙硫代酸s-[2-([[1-(2-乙基丁基)-环己基]-羰基]氨基)苯基]酯和交联羧甲基纤维素钠的组合物 |
| WO2012076443A1 (en) | 2010-12-08 | 2012-06-14 | F. Hoffmann-La Roche Ag | Liposomal formulation of dalcetrapib |
| CA2824639A1 (en) * | 2011-02-17 | 2012-08-23 | Ashish Chatterji | A process for controlled crystallization of an active pharmaceutical ingredient from supercooled liquid state by hot melt extrusion |
| MX2016005505A (es) * | 2013-12-19 | 2016-07-22 | Hoffmann La Roche | Modulador de la proteina de transferencia de ester de colesterilo (cetp) para usarse en el tratamiento de enfermedades oculares. |
| AU2019319089A1 (en) * | 2018-08-09 | 2021-02-25 | Dalcor Pharma Uk Ltd., Leatherhead, Zug Branch | Methods for delaying occurrence of new-onset type 2 diabetes and for slowing progression of and treating type 2 diabetes |
| WO2023064794A1 (en) * | 2021-10-12 | 2023-04-20 | Hdl Therapeutics, Inc. | Methods and systems for prophylactically preventing, slowing the progression of, or treating cerebral amyloid angiopathy, alzheimer's disease and/or acute stroke |
Family Cites Families (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US36481A (en) * | 1862-09-16 | Improvement in apparatus for distilling petroleum and other oils | ||
| US36520A (en) * | 1862-09-23 | Improvement in the manufacture of tobacco | ||
| US3576830A (en) * | 1966-08-12 | 1971-04-27 | Sumitomo Chemical Co | Amides containing sulfur |
| US4346277A (en) * | 1979-10-29 | 1982-08-24 | Eaton Corporation | Packaged electrical heating element |
| US4444784A (en) * | 1980-08-05 | 1984-04-24 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| US5354772A (en) * | 1982-11-22 | 1994-10-11 | Sandoz Pharm. Corp. | Indole analogs of mevalonolactone and derivatives thereof |
| US4681893A (en) * | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| US4740438A (en) * | 1986-12-10 | 1988-04-26 | Eastman Kodak Company | Organic disulfides as image dye stabilizers |
| US4853319A (en) * | 1986-12-22 | 1989-08-01 | Eastman Kodak Company | Photographic silver halide element and process |
| JP2569746B2 (ja) * | 1987-08-20 | 1997-01-08 | 日産化学工業株式会社 | キノリン系メバロノラクトン類 |
| US5356869A (en) * | 1987-09-28 | 1994-10-18 | Arch Development Corporation | Metal oxide superconducting powder comprised of flake-like single crystal particles |
| US5030447A (en) * | 1988-03-31 | 1991-07-09 | E. R. Squibb & Sons, Inc. | Pharmaceutical compositions having good stability |
| US5180589A (en) * | 1988-03-31 | 1993-01-19 | E. R. Squibb & Sons, Inc. | Pravastatin pharmaceuatical compositions having good stability |
| US5118583A (en) * | 1988-10-12 | 1992-06-02 | Mitsubishi Paper Mills Limited | Processing composition for printing plate |
| FI94339C (fi) * | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| US5622985A (en) * | 1990-06-11 | 1997-04-22 | Bristol-Myers Squibb Company | Method for preventing a second heart attack employing an HMG CoA reductase inhibitor |
| FR2665450B1 (fr) * | 1990-08-01 | 1994-04-08 | Rhone Poulenc Chimie | Procede de preparation de dispersions aqueuses de copolymeres. |
| JP2648897B2 (ja) * | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
| WO1993011782A1 (en) * | 1991-12-19 | 1993-06-24 | Southwest Foundation For Biomedical Research | Cetp inhibitor polypeptide, antibodies against the synthetic polypeptide and prophylactic and therapeutic anti-atherosclerosis treatments |
