SK2592003A3 - Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors - Google Patents
Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors Download PDFInfo
- Publication number
- SK2592003A3 SK2592003A3 SK259-2003A SK2592003A SK2592003A3 SK 2592003 A3 SK2592003 A3 SK 2592003A3 SK 2592003 A SK2592003 A SK 2592003A SK 2592003 A3 SK2592003 A3 SK 2592003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- carbamoyl
- pyrrole
- thieno
- alkyl
- carbon atoms
- Prior art date
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- -1 Bicyclic pyrrolyl amides Chemical class 0.000 title claims abstract description 684
- 239000003112 inhibitor Substances 0.000 title description 8
- 102000009097 Phosphorylases Human genes 0.000 title 1
- 108010073135 Phosphorylases Proteins 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 150000002148 esters Chemical class 0.000 claims abstract description 31
- 238000001727 in vivo Methods 0.000 claims abstract description 28
- 102000007390 Glycogen Phosphorylase Human genes 0.000 claims abstract description 19
- 108010046163 Glycogen Phosphorylase Proteins 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 439
- 125000004432 carbon atom Chemical group C* 0.000 claims description 382
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 332
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 265
- 150000001875 compounds Chemical class 0.000 claims description 176
- 229910052757 nitrogen Inorganic materials 0.000 claims description 174
- 229910052739 hydrogen Inorganic materials 0.000 claims description 116
- 125000003545 alkoxy group Chemical group 0.000 claims description 96
- 239000001257 hydrogen Substances 0.000 claims description 79
- 229910052799 carbon Inorganic materials 0.000 claims description 64
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 47
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 44
- 125000000623 heterocyclic group Chemical group 0.000 claims description 43
- 150000002431 hydrogen Chemical class 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 37
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 27
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 23
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 21
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000004423 acyloxy group Chemical group 0.000 claims description 20
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 17
- 241001465754 Metazoa Species 0.000 claims description 17
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 13
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000005002 aryl methyl group Chemical group 0.000 claims description 12
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 12
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 11
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 11
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 10
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052698 phosphorus Inorganic materials 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 4
- JATXYZPMRXZLHH-UHFFFAOYSA-N 2,3-dichloro-n-(2,3-dihydro-1h-inden-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1C2=CC=CC=C2CC1NC(=O)C1=CC(SC(=C2Cl)Cl)=C2N1 JATXYZPMRXZLHH-UHFFFAOYSA-N 0.000 claims description 3
- VIXSCUOQQOJRRG-UHFFFAOYSA-N 2,3-dichloro-n-(2-oxo-3,4-dihydro-1h-quinolin-3-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1C2=CC=CC=C2NC(=O)C1NC(=O)C1=CC(SC(=C2Cl)Cl)=C2N1 VIXSCUOQQOJRRG-UHFFFAOYSA-N 0.000 claims description 3
