JP2007505091A - 抗ウイルス薬としてのチエノピロール - Google Patents
抗ウイルス薬としてのチエノピロール Download PDFInfo
- Publication number
- JP2007505091A JP2007505091A JP2006525884A JP2006525884A JP2007505091A JP 2007505091 A JP2007505091 A JP 2007505091A JP 2006525884 A JP2006525884 A JP 2006525884A JP 2006525884 A JP2006525884 A JP 2006525884A JP 2007505091 A JP2007505091 A JP 2007505091A
- Authority
- JP
- Japan
- Prior art keywords
- thieno
- cyclohexyl
- pyrrole
- alkyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003443 antiviral agent Substances 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 229910052786 argon Inorganic materials 0.000 claims abstract description 9
- 229910052796 boron Inorganic materials 0.000 claims abstract description 4
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 141
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 120
- -1 hydroxy, carboxy, amino Chemical group 0.000 claims description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 229910052717 sulfur Inorganic materials 0.000 claims description 41
- 229910052760 oxygen Inorganic materials 0.000 claims description 40
- 125000006413 ring segment Chemical group 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 150000002431 hydrogen Chemical group 0.000 claims description 33
- 125000001153 fluoro group Chemical group F* 0.000 claims description 32
- 229910052731 fluorine Inorganic materials 0.000 claims description 31
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 30
- 239000000460 chlorine Substances 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 claims description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 28
- 239000011737 fluorine Substances 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 18
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 claims description 12
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 8
- 150000002825 nitriles Chemical class 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 241000711549 Hepacivirus C Species 0.000 claims description 6
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- QUOTYKIQXYAEFL-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 QUOTYKIQXYAEFL-UHFFFAOYSA-N 0.000 claims description 5
- MVKNSOMELSVNOY-UHFFFAOYSA-N 6-cyclopentyl-5-phenyl-4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(=O)O)=CC=2NC(C=2C=CC=CC=2)=C1C1CCCC1 MVKNSOMELSVNOY-UHFFFAOYSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- VLNRFOBEOKWKKS-UHFFFAOYSA-N 4-cyclohexyl-5-phenyl-6h-thieno[2,3-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C=1NC=2SC(C(=O)O)=CC=2C=1C1CCCCC1 VLNRFOBEOKWKKS-UHFFFAOYSA-N 0.000 claims description 4
- KLLNDNYCXQKSDJ-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[methyl-(1-propan-2-ylpyrrolidin-3-yl)amino]-2-oxoethyl]-3-[(2-methylpropylamino)methyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N(C)C2CN(CC2)C(C)C)C=2C(CNCC(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 KLLNDNYCXQKSDJ-UHFFFAOYSA-N 0.000 claims description 4
- MLNJWPGFXYKPAF-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C(C=2C=CC=CC=2)=C1C1CCCCC1 MLNJWPGFXYKPAF-UHFFFAOYSA-N 0.000 claims description 4
- KWJJDJJGUBFGKF-UHFFFAOYSA-N 6-cyclohexyl-5-phenyl-4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(=O)O)=CC=2NC(C=2C=CC=CC=2)=C1C1CCCCC1 KWJJDJJGUBFGKF-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- CQTRNSLAUNFUKJ-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)OC)=CC=2N1CC(=O)N1CCOCC1 CQTRNSLAUNFUKJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- PIJIZWLIYOYKMH-UHFFFAOYSA-N 4-benzyl-6-cyclohexyl-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC1=CC=CC=C1 PIJIZWLIYOYKMH-UHFFFAOYSA-N 0.000 claims description 3
- OFQMOHBSPCNHAT-UHFFFAOYSA-N 4-cyclohexyl-6-[2-(dimethylamino)-2-oxoethyl]-5-phenylthieno[2,3-b]pyrrole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)SC=2N(CC(=O)N(C)C)C(C=2C=CC=CC=2)=C1C1CCCCC1 OFQMOHBSPCNHAT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- IOFCTOAWJQMYOD-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 IOFCTOAWJQMYOD-UHFFFAOYSA-N 0.000 claims description 3
- ZOTDYFDFFOUTDU-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-n-ethylsulfonyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxamide Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)NS(=O)(=O)CC)=CC=2N1CC(=O)N1CCOCC1 ZOTDYFDFFOUTDU-UHFFFAOYSA-N 0.000 claims description 3
- RFILEOFRKQSWRQ-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-n-methyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxamide Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)NC)=CC=2N1CC(=O)N1CCOCC1 RFILEOFRKQSWRQ-UHFFFAOYSA-N 0.000 claims description 3
- POUAVDPFIPNUCW-UHFFFAOYSA-N 6-cyclohexyl-3-[(dimethylamino)methyl]-5-phenyl-4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C=1NC=2C(CN(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 POUAVDPFIPNUCW-UHFFFAOYSA-N 0.000 claims description 3
- YIJDUUFLVVHVJH-UHFFFAOYSA-N 6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 YIJDUUFLVVHVJH-UHFFFAOYSA-N 0.000 claims description 3
- JLWXGJRYHOLKSK-UHFFFAOYSA-N 6-cyclohexyl-4-methyl-5-(1,3-oxazol-5-yl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1CCCCC1C=1C=2SC(C(O)=O)=CC=2N(C)C=1C1=CN=CO1 JLWXGJRYHOLKSK-UHFFFAOYSA-N 0.000 claims description 3