| US5519001A (en) * | 1991-12-19 | 1996-05-21 | Southwest Foundation For Biomedical Research | CETP inhibitor polypeptide antibodies against the synthetic polypeptide and prophylactic and therapeutic anti-atherosclerosis treatments |
| US5217859A (en) * | 1992-04-16 | 1993-06-08 | Eastman Kodak Company | Aqueous, solid particle dispersions of dichalcogenides for photographic emulsions and coatings |
| US5219721A (en) * | 1992-04-16 | 1993-06-15 | Eastman Kodak Company | Silver halide photographic emulsions sensitized in the presence of organic dichalcogenides |
| JP3254219B2 (ja) * | 1993-01-19 | 2002-02-04 | ワーナー−ランバート・コンパニー | 安定な経口用のci−981製剤およびその製法 |
| US5350667A (en) * | 1993-06-17 | 1994-09-27 | Eastman Kodak Company | Photographic elements containing magenta couplers and process for using same |
| US5534529A (en) * | 1993-06-30 | 1996-07-09 | Sankyo Company, Limited | Substituted aromatic amides and ureas derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses |
| JP3894949B2 (ja) * | 1993-06-30 | 2007-03-22 | ザ、ウェルカム、ファンデーション、リミテッド | 抗アテローム性動脈硬化症ジアリール化合物 |
| US5446207A (en) * | 1993-09-01 | 1995-08-29 | Harbor Branch Oceanographic Institution, Inc. | Anti-dyslipidemic agents |
| US5996156A (en) * | 1995-01-31 | 1999-12-07 | Kelley Company, Inc. | Dock leveler raised by deflating an inflatable member |
| US5459154A (en) * | 1993-11-08 | 1995-10-17 | American Home Products Corporation | N-hydroxyureas as 5-lipoxygenase inhibitors and inhibitors of oxidative modification of low density lipoprotein |
| US5405969A (en) * | 1993-12-10 | 1995-04-11 | Eastman Kodak Company | Manufacture of thioether compounds |
| JP3304189B2 (ja) * | 1994-03-18 | 2002-07-22 | マツダ株式会社 | 加硫スクラップゴムを含有する成形用ゴム組成物及びその製造方法 |
| US5654134A (en) * | 1994-05-18 | 1997-08-05 | Fuji Photo Film Co., Ltd. | Silver halide emulsion |
| DE4428457C1 (de) * | 1994-08-11 | 1995-10-05 | Bayer Ag | Geformte, paraffinhaltige Mastiziermittel |
| JPH09501186A (ja) * | 1994-11-12 | 1997-02-04 | 株式会社エルジ化学 | コレステリルエステル運搬蛋白質阻害ペプチドおよびこれを含む動脈硬化症のための予防および治療剤 |
| DE69520345T2 (de) * | 1994-12-26 | 2001-09-06 | Nisshin Flour Milling Co., Ltd. | Diphenyl-disulfid Verbindungen |
| DE19610932A1 (de) * | 1996-03-20 | 1997-09-25 | Bayer Ag | 2-Aryl-substituierte Pyridine |
| US6207671B1 (en) * | 1996-07-08 | 2001-03-27 | Bayer Aktiengesellschaft | Cycloalkano-pyridines |
| HRP970330B1 (en) * | 1996-07-08 | 2004-06-30 | Bayer Ag | Cycloalkano pyridines |
| DE19627431A1 (de) * | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| AR008789A1 (es) | 1996-07-31 | 2000-02-23 | Bayer Corp | Piridinas y bifenilos substituidos |
| JP2894445B2 (ja) * | 1997-02-12 | 1999-05-24 | 日本たばこ産業株式会社 | Cetp活性阻害剤として有効な化合物 |
| JP3290962B2 (ja) * | 1997-02-12 | 2002-06-10 | 日本たばこ産業株式会社 | Cetp活性阻害剤 |
| CN1275596C (zh) * | 1997-05-14 | 2006-09-20 | 阿特罗吉尼克斯公司 | 普罗布考单酯在制备用于治疗心血管疾病和炎性疾病的药物中的应用 |
| US6093573A (en) * | 1997-06-20 | 2000-07-25 | Xoma | Three-dimensional structure of bactericidal/permeability-increasing protein (BPI) |
| WO1999014204A1 (en) | 1997-09-16 | 1999-03-25 | G.D. Searle & Co. | Substituted 1,2,4-triazoles useful for inhibiting cholesteryl ester transfer protein activity |
| MA24643A1 (fr) | 1997-09-18 | 1999-04-01 | Bayer Ag | Tetrahydro-naphtalenes substitues et composes analogues |