- LKFDCLSAXTWUPP-UHFFFAOYSA-N 2,3-dichloro-n-(2-thiophen-2-ylethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCC1=CC=CS1 LKFDCLSAXTWUPP-UHFFFAOYSA-N 0.000 claims description 3
- SSWWVPHAJRVZTR-UHFFFAOYSA-N 2,3-dichloro-n-(4-hydroxy-1,1-dioxothiolan-3-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound OC1CS(=O)(=O)CC1NC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 SSWWVPHAJRVZTR-UHFFFAOYSA-N 0.000 claims description 3
- XNICNUOMZXJHOP-UHFFFAOYSA-N 2,3-dichloro-n-(5-oxo-3-phenyl-4h-1,2-oxazol-4-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NC1C(=O)ON=C1C1=CC=CC=C1 XNICNUOMZXJHOP-UHFFFAOYSA-N 0.000 claims description 3
- VRACKEYFARMVJV-UHFFFAOYSA-N 2,3-dichloro-n-[2-(3-methoxyphenyl)ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound COC1=CC=CC(CCNC(=O)C=2NC=3C(Cl)=C(Cl)SC=3C=2)=C1 VRACKEYFARMVJV-UHFFFAOYSA-N 0.000 claims description 3
- NQDKMZZPUJRMFX-UHFFFAOYSA-N 2,3-dichloro-n-phenacyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCC(=O)C1=CC=CC=C1 NQDKMZZPUJRMFX-UHFFFAOYSA-N 0.000 claims description 3
- JPQPVYASXUNYSU-UHFFFAOYSA-N 2-chloro-n-(1-methyl-2-oxo-3,4-dihydroquinolin-3-yl)-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2N(C)C(=O)C(NC(=O)C=3NC=4SC(Cl)=CC=4C=3)CC2=C1 JPQPVYASXUNYSU-UHFFFAOYSA-N 0.000 claims description 3
- ATTPRGDXYWVKCI-UHFFFAOYSA-N 2-chloro-n-[2-(2-methoxyphenyl)ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound COC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C=C(Cl)S2 ATTPRGDXYWVKCI-UHFFFAOYSA-N 0.000 claims description 3
- DERXKERCNNBZMF-UHFFFAOYSA-N 2-chloro-n-[2-[methyl(methylsulfonyl)amino]-1-(1,3-thiazol-2-yl)ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C=1C=2SC(Cl)=CC=2NC=1C(=O)NC(CN(C)S(C)(=O)=O)C1=NC=CS1 DERXKERCNNBZMF-UHFFFAOYSA-N 0.000 claims description 3
- NDIOKJQXEHMGDB-UHFFFAOYSA-N 2-chloro-n-phenacyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C=1C=2SC(Cl)=CC=2NC=1C(=O)NCC(=O)C1=CC=CC=C1 NDIOKJQXEHMGDB-UHFFFAOYSA-N 0.000 claims description 3
- APBGPCAPGLJDQR-UHFFFAOYSA-N 3-chloro-n-(2-phenylcyclopropyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=CSC=2C=C1C(=O)NC1CC1C1=CC=CC=C1 APBGPCAPGLJDQR-UHFFFAOYSA-N 0.000 claims description 3
- LHKOEGIODVFMQP-UHFFFAOYSA-N 3-chloro-n-(2-thiophen-2-ylethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=CSC=2C=C1C(=O)NCCC1=CC=CS1 LHKOEGIODVFMQP-UHFFFAOYSA-N 0.000 claims description 3
- IMMNOFWGJIRZSV-UHFFFAOYSA-N 3-chloro-n-[2-(4-fluorophenyl)ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC(F)=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=CS2 IMMNOFWGJIRZSV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
- VLGHAALCRDNBFW-UHFFFAOYSA-N methyl 2-[2-[2-[(2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carbonyl)amino]ethyl]phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 VLGHAALCRDNBFW-UHFFFAOYSA-N 0.000 claims description 3
- ZMHCCEWPRHUVJZ-UHFFFAOYSA-N n-[3-(4-acetamidophenoxy)-2-hydroxypropyl]-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC(NC(=O)C)=CC=C1OCC(O)CNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 ZMHCCEWPRHUVJZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- LUXLMNNGEKJWCH-UHFFFAOYSA-N tert-butyl n-[2-[(2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carbonyl)amino]-2,3-dihydro-1h-inden-1-yl]carbamate Chemical compound C1=CC=C2C(NC(=O)OC(C)(C)C)C(NC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CC2=C1 LUXLMNNGEKJWCH-UHFFFAOYSA-N 0.000 claims description 3
- CWEPYRUQSUKFIC-UHFFFAOYSA-N 2,3-dichloro-n-(1,2,3,4-tetrahydronaphthalen-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1CC2=CC=CC=C2CC1NC(=O)C1=CC(SC(=C2Cl)Cl)=C2N1 CWEPYRUQSUKFIC-UHFFFAOYSA-N 0.000 claims description 2
- OSKSLASJZCOWHQ-UHFFFAOYSA-N 2,3-dichloro-n-(1-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2C(O)C(NC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CCC2=C1 OSKSLASJZCOWHQ-UHFFFAOYSA-N 0.000 claims description 2
- FSFFDXIWVZJNNU-UHFFFAOYSA-N 2,3-dichloro-n-(1-hydroxy-3-phenylpropan-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C=1C=2SC(Cl)=C(Cl)C=2NC=1C(=O)NC(CO)CC1=CC=CC=C1 FSFFDXIWVZJNNU-UHFFFAOYSA-N 0.000 claims description 2
- BZWIVNBVZLWQSN-UHFFFAOYSA-N 2,3-dichloro-n-(2-morpholin-4-yl-2-oxoethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCC(=O)N1CCOCC1 BZWIVNBVZLWQSN-UHFFFAOYSA-N 0.000 claims description 2
- DPEDUCZSPJJIQI-UHFFFAOYSA-N 2,3-dichloro-n-(2-phenoxyethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCOC1=CC=CC=C1 DPEDUCZSPJJIQI-UHFFFAOYSA-N 0.000 claims description 2
- OLVIPIFAMYRLRW-UHFFFAOYSA-N 2,3-dichloro-n-(2-phenylcyclopropyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NC1CC1C1=CC=CC=C1 OLVIPIFAMYRLRW-UHFFFAOYSA-N 0.000 claims description 2
- LKAMUERYPRRVDB-UHFFFAOYSA-N 2,3-dichloro-n-(2-phenylethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCC1=CC=CC=C1 LKAMUERYPRRVDB-UHFFFAOYSA-N 0.000 claims description 2
- YCWIYWJVBBCPPD-UHFFFAOYSA-N 2,3-dichloro-n-(2-pyridazin-3-yloxyethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCOC1=CC=CN=N1 YCWIYWJVBBCPPD-UHFFFAOYSA-N 0.000 claims description 2
- LYKLOOLNTGYSNQ-UHFFFAOYSA-N 2,3-dichloro-n-(2-pyridin-2-ylethyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCC1=CC=CC=N1 LYKLOOLNTGYSNQ-UHFFFAOYSA-N 0.000 claims description 2
- YVWYKRPEVYLNQC-UHFFFAOYSA-N 2,3-dichloro-n-(3-phenylpropyl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCCCC1=CC=CC=C1 YVWYKRPEVYLNQC-UHFFFAOYSA-N 0.000 claims description 2
- WZBMLEXOPJGZEU-UHFFFAOYSA-N 2,3-dichloro-n-(5-hydroxy-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-4-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1C(=O)NC2=CC=CC=C2C(O)C1NC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 WZBMLEXOPJGZEU-UHFFFAOYSA-N 0.000 claims description 2
- LKYXKTBZJHVQIR-UHFFFAOYSA-N 2,3-dichloro-n-(6-fluoro-1-hydroxy-2,3-dihydro-1h-inden-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=C(F)C=C2C(O)C(NC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CC2=C1 LKYXKTBZJHVQIR-UHFFFAOYSA-N 0.000 claims description 2
- ZAGSWVIXOZESBN-UHFFFAOYSA-N 2,3-dichloro-n-(7-methoxy-1-oxo-3,4-dihydro-2h-naphthalen-2-yl)-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound O=C1C2=CC(OC)=CC=C2CCC1NC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 ZAGSWVIXOZESBN-UHFFFAOYSA-N 0.000 claims description 2
- QWMSIRNIFBXDIS-UHFFFAOYSA-N 2,3-dichloro-n-[(3-methyl-1,2-oxazol-5-yl)methyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound O1N=C(C)C=C1CNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 QWMSIRNIFBXDIS-UHFFFAOYSA-N 0.000 claims description 2
- LYCQTQJFUNMFHJ-UHFFFAOYSA-N 2,3-dichloro-n-[(4-sulfamoylphenyl)methyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 LYCQTQJFUNMFHJ-UHFFFAOYSA-N 0.000 claims description 2
- ACTUCSTUPDQLEC-UHFFFAOYSA-N 2,3-dichloro-n-[2-(1,1-dioxo-1,4-thiazinan-4-yl)-2-oxoethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCC(=O)N1CCS(=O)(=O)CC1 ACTUCSTUPDQLEC-UHFFFAOYSA-N 0.000 claims description 2
- JNHNHYYHRBHDQY-UHFFFAOYSA-N 2,3-dichloro-n-[2-(2-hydroxyphenyl)ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound OC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 JNHNHYYHRBHDQY-UHFFFAOYSA-N 0.000 claims description 2
- ACJYBCOMUPCYDN-UHFFFAOYSA-N 2,3-dichloro-n-[2-[2-(2-methoxyethoxy)phenyl]ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound COCCOC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 ACJYBCOMUPCYDN-UHFFFAOYSA-N 0.000 claims description 2
- NVSMDIROKXNRSW-UHFFFAOYSA-N 2,3-dichloro-n-[2-[2-[2-(4-hydroxypiperidin-1-yl)-2-oxoethoxy]phenyl]ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1CC(O)CCN1C(=O)COC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 NVSMDIROKXNRSW-UHFFFAOYSA-N 0.000 claims description 2
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- WEGGLKYGVCJOTP-UHFFFAOYSA-N methyl 3-(4-chlorophenyl)-2-[(2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carbonyl)amino]-3-hydroxypropanoate Chemical compound C=1C=2SC(Cl)=C(Cl)C=2NC=1C(=O)NC(C(=O)OC)C(O)C1=CC=C(Cl)C=C1 WEGGLKYGVCJOTP-UHFFFAOYSA-N 0.000 description 1
- BEMUCZOBFBMGJZ-UHFFFAOYSA-N methyl 3-chloro-4h-thieno[3,2-b]pyrrole-5-carboxylate Chemical compound S1C=C(Cl)C2=C1C=C(C(=O)OC)N2 BEMUCZOBFBMGJZ-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 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
- KYMXBGUBBFKNRL-UHFFFAOYSA-N n-(1-acetamido-2,3-dihydro-1h-inden-2-yl)-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2C(NC(=O)C)C(NC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CC2=C1 KYMXBGUBBFKNRL-UHFFFAOYSA-N 0.000 description 1
- BMPQTOZEDDKBBV-UHFFFAOYSA-N n-(1-amino-2,3-dihydro-1h-inden-2-yl)-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2C(N)C(NC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CC2=C1 BMPQTOZEDDKBBV-UHFFFAOYSA-N 0.000 description 1
- HJBVBVBDLHCAJG-UHFFFAOYSA-N n-(1-benzylsulfanyl-3-hydroxypropan-2-yl)-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C=1C=2SC(Cl)=C(Cl)C=2NC=1C(=O)NC(CO)CSCC1=CC=CC=C1 HJBVBVBDLHCAJG-UHFFFAOYSA-N 0.000 description 1
- KTXYHWOVCSGHBD-NXEZZACHSA-N n-[(1r,2r)-2-amino-2,3-dihydro-1h-inden-1-yl]methanesulfonamide Chemical compound C1=CC=C2[C@@H](NS(=O)(=O)C)[C@H](N)CC2=C1 KTXYHWOVCSGHBD-NXEZZACHSA-N 0.000 description 1
- KWTXDUHPTGHLNG-UHFFFAOYSA-N n-[2-[2-(2-amino-2-oxoethoxy)phenyl]ethyl]-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)COC1=CC=CC=C1CCNC(=O)C(N1)=CC2=C1C(Cl)=C(Cl)S2 KWTXDUHPTGHLNG-UHFFFAOYSA-N 0.000 description 1
- LNMZXBZZCUKWLI-UHFFFAOYSA-N n-[[6-(1,3-benzodioxol-5-yl)-4-methylmorpholin-2-yl]methyl]-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=C2OCOC2=CC(C2OC(CNC(=O)C=3NC=4C(Cl)=C(Cl)SC=4C=3)CN(C2)C)=C1 LNMZXBZZCUKWLI-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- DUIVBXGYYJPSJX-UHFFFAOYSA-N n-methylpropane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC DUIVBXGYYJPSJX-UHFFFAOYSA-N 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 108091000115 phosphomannomutase Proteins 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- HCSQZBYHTOEESB-KRWDZBQOSA-N tert-butyl N-[(1S)-2-phenyl-1-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)C=1ON=C(N=1)C=1C=CC=CC=1)C1=CC=CC=C1 HCSQZBYHTOEESB-KRWDZBQOSA-N 0.000 description 1
- XAJYUOBKHFIVFN-VXGBXAGGSA-N tert-butyl n-[(1r,2r)-2-amino-2,3-dihydro-1h-inden-1-yl]carbamate Chemical compound C1=CC=C2[C@@H](NC(=O)OC(C)(C)C)[C@H](N)CC2=C1 XAJYUOBKHFIVFN-VXGBXAGGSA-N 0.000 description 1
- CNFLJIVQBBJRKF-QWHCGFSZSA-N tert-butyl n-[(1r,2s)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]-n-methylcarbamate Chemical compound C1=CC=C2[C@@H](N(C)C(=O)OC(C)(C)C)[C@@H](O)CC2=C1 CNFLJIVQBBJRKF-QWHCGFSZSA-N 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 238000001665 trituration Methods 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
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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyrrole Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0021831.3A GB0021831D0 (en) | 2000-09-06 | 2000-09-06 | Chemical compounds |
PCT/SE2001/001880 WO2002020530A1 (en) | 2000-09-06 | 2001-08-31 | Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
SK2592003A3 true SK2592003A3 (en) | 2003-08-05 |
Family
ID=9898927
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK259-2003A SK2592003A3 (en) | 2000-09-06 | 2001-08-31 | Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors |
Country Status (31)
Country | Link |
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US (1) | US20030232875A1 (ru) |
EP (1) | EP1317459B1 (ru) |
JP (1) | JP2004508376A (ru) |
KR (1) | KR100802369B1 (ru) |
CN (2) | CN1896078A (ru) |
AT (1) | ATE263772T1 (ru) |
AU (2) | AU8283301A (ru) |
BG (1) | BG107624A (ru) |
BR (1) | BR0113606A (ru) |
CA (1) | CA2417594A1 (ru) |
CZ (1) | CZ2003616A3 (ru) |
DE (1) | DE60102710T2 (ru) |
DK (1) | DK1317459T3 (ru) |
EE (1) | EE200300083A (ru) |
ES (1) | ES2217183T3 (ru) |
GB (1) | GB0021831D0 (ru) |
HK (1) | HK1055299A1 (ru) |
HU (1) | HUP0400784A3 (ru) |
IL (1) | IL154291A0 (ru) |
IS (1) | IS2110B (ru) |
MX (1) | MXPA03001512A (ru) |
NO (1) | NO20031024D0 (ru) |
NZ (1) | NZ524011A (ru) |
PL (1) | PL361024A1 (ru) |
PT (1) | PT1317459E (ru) |
RU (1) | RU2003104013A (ru) |
SK (1) | SK2592003A3 (ru) |
TR (1) | TR200401659T4 (ru) |
UA (1) | UA73781C2 (ru) |
WO (1) | WO2002020530A1 (ru) |
ZA (1) | ZA200301013B (ru) |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
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CO5271699A1 (es) * | 2000-01-24 | 2003-04-30 | Pfizer Prod Inc | Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa |
PE20020856A1 (es) * | 2001-02-13 | 2002-11-11 | Aventis Pharma Gmbh | 1,2,3,4-tetrahidronaftil aminas aciladas |
TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
GB0205175D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205162D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205170D0 (en) * | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205165D0 (en) * | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205166D0 (en) * | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
GB0205176D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
DE10215908B4 (de) * | 2002-04-11 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Acyl-3-carboxyphenyl-harnstoffderivate und deren Verwendung als Arzneimittel |
IL164249A0 (en) * | 2002-04-11 | 2005-12-18 | Aventis Pharma Gmbh | Acyl-3-carboxphenylurea derivatives, processes forpreparing them and their use |
US7057046B2 (en) * | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
