OA12619A - Self-emulsifying formulations of cholesteryl estertransfer protein inhibitors. - Google Patents

Self-emulsifying formulations of cholesteryl estertransfer protein inhibitors. Download PDF

Info

Publication number: OA12619A
Authority: OA; OAPI
Prior art keywords: substituted; trifluoromethyl; chain; mono; optionally
Prior art date: 2001-06-21

Application number

OA1200300317A

Other languages

English (en)

Inventor

Michael Jon Gumkowski

Franco LOMBARDO

Sharad Balasaheb Murdande

Michael Ellis Perlman

Original Assignee

Pfizer Prod Inc

Priority date (The priority date 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 date listed.)

2001-06-21

Filing date

2002-05-03

Publication date

2006-06-12

2002-05-03 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2006-06-12 Publication of OA12619A publication Critical patent/OA12619A/en

Links

239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title claims abstract description 103
239000000203 mixture Substances 0.000 title claims abstract description 70
238000009472 formulation Methods 0.000 title description 24
239000004094 surface-active agent Substances 0.000 claims abstract description 81
229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims abstract description 51
239000006184 cosolvent Substances 0.000 claims abstract description 28
239000002904 solvent Substances 0.000 claims abstract description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 455
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 311
125000004432 carbon atom Chemical group C* 0.000 claims description 285
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 285
125000000217 alkyl group Chemical group 0.000 claims description 280
-1 polyethylene Polymers 0.000 claims description 263
125000004043 oxo group Chemical group O=* 0.000 claims description 220
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 217
229910052717 sulfur Inorganic materials 0.000 claims description 215
229920006395 saturated elastomer Polymers 0.000 claims description 211
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 196
229910052757 nitrogen Inorganic materials 0.000 claims description 188
229910052799 carbon Inorganic materials 0.000 claims description 178
125000003545 alkoxy group Chemical group 0.000 claims description 165
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 157
239000011593 sulfur Substances 0.000 claims description 157
229910052760 oxygen Inorganic materials 0.000 claims description 152
125000003118 aryl group Chemical group 0.000 claims description 148
229910052739 hydrogen Inorganic materials 0.000 claims description 147
239000001257 hydrogen Substances 0.000 claims description 145
125000005843 halogen group Chemical group 0.000 claims description 143
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 132
125000005842 heteroatom Chemical group 0.000 claims description 128
239000001301 oxygen Substances 0.000 claims description 126
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 120
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 119
229910052736 halogen Inorganic materials 0.000 claims description 113
125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 claims description 111
125000004093 cyano group Chemical group *C#N 0.000 claims description 107
150000002431 hydrogen Chemical class 0.000 claims description 103
125000000623 heterocyclic group Chemical group 0.000 claims description 100
125000001424 substituent group Chemical group 0.000 claims description 95
125000004414 alkyl thio group Chemical group 0.000 claims description 94
150000002367 halogens Chemical class 0.000 claims description 93
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 92
125000000753 cycloalkyl group Chemical group 0.000 claims description 83
125000003342 alkenyl group Chemical group 0.000 claims description 81
125000001072 heteroaryl group Chemical group 0.000 claims description 75
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 72
125000000876 trifluoromethoxy group Chemical class FC(F)(F)O* 0.000 claims description 70
125000000304 alkynyl group Chemical group 0.000 claims description 68
125000003282 alkyl amino group Chemical group 0.000 claims description 67
125000002252 acyl group Chemical group 0.000 claims description 53
125000004429 atom Chemical group 0.000 claims description 52
150000001875 compounds Chemical class 0.000 claims description 52
150000003254 radicals Chemical class 0.000 claims description 52
239000003921 oil Substances 0.000 claims description 51
235000019198 oils Nutrition 0.000 claims description 51
125000001153 fluoro group Chemical group F* 0.000 claims description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 41
235000019000 fluorine Nutrition 0.000 claims description 39
125000001188 haloalkyl group Chemical group 0.000 claims description 39
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 37
125000000392 cycloalkenyl group Chemical group 0.000 claims description 32
125000000262 haloalkenyl group Chemical group 0.000 claims description 31
URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 31
125000002947 alkylene group Chemical group 0.000 claims description 28
125000002619 bicyclic group Chemical group 0.000 claims description 28
125000003710 aryl alkyl group Chemical group 0.000 claims description 27
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
125000004104 aryloxy group Chemical group 0.000 claims description 23
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 20
125000005553 heteroaryloxy group Chemical group 0.000 claims description 19
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 19
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 19
125000004434 sulfur atom Chemical group 0.000 claims description 19
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 17
125000005110 aryl thio group Chemical group 0.000 claims description 16
125000004494 ethyl ester group Chemical group 0.000 claims description 16
125000001145 hydrido group Chemical group *[H] 0.000 claims description 16
239000001087 glyceryl triacetate Substances 0.000 claims description 15
235000013773 glyceryl triacetate Nutrition 0.000 claims description 15
125000000232 haloalkynyl group Chemical group 0.000 claims description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
229960002622 triacetin Drugs 0.000 claims description 15
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
125000005164 aryl thioalkyl group Chemical group 0.000 claims description 14
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 14
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 14
125000005368 heteroarylthio group Chemical group 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
229920000053 polysorbate 80 Polymers 0.000 claims description 13
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 12
LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims description 12