| DE19741051A1 (de) | 1997-09-18 | 1999-03-25 | Bayer Ag | Hetero-Tetrahydrochinoline |
| US5916595A (en) * | 1997-12-12 | 1999-06-29 | Andrx Pharmaceutials, Inc. | HMG co-reductase inhibitor |
| AU3285499A (en) | 1998-02-13 | 1999-08-30 | G.D. Searle & Co. | Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity |
| US6080778A (en) * | 1998-03-23 | 2000-06-27 | Children's Medical Center Corporation | Methods for decreasing beta amyloid protein |
| EP0945134A1 (de) * | 1998-03-27 | 1999-09-29 | Boehringer Ingelheim Pharma KG | Neue galenische Zubereitungsformen von Meloxicam zur oralen Applikation |
| US6147089A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6147090A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6140342A (en) * | 1998-09-17 | 2000-10-31 | Pfizer Inc. | Oxy substituted 4-carboxyamino-2-methyl-1,2,3,4-tetrahydroquinolines |
| US6197786B1 (en) * | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines |
| AU2157400A (en) * | 1998-12-23 | 2000-07-31 | G.D. Searle & Co. | Combinations of cholesteryl ester transfer protein inhibitors and hmg coa reductase inhibitors for cardiovascular indications |
| DE19917233A1 (de) * | 1999-04-16 | 2000-10-19 | Aventis Pharma Gmbh | Kristalline Formen des Natriumsalzes des 5-Chlor-2-methoxy-N-(2-(4-methoxy-3-methylaminothiocarbonylaminosulfonyl-phenyl)-ethyl)- benzamids |
| US6479552B2 (en) * | 1999-09-23 | 2002-11-12 | G.D. Searle & Co. | Use of substituted N, N-disubstituted diamino compounds for inhibiting cholesteryl ester transfer protein activity |
| US20010018446A1 (en) * | 1999-09-23 | 2001-08-30 | G.D. Searle & Co. | Substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity |
| HN2000000203A (es) * | 1999-11-30 | 2001-06-13 | Pfizer Prod Inc | Procedimiento para la obtencion de 1,2,3,4-tetrahidroquinolinas 4-carboxiamino-2- sustituidas. |
| US6242003B1 (en) * | 2000-04-13 | 2001-06-05 | Novartis Ag | Organic compounds |
| US7115279B2 (en) * | 2000-08-03 | 2006-10-03 | Curatolo William J | Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors |
| US7049283B2 (en) * | 2000-12-06 | 2006-05-23 | Novartis Ag | Pharmaceutical compositions for the oral delivery of pharmacologically active agents |
| WO2002092094A1 (en) * | 2001-03-27 | 2002-11-21 | Sumitomo Pharmaceuticals Co., Ltd. | Crystalline isoxazole derivative and medical preparation thereof |
| EA200301139A1 (ru) * | 2001-06-21 | 2004-12-30 | Пфайзер Продактс Инк. | Самоэмульгирующиеся препараты ингибиторов белка-переносчика эфиров холестерина |
| JP2004534812A (ja) * | 2001-06-22 | 2004-11-18 | ファイザー・プロダクツ・インク | 薬物および中性ポリマーの分散物の医薬組成物 |
| EP1269994A3 (en) * | 2001-06-22 | 2003-02-12 | Pfizer Products Inc. | Pharmaceutical compositions comprising drug and concentration-enhancing polymers |
| AR038375A1 (es) * | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
| US7071210B2 (en) * | 2002-07-02 | 2006-07-04 | Pfizer Inc. | CETP inhibitors in combination with antihypertensive agents and uses thereof |
| US20040053842A1 (en) * | 2002-07-02 | 2004-03-18 | Pfizer Inc. | Methods of treatment with CETP inhibitors and antihypertensive agents |
| PT1603553E (pt) * | 2003-03-17 | 2012-02-03 | Japan Tobacco Inc | Composições farmacêuticas de inibidores de cetp |
-
2004