- BNIGSPMLDODEAJ-UHFFFAOYSA-N 6-cyclohexyl-4-methyl-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(C)C(C=2C=CC=CC=2)=C1C1CCCCC1 BNIGSPMLDODEAJ-UHFFFAOYSA-N 0.000 claims description 3
- IBPDPOIIZGXYEX-UHFFFAOYSA-N 6-cyclohexyl-5-phenyl-4-(2-pyrrolidin-1-ium-1-ylethyl)thieno[3,2-b]pyrrole-2-carboxylic acid;2,2,2-trifluoroacetate Chemical compound OC(=O)C(F)(F)F.C=1C=CC=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CCN1CCCC1 IBPDPOIIZGXYEX-UHFFFAOYSA-N 0.000 claims description 3
- WPJMYSSUWNPXRV-UHFFFAOYSA-N 6-cyclohexyl-5-phenyl-4-(pyridin-1-ium-3-ylmethyl)thieno[3,2-b]pyrrole-2-carboxylic acid;2,2,2-trifluoroacetate Chemical compound OC(=O)C(F)(F)F.C=1C=CC=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC1=CC=CN=C1 WPJMYSSUWNPXRV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- MZANQBDSGYVDQA-UHFFFAOYSA-N methyl 6-benzyl-4-cyclohexyl-5-phenylthieno[2,3-b]pyrrole-2-carboxylate Chemical compound C=1C=CC=CC=1C=1N(CC=2C=CC=CC=2)C=2SC(C(=O)OC)=CC=2C=1C1CCCCC1 MZANQBDSGYVDQA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- ZQWQDKJZNSFUNM-UHFFFAOYSA-N 3-[(benzylamino)methyl]-6-cyclohexyl-4-(methoxymethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CNCC=3C=CC=CC=3)C=2N(COC)C(C=2C=CC=CC=2)=C1C1CCCCC1 ZQWQDKJZNSFUNM-UHFFFAOYSA-N 0.000 claims description 2
- JLZUJSKTVKGVEF-UHFFFAOYSA-N 3-[[benzyl(methyl)amino]methyl]-6-cyclohexyl-4-(methoxymethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CN(C)CC=3C=CC=CC=3)C=2N(COC)C(C=2C=CC=CC=2)=C1C1CCCCC1 JLZUJSKTVKGVEF-UHFFFAOYSA-N 0.000 claims description 2
- HZYUMMHNVWNXNV-UHFFFAOYSA-N 5-(3-chloro-4-methoxyphenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=C(Cl)C(OC)=CC=C1C(N(C=1C=C(SC=11)C(O)=O)CC(=O)N2CCOCC2)=C1C1CCCCC1 HZYUMMHNVWNXNV-UHFFFAOYSA-N 0.000 claims description 2
- HOXZODAALGCXLC-UHFFFAOYSA-N 5-(3-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC(Cl)=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 HOXZODAALGCXLC-UHFFFAOYSA-N 0.000 claims description 2
- OVQKESNUSXTBDT-UHFFFAOYSA-N 5-(3-chlorophenyl)-6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C(C=2C=C(Cl)C=CC=2)=C1C1CCCCC1 OVQKESNUSXTBDT-UHFFFAOYSA-N 0.000 claims description 2
- VVRMCANIYITKHD-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-(1,3-dihydroisoindol-2-ylmethyl)-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CN3CC4=CC=CC=C4C3)=C(C(=O)O)SC=2C=1C1CCCCC1 VVRMCANIYITKHD-UHFFFAOYSA-N 0.000 claims description 2
- RFGZENZGVSWACO-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-(1,3-dihydroisoindol-2-ylmethyl)-4-methylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CN3CC4=CC=CC=C4C3)C=2N(C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 RFGZENZGVSWACO-UHFFFAOYSA-N 0.000 claims description 2
- WVCIKFSHOZWUSM-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-[(2-methylpropylamino)methyl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CNCC(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 WVCIKFSHOZWUSM-UHFFFAOYSA-N 0.000 claims description 2
- XMIYIICEBQXOIQ-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=C(C(O)=O)SC2=C1N(CC(=O)N1CCOCC1)C(C=1C=CC(Cl)=CC=1)=C2C1CCCCC1 XMIYIICEBQXOIQ-UHFFFAOYSA-N 0.000 claims description 2
- GPCJDWNZBAJPFP-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-[(dimethylamino)methyl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CN(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 GPCJDWNZBAJPFP-UHFFFAOYSA-N 0.000 claims description 2
- FFDSHANOHHBPKU-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-[(dimethylamino)methyl]-4-methylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(C)C=2C(CN(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 FFDSHANOHHBPKU-UHFFFAOYSA-N 0.000 claims description 2
- AGTYRXITTZPBPH-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-3-(pyrrolidin-1-ylmethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CN3CCCC3)=C(C(=O)O)SC=2C=1C1CCCCC1 AGTYRXITTZPBPH-UHFFFAOYSA-N 0.000 claims description 2
- AVYXWNIRWFXLGM-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-3-[(propan-2-ylamino)methyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CNC(C)C)=C(C(O)=O)SC=2C=1C1CCCCC1 AVYXWNIRWFXLGM-UHFFFAOYSA-N 0.000 claims description 2
- SMWMLRIKPDWMLY-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[2-[(dimethylamino)methyl]morpholin-4-yl]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1COC(CN(C)C)CN1C(=O)CN1C(C=C(S2)C(O)=O)=C2C(C2CCCCC2)=C1C1=CC=C(Cl)C=C1 SMWMLRIKPDWMLY-UHFFFAOYSA-N 0.000 claims description 2
- XRUROXFDVMPNED-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[methyl-(1-propan-2-ylpyrrolidin-3-yl)amino]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1N(C(C)C)CCC1N(C)C(=O)CN1C(C=C(S2)C(O)=O)=C2C(C2CCCCC2)=C1C1=CC=C(Cl)C=C1 XRUROXFDVMPNED-UHFFFAOYSA-N 0.000 claims description 2
- XJVIDSGOGXOVQM-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[methyl-[(1-methylpiperidin-3-yl)methyl]amino]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(O)=O)=CC=2N1CC(=O)N(C)CC1CCCN(C)C1 XJVIDSGOGXOVQM-UHFFFAOYSA-N 0.000 claims description 2
- AIQPFNLAOFFFFL-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N(CC1)CCC1N1CCCC1 AIQPFNLAOFFFFL-UHFFFAOYSA-N 0.000 claims description 2
- YCWQSHPHRHGDJC-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-methyl-3-(pyrrolidin-1-ylmethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CN3CCCC3)C=2N(C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 YCWQSHPHRHGDJC-UHFFFAOYSA-N 0.000 claims description 2
- OPXYMXPJBCYOFV-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-methyl-3-[(4-methylpiperazin-1-yl)methyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1CN(C)CCN1CC1=C(C(O)=O)SC2=C1N(C)C(C=1C=CC(Cl)=CC=1)=C2C1CCCCC1 OPXYMXPJBCYOFV-UHFFFAOYSA-N 0.000 claims description 2
- PBTULURDYPEQSS-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-methyl-3-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CN3CCN(CC3)S(C)(=O)=O)C=2N(C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 PBTULURDYPEQSS-UHFFFAOYSA-N 0.000 claims description 2
- KAHHNLVHNLNJHI-UHFFFAOYSA-N 6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-5-(4-phenylmethoxyphenyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 KAHHNLVHNLNJHI-UHFFFAOYSA-N 0.000 claims description 2
- RKTFEWHUGWAZEB-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-(3-formylphenyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C(C=2C=C(C=O)C=CC=2)=C1C1CCCCC1 RKTFEWHUGWAZEB-UHFFFAOYSA-N 0.000 claims description 2
- ZWCPYWFWUKADQO-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-(3-methoxyphenyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound COC1=CC=CC(C=2N(C=3C=C(SC=3C=2C2CCCCC2)C(O)=O)CC(=O)N(C)C)=C1 ZWCPYWFWUKADQO-UHFFFAOYSA-N 0.000 claims description 2
- IBORFVJNRXYVAS-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-(4-formylphenyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C(C=2C=CC(C=O)=CC=2)=C1C1CCCCC1 IBORFVJNRXYVAS-UHFFFAOYSA-N 0.000 claims description 2
- PAIUXPOFNMYAMW-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-(6-methoxypyridin-3-yl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=NC(OC)=CC=C1C(N(C=1C=C(SC=11)C(O)=O)CC(=O)N(C)C)=C1C1CCCCC1 PAIUXPOFNMYAMW-UHFFFAOYSA-N 0.000 claims description 2
- LDQIMGHSERASIK-UHFFFAOYSA-N 6-cyclohexyl-4-[2-(dimethylamino)-2-oxoethyl]-5-(furan-3-yl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1CCCCC1C=1C=2SC(C(O)=O)=CC=2N(CC(=O)N(C)C)C=1C=1C=COC=1 LDQIMGHSERASIK-UHFFFAOYSA-N 0.000 claims description 2
- ZBRHTWQOCJIYSW-UHFFFAOYSA-N 6-cyclohexyl-5-(4-fluorophenyl)-4-[2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N(CC1)CCC1N1CCCC1 ZBRHTWQOCJIYSW-UHFFFAOYSA-N 0.000 claims description 2
- QKIQVHCJCYHOGU-UHFFFAOYSA-N 6-cyclohexyl-5-(4-formylphenyl)-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(C=O)C=CC=1C1=C(C2CCCCC2)C=2SC(C(=O)O)=CC=2N1CC(=O)N1CCOCC1 QKIQVHCJCYHOGU-UHFFFAOYSA-N 0.000 claims description 2
- UBYRXPDIILUWAZ-UHFFFAOYSA-N 6-cyclohexyl-5-(4-methoxyphenyl)-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(N(C=1C=C(SC=11)C(O)=O)CC(=O)N2CCOCC2)=C1C1CCCCC1 UBYRXPDIILUWAZ-UHFFFAOYSA-N 0.000 claims description 2
- NNYCXADZGPOLRZ-UHFFFAOYSA-N 6-cyclohexyl-5-(4-methylphenyl)-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C(N(C=1C=C(SC=11)C(O)=O)CC(=O)N2CCOCC2)=C1C1CCCCC1 NNYCXADZGPOLRZ-UHFFFAOYSA-N 0.000 claims description 2
- GUJWSSYJMOQKIT-UHFFFAOYSA-N 6-cyclohexyl-5-[3-[(dimethylamino)methyl]phenyl]-4-[2-(dimethylamino)-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound CN(C)CC1=CC=CC(C=2N(C=3C=C(SC=3C=2C2CCCCC2)C(O)=O)CC(=O)N(C)C)=C1 GUJWSSYJMOQKIT-UHFFFAOYSA-N 0.000 claims description 2
- LJIYGIMFCMAMAI-UHFFFAOYSA-N 6-cyclohexyl-5-[4-[2-(dimethylamino)ethoxy]phenyl]-4-[2-(dimethylamino)-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=CC(OCCN(C)C)=CC=C1C(N(C=1C=C(SC=11)C(O)=O)CC(=O)N(C)C)=C1C1CCCCC1 LJIYGIMFCMAMAI-UHFFFAOYSA-N 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- KGPQKNJSZNXOPV-UHFFFAOYSA-N moniliformin Chemical compound OC1=CC(=O)C1=O KGPQKNJSZNXOPV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004151 quinonyl group Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims 2
- ADFBLMKUIZMZNV-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-methyl-3-[(pyridin-4-ylmethylamino)methyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(CNCC=3C=CN=CC=3)C=2N(C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 ADFBLMKUIZMZNV-UHFFFAOYSA-N 0.000 claims 1
- 102000006992 Interferon-alpha Human genes 0.000 claims 1
- 108010047761 Interferon-alpha Proteins 0.000 claims 1
- 102000003996 Interferon-beta Human genes 0.000 claims 1
- 108090000467 Interferon-beta Proteins 0.000 claims 1
- 102000008070 Interferon-gamma Human genes 0.000 claims 1
- 108010074328 Interferon-gamma Proteins 0.000 claims 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 229940044627 gamma-interferon Drugs 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 208000005176 Hepatitis C Diseases 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 4
- 208000010710 hepatitis C virus infection Diseases 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 255
- 239000000243 solution Substances 0.000 description 142
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 98
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 74
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 239000002904 solvent Substances 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 239000012074 organic phase Substances 0.000 description 45
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 44
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 44
- 239000012267 brine Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- 239000012047 saturated solution Substances 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 238000003818 flash chromatography Methods 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 238000001816 cooling Methods 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 238000001704 evaporation Methods 0.000 description 25
- 239000003208 petroleum Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000003643 water by type Substances 0.000 description 24
- 238000004007 reversed phase HPLC Methods 0.000 description 23
- 238000010992 reflux Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 230000008020 evaporation Effects 0.000 description 21
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 16
- 239000000725 suspension Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- VONGYFFEWFJHNP-UHFFFAOYSA-N methyl 1h-pyrrole-2-carboxylate Chemical compound COC(=O)C1=CC=CN1 VONGYFFEWFJHNP-UHFFFAOYSA-N 0.000 description 14
- 239000002480 mineral oil Substances 0.000 description 13
- 235000010446 mineral oil Nutrition 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- 239000006185 dispersion Substances 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 239000007821 HATU Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 7
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 125000002757 morpholinyl group Chemical group 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 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 5
- 239000012044 organic layer Substances 0.000 description 5
- 125000004193 piperazinyl group Chemical group 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 4
- 101150003085 Pdcl gene Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108091034057 RNA (poly(A)) Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 125000000068 chlorophenyl group Chemical group 0.000 description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- OSZRKQNJIOWIFE-UHFFFAOYSA-N methyl 4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound N1C=CC2=C1C=C(C(=O)OC)S2 OSZRKQNJIOWIFE-UHFFFAOYSA-N 0.000 description 3
- JJNGVZWEQPWMRY-UHFFFAOYSA-N methyl 6-cyclohexyl-5-phenyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2NC(C=2C=CC=CC=2)=C1C1CCCCC1 JJNGVZWEQPWMRY-UHFFFAOYSA-N 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- NSDGDKMUKDINNX-UHFFFAOYSA-N 2-(6-cyclohexyl-2-methoxycarbonyl-5-phenylthieno[3,2-b]pyrrol-4-yl)acetic acid Chemical compound C1=2SC(C(=O)OC)=CC=2N(CC(O)=O)C(C=2C=CC=CC=2)=C1C1CCCCC1 NSDGDKMUKDINNX-UHFFFAOYSA-N 0.000 description 2
- XBPPLECAZBTMMK-UHFFFAOYSA-N 2-chloro-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CCl XBPPLECAZBTMMK-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- WPBQDWFVRQBPIT-UHFFFAOYSA-N 4-o-tert-butyl 2-o-methyl 5-(4-chlorophenyl)-6-cyclohexylthieno[3,2-b]pyrrole-2,4-dicarboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2N(C(=O)OC(C)(C)C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 WPBQDWFVRQBPIT-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- HZLRTBHJCOVMTG-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(=O)O)=CC=2NC(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 HZLRTBHJCOVMTG-UHFFFAOYSA-N 0.000 description 2
- GJJFMJZYYPRUFV-UHFFFAOYSA-N 6-cyclohexyl-3-formyl-4-(methoxymethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=C(C=O)C=2N(COC)C(C=2C=CC=CC=2)=C1C1CCCCC1 GJJFMJZYYPRUFV-UHFFFAOYSA-N 0.000 description 2
- JIOBSRRTPVVCDB-UHFFFAOYSA-N 6-cyclohexyl-5-(furan-3-yl)-4-[2-[methyl-(1-propan-2-ylpyrrolidin-3-yl)amino]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1N(C(C)C)CCC1N(C)C(=O)CN1C(C=C(S2)C(O)=O)=C2C(C2CCCCC2)=C1C1=COC=C1 JIOBSRRTPVVCDB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- PAEYAKGINDQUCT-UHFFFAOYSA-N Ethyl 2-pyrrolecarboxylate Chemical compound CCOC(=O)C1=CC=CN1 PAEYAKGINDQUCT-UHFFFAOYSA-N 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 2
- 101100189356 Mus musculus Papolb gene Proteins 0.000 description 2
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 2
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108091027544 Subgenomic mRNA Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- OTOWOQKLYHSHTO-UHFFFAOYSA-N ethyl 4-acetamidothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC(NC(C)=O)=CS1 OTOWOQKLYHSHTO-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229920000140 heteropolymer Polymers 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 2
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 2
- 159000000029 imidazo[1,2-b]thiazoles Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- KLRMEBDUUHLVMV-UHFFFAOYSA-N methyl 2-chloro-5-phenyl-1h-pyrrole-3-carboxylate Chemical compound N1C(Cl)=C(C(=O)OC)C=C1C1=CC=CC=C1 KLRMEBDUUHLVMV-UHFFFAOYSA-N 0.000 description 2
- CXVYFUQLVGYIDF-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-3-(1,3-dioxolan-2-yl)-4-methylthieno[3,2-b]pyrrole-2-carboxylate Chemical compound C=1C=C(Cl)C=CC=1C=1N(C)C=2C(C3OCCO3)=C(C(=O)OC)SC=2C=1C1CCCCC1 CXVYFUQLVGYIDF-UHFFFAOYSA-N 0.000 description 2
- FJLXNRXIXXQCGJ-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-3-formyl-4-(methoxymethyl)thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=C(C=O)C=2N(COC)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 FJLXNRXIXXQCGJ-UHFFFAOYSA-N 0.000 description 2
- XRRKEBZCNXBCLN-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-3-formyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C=1C=C(Cl)C=CC=1C=1NC=2C(C=O)=C(C(=O)OC)SC=2C=1C1CCCCC1 XRRKEBZCNXBCLN-UHFFFAOYSA-N 0.000 description 2
- QXIFGUCZQLEFBZ-UHFFFAOYSA-N methyl 5-methyl-4-nitrothiophene-2-carboxylate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=C(C)S1 QXIFGUCZQLEFBZ-UHFFFAOYSA-N 0.000 description 2
- MSLQQXYPTVSSCQ-UHFFFAOYSA-N methyl 5-phenyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C=1C=2SC(C(=O)OC)=CC=2NC=1C1=CC=CC=C1 MSLQQXYPTVSSCQ-UHFFFAOYSA-N 0.000 description 2
- YOPFFIMUVJUYQK-UHFFFAOYSA-N n-methyl-1-propan-2-ylpyrrolidin-3-amine Chemical compound CNC1CCN(C(C)C)C1 YOPFFIMUVJUYQK-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002755 pyrazolinyl group Chemical group 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ACBXCZWSUAHUCM-UHFFFAOYSA-N (1-benzyl-2-chloro-5-phenylpyrrol-3-yl)methanol Chemical compound C=1C=CC=CC=1CN1C(Cl)=C(CO)C=C1C1=CC=CC=C1 ACBXCZWSUAHUCM-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- RMGFLMXDCGQKPS-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine Chemical compound ClCCN1CCCC1 RMGFLMXDCGQKPS-UHFFFAOYSA-N 0.000 description 1
- HGHYFKUMLWEAMR-UHFFFAOYSA-N 1-(isocyanomethyl)-4-methylbenzene Chemical compound CC1=CC=C(C[N+]#[C-])C=C1 HGHYFKUMLWEAMR-UHFFFAOYSA-N 0.000 description 1
- OOYSQUYLEZZKLW-UHFFFAOYSA-N 1-benzyl-2-chloro-5-phenylpyrrole-3-carbaldehyde Chemical compound C=1C=CC=CC=1CN1C(Cl)=C(C=O)C=C1C1=CC=CC=C1 OOYSQUYLEZZKLW-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- COLZOTSDWLRGIM-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-6-cyclohexyl-2-methoxycarbonyl-5-phenyl-2h-thieno[3,2-b]pyrrol-4-yl]acetic acid Chemical compound C=1C=CC=CC=1C1(C=2C=CC(Cl)=CC=2)N(CC(O)=O)C2=CC(C(=O)OC)SC2=C1C1CCCCC1 COLZOTSDWLRGIM-UHFFFAOYSA-N 0.000 description 1
- AQJIUYSYWUFYSY-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-6-cyclohexyl-2-methoxycarbonylthieno[3,2-b]pyrrol-4-yl]acetic acid Chemical compound C1=2SC(C(=O)OC)=CC=2N(CC(O)=O)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 AQJIUYSYWUFYSY-UHFFFAOYSA-N 0.000 description 1
- UPEWZSHKLYFFSE-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-6-cyclohexyl-3-formyl-2-methoxycarbonylthieno[3,2-b]pyrrol-4-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(O)=O)C=2C(C=O)=C(C(=O)OC)SC=2C=1C1CCCCC1 UPEWZSHKLYFFSE-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 1
- LYTXXAOHBLJBEA-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphol-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)C=CN1C LYTXXAOHBLJBEA-UHFFFAOYSA-N 0.000 description 1
- UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
- LTFGKKLLQUAPGE-UHFFFAOYSA-N 3-nitrothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC=CC=1[N+]([O-])=O LTFGKKLLQUAPGE-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- YWFHAWOMPBNXAM-UHFFFAOYSA-N 4-cyclohexyl-6-[2-[methyl-[(1-methylpiperidin-3-yl)methyl]amino]-2-oxoethyl]-5-phenylthieno[2,3-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C1=C(C2CCCCC2)C=2C=C(C(O)=O)SC=2N1CC(=O)N(C)CC1CCCN(C)C1 YWFHAWOMPBNXAM-UHFFFAOYSA-N 0.000 description 1
- XGQCZEPDWWZGEX-UHFFFAOYSA-N 4-o-tert-butyl 2-o-methyl 5-bromo-6-cyclohexylthieno[3,2-b]pyrrole-2,4-dicarboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2N(C(=O)OC(C)(C)C)C(Br)=C1C1CCCCC1 XGQCZEPDWWZGEX-UHFFFAOYSA-N 0.000 description 1
- IULABJQOVJBYGK-UHFFFAOYSA-N 4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound N1C=CC2=C1C=C(C(=O)O)S2 IULABJQOVJBYGK-UHFFFAOYSA-N 0.000 description 1
- LVHZTJAIZQRNBP-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-3-[(cyclopropylmethylamino)methyl]-4-(2-morpholin-4-yl-2-oxoethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C=1C=C(Cl)C=CC=1C=1N(CC(=O)N2CCOCC2)C=2C(CNCC3CC3)=C(C(=O)O)SC=2C=1C1CCCCC1 LVHZTJAIZQRNBP-UHFFFAOYSA-N 0.000 description 1
- URLIYBQKYRZVSJ-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-(methoxymethyl)thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(COC)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 URLIYBQKYRZVSJ-UHFFFAOYSA-N 0.000 description 1
- MLSHEENNVBKBSI-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)CN1C2=C(C(=C1C3=CC=C(C=C3)Cl)C4CCCCC4)SC(=C2)C(=O)O MLSHEENNVBKBSI-UHFFFAOYSA-N 0.000 description 1
- LCRZPXWVVPCKHA-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-cyclohexyl-4-methylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 LCRZPXWVVPCKHA-UHFFFAOYSA-N 0.000 description 1
- FHODEAKPFRVVJC-UHFFFAOYSA-N 5-phenyl-6H-thieno[2,3-b]pyrrole-2,4-dicarboxylic acid Chemical compound C1=CC=C(C=C1)C2=C(C3=C(N2)SC(=C3)C(=O)O)C(=O)O FHODEAKPFRVVJC-UHFFFAOYSA-N 0.000 description 1
- XVOHMWPYMJTCKH-UHFFFAOYSA-N 6-(cyclohexen-1-yl)-4h-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(=O)O)=CC=2NC=C1C1=CCCCC1 XVOHMWPYMJTCKH-UHFFFAOYSA-N 0.000 description 1
- NPZZFAOKYGOQNB-UHFFFAOYSA-N 6-(cyclohexen-1-yl)-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1CCC(=CC1)C2=C(NC3=C2SC(=C3)C(=O)O)C4=CC=CC=C4 NPZZFAOKYGOQNB-UHFFFAOYSA-N 0.000 description 1
- KQKINSLMJKHTDJ-UHFFFAOYSA-N 6-benzyl-4-(cyclohexen-1-yl)-5-phenylthieno[2,3-b]pyrrole-2-carboxylic acid Chemical compound C1CCC(=CC1)C2=C(N(C3=C2C=C(S3)C(=O)O)CC4=CC=CC=C4)C5=CC=CC=C5 KQKINSLMJKHTDJ-UHFFFAOYSA-N 0.000 description 1
- KVFKBFKQPYRAPV-UHFFFAOYSA-N 6-benzyl-4-cyclohexyl-5-phenylthieno[2,3-b]pyrrole-2-carboxylic acid Chemical compound C=1C=CC=CC=1C=1N(CC=2C=CC=CC=2)C=2SC(C(=O)O)=CC=2C=1C1CCCCC1 KVFKBFKQPYRAPV-UHFFFAOYSA-N 0.000 description 1
- CUSLAYCYPWHPTM-UHFFFAOYSA-N 6-cyclohexyl-4-(methoxymethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound C1=2SC(C(O)=O)=CC=2N(COC)C(C=2C=CC=CC=2)=C1C1CCCCC1 CUSLAYCYPWHPTM-UHFFFAOYSA-N 0.000 description 1
- FTSVILHNZQHFJR-UHFFFAOYSA-N 6-cyclohexyl-4-[(2-methylpropan-2-yl)oxycarbonyl]thieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C=C(C2=C1C=C(S2)C(=O)O)C3CCCCC3 FTSVILHNZQHFJR-UHFFFAOYSA-N 0.000 description 1
- GQLPANJXSRPOOX-UHFFFAOYSA-N 6-cyclohexyl-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-phenylthieno[3,2-b]pyrrole-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)CN1C2=C(C(=C1C3=CC=CC=C3)C4CCCCC4)SC(=C2)C(=O)O GQLPANJXSRPOOX-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241001553178 Arachis glabrata Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- ZRIGPWBVLMHCTN-UHFFFAOYSA-N C1=2SC(C(O)=O)=CC=2N(C(=O)OC(C)(C)C)C(Br)=C1C1CCCCC1 Chemical compound C1=2SC(C(O)=O)=CC=2N(C(=O)OC(C)(C)C)C(Br)=C1C1CCCCC1 ZRIGPWBVLMHCTN-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- BYMMIQCVDHHYGG-UHFFFAOYSA-N Cl.OP(O)(O)=O Chemical compound Cl.OP(O)(O)=O BYMMIQCVDHHYGG-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010549 co-Evaporation Methods 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- HOYBABTVTOMCCO-UHFFFAOYSA-N cyclohexyl 4H-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1(CCCCC1)OC(=O)C1=CC=2NC=CC=2S1 HOYBABTVTOMCCO-UHFFFAOYSA-N 0.000 description 1
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- VIYFPAMJCJLZKD-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate Chemical compound [Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 VIYFPAMJCJLZKD-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 1
- PPFQKHAYOJKICE-UHFFFAOYSA-N ethyl 4-cyclohexyl-5-phenyl-6h-thieno[2,3-b]pyrrole-2-carboxylate Chemical compound C=1C=CC=CC=1C=1NC=2SC(C(=O)OCC)=CC=2C=1C1CCCCC1 PPFQKHAYOJKICE-UHFFFAOYSA-N 0.000 description 1
- JZGZKRJVTIRPOK-UHFFFAOYSA-N ethyl thiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=CS1 JZGZKRJVTIRPOK-UHFFFAOYSA-N 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012054 flavored emulsion Substances 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- FOFAUNQSHDBIGC-UHFFFAOYSA-N methyl 1-benzyl-2-chloro-5-phenylpyrrole-3-carboxylate Chemical compound C=1C=CC=CC=1CN1C(Cl)=C(C(=O)OC)C=C1C1=CC=CC=C1 FOFAUNQSHDBIGC-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- MHXYWUNYSPAWFW-UHFFFAOYSA-N methyl 2-cyano-3-oxo-3-phenylpropanoate Chemical compound COC(=O)C(C#N)C(=O)C1=CC=CC=C1 MHXYWUNYSPAWFW-UHFFFAOYSA-N 0.000 description 1
- VXSHMVBFZUGTOW-UHFFFAOYSA-N methyl 2-cyano-4-oxo-4-phenylbutanoate Chemical compound COC(=O)C(C#N)CC(=O)C1=CC=CC=C1 VXSHMVBFZUGTOW-UHFFFAOYSA-N 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- DDLFZCCIZTVFBQ-UHFFFAOYSA-N methyl 3-nitrothiophene-2-carboxylate Chemical compound COC(=O)C=1SC=CC=1[N+]([O-])=O DDLFZCCIZTVFBQ-UHFFFAOYSA-N 0.000 description 1
- ABWPLDHHOYVTPB-UHFFFAOYSA-N methyl 4-nitrothiophene-2-carboxylate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CS1 ABWPLDHHOYVTPB-UHFFFAOYSA-N 0.000 description 1
- YCJTYGKOEJHWIZ-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C=1C=2SC(C(=O)OC)=CC=2NC=1C1=CC=C(Cl)C=C1 YCJTYGKOEJHWIZ-UHFFFAOYSA-N 0.000 description 1
- JWRCZLFMNHCIPW-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2N(CC(=O)OC(C)(C)C)C(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 JWRCZLFMNHCIPW-UHFFFAOYSA-N 0.000 description 1
- JGNTTXXZXNSDFQ-UHFFFAOYSA-N methyl 5-(4-chlorophenyl)-6-cyclohexyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2NC(C=2C=CC(Cl)=CC=2)=C1C1CCCCC1 JGNTTXXZXNSDFQ-UHFFFAOYSA-N 0.000 description 1
- XYQZSZXBODAMID-QPJJXVBHSA-N methyl 5-[(e)-2-(4-chlorophenyl)ethenyl]-4-nitrothiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC([N+]([O-])=O)=C1\C=C\C1=CC=C(Cl)C=C1 XYQZSZXBODAMID-QPJJXVBHSA-N 0.000 description 1
- BQSDMYFUBNSFQC-UHFFFAOYSA-N methyl 6-cyclohexyl-4-(methoxymethyl)-5-phenylthieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2N(COC)C(C=2C=CC=CC=2)=C1C1CCCCC1 BQSDMYFUBNSFQC-UHFFFAOYSA-N 0.000 description 1
- SZTCCIABQXDUID-UHFFFAOYSA-N methyl 6-cyclohexyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC)=CC=2NC=C1C1CCCCC1 SZTCCIABQXDUID-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OUBNEVZXIXKNJE-UHFFFAOYSA-N n-methyl-1-(1-methylpiperidin-3-yl)methanamine Chemical compound CNCC1CCCN(C)C1 OUBNEVZXIXKNJE-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229940053050 neomycin sulfate Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- MCBUQVRZXAZENC-UHFFFAOYSA-N tert-butyl 5-bromo-6-cyclohexyl-4h-thieno[3,2-b]pyrrole-2-carboxylate Chemical compound C1=2SC(C(=O)OC(C)(C)C)=CC=2NC(Br)=C1C1CCCCC1 MCBUQVRZXAZENC-UHFFFAOYSA-N 0.000 description 1
- FESDUDPSRMWIDL-UHFFFAOYSA-N tert-butyl n,n'-di(propan-2-yl)carbamimidate Chemical compound CC(C)NC(OC(C)(C)C)=NC(C)C FESDUDPSRMWIDL-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0321003.6A GB0321003D0 (en) | 2003-09-09 | 2003-09-09 | Compounds, compositions and uses |
| PCT/GB2004/003838 WO2005023819A1 (en) | 2003-09-09 | 2004-09-07 | Thienopyrroles as antiviral agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007505091A true JP2007505091A (ja) | 2007-03-08 |
| JP2007505091A5 JP2007505091A5 (cg-RX-API-DMAC10.html) | 2007-07-05 |
Family
ID=29226699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006525884A Pending JP2007505091A (ja) | 2003-09-09 | 2004-09-07 | 抗ウイルス薬としてのチエノピロール |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7781431B2 (cg-RX-API-DMAC10.html) |
| EP (1) | EP1664059B1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP2007505091A (cg-RX-API-DMAC10.html) |
| CN (1) | CN1849323A (cg-RX-API-DMAC10.html) |
| AT (1) | ATE373005T1 (cg-RX-API-DMAC10.html) |
| AU (1) | AU2004270470A1 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2537545A1 (cg-RX-API-DMAC10.html) |
| DE (1) | DE602004008945T2 (cg-RX-API-DMAC10.html) |
| ES (1) | ES2291933T3 (cg-RX-API-DMAC10.html) |
| GB (1) | GB0321003D0 (cg-RX-API-DMAC10.html) |
| WO (1) | WO2005023819A1 (cg-RX-API-DMAC10.html) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2005049622A1 (ja) * | 2003-11-19 | 2007-06-07 | 日本たばこ産業株式会社 | ５−５員縮合複素環化合物及びそのｈｃｖポリメラーゼ阻害剤としての用途 |
| JPWO2006052013A1 (ja) * | 2004-11-12 | 2008-05-29 | 日本たばこ産業株式会社 | チエノピロール化合物及びそのｈｃｖポリメラーゼ阻害剤としての利用 |
| JP2017530958A (ja) * | 2014-09-12 | 2017-10-19 | 蘇州旺山旺水生物医薬有限公司 | アミノスルホニル系化合物、その製造方法、および使用 |
| JP2019519520A (ja) * | 2016-05-18 | 2019-07-11 | イスティトゥート エウロペオ ディ オンコロジア エセ．エレ．エッレ． | ヒストンデメチラーゼ阻害剤としてのイミダゾール |
| WO2020040104A1 (ja) * | 2018-08-21 | 2020-02-27 | 杏林製薬株式会社 | ２環性ヘテロ芳香環誘導体 |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0413234A (pt) | 2003-08-01 | 2006-10-03 | Genelabs Tech Inc | derivados de imidazola bicìclica contra flaviviridae |
| US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
| GB0416396D0 (en) * | 2004-07-22 | 2004-08-25 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| AU2006242475B2 (en) | 2005-05-02 | 2011-07-07 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| GB0509326D0 (en) | 2005-05-09 | 2005-06-15 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US8278322B2 (en) | 2005-08-01 | 2012-10-02 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| GB0609492D0 (en) | 2006-05-15 | 2006-06-21 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| GB0612423D0 (en) | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
| CN101583372A (zh) | 2006-10-24 | 2009-11-18 | 默克公司 | Hcv ns3蛋白酶抑制剂 |
| US8138164B2 (en) | 2006-10-24 | 2012-03-20 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| CA2667165A1 (en) | 2006-10-24 | 2008-05-02 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| WO2008057208A2 (en) | 2006-10-27 | 2008-05-15 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
| JP5268927B2 (ja) | 2006-10-27 | 2013-08-21 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｈｃｖｎｓ３プロテアーゼ阻害剤 |
| GB0625349D0 (en) | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| GB0625345D0 (en) | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| US8101595B2 (en) | 2006-12-20 | 2012-01-24 | Istituto di Ricerche di Biologia Molecolare P. Angletti SpA | Antiviral indoles |
| AU2008277442A1 (en) | 2007-07-17 | 2009-01-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Macrocyclic indole derivatives for the treatment of hepatitis C infections |
| CN101754974B (zh) | 2007-07-19 | 2016-02-03 | Msd意大利有限公司 | 作为抗病毒剂的大环化合物 |
| EP2234977A4 (en) | 2007-12-19 | 2011-04-13 | Boehringer Ingelheim Int | VIRAL POLYMERASE INHIBITORS |
| CN102014911A (zh) | 2008-04-28 | 2011-04-13 | 默沙东公司 | Hcv ns3蛋白酶抑制剂 |
| US8126839B2 (en) * | 2008-06-19 | 2012-02-28 | Yahoo! Inc. | Methods and apparatuses for adapting a ranking function of a search engine for use with a specific domain |
| ES2392611T3 (es) | 2008-07-22 | 2012-12-12 | Merck Sharp & Dohme Corp. | Compuestos de quinoxalina macrocíclica como inhibidores de la proteasa NS3 del VHC |
| KR20110116136A (ko) | 2009-01-07 | 2011-10-25 | 싸이넥시스, 인크. | Ｈｃｖ 및 ｈｉｖ 감염의 치료에 사용하기 위한 사이클로스포린 유도체 |
| US8828930B2 (en) | 2009-07-30 | 2014-09-09 | Merck Sharp & Dohme Corp. | Hepatitis C virus NS3 protease inhibitors |
| TW201130852A (en) * | 2009-12-23 | 2011-09-16 | Abbott Lab | Novel thienopyrrole compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003010140A2 (en) * | 2001-07-25 | 2003-02-06 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c virus polymerase inhibitors with heterobicyclic structure |
| JP2003212846A (ja) * | 2001-06-26 | 2003-07-30 | Japan Tobacco Inc | 縮合環化合物及びｃ型肝炎治療剤 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3706810A (en) * | 1970-09-15 | 1972-12-19 | American Cyanamid Co | N-morpholinoalkyl-thieno(3,2-b)pyrrole-5-carboxamides |
| SU367098A1 (ru) * | 1971-01-20 | 1973-01-23 | Способ получения производных 4,5-диоксотиено- - | |
| SU478833A1 (ru) * | 1972-12-29 | 1975-07-30 | Всесоюзный Научно-Исследовательский Химико-Фармацевтический Институт Им.С.Орджоникидзе | Способ получени производных тиено -(3,2-в)-пиррола |
| JPH04356029A (ja) | 1990-07-02 | 1992-12-09 | Japan Synthetic Rubber Co Ltd | 非線形光学素子 |
| JPH04179949A (ja) * | 1990-11-15 | 1992-06-26 | Fuji Photo Film Co Ltd | 新規な色素形成カプラーおよび該カプラーを用いたハロゲン化銀カラー写真感光材料 |
| US5340833A (en) * | 1992-05-01 | 1994-08-23 | Eisai Co., Ltd. | Urokinase inhibitors |
| CZ20013424A3 (cs) | 1999-12-27 | 2002-02-13 | Japan Tobacco Inc. | Sloučeniny s fúzovanými kruhy a jejich pouľití jako léčiva |
| US6448281B1 (en) | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| AR035543A1 (es) | 2001-06-26 | 2004-06-16 | Japan Tobacco Inc | Agente terapeutico para la hepatitis c que comprende un compuesto de anillo condensado, compuesto de anillo condensado, composicion farmaceutica que lo comprende, compuestos de benzimidazol, tiazol y bifenilo utiles como intermediarios para producir dichos compuestos, uso del compuesto de anillo con |
| CA2448737C (en) | 2001-07-20 | 2010-06-01 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| US20030134853A1 (en) | 2001-09-26 | 2003-07-17 | Priestley Eldon Scott | Compounds useful for treating hepatitis C virus |
| GB0222909D0 (en) * | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| CA2522225A1 (en) * | 2003-04-17 | 2004-10-28 | Pfizer Products Inc. | Carboxamide derivatives as anti-diabetic agents |
-
2003
- 2003-09-09 GB GBGB0321003.6A patent/GB0321003D0/en not_active Ceased
-
2004
- 2004-09-07 AT AT04768385T patent/ATE373005T1/de not_active IP Right Cessation
- 2004-09-07 DE DE602004008945T patent/DE602004008945T2/de not_active Expired - Lifetime
- 2004-09-07 JP JP2006525884A patent/JP2007505091A/ja active Pending
- 2004-09-07 CN CNA2004800257994A patent/CN1849323A/zh active Pending
- 2004-09-07 US US10/571,234 patent/US7781431B2/en not_active Expired - Fee Related
- 2004-09-07 AU AU2004270470A patent/AU2004270470A1/en not_active Abandoned
- 2004-09-07 WO PCT/GB2004/003838 patent/WO2005023819A1/en not_active Ceased
- 2004-09-07 ES ES04768385T patent/ES2291933T3/es not_active Expired - Lifetime
- 2004-09-07 CA CA002537545A patent/CA2537545A1/en not_active Abandoned
- 2004-09-07 EP EP04768385A patent/EP1664059B1/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003212846A (ja) * | 2001-06-26 | 2003-07-30 | Japan Tobacco Inc | 縮合環化合物及びｃ型肝炎治療剤 |
| WO2003010140A2 (en) * | 2001-07-25 | 2003-02-06 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c virus polymerase inhibitors with heterobicyclic structure |
| WO2003010141A2 (en) * | 2001-07-25 | 2003-02-06 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c virus polymerase inhibitors with a heterobicyclic structure |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2005049622A1 (ja) * | 2003-11-19 | 2007-06-07 | 日本たばこ産業株式会社 | ５−５員縮合複素環化合物及びそのｈｃｖポリメラーゼ阻害剤としての用途 |
| JPWO2006052013A1 (ja) * | 2004-11-12 | 2008-05-29 | 日本たばこ産業株式会社 | チエノピロール化合物及びそのｈｃｖポリメラーゼ阻害剤としての利用 |
| JP2017530958A (ja) * | 2014-09-12 | 2017-10-19 | 蘇州旺山旺水生物医薬有限公司 | アミノスルホニル系化合物、その製造方法、および使用 |
| JP2019519520A (ja) * | 2016-05-18 | 2019-07-11 | イスティトゥート エウロペオ ディ オンコロジア エセ．エレ．エッレ． | ヒストンデメチラーゼ阻害剤としてのイミダゾール |
| WO2020040104A1 (ja) * | 2018-08-21 | 2020-02-27 | 杏林製薬株式会社 | ２環性ヘテロ芳香環誘導体 |
| JPWO2020040104A1 (ja) * | 2018-08-21 | 2021-08-12 | 杏林製薬株式会社 | ２環性ヘテロ芳香環誘導体 |
| JP7309725B2 (ja) | 2018-08-21 | 2023-07-18 | 杏林製薬株式会社 | ２環性ヘテロ芳香環誘導体 |
| US11952387B2 (en) | 2018-08-21 | 2024-04-09 | Kyorin Pharmaceutical Co., Ltd | Bicyclic heteroaromatic ring derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005023819A1 (en) | 2005-03-17 |
| WO2005023819A9 (en) | 2006-03-23 |
| GB0321003D0 (en) | 2003-10-08 |
| DE602004008945T2 (de) | 2008-05-29 |
| US7781431B2 (en) | 2010-08-24 |
| CN1849323A (zh) | 2006-10-18 |
| ES2291933T3 (es) | 2008-03-01 |
| AU2004270470A1 (en) | 2005-03-17 |
| DE602004008945D1 (en) | 2007-10-25 |
| EP1664059A1 (en) | 2006-06-07 |
| ATE373005T1 (de) | 2007-09-15 |
| CA2537545A1 (en) | 2005-03-17 |
| US20090036443A1 (en) | 2009-02-05 |
| EP1664059B1 (en) | 2007-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7781431B2 (en) | Thienopyrroles as antiviral agents | |
| JP6457525B2 (ja) | Ｔｎｆ活性のモジュレーターとしてのピラゾロピリジン誘導体 | |
| US7973026B2 (en) | Thienopyrroles as antiviral agents | |
| RU2677699C1 (ru) | Производные имидазотриазина в качестве модуляторов активности tnf | |
| JP2007508286A (ja) | 抗ウイルス薬としてのインドール及びアザインドール | |
| US20070167447A1 (en) | Indole acetamides as inhibitors of the hepatitis c virus ns5b polymerase | |
| JPWO2002051849A1 (ja) | Ｃｄｋ４活性阻害剤 | |
| US7786048B2 (en) | Condensed heterocyclic pyrazole derivatives as kinase inhibitors | |
| JP2006512313A (ja) | 抗炎症剤 | |
| US20040209897A1 (en) | Mitogen activated protein kinase-activated protein kinase-2 inhibiting compounds | |
| JPH01316363A (ja) | ピペラジン誘導体およびその塩 | |
| JP2006501191A (ja) | キナーゼ阻害剤としてのヘテロ二環式ピラゾール誘導体 | |
| CN101501034A (zh) | 1，7-萘啶衍生物作为p38裂原活化蛋白激酶抑制剂 | |
| JPWO2003004497A1 (ja) | 新規複素環化合物 | |
| JP2009515865A (ja) | 抗ウイルス薬としての四環式インドール誘導体 | |
| US6214838B1 (en) | Thienodipyridine derivatives, production and use thereof | |
| JP5159630B2 (ja) | 縮環複素環誘導体 | |
| ES2290492T3 (es) | 1-aza-dibenzoazulenos como inhibidores de la produccion del factor de necrosis tumoral e intermedios para su peparacion. | |
| JP2009544668A (ja) | ピリミジノンの誘導体及びそれらの医薬としての利用 | |
| US7485661B2 (en) | Heterobicyclic pyrazole derivatives as kinase inhibitors | |
| RS99404A (sr) | 1-oksa-dibenzoazuleni kao inhibitori stvaranja faktora tumorske nekroze i međuproizvodi za njihovo pripremanje | |
| JP2662426B2 (ja) | ヘテロ環式化合物ならびにその製造方法および使用方法 | |
| JP2026507091A (ja) | アリール基三環式ｓｔｉｎｇ作動薬及びその使用 | |
| JP2010006717A (ja) | ジヒドロチエノ［２，３−ｅ］インダゾール化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070517 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070517 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100629 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100924 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101001 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110301 |