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 12
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 12
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 11
229940068968 polysorbate 80 Drugs 0.000 claims description 11
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 10
125000005108 alkenylthio group Chemical group 0.000 claims description 10
125000005109 alkynylthio group Chemical group 0.000 claims description 10
239000004359 castor oil Substances 0.000 claims description 10
235000019438 castor oil Nutrition 0.000 claims description 10
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 10
125000003106 haloaryl group Chemical group 0.000 claims description 10
125000005216 haloheteroaryl group Chemical group 0.000 claims description 10
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 9
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 9
235000014113 dietary fatty acids Nutrition 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 9
239000000194 fatty acid Substances 0.000 claims description 9
229930195729 fatty acid Natural products 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
125000004450 alkenylene group Chemical group 0.000 claims description 8
125000002837 carbocyclic group Chemical group 0.000 claims description 8
125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 8
125000004468 heterocyclylthio group Chemical group 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 7
125000005055 alkyl alkoxy group Chemical group 0.000 claims description 7
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
239000004698 Polyethylene Substances 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
229940116333 ethyl lactate Drugs 0.000 claims description 6
150000002825 nitriles Chemical class 0.000 claims description 6
125000005254 oxyacyl group Chemical group 0.000 claims description 6
229920000573 polyethylene Polymers 0.000 claims description 6
125000005353 silylalkyl group Chemical group 0.000 claims description 6
239000003981 vehicle Substances 0.000 claims description 6
125000001769 aryl amino group Chemical group 0.000 claims description 5
125000005241 heteroarylamino group Chemical group 0.000 claims description 5
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
229920001223 polyethylene glycol Polymers 0.000 claims description 5
RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 claims description 5
125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 4
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims description 4
229920001213 Polysorbate 20 Polymers 0.000 claims description 4
125000000051 benzyloxy group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims description 4
150000004665 fatty acids Chemical class 0.000 claims description 4
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical class CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 4
125000004430 oxygen atom Chemical group O* 0.000 claims description 4
KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 claims description 4
150000003222 pyridines Chemical class 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
CMSGWTNRGKRWGS-NQIIRXRSSA-N torcetrapib Chemical compound COC(=O)N([C@H]1C[C@@H](CC)N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CMSGWTNRGKRWGS-NQIIRXRSSA-N 0.000 claims description 4
125000005389 trialkylsiloxy group Chemical group 0.000 claims description 4
OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 claims description 3
239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 3
RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 3
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
125000004103 aminoalkyl group Chemical group 0.000 claims description 3
239000002285 corn oil Substances 0.000 claims description 3
235000005687 corn oil Nutrition 0.000 claims description 3
XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 3
RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 3
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 3
125000003003 spiro group Chemical group 0.000 claims description 3
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
125000004665 trialkylsilyl group Chemical group 0.000 claims description 3
MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 claims description 2
CPHKBJBFYKJFHT-UHFFFAOYSA-N 1-methyl-n-[2-[[2-[(1-methylcyclohexanecarbonyl)amino]phenyl]disulfanyl]phenyl]cyclohexane-1-carboxamide Chemical compound C=1C=CC=C(SSC=2C(=CC=CC=2)NC(=O)C2(C)CCCCC2)C=1NC(=O)C1(C)CCCCC1 CPHKBJBFYKJFHT-UHFFFAOYSA-N 0.000 claims description 2
CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 claims description 2
IPYXWSIBCVUPBE-UHFFFAOYSA-N 2-cyclopentyl-4-(4-fluorophenyl)-3-[fluoro-[4-(trifluoromethyl)phenyl]methyl]-7,7-dimethyl-6,8-dihydro-5h-quinolin-5-ol Chemical compound C1C(C)(C)CC(O)C(C(=C2C(F)C=3C=CC(=CC=3)C(F)(F)F)C=3C=CC(F)=CC=3)=C1N=C2C1CCCC1 IPYXWSIBCVUPBE-UHFFFAOYSA-N 0.000 claims description 2
BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 claims description 2
OTKLKVYZDAIPKO-UHFFFAOYSA-N 4-(1,3-benzodioxol-5-yl)-3-tridecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=C(OCO2)C2=C1 OTKLKVYZDAIPKO-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
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
150000001204 N-oxides Chemical class 0.000 claims description 2
AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 claims description 2
125000006323 alkenyl amino group Chemical group 0.000 claims description 2
125000005082 alkoxyalkenyl group Chemical group 0.000 claims description 2
125000004947 alkyl aryl amino group Chemical group 0.000 claims description 2
125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 claims description 2
125000006319 alkynyl amino group Chemical group 0.000 claims description 2
125000003368 amide group Chemical group 0.000 claims description 2
125000005021 aminoalkenyl group Chemical group 0.000 claims description 2
125000005014 aminoalkynyl group Chemical group 0.000 claims description 2
125000005001 aminoaryl group Chemical group 0.000 claims description 2
125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 2
125000005214 aminoheteroaryl group Chemical group 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
125000005333 aroyloxy group Chemical group 0.000 claims description 2
125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
125000000732 arylene group Chemical group 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
125000000422 delta-lactone group Chemical group 0.000 claims description 2
125000004986 diarylamino group Chemical group 0.000 claims description 2
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
125000005240 diheteroarylamino group Chemical group 0.000 claims description 2
DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 claims description 2
CUSXLPZVXIVBBD-CJNGLKHVSA-N ethyl (2r,4s)-4-[(2,6-dichloropyridin-4-yl)methyl-methoxycarbonylamino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC(=O)N([C@H]1C[C@@H](C)N(C2=CC(OC)=C(OC)C=C21)C(=O)OCC)CC1=CC(Cl)=NC(Cl)=C1 CUSXLPZVXIVBBD-CJNGLKHVSA-N 0.000 claims description 2
VPZXZXQNQHIMRN-KUHUBIRLSA-N ethyl (2r,4s)-4-[(3,5-dichlorophenyl)methyl-methoxycarbonylamino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC(=O)N([C@H]1C[C@@H](C)N(C2=CC(OC)=C(OC)C=C21)C(=O)OCC)CC1=CC(Cl)=CC(Cl)=C1 VPZXZXQNQHIMRN-KUHUBIRLSA-N 0.000 claims description 2
WQIQOGPRSXTADI-YJYMSZOUSA-N ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-methyl-7-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC(=O)N([C@H]1C[C@@H](C)N(C2=CC(=CC=C21)C(F)(F)F)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WQIQOGPRSXTADI-YJYMSZOUSA-N 0.000 claims description 2
NJNVNQZBKCXDGK-UHFFFAOYSA-N ethyl 4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-methyl-3,4,6,8-tetrahydro-2h-furo[3,4-g]quinoline-1-carboxylate Chemical compound C12=CC=3COCC=3C=C2N(C(=O)OCC)C(C)CC1N(C(=O)OC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NJNVNQZBKCXDGK-UHFFFAOYSA-N 0.000 claims description 2
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 claims description 2
229940074046 glyceryl laurate Drugs 0.000 claims description 2
125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 2
150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
150000002430 hydrocarbons Chemical class 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
229940049964 oleate Drugs 0.000 claims description 2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
229940026235 propylene glycol monolaurate Drugs 0.000 claims description 2
239000001944 prunus armeniaca kernel oil Substances 0.000 claims description 2
ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 2
125000005106 triarylsilyl group Chemical group 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 2
RAUXOEICRZHZRF-BLVKFPJESA-N (2R,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-methyl-3,4,6,8-tetrahydro-2H-thieno[3,4-g]quinoline-1-carboxylic acid Chemical compound FC(C=1C=C(CN([C@H]2C[C@H](N(C=3C=C4C(=CC23)CSC4)C(=O)O)C)C(=O)OC)C=C(C1)C(F)(F)F)(F)F RAUXOEICRZHZRF-BLVKFPJESA-N 0.000 claims 1
PYRFHJUXDGQZPM-UHFFFAOYSA-N 1,2,4-triazole-3-thione Chemical compound S=C1N=CN=N1 PYRFHJUXDGQZPM-UHFFFAOYSA-N 0.000 claims 1
WCHRXPOAPJPGEP-UHFFFAOYSA-N 1-(3-methylbutyl)-n-[2-[[2-[[1-(3-methylbutyl)cyclopentanecarbonyl]amino]phenyl]disulfanyl]phenyl]cyclopentane-1-carboxamide Chemical compound C=1C=CC=C(SSC=2C(=CC=CC=2)NC(=O)C2(CCC(C)C)CCCC2)C=1NC(=O)C1(CCC(C)C)CCCC1 WCHRXPOAPJPGEP-UHFFFAOYSA-N 0.000 claims 1
QQKYOVRCWBXJDW-UHFFFAOYSA-N 2-cyclopentyl-3-[fluoro-[4-(trifluoromethyl)phenyl]methyl]-7,7-dimethyl-4-thiophen-3-yl-6,8-dihydro-5h-quinolin-5-ol Chemical compound C1C(C)(C)CC(O)C(C(=C2C(F)C=3C=CC(=CC=3)C(F)(F)F)C3=CSC=C3)=C1N=C2C1CCCC1 QQKYOVRCWBXJDW-UHFFFAOYSA-N 0.000 claims 1
AQZMNAWNLGAUDN-UHFFFAOYSA-N 2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-[4-(trifluoromethyl)benzoyl]-1,4,6,8-tetrahydroquinolin-5-one Chemical compound C1C(C)(C)CC(=O)C(C(C=2C(=O)C=3C=CC(=CC=3)C(F)(F)F)C=3C=CC(F)=CC=3)=C1NC=2C1CCCC1 AQZMNAWNLGAUDN-UHFFFAOYSA-N 0.000 claims 1
DIDGMJDNRZOGLE-UHFFFAOYSA-N 2-cyclopentyl-4-(4-fluorophenyl)-7,7-dimethyl-3-[4-(trifluoromethyl)benzoyl]-6,8-dihydroquinolin-5-one Chemical compound C1C(C)(C)CC(=O)C(C(=C2C(=O)C=3C=CC(=CC=3)C(F)(F)F)C=3C=CC(F)=CC=3)=C1N=C2C1CCCC1 DIDGMJDNRZOGLE-UHFFFAOYSA-N 0.000 claims 1
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 1
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CXMYSDLCKRTJIM-UHFFFAOYSA-N 3-dodecyl-4-(3-methoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCC1=NNC(=S)N1C1=CC=CC(OC)=C1 CXMYSDLCKRTJIM-UHFFFAOYSA-N 0.000 claims 1
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DDZIFEIGSSYBIV-UHFFFAOYSA-N n-[2-[[2-(2,2-dimethylpropanoylamino)phenyl]disulfanyl]phenyl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC=C1SSC1=CC=CC=C1NC(=O)C(C)(C)C DDZIFEIGSSYBIV-UHFFFAOYSA-N 0.000 description 1
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TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical group CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
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230000003389 potentiating effect Effects 0.000 description 1
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IKKBFQQGQVJFHF-REWPJTCUSA-N propan-2-yl (2s,4s)-4-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-(methoxymethyl)-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound CC(=O)N([C@H]1C[C@H](N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OC(C)C)COC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IKKBFQQGQVJFHF-REWPJTCUSA-N 0.000 description 1
KZPNHUVBHNWBAT-UHFFFAOYSA-N propan-2-yl 2-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(C(F)(F)F)CCC2=C1 KZPNHUVBHNWBAT-UHFFFAOYSA-N 0.000 description 1
RRPVNLZHOJXQAR-UHFFFAOYSA-N propan-2-yl 4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-cyclobutyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1C(C2CCC2)N(C(=O)OC(C)C)C2=CC=C(C(F)(F)F)C=C2C1N(C(=O)OC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RRPVNLZHOJXQAR-UHFFFAOYSA-N 0.000 description 1
FSNBAISAVIPNME-UHFFFAOYSA-N propan-2-yl 6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound FC(F)(F)C1=CC=C2N(C(=O)OC(C)C)CCCC2=C1 FSNBAISAVIPNME-UHFFFAOYSA-N 0.000 description 1
DOGXLVNKKVKOGC-UHFFFAOYSA-N propyl 3,4,6,7,8,9-hexahydro-2H-benzo[g]quinoline-1-carboxylate Chemical compound CCCOC(=O)N1CCCc2cc3CCCCc3cc12 DOGXLVNKKVKOGC-UHFFFAOYSA-N 0.000 description 1
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LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
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IRYKICKCAXOYHW-UHFFFAOYSA-N tert-butyl-[[2-cyclopentyl-4-(4-fluorophenyl)-3-[fluoro-[4-(trifluoromethyl)phenyl]methyl]-7,7-dimethyl-6,8-dihydro-5h-quinolin-5-yl]oxy]-dimethylsilane Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(F)C=1C(C=2C=CC(F)=CC=2)=C2C(O[Si](C)(C)C(C)(C)C)CC(C)(C)CC2=NC=1C1CCCC1 IRYKICKCAXOYHW-UHFFFAOYSA-N 0.000 description 1
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- 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
- 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
- A61K31/255—Esters, e.g. nitroglycerine, selenocyanates of sulfoxy acids or sulfur analogues thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Biophysics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Dispersion Chemistry (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Emergency Medicine (AREA)
Oil, Petroleum & Natural Gas (AREA)
Hematology (AREA)
Obesity (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Cosmetics (AREA)
Emulsifying, Dispersing, Foam-Producing Or Wetting Agents (AREA)
Colloid Chemistry (AREA)
Steroid Compounds (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Quinoline Compounds (AREA)
Pyridine Compounds (AREA)

OA1200300317A 2001-06-21 2002-05-03 Self-emulsifying formulations of cholesteryl estertransfer protein inhibitors. OA12619A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US30002801P	2001-06-21	2001-06-21

Publications (1)

Publication Number	Publication Date
OA12619A true OA12619A (en)	2006-06-12

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ID=23157363

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200300317A OA12619A (en)	2001-06-21	2002-05-03	Self-emulsifying formulations of cholesteryl estertransfer protein inhibitors.

Country Status (33)

Country	Link
US (2)	US6962931B2 (fr)
EP (1)	EP1453544A2 (fr)
JP (1)	JP2005500314A (fr)
KR (1)	KR20040015746A (fr)
CN (1)	CN1635911A (fr)
AP (1)	AP2002002559A0 (fr)
AR (1)	AR034599A1 (fr)
BG (1)	BG108486A (fr)
BR (1)	BR0210505A (fr)
CA (1)	CA2455288A1 (fr)
CR (1)	CR7163A (fr)
CZ (1)	CZ20033341A3 (fr)
EA (1)	EA200301139A1 (fr)
EC (1)	ECSP034875A (fr)
EE (1)	EE200400024A (fr)
GT (1)	GT200200124A (fr)
HN (1)	HN2002000153A (fr)
HU (1)	HUP0400263A2 (fr)
IL (1)	IL158765A0 (fr)
IS (1)	IS7014A (fr)
MA (1)	MA27034A1 (fr)
MX (1)	MXPA04000014A (fr)
NO (1)	NO20035632L (fr)
OA (1)	OA12619A (fr)
PA (1)	PA8548601A1 (fr)
PE (1)	PE20030128A1 (fr)
PL (1)	PL368850A1 (fr)
SK (1)	SK15172003A3 (fr)
SV (1)	SV2003001103A (fr)
TN (1)	TNSN03139A1 (fr)
UY (1)	UY27344A1 (fr)
WO (1)	WO2003000295A2 (fr)
ZA (1)	ZA200308561B (fr)