- 2004-03-17 PT PT04721345T patent/PT1603553E/pt unknown
- 2004-03-17 BR BRPI0408466A patent/BRPI0408466B8/pt not_active IP Right Cessation
- 2004-03-17 DK DK04721345.9T patent/DK1603553T3/da active
- 2004-03-17 SI SI200431822T patent/SI1603553T1/sl unknown
- 2004-03-17 EP EP10179280A patent/EP2289507A1/en not_active Withdrawn
- 2004-03-17 AU AU2004222434A patent/AU2004222434B2/en not_active Expired
- 2004-03-17 PL PL04721345T patent/PL1603553T3/pl unknown
- 2004-03-17 KR KR1020087000175A patent/KR20080008440A/ko not_active Withdrawn
- 2004-03-17 JP JP2006507668A patent/JP5546715B2/ja not_active Expired - Lifetime
- 2004-03-17 US US10/802,220 patent/US20040225018A1/en not_active Abandoned
- 2004-03-17 NZ NZ542852A patent/NZ542852A/en not_active IP Right Cessation
- 2004-03-17 ES ES04721345T patent/ES2377121T3/es not_active Expired - Lifetime
- 2004-03-17 AT AT04721345T patent/ATE534381T1/de active
- 2004-03-17 CA CA002519432A patent/CA2519432C/en not_active Expired - Fee Related
- 2004-03-17 KR KR1020057017449A patent/KR100857759B1/ko not_active Expired - Lifetime
- 2004-03-17 MX MXPA05009848A patent/MXPA05009848A/es active IP Right Grant
- 2004-03-17 WO PCT/JP2004/003585 patent/WO2004082593A2/en not_active Ceased
- 2004-03-17 EP EP04721345A patent/EP1603553B9/en not_active Expired - Lifetime
-
2005
- 2005-09-08 IL IL170749A patent/IL170749A/en active IP Right Grant
- 2005-10-14 CO CO05105279A patent/CO5640101A2/es not_active Application Discontinuation
- 2005-10-14 NO NO20054740A patent/NO336891B1/no not_active IP Right Cessation
-
2010
- 2010-11-10 JP JP2010252215A patent/JP2011052006A/ja active Pending
-
2012
- 2012-02-06 CY CY20121100126T patent/CY1112324T1/el unknown
-
2013
- 2013-07-26 US US13/951,909 patent/US20140243414A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100857759B1 (ko) | Cetp 억제제의 약제학적 조성물 | |
| KR100324183B1 (ko) | Cetp 활성저해제 | |
| AU2015283905B2 (en) | Methods and compositions for treating obesity, preventing weight gain, promoting weight loss, promoting slimming, or treating or preventing the development of diabetes | |
| US20080045599A1 (en) | Method for Increasing the Bioavailability of the Active Form of S-[2-([[1-(2-Ethylbutyl)Cyclohexyl]Carbonyl] Amino)Phenyl] 2-Methylpropanethioate | |
| KR101420319B1 (ko) | 고지혈증 예방 및/또는 치료제 | |
| US20110189210A1 (en) | Method of inhibiting remnant lipoprotein production | |
| EP3177284B1 (en) | Oligomeric forms of 3-hydroxybutyrate | |
| RU2318504C2 (ru) | Фармацевтические композиции сетр-ингибиторов | |
| ZA200508159B (en) | Pharmaceutical compositions of CETP inhibitors | |
| EP1772147A2 (en) | Method for increasing the oral bioavailability of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]-2-methylpropanethioate | |
| EP1146867A1 (en) | Antibacterial hydroxamic acid derivatives | |
| AU2008201550B2 (en) | Method of inhibiting remnant lipoprotein production | |
| HK1157207A (en) | Method of inhibiting remnant lipoprotein production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A107 | Divisional application of patent | ||
| PA0104 | Divisional application for international application |
Comment text: Divisional Application for International Patent Patent event code: PA01041R01D Patent event date: 20080103 |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |