ZA200300869B - Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors. - Google Patents
Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors. Download PDFInfo
- Publication number
- ZA200300869B ZA200300869B ZA200300869A ZA200300869A ZA200300869B ZA 200300869 B ZA200300869 B ZA 200300869B ZA 200300869 A ZA200300869 A ZA 200300869A ZA 200300869 A ZA200300869 A ZA 200300869A ZA 200300869 B ZA200300869 B ZA 200300869B
- Authority
- ZA
- South Africa
- Prior art keywords
- substituted
- optionally
- trifluoromethyl
- chain
- alkyl
- Prior art date
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- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title claims description 175
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 208
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 175
- 125000000217 alkyl group Chemical group 0.000 claims description 144
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 129
- 229920006395 saturated elastomer Polymers 0.000 claims description 120
- 239000000203 mixture Substances 0.000 claims description 119
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 110
- 125000004043 oxo group Chemical group O=* 0.000 claims description 108
- 229910052717 sulfur Inorganic materials 0.000 claims description 107
- 229910052757 nitrogen Inorganic materials 0.000 claims description 99
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 89
- 239000011593 sulfur Substances 0.000 claims description 89
- 125000003545 alkoxy group Chemical group 0.000 claims description 88
- -1 cholesteryl ester Chemical class 0.000 claims description 78
- 125000005843 halogen group Chemical group 0.000 claims description 75
- 125000005842 heteroatom Chemical group 0.000 claims description 73
- 229910052760 oxygen Inorganic materials 0.000 claims description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- 239000001257 hydrogen Substances 0.000 claims description 72
- 239000001301 oxygen Substances 0.000 claims description 72
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 69
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 66
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 56
- 150000002431 hydrogen Chemical class 0.000 claims description 55
- 229920000642 polymer Polymers 0.000 claims description 55
- 125000003342 alkenyl group Chemical group 0.000 claims description 52
- 125000004414 alkyl thio group Chemical group 0.000 claims description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 51
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
- 125000003282 alkyl amino group Chemical group 0.000 claims description 43
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 43
- 239000003814 drug Substances 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 239000006185 dispersion Substances 0.000 claims description 33
- 125000001153 fluoro group Chemical group F* 0.000 claims description 27
- 235000019000 fluorine Nutrition 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000002619 bicyclic group Chemical group 0.000 claims description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
- 230000002209 hydrophobic effect Effects 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 15
- 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
- 238000001727 in vivo Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 239000007787 solid Substances 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 238000000338 in vitro Methods 0.000 claims description 7
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 6
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 208000037487 Endotoxemia Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 206010021024 Hypolipidaemia Diseases 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 3
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 3
- 208000029498 hypoalphalipoproteinemia Diseases 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 208000031225 myocardial ischemia Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 238000012546 transfer Methods 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims description 2
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims description 2
- 229940121649 protein inhibitor Drugs 0.000 claims description 2