Families Citing this family (75)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE404172T1 (de) *	1998-12-30	2008-08-15	Dexcel Ltd	Dispergierbares konzentrat zur verabreichung von cyclosporin
US7732404B2 (en) *	1999-12-30	2010-06-08	Dexcel Ltd	Pro-nanodispersion for the delivery of cyclosporin
JP4031232B2 (ja) *	2001-11-09	2008-01-09	カプスゲル・ジャパン株式会社	新規カプセル
MXPA04007438A (es) *	2002-02-01	2004-10-11	Pfizer Prod Inc	Composiciones farmaceuticas de dispersiones amorfas de farmacos y materiales que forman microfases lipofilas.
WO2003074833A2 (fr) *	2002-03-01	2003-09-12	Cesi Chemical, A Flotek Company	Composition et procede pour nettoyer un puits
US20040175341A1 (en) *	2003-03-04	2004-09-09	Manning Monna Marie	Microemulsion for cosmetic or pharmaceutical use containing an active ingredient
ZA200508160B (en) *	2003-03-17	2007-01-31	Japan Tobacco Inc	Method for increasing the oral bioavailability of S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl) 2-methyl-propanethioate
BRPI0408466B8 (pt) *	2003-03-17	2021-05-25	Japan Tobacco Inc	composição farmacêutica e uso de inibidor de proteína de transferência de colesteril éster e crospovidona
AU2004222436A1 (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
JP2007501218A (ja) *	2003-08-04	2007-01-25	ファイザー・プロダクツ・インク	非晶質薬物の吸着物および親油性ミクロ相形成物質の医薬組成物
WO2005033082A2 (fr) *	2003-09-30	2005-04-14	Pfizer Products Inc.	Inhibiteurs de la proteine de transfert d'ester de cholesteryle (cetp) et leurs metabolites
PL1670768T3 (pl) *	2003-10-08	2010-01-29	Lilly Co Eli	Związki i sposoby leczenia dyslipidemii
US20050220866A1 (en) *	2004-04-02	2005-10-06	Dr. Reddy's Laboratories Limited	Novel capsule formulations of etoposide for oral use
WO2006069162A1 (fr)	2004-12-20	2006-06-29	Reddy Us Therapeutics, Inc.	Nouveaux composes heterocycliques et leurs compositions pharmaceutiques
US8604055B2 (en)	2004-12-31	2013-12-10	Dr. Reddy's Laboratories Ltd.	Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors
JP5096927B2 (ja)	2004-12-31	2012-12-12	レディユーエスセラピューティックス，インコーポレイテッド	Ｃｅｔｐインヒビターとしての新規ベンジルアミン誘導体
WO2006085217A2 (fr) *	2005-02-08	2006-08-17	Pfizer Products Inc.	Adsorbes solides de medicaments hydrophobes
US7623458B2 (en) *	2005-09-30	2009-11-24	The Boeing Company	System and method for providing integrated services across cryptographic boundaries in a network
WO2007067593A2 (fr) *	2005-12-05	2007-06-14	Merck & Co., Inc.	Formulations d'inhibiteur de cetp
WO2007076699A1 (fr) *	2005-12-31	2007-07-12	Tianjin Tasly Pharmaceutical Co. Ltd., China	Composition pharmaceutique contenant un extrait de chenopodium ambrosioides et son procédé de préparation et son application
US20080026050A1 (en) *	2006-06-30	2008-01-31	Rajan Gupta	Solid dose formulations of a thrombin receptor antagonist
EP1961412A1 (fr) *	2006-12-27	2008-08-27	LEK Pharmaceuticals D.D.	Systèmes auto-microémulsifiants pour l'administration de médicaments
US9222013B1 (en)	2008-11-13	2015-12-29	Cesi Chemical, Inc.	Water-in-oil microemulsions for oilfield applications
EP2373344B1 (fr) *	2008-12-08	2016-03-30	F. Hoffmann-La Roche AG	Administration conjointe
US20100273730A1 (en) *	2009-04-27	2010-10-28	Innopharmax, Inc.	Self-emulsifying pharmaceutical compositions of hydrophilic drugs and preparation thereof
SMT202000093T1 (it)	2009-06-16	2020-03-13	Pfizer	Forme di dosaggio di apixaban
SG195015A1 (en) *	2011-05-20	2013-12-30	Aventis Pharma Inc	Pharmaceutical composition comprising fexofenadine
JP5964965B2 (ja)	2011-08-18	2016-08-03	ドクターレディズラボラトリーズリミテッド	コレステリルエステル転送タンパク質（ｃｅｔｐ）インヒビターとしての置換複素環式アミン化合物
HK1197238A1 (en)	2011-09-27	2015-01-09	雷迪博士实验室有限公司	5 - benzylaminomethyl - 6 - aminopyrazolo [3, 4 -b] pyridine derivatives as cholesteryl ester -transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis
US10874635B2 (en)	2011-10-21	2020-12-29	First Tech International Limited	Tocotrienol compositions
EP2838970B1 (fr)	2012-04-15	2016-12-28	Flotek Chemistry, LLC	Formulations de tensio-actif pour injection de mousse
US9200192B2 (en)	2012-05-08	2015-12-01	Cesi Chemical, Inc.	Compositions and methods for enhancement of production of liquid and gaseous hydrocarbons
US11407930B2 (en)	2012-05-08	2022-08-09	Flotek Chemistry, Llc	Compositions and methods for enhancement of production of liquid and gaseous hydrocarbons
US20160000799A1 (en) *	2013-02-21	2016-01-07	Dr. Reddy's Laboratories Ltd.	Pharmaceutical compositions of cetp inhibitors
US9068108B2 (en)	2013-03-14	2015-06-30	Cesi Chemical, Inc.	Methods and compositions for stimulating the production of hydrocarbons from subterranean formations
US11254856B2 (en)	2013-03-14	2022-02-22	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US9868893B2 (en)	2013-03-14	2018-01-16	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US10941106B2 (en)	2013-03-14	2021-03-09	Flotek Chemistry, Llc	Methods and compositions incorporating alkyl polyglycoside surfactant for use in oil and/or gas wells
US10287483B2 (en)	2013-03-14	2019-05-14	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells comprising a terpene alcohol
US9428683B2 (en)	2013-03-14	2016-08-30	Flotek Chemistry, Llc	Methods and compositions for stimulating the production of hydrocarbons from subterranean formations
US10053619B2 (en)	2013-03-14	2018-08-21	Flotek Chemistry, Llc	Siloxane surfactant additives for oil and gas applications
US9464223B2 (en)	2013-03-14	2016-10-11	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US10000693B2 (en)	2013-03-14	2018-06-19	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US10421707B2 (en)	2013-03-14	2019-09-24	Flotek Chemistry, Llc	Methods and compositions incorporating alkyl polyglycoside surfactant for use in oil and/or gas wells
US10717919B2 (en)	2013-03-14	2020-07-21	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US10590332B2 (en)	2013-03-14	2020-03-17	Flotek Chemistry, Llc	Siloxane surfactant additives for oil and gas applications
US10577531B2 (en)	2013-03-14	2020-03-03	Flotek Chemistry, Llc	Polymers and emulsions for use in oil and/or gas wells
US11180690B2 (en)	2013-03-14	2021-11-23	Flotek Chemistry, Llc	Diluted microemulsions with low surface tensions
US9884988B2 (en)	2013-03-14	2018-02-06	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
US9321955B2 (en)	2013-06-14	2016-04-26	Flotek Chemistry, Llc	Methods and compositions for stimulating the production of hydrocarbons from subterranean formations
CN104706586A (zh) *	2013-12-16	2015-06-17	天津迈迪瑞康生物医药科技有限公司	一种丁酸氯维地平脂肪乳浓缩液、其制备方法及用途
CN104706689A (zh) *	2013-12-16	2015-06-17	天津迈迪瑞康生物医药科技有限公司	一种鸦胆子油脂肪乳浓缩液、其制备方法及用途
CN104706587A (zh) *	2013-12-16	2015-06-17	天津迈迪瑞康生物医药科技有限公司	一种依托咪酯脂肪乳浓缩液、其制备方法及用途
US9890625B2 (en)	2014-02-28	2018-02-13	Eclipse Ior Services, Llc	Systems and methods for the treatment of oil and/or gas wells with an obstruction material
US9890624B2 (en)	2014-02-28	2018-02-13	Eclipse Ior Services, Llc	Systems and methods for the treatment of oil and/or gas wells with a polymeric material
US9505970B2 (en)	2014-05-14	2016-11-29	Flotek Chemistry, Llc	Methods and compositions for use in oil and/or gas wells
CA3042567C (fr)	2014-07-28	2021-12-14	Flotek Chemistry, Llc	Methodes et compositions associees aux couches gelifiees dans les puits de petrole ou de gaz
US11331376B2 (en) *	2014-11-04	2022-05-17	Innopharmax, Inc.	Oral administration of unstable or poorly-absorbed drugs
CN104546710A (zh) *	2014-12-20	2015-04-29	长沙佰顺生物科技有限公司	一种安塞曲匹纳米乳及其制备方法
CN104490775A (zh) *	2014-12-20	2015-04-08	长沙佰顺生物科技有限公司	一种安塞曲匹脂肪乳及其制备方法
KR101590072B1 (ko) *	2014-12-23	2016-01-29	한미약품 주식회사	두타스테라이드를 포함하는 자가유화 약물전달 시스템용 조성물
CN117547528A (zh)	2015-05-28	2024-02-13	瑞迪博士实验室有限公司	用于治疗疼痛的塞来昔布口服组合物
KR20180129943A (ko)	2016-04-15	2018-12-05	노비라 테라퓨틱스, 인코포레이티드	캡시드 조립 억제제를 포함하는 배합물 및 방법
US10934472B2 (en)	2017-08-18	2021-03-02	Flotek Chemistry, Llc	Compositions comprising non-halogenated solvents for use in oil and/or gas wells and related methods
US11053433B2 (en)	2017-12-01	2021-07-06	Flotek Chemistry, Llc	Methods and compositions for stimulating the production of hydrocarbons from subterranean formations
CA3092238A1 (fr)	2018-03-14	2019-09-19	KaNDy Therapeutics Limited	Nouvelle formulation pharmaceutique comprenant des antagonistes doubles des recepteurs nk-1/nk-3
EP3765011A1 (fr)	2018-03-14	2021-01-20	Janssen Sciences Ireland Unlimited Company	Schéma posologique de modulateur d'assemblage de capside
BR112021009967A2 (pt) *	2018-11-26	2021-08-17	Hepion Pharmaceuticals, Inc.	formulações farmacêuticas de análogos de ciclosporina
KR20210151185A (ko)	2019-04-11	2021-12-13	알.피.쉐러 테크놀러지즈 엘엘씨	난투과성 단백질, 펩타이드 및 소분자의 경구 전달을 위한 제형
CN110252395B (zh) *	2019-07-01	2020-10-16	湖北远大生命科学与技术有限责任公司	一种用于制备高纯度牛磺酸的催化剂及其应用
US11104843B2 (en)	2019-10-10	2021-08-31	Flotek Chemistry, Llc	Well treatment compositions and methods comprising certain microemulsions and certain clay control additives exhibiting synergistic effect of enhancing clay swelling protection and persistency
FR3110852B1 (fr)	2020-05-27	2024-03-15	Centre Nat Rech Scient	Emulsions pour liberation controlee de medicaments
US11512243B2 (en)	2020-10-23	2022-11-29	Flotek Chemistry, Llc	Microemulsions comprising an alkyl propoxylated sulfate surfactant, and related methods
WO2022144590A1 (fr)	2020-12-28	2022-07-07	Dr. Reddy's Laboratories Ltd.	Célécoxib pour le traitement de la douleur

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2907460A1 (de) *	1978-03-07	1979-09-13	Sandoz Ag	Neue resorbierbare galenische kompositionen
GB9208712D0 (en)	1992-04-22	1992-06-10	Sandoz Ltd	Pharmaceutical compositions containing cyclosporin derivates
WO1995031979A1 (fr)	1994-05-19	1995-11-30	R.P. Scherer International Corporation	Solutions d'acides alcanoiques a substitution aryle ou heteroaryle dans des solvants lipophiles, et capsules de gelatine molle contenant de telles solutions
AU692255B2 (en) *	1995-04-24	1998-06-04	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Self-emulsifiable formulation producing an oil-in-water emulsion
GB9608719D0 (en)	1996-04-26	1996-07-03	Scherer Ltd R P	Pharmaceutical compositions
US5993858A (en) *	1996-06-14	1999-11-30	Port Systems L.L.C.	Method and formulation for increasing the bioavailability of poorly water-soluble drugs
EP0869810B1 (fr)	1996-06-19	2004-10-06	Novartis AG	Preparations de gelules molles contenant de la cyclosporine
US5958876A (en) *	1996-06-19	1999-09-28	Novartis Ag	Cyclosporin-containing pharmaceutical compositions
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
AU9297798A (en) *	1997-09-16	1999-04-05	G.D. Searle & Co.	Substituted 1,2,4-triazoles useful for inhibiting cholesteryl ester transfer protein activity
DE19741399A1 (de) *	1997-09-19	1999-03-25	Bayer Ag	Tetrahydrochinoline
US6063762A (en)	1997-12-05	2000-05-16	Chong Kun Dang Corp.	Cyclosporin-containing microemulsion preconcentrate composition
US6605624B1 (en) *	1998-02-13	2003-08-12	Pharmacia Corporation	Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity
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
US6147089A (en) *	1998-09-17	2000-11-14	Pfizer Inc.	Annulated 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines
JP2002525350A (ja) *	1998-09-25	2002-08-13	モンサントカンパニー	コレステロールエステル輸送タンパク質活性阻害に有効な置換されたｎ−脂肪族−ｎ−芳香族第三級ヘテロアルキルアミン
ATE404172T1 (de)	1998-12-30	2008-08-15	Dexcel Ltd	Dispergierbares konzentrat zur verabreichung von cyclosporin
CO5271716A1 (es) *	1999-11-30	2003-04-30	Pfizer Prod Inc	Cristales de 4- carboxamino 1,2,3,4-tetrahidroquinolina 2- sustituida
US6482862B1 (en) *	1999-12-20	2002-11-19	G.D. Searle & Co.	Method of using substituted N-benzyl-N-phenyl aminoalcohols for inhibiting cholesteryl ester transfer protein activity
US7115279B2 (en) *	2000-08-03	2006-10-03	Curatolo William J	Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors
EP1269994A3 (fr) *	2001-06-22	2003-02-12	Pfizer Products Inc.	Compositions Pharmaceutiques comprenant un médicament et un polymère permettant d'améliorer la concentration du médicament
BR0210520A (pt) *	2001-06-22	2004-06-22	Pfizer Prod Inc	Composições farmacêuticas de dispersões de fármacos amorfos misturados com polìmeros
AU2002309172A1 (en) *	2001-06-22	2003-01-08	Pfizer Products Inc.	Pharmaceutical compositions containing polymer and drug assemblies
PT1404300E (pt) *	2001-06-22	2009-11-09	Bend Res Inc	Composições farmacêuticas de dispersões de fármacos e polímeros neutros
RU2004123621A (ru) *	2002-02-01	2005-04-10	Пфайзер Продактс Инк. (Us)	Лекарственные формы с немедленным высвобождением, содержащие твердые дисперсии лекарств
MXPA04007438A (es) *	2002-02-01	2004-10-11	Pfizer Prod Inc	Composiciones farmaceuticas de dispersiones amorfas de farmacos y materiales que forman microfases lipofilas.
US20040132771A1 (en) *	2002-12-20	2004-07-08	Pfizer Inc	Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors
WO2004056359A1 (fr) *	2002-12-20	2004-07-08	Pfizer Products Inc.	Formes posologiques comprenant un inhibiteur de la cetp et un inhibiteur de la hmg-coa reductase

