OA12625A - Pharmaceutical compositions of adsorbates of amorphous drug. - Google Patents
Pharmaceutical compositions of adsorbates of amorphous drug. Download PDFInfo
- Publication number
- OA12625A OA12625A OA1200300326A OA1200300326A OA12625A OA 12625 A OA12625 A OA 12625A OA 1200300326 A OA1200300326 A OA 1200300326A OA 1200300326 A OA1200300326 A OA 1200300326A OA 12625 A OA12625 A OA 12625A
- Authority
- OA
- OAPI
- Prior art keywords
- phenyl
- alkyl
- amino
- trifluoromethyl
- trifluoro
- Prior art date
Links
- 229940079593 drug Drugs 0.000 title claims abstract description 333
- 239000003814 drug Substances 0.000 title claims abstract description 333
- 239000002156 adsorbate Substances 0.000 title claims abstract description 114
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
- 239000000758 substrate Substances 0.000 claims abstract description 148
- 229920000642 polymer Polymers 0.000 claims abstract description 116
- 239000000203 mixture Substances 0.000 claims abstract description 110
- -1 polypropylene Polymers 0.000 claims description 237
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 135
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 124
- 239000002904 solvent Substances 0.000 claims description 90
- 238000000034 method Methods 0.000 claims description 82
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 claims description 51
- 229940081735 acetylcellulose Drugs 0.000 claims description 25
- 229920002301 cellulose acetate Polymers 0.000 claims description 25
- 239000007787 solid Substances 0.000 claims description 20
- 239000006185 dispersion Substances 0.000 claims description 18
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 claims description 17
- 238000004090 dissolution Methods 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 16
- 206010053317 Hydrophobia Diseases 0.000 claims description 15
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 15
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 15
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 15
- 239000003112 inhibitor Substances 0.000 claims description 15
- 239000000725 suspension Substances 0.000 claims description 15
- 238000001704 evaporation Methods 0.000 claims description 13
- 239000001913 cellulose Substances 0.000 claims description 10
- 235000010980 cellulose Nutrition 0.000 claims description 10
- 229920002678 cellulose Polymers 0.000 claims description 10
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 10
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 10
- 229920002554 vinyl polymer Polymers 0.000 claims description 10
- 238000002844 melting Methods 0.000 claims description 9
- 230000008018 melting Effects 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims description 8
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 8
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 8
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 8
- 229920000609 methyl cellulose Polymers 0.000 claims description 8
- 235000010981 methylcellulose Nutrition 0.000 claims description 8
- 239000001923 methylcellulose Substances 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims description 7
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 7
- 229920001577 copolymer Polymers 0.000 claims description 7
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 claims description 6
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 claims description 6
- 239000004698 Polyethylene Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 229920000573 polyethylene Polymers 0.000 claims description 6
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- 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 description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
- 229920006218 cellulose propionate Polymers 0.000 claims description 4
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- 229920000058 polyacrylate Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 4
- 125000005591 trimellitate group Chemical group 0.000 claims description 4
- 229920006163 vinyl copolymer Polymers 0.000 claims description 4
- JMMYFHCNNAAPNT-XLIONFOSSA-N (2r,4s)-4-[acetyl-[[3,5-bis(trifluoromethyl)phenyl]methyl]amino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylic acid Chemical compound CC(=O)N([C@H]1C[C@H](N(C2=CC=C(C=C21)C(F)(F)F)C(O)=O)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JMMYFHCNNAAPNT-XLIONFOSSA-N 0.000 claims description 3
- CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 claims description 3
- FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 claims description 3
- DQEFEBPAPFSJLV-UHFFFAOYSA-N Cellulose propionate Chemical compound CCC(=O)OCC1OC(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C1OC1C(OC(=O)CC)C(OC(=O)CC)C(OC(=O)CC)C(COC(=O)CC)O1 DQEFEBPAPFSJLV-UHFFFAOYSA-N 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 229920001400 block copolymer Polymers 0.000 claims description 3
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims description 3
- 229920000193 polymethacrylate Polymers 0.000 claims description 3
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- ZNNQGSGPVUYWOS-UHFFFAOYSA-N 2-(3-hydroxypropoxy)benzoic acid Chemical compound OCCCOC1=CC=CC=C1C(O)=O ZNNQGSGPVUYWOS-UHFFFAOYSA-N 0.000 claims description 2
- OEXIDSNKGPWFGB-UHFFFAOYSA-N 2-ethyl-3-(3-hydroxypropyl)benzoic acid Chemical compound CCC1=C(CCCO)C=CC=C1C(O)=O OEXIDSNKGPWFGB-UHFFFAOYSA-N 0.000 claims description 2
- NMGBFVPQUCLJGM-UHFFFAOYSA-N 3-ethylphthalic acid Chemical compound CCC1=CC=CC(C(O)=O)=C1C(O)=O NMGBFVPQUCLJGM-UHFFFAOYSA-N 0.000 claims description 2
- INTNEELQXPKMNM-UHFFFAOYSA-N 3-ethylpyridine-2-carboxylic acid Chemical compound CCC1=CC=CN=C1C(O)=O INTNEELQXPKMNM-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 2