- 239000012268 protein inhibitor Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 143
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 100
- 125000003118 aryl group Chemical group 0.000 claims 65
- 229910052736 halogen Inorganic materials 0.000 claims 56
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 48
- 125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 claims 48
- 150000002367 halogens Chemical class 0.000 claims 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims 44
- 125000000623 heterocyclic group Chemical group 0.000 claims 44
- 125000001072 heteroaryl group Chemical group 0.000 claims 32
- 125000000876 trifluoromethoxy group Chemical class FC(F)(F)O* 0.000 claims 32
- 125000000304 alkynyl group Chemical group 0.000 claims 30
- 150000003254 radicals Chemical class 0.000 claims 29
- 125000002252 acyl group Chemical group 0.000 claims 21
- 125000002947 alkylene group Chemical group 0.000 claims 16
- 125000004434 sulfur atom Chemical group 0.000 claims 10
- 125000004104 aryloxy group Chemical group 0.000 claims 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 9
- 125000001188 haloalkyl group Chemical group 0.000 claims 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 8
- 125000000262 haloalkenyl group Chemical group 0.000 claims 8
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 7
- 125000002837 carbocyclic group Chemical group 0.000 claims 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 6
- 125000000232 haloalkynyl group Chemical group 0.000 claims 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 5
- 125000005108 alkenylthio group Chemical group 0.000 claims 5
- 125000005109 alkynylthio group Chemical group 0.000 claims 5
- 125000005110 aryl thio group Chemical group 0.000 claims 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 5
- 125000004468 heterocyclylthio group Chemical group 0.000 claims 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 4
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 4
- 125000003106 haloaryl group Chemical group 0.000 claims 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 4
- 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 4
- 125000001544 thienyl group Chemical class 0.000 claims 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims 3
- 125000004450 alkenylene group Chemical group 0.000 claims 3
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 3
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 3
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 3
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims 3
- 125000000051 benzyloxy group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 3
- 150000001721 carbon Chemical group 0.000 claims 3
- 229920002301 cellulose acetate Polymers 0.000 claims 3
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 claims 3
- 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 3
- GZVVNAWGGPWOOK-UHFFFAOYSA-N ethyl 2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OCC)CC=CC2=C1 GZVVNAWGGPWOOK-UHFFFAOYSA-N 0.000 claims 3
- 125000005368 heteroarylthio group Chemical group 0.000 claims 3
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 150000002825 nitriles Chemical class 0.000 claims 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 3
- 125000005254 oxyacyl group Chemical group 0.000 claims 3
- 125000005353 silylalkyl group Chemical group 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 2
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 2
- 241001061127 Thione Species 0.000 claims 2
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 2
- 125000005216 haloheteroaryl group Chemical group 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group 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 claims 2
- 229920000609 methyl cellulose Polymers 0.000 claims 2
- 239000001923 methylcellulose Substances 0.000 claims 2
- 235000010981 methylcellulose Nutrition 0.000 claims 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- KOODSCBKXPPKHE-UHFFFAOYSA-N propanethioic s-acid Chemical compound CCC(S)=O KOODSCBKXPPKHE-UHFFFAOYSA-N 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 125000003003 spiro group Chemical group 0.000 claims 2
- 125000005389 trialkylsiloxy group Chemical group 0.000 claims 2
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims 2