2002
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- 2002-05-03 EP EP02732994A patent/EP1453544A2/fr not_active Withdrawn
- 2002-05-03 CA CA002455288A patent/CA2455288A1/fr not_active Abandoned
- 2002-05-03 PL PL02368850A patent/PL368850A1/xx not_active Application Discontinuation
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- 2002-05-03 WO PCT/IB2002/001571 patent/WO2003000295A2/fr not_active Ceased
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- 2002-05-03 KR KR10-2003-7016651A patent/KR20040015746A/ko not_active Ceased
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- 2002-05-03 OA OA1200300317A patent/OA12619A/en unknown
- 2002-05-03 TN TNPCT/IB2002/001571A patent/TNSN03139A1/fr unknown
- 2002-05-03 SK SK1517-2003A patent/SK15172003A3/sk not_active Application Discontinuation
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- 2003-12-17 NO NO20035632A patent/NO20035632L/no not_active Application Discontinuation
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Also Published As

Publication number	Publication date
EE200400024A (et)	2004-06-15
PA8548601A1 (es)	2003-09-05
IL158765A0 (en)	2004-05-12
SK15172003A3 (en)	2004-11-03
CR7163A (es)	2004-02-23
MXPA04000014A (es)	2004-05-21
EA200301139A1 (ru)	2004-12-30
US6962931B2 (en)	2005-11-08
HUP0400263A2 (hu)	2005-03-29
UY27344A1 (es)	2003-01-31
CN1635911A (zh)	2005-07-06
BR0210505A (pt)	2004-05-18
NO20035632D0 (no)	2003-12-17
EP1453544A2 (fr)	2004-09-08
WO2003000295A2 (fr)	2003-01-03
ZA200308561B (en)	2004-11-17
WO2003000295A3 (fr)	2004-05-27
PE20030128A1 (es)	2003-02-28
SV2003001103A (es)	2003-03-18
CZ20033341A3 (cs)	2004-10-13
US20060014788A1 (en)	2006-01-19
NO20035632L (no)	2004-02-18
JP2005500314A (ja)	2005-01-06
AR034599A1 (es)	2004-03-03
HN2002000153A (es)	2002-11-05
ECSP034875A (es)	2004-01-28
KR20040015746A (ko)	2004-02-19
US20030022944A1 (en)	2003-01-30
TNSN03139A1 (fr)	2005-12-23
MA27034A1 (fr)	2004-12-20
PL368850A1 (en)	2005-04-04
IS7014A (is)	2003-10-31
GT200200124A (es)	2003-09-22
AP2002002559A0 (en)	2002-06-30
BG108486A (bg)	2005-03-31
CA2455288A1 (fr)	2003-01-03

Publication	Publication Date	Title
OA12619A (en)	2006-06-12	Self-emulsifying formulations of cholesteryl estertransfer protein inhibitors.
US20050038007A1 (en)	2005-02-17	Dosage forms of cholesteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors
EP2305217B1 (fr)	2014-07-30	Prodedé de fabrication de compositions pharmaceutiques comprenant une dispersion amorphe solide des inhibiteurs de la proteine de transfert des esters de cholesterol
EP1581210B1 (fr)	2008-03-19	Formes posologiques comprenant un inhibiteur de la cetp et un inhibiteur de la hmg-coa reductase
US8389011B2 (en)	2013-03-05	Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors
US20040185102A1 (en)	2004-09-23	Dosage forms comprising a CETP inhibitor and an HMG-CoA reductase inhibitor
US20070104780A1 (en)	2007-05-10	Formulation comprising a drug of low water solubility and method of use thereof
JP6445591B2 (ja)	2018-12-26	シロリムス及びその誘導体の複合体、それらの調製方法ならびにそれらを含有する医薬組成物
EP1269994A2 (fr)	2003-01-02	Compositions Pharmaceutiques comprenant un médicament et un polymère permettant d'améliorer la concentration du médicament
WO2004056396A1 (fr)	2004-07-08	Formes posologiques d'inhibiteurs de la proteine de transfert du cholesterol esterifie et d'inhibiteurs de la hmg-coa reductase presentant une efficacite amelioree
EP1330244B1 (fr)	2008-12-17	Compositions comprenant des composes de modafinil
NZ584544A (en)	2012-04-27	Novel taxane compositions comprising lecithin and an anionic surfactant
CA2425338C (fr)	2010-04-20	Compositions comprenant des composes de modafinil
AU2002304366A1 (en)	2003-01-08	Self-emulsifying formulations of cholesteryl ester transfer protein inhibitors
RU2343915C2 (ru)	2009-01-20	Полутвердые системы, содержащие производные азетидина
KR100580577B1 (ko)	2006-05-16	자가 미세 유화형 약물 전달 시스템을 이용하는 소염 진통활성을 갖는 약제 조성물
KR101519887B1 (ko)	2015-05-14	고지혈증치료제 및 오메가-3 지방산을 함유하는 복합제제
HK1070840A1 (zh)	2005-06-30	含有氮雜環丁烷衍生物的藥物組合物