- 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 description 2
- DUFVNVZBEVZTPT-UHFFFAOYSA-N butanedioic acid;butanoic acid Chemical compound CCCC(O)=O.OC(=O)CCC(O)=O DUFVNVZBEVZTPT-UHFFFAOYSA-N 0.000 claims description 2
- VHEMBTYWURNBQQ-UHFFFAOYSA-N butanoic acid;phthalic acid Chemical compound CCCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O VHEMBTYWURNBQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229920003064 carboxyethyl cellulose Polymers 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229920001727 cellulose butyrate Polymers 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000009477 glass transition Effects 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229920013819 hydroxyethyl ethylcellulose Polymers 0.000 claims description 2
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 2
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- HFFFFTQVPXWDLI-KNQAVFIVSA-N propan-2-yl (2r,4s)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound COC(=O)N([C@H]1C[C@H](N(C2=CC=C(C=C21)C(F)(F)F)C(=O)OC(C)C)CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HFFFFTQVPXWDLI-KNQAVFIVSA-N 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 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 claims 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000004743 Polypropylene Substances 0.000 claims 1
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical group [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
- PLEULVPCZZDBNB-UHFFFAOYSA-N acetic acid;butanedioic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O PLEULVPCZZDBNB-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
- WLXHIYCDCMGCRN-UHFFFAOYSA-N n-[5-(4,4-difluoro-1-hydroxycyclohexyl)-3-hydroxy-6-(hydroxyamino)-6-oxo-1-phenylhexan-2-yl]quinoxaline-2-carboxamide Chemical compound C1CC(F)(F)CCC1(O)C(C(=O)NO)CC(O)C(NC(=O)C=1N=C2C=CC=CC2=NC=1)CC1=CC=CC=C1 WLXHIYCDCMGCRN-UHFFFAOYSA-N 0.000 claims 1
- 229960003512 nicotinic acid Drugs 0.000 claims 1
- 235000001968 nicotinic acid Nutrition 0.000 claims 1
- 239000011664 nicotinic acid Substances 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 229920001155 polypropylene Polymers 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 450
- 125000000217 alkyl group Chemical group 0.000 description 319
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 272
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 176
- 125000004432 carbon atom Chemical group C* 0.000 description 155
- 229910052717 sulfur Inorganic materials 0.000 description 130
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 119
- 125000003545 alkoxy group Chemical group 0.000 description 115
- 150000001875 compounds Chemical class 0.000 description 110
- 229910052757 nitrogen Inorganic materials 0.000 description 110
- 229920006395 saturated elastomer Polymers 0.000 description 109
- 229910052799 carbon Inorganic materials 0.000 description 108
- 125000004043 oxo group Chemical group O=* 0.000 description 107
- 229910052739 hydrogen Inorganic materials 0.000 description 102
- 239000001257 hydrogen Substances 0.000 description 100
- 125000005843 halogen group Chemical group 0.000 description 95
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 93
- 229910052760 oxygen Inorganic materials 0.000 description 91
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 88
- 125000003118 aryl group Chemical group 0.000 description 88
- 239000011593 sulfur Substances 0.000 description 88
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 77
- 229910052736 halogen Inorganic materials 0.000 description 72
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 71
- 125000001072 heteroaryl group Chemical group 0.000 description 70
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 70
- 239000001301 oxygen Substances 0.000 description 68
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 67
- 125000004093 cyano group Chemical group *C#N 0.000 description 67
- 125000000623 heterocyclic group Chemical group 0.000 description 61
- 125000000753 cycloalkyl group Chemical group 0.000 description 58
- 150000002367 halogens Chemical class 0.000 description 56
- 125000003342 alkenyl group Chemical group 0.000 description 52
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 48
- 125000004414 alkyl thio group Chemical group 0.000 description 47
- 125000006850 spacer group Chemical group 0.000 description 44
- 125000004429 atom Chemical group 0.000 description 43
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 41
- 125000000304 alkynyl group Chemical group 0.000 description 41
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 41
- 125000002252 acyl group Chemical group 0.000 description 38
- 125000003282 alkyl amino group Chemical group 0.000 description 37
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 36
- 125000005842 heteroatom Chemical group 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 125000001188 haloalkyl group Chemical group 0.000 description 29
- 229960004592 isopropanol Drugs 0.000 description 29
- 150000003254 radicals Chemical class 0.000 description 29
- 239000000243 solution Substances 0.000 description 27
- 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 26
- 230000008569 process Effects 0.000 description 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 description 23
- 125000000262 haloalkenyl group Chemical group 0.000 description 23
- 125000001153 fluoro group Chemical group F* 0.000 description 22
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 21
- KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 description 20
- 235000019000 fluorine Nutrition 0.000 description 20
- 239000010410 layer Substances 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 20
- 239000000463 material Substances 0.000 description 20
- 125000002947 alkylene group Chemical group 0.000 description 19
- 125000003710 aryl alkyl group Chemical group 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000001694 spray drying Methods 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 125000004104 aryloxy group Chemical group 0.000 description 16
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000002619 bicyclic group Chemical group 0.000 description 15
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 15
- 230000003993 interaction Effects 0.000 description 15
- 238000002156 mixing Methods 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 125000004438 haloalkoxy group Chemical group 0.000 description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 14
- 125000001145 hydrido group Chemical group *[H] 0.000 description 14
- 239000002245 particle Substances 0.000 description 14
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 14
- 125000006350 alkyl thio alkyl group Chemical group 0.000 description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
- 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 13
- 125000005326 heteroaryloxy alkyl group Chemical group 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000005110 aryl thio group Chemical group 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 11
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 11
- 125000005553 heteroaryloxy group Chemical group 0.000 description 11
- 125000004434 sulfur atom Chemical group 0.000 description 11
- 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 description 10
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 10
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 10
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 10
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 10
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 229910020008 S(O) Inorganic materials 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 9
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 description 9
- 125000003435 aroyl group Chemical group 0.000 description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 9
- 125000006769 halocycloalkoxy group Chemical group 0.000 description 9
- 125000005347 halocycloalkyl group Chemical group 0.000 description 9
- 125000005368 heteroarylthio group Chemical group 0.000 description 9
- 125000004468 heterocyclylthio group Chemical group 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 125000005452 alkenyloxyalkyl group Chemical group 0.000 description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 8
- 150000003857 carboxamides Chemical class 0.000 description 8
- 125000004181 carboxyalkyl group Chemical group 0.000 description 8
- 125000005356 cycloalkylalkenyl group Chemical group 0.000 description 8
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 description 8
- 125000000232 haloalkynyl group Chemical group 0.000 description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 8
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 description 8
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 8
- 125000001624 naphthyl group Chemical group 0.000 description 8
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ATE403432T1 (de) * | 2002-02-01 | 2008-08-15 | Pfizer Prod Inc | Pharmazeutische darreichungsform mit gesteuerter freigabe eines cholesterylester- transferproteininhibitors |
CA2474838C (en) | 2002-02-01 | 2009-01-06 | Pfizer Products Inc. | Pharmaceutical compositions of amorphous dispersions of drugs and lipophilic microphase-forming materials |
US20040132771A1 (en) * | 2002-12-20 | 2004-07-08 | Pfizer Inc | Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors |
US7838029B1 (en) * | 2003-07-31 | 2010-11-23 | Watson Laboratories, Inc. | Mirtazapine solid dosage forms |
MXPA06001417A (es) | 2003-08-04 | 2006-05-15 | Pfizer Prod Inc | Composiciones farmaceuticas de adsorbatos de farmacos amorfos y materiales que forman microfases lipofilas. |
US7390503B1 (en) | 2003-08-22 | 2008-06-24 | Barr Laboratories, Inc. | Ondansetron orally disintegrating tablets |
US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
WO2005023225A1 (en) * | 2003-09-05 | 2005-03-17 | Ranbaxy Laboratories Limited | Cilostazol adsorbate |
DE50306684D1 (de) * | 2003-11-18 | 2007-04-12 | Helm Ag | Verfahren zur Herstellung von freifliessenden, pulverförmigen Atorvastatin-Adsorbaten |
ATE344020T1 (de) * | 2004-02-06 | 2006-11-15 | Helm Ag | Pharmazeutische zubereitungen mit amorphem tibolon |
MY142989A (en) * | 2004-03-10 | 2011-02-14 | Bayer Schering Pharma Ag | Stabilised supersaturated solids of lipophilic drugs |
RU2007106036A (ru) * | 2004-08-31 | 2008-10-10 | Пфайзер Продактс Инк. (Us) | Антитело к cd40: препарат и способы |
GB2419094A (en) * | 2004-10-12 | 2006-04-19 | Sandoz Ag | Pharmaceutical composition of unpleasnt tasing active substances |
DE102004055229A1 (de) * | 2004-11-17 | 2006-05-18 | Heidelberger Druckmaschinen Ag | Zustandsabhängige Absicherung von Maschinen |
WO2006069162A1 (en) * | 2004-12-20 | 2006-06-29 | Reddy Us Therapeutics, Inc. | Novel heterocyclic compounds and their pharmaceutical compositions |
EP1848430B1 (en) * | 2004-12-31 | 2017-08-02 | Dr. Reddy's Laboratories Ltd. | Novel benzylamine derivatives as cetp inhibitors |
US8604055B2 (en) * | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
WO2006080312A1 (ja) * | 2005-01-25 | 2006-08-03 | Kowa Co., Ltd. | 吸着多孔体の製造法 |
PT1855652E (pt) | 2005-01-28 | 2016-01-26 | Bend Res Inc | Secagem de partículas contendo fármacos |
EP1844078B1 (en) * | 2005-02-03 | 2016-09-28 | Bend Research, Inc | Pharmaceutical compositions with enhanced performance |
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