- 229920002554 vinyl polymer Polymers 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- ANRGGUOSHLLQRY-UHFFFAOYSA-N 1-[2,4-bis(4-fluorophenyl)-5-[fluoro-[4-(trifluoromethyl)phenyl]methyl]-6-propan-2-ylpyridin-3-yl]ethanol Chemical compound CC(O)C=1C(C=2C=CC(F)=CC=2)=C(C(F)C=2C=CC(=CC=2)C(F)(F)F)C(C(C)C)=NC=1C1=CC=C(F)C=C1 ANRGGUOSHLLQRY-UHFFFAOYSA-N 0.000 claims 1
- KNLQKAHSRLBMAF-UHFFFAOYSA-N 2,2,2-trifluoroethyl 4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C1C(C)N(C(=O)OCC(F)(F)F)C2=CC(OC)=C(OC)C=C2C1N(C(=O)OC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KNLQKAHSRLBMAF-UHFFFAOYSA-N 0.000 claims 1
- DMNKXKHLUXAYPK-UHFFFAOYSA-N 2,2-dimethylpropanamide Chemical compound [CH2]C(C)(C)C(N)=O DMNKXKHLUXAYPK-UHFFFAOYSA-N 0.000 claims 1
- ICRAPXISGUIWEQ-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-pentadecyl-1h-1,2,4-triazole-3-thione Chemical compound S=C1NC(CCCCCCCCCCCCCCC)=NN1C1=CC=C(OC)C=C1 ICRAPXISGUIWEQ-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
- CISJAEWNKCDPLC-UHFFFAOYSA-N 2-hydroxyethyl 4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound C12=CC(C(F)(F)F)=CC=C2N(C(=O)OCCO)C(CC)CC1N(C(=O)OC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CISJAEWNKCDPLC-UHFFFAOYSA-N 0.000 claims 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
- SHNMAZJVVFUXAQ-UHFFFAOYSA-N 2h-quinoline-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CC=CC2=C1 SHNMAZJVVFUXAQ-UHFFFAOYSA-N 0.000 claims 1
- 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
- LXFBGDVYRAOFPG-UHFFFAOYSA-N 3-tridecyl-4-[3-(trifluoromethyl)phenyl]-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=CC(C(F)(F)F)=C1 LXFBGDVYRAOFPG-UHFFFAOYSA-N 0.000 claims 1
- UNQVXTZCFDXMRU-UHFFFAOYSA-N 4-(3-chloro-4-methylphenyl)-3-tridecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=C(C)C(Cl)=C1 UNQVXTZCFDXMRU-UHFFFAOYSA-N 0.000 claims 1
- RUZXGADUEMYARJ-UHFFFAOYSA-N 4-(3-methoxyphenyl)-3-tetradecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=CC(OC)=C1 RUZXGADUEMYARJ-UHFFFAOYSA-N 0.000 claims 1
- YULMFDKUAMUBHP-UHFFFAOYSA-N 4-(3-methoxyphenyl)-3-tridecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=CC(OC)=C1 YULMFDKUAMUBHP-UHFFFAOYSA-N 0.000 claims 1
- ARYGZDOADGGOPU-UHFFFAOYSA-N 4-(3-methoxyphenyl)-3-undecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCC1=NNC(=S)N1C1=CC=CC(OC)=C1 ARYGZDOADGGOPU-UHFFFAOYSA-N 0.000 claims 1
- ZECLWJRIUPEVJU-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-tridecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=C(OC)C=C1 ZECLWJRIUPEVJU-UHFFFAOYSA-N 0.000 claims 1
- UUHUXSPURVSFIS-UHFFFAOYSA-N 4-(4-phenoxyphenyl)-3-tridecyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C(C=C1)=CC=C1OC1=CC=CC=C1 UUHUXSPURVSFIS-UHFFFAOYSA-N 0.000 claims 1
- TZBZFBNAKUDGIX-UHFFFAOYSA-N 4-(5-sulfanylidene-3-tridecyl-1h-1,2,4-triazol-4-yl)benzenesulfonamide Chemical compound CCCCCCCCCCCCCC1=NNC(=S)N1C1=CC=C(S(N)(=O)=O)C=C1 TZBZFBNAKUDGIX-UHFFFAOYSA-N 0.000 claims 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- 101150006573 PAN1 gene Proteins 0.000 claims 1
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims 1
- ZNPLZHBZUSCANM-UHFFFAOYSA-N acetic acid;benzene-1,3-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC(C(O)=O)=C1 ZNPLZHBZUSCANM-UHFFFAOYSA-N 0.000 claims 1
- FMTQGBMMIVVKSN-UHFFFAOYSA-N acetic acid;terephthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=C(C(O)=O)C=C1 FMTQGBMMIVVKSN-UHFFFAOYSA-N 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 claims 1
- 125000006323 alkenyl amino group Chemical group 0.000 claims 1
- 125000005082 alkoxyalkenyl group Chemical group 0.000 claims 1
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 claims 1
- 125000005157 alkyl carboxy group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims 1
- 125000006319 alkynyl amino group Chemical group 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000005021 aminoalkenyl group Chemical group 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 125000005014 aminoalkynyl group Chemical group 0.000 claims 1
- 125000005001 aminoaryl group Chemical group 0.000 claims 1
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims 1
- 125000005214 aminoheteroaryl group Chemical group 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 125000005333 aroyloxy group Chemical group 0.000 claims 1
- 125000001769 aryl amino group Chemical group 0.000 claims 1
- 125000005129 aryl carbonyl group Chemical group 0.000 claims 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims 1
- 125000000732 arylene group Chemical group 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 150000007942 carboxylates Chemical class 0.000 claims 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004966 cyanoalkyl group Chemical group 0.000 claims 1
- 125000005366 cycloalkylthio group Chemical group 0.000 claims 1
- RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000004986 diarylamino group Chemical group 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 125000005240 diheteroarylamino group Chemical group 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 claims 1
- QCLAORQMXJANRH-KUHUBIRLSA-N ethyl (2r,4s)-4-[(3,5-dinitrophenyl)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([N+]([O-])=O)=CC([N+]([O-])=O)=C1 QCLAORQMXJANRH-KUHUBIRLSA-N 0.000 claims 1
- GDFGJOCKHLVYEP-IERDGZPVSA-N ethyl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2,6,7-trimethyl-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC(=O)N([C@H]1C[C@@H](C)N(C2=CC(C)=C(C)C=C21)C(=O)OCC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GDFGJOCKHLVYEP-IERDGZPVSA-N 0.000 claims 1
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Classifications
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- 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
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- 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
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| WO2003063822A2 (en) | 2002-02-01 | 2003-08-07 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions utilizing modified spray-drying apparatus |
| AR038375A1 (es) * | 2002-02-01 | 2005-01-12 | Pfizer Prod Inc | Composiciones farmaceuticas de inhibidores de la proteina de transferencia de esteres de colesterilo |
| WO2004056359A1 (en) * | 2002-12-20 | 2004-07-08 | Pfizer Products Inc. | Dosage forms comprising a cetp inhibitor and an hmg-coa reductase inhibitor |
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2001
- 2001-07-30 US US09/918,127 patent/US7115279B2/en not_active Expired - Fee Related
- 2001-07-31 DE DE60144332T patent/DE60144332D1/de not_active Expired - Lifetime
- 2001-07-31 WO PCT/IB2001/001391 patent/WO2002011710A2/en active IP Right Grant
- 2001-07-31 CN CN01815834A patent/CN1458840A/zh active Pending
- 2001-07-31 SK SK103-2003A patent/SK1032003A3/sk not_active Application Discontinuation
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- 2001-07-31 EP EP20100180614 patent/EP2258352B1/de not_active Expired - Lifetime
- 2001-07-31 HU HU0300676A patent/HUP0300676A2/hu unknown
- 2001-07-31 CA CA002417755A patent/CA2417755A1/en not_active Abandoned
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- 2001-07-31 OA OA1200300022A patent/OA12350A/en unknown
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- 2001-07-31 AT AT01984472T patent/ATE503462T1/de not_active IP Right Cessation
- 2001-08-01 DO DO2001P000224A patent/DOP2001000224A/es unknown
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- 2001-08-02 AP APAP/P/2001/002235A patent/AP2001002235A0/en unknown
- 2001-08-02 TN TNTNSN01119A patent/TNSN01119A1/fr unknown
- 2001-08-03 PA PA20018523901A patent/PA8523901A1/es unknown
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2003
- 2003-01-13 BG BG107456A patent/BG107456A/bg unknown
- 2003-01-16 CR CR6883A patent/CR6883A/es not_active Application Discontinuation
- 2003-01-16 IS IS6688A patent/IS6688A/is unknown
- 2003-01-23 MA MA27010A patent/MA26935A1/fr unknown
- 2003-01-31 NO NO20030506A patent/NO20030506D0/no not_active Application Discontinuation
- 2003-01-31 ZA ZA200300869A patent/ZA200300869B/en unknown
- 2003-02-03 EC EC2003004462A patent/ECSP034462A/es unknown
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2006
- 2006-06-02 US US11/421,888 patent/US8048452B2/en not_active Expired - Fee Related
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2007
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2012
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