DE10225635C1 (de) * | 2002-06-07 | 2003-12-24 | Aventis Pharma Gmbh | N-Benzoylureido-Zimtsäurederivate, Verfahren zu deren Herstellung und deren Verwendung |
PT1375477E (pt) * | 2002-06-17 | 2009-11-20 | Saltigo Gmbh | Processo para a preparação de diaminas mono-nsulfoniladas |
DE50311923D1 (de) * | 2002-07-11 | 2009-10-29 | Sanofi Aventis Deutschland | Harnstoff- und urethan-substituierte acylharnstoffe, verfahren zu deren herstellung und deren verwendung als arzneimittel |
EP1388535A1 (en) * | 2002-08-07 | 2004-02-11 | Aventis Pharma Deutschland GmbH | Acylated arylcycloalkylamines and their use as pharmaceuticals |
US7186735B2 (en) | 2002-08-07 | 2007-03-06 | Sanofi-Aventis Deutschland Gmbh | Acylated arylcycloalkylamines and their use as pharmaceuticals |
GB0222909D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
GB0222912D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
WO2004041780A2 (en) * | 2002-11-07 | 2004-05-21 | Pfizer Products Inc. | N-(indole-2-carbonyl) amides as anti-diabetic agents |
BRPI0409465A (pt) | 2003-04-17 | 2006-05-02 | Pfizer Prod Inc | derivados de carboxamida como agentes antidiabéticos |
US7405210B2 (en) | 2003-05-21 | 2008-07-29 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase |
EP1636224B1 (en) * | 2003-05-21 | 2010-07-14 | Prosidion Limited | Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phoshorylase |
WO2004113345A1 (ja) * | 2003-06-20 | 2004-12-29 | Japan Tobacco Inc. | 縮合ピロール化合物及びその医薬用途 |
GB0318464D0 (en) * | 2003-08-07 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
GB0318463D0 (en) * | 2003-08-07 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
GB0319690D0 (en) * | 2003-08-22 | 2003-09-24 | Astrazeneca Ab | Chemical compounds |
GB0319759D0 (en) * | 2003-08-22 | 2003-09-24 | Astrazeneca Ab | Chemical compounds |
WO2005020986A1 (en) * | 2003-08-29 | 2005-03-10 | Astrazeneca Ab | Heterocyclic amide derivatives which posses glycogen phosphorylase inhibitory activity |
WO2005020985A1 (en) * | 2003-08-29 | 2005-03-10 | Astrazeneca Ab | Indolamide derivatives which possess glycogen phosphorylase inhibitory activity |
GB0320422D0 (en) * | 2003-08-30 | 2003-10-01 | Astrazeneca Ab | Chemical compounds |
PL380887A1 (pl) | 2003-12-29 | 2007-04-02 | Sepracor Inc. | Pirolowe i pirazolowe inhibitory DAAO |
US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
US7226942B2 (en) | 2004-11-15 | 2007-06-05 | Bristol-Myers Squibb Company | 2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
US7214704B2 (en) | 2004-11-15 | 2007-05-08 | Bristol-Myers Squibb Company | 2-Amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
US7223786B2 (en) | 2004-11-15 | 2007-05-29 | Bristol-Myers Squibb Company | 2-aminonaphthalene derivatives and related glycogen phosphorylase inhibitors |
US7365061B2 (en) | 2004-11-15 | 2008-04-29 | Bristol-Myers Squibb Company | 2-Amino-3-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
WO2006059163A1 (en) * | 2004-12-02 | 2006-06-08 | Prosidion Limited | Treatment of diabetes with glycogen phosphorylase inhibitors |
ES2309822T3 (es) * | 2004-12-02 | 2008-12-16 | Prosidion Limited | Derivado de amida del acido pirrolopiridina-2-carboxilico util como inhibidor de la glucogeno-fosforilasa. |
US8338614B2 (en) | 2005-01-19 | 2012-12-25 | Merck, Sharp & Dohme Corp. | Tertiary carbinamines having substituted heterocycles which are active as β-secretase inhibitors for the treatment of alzheimer's disease |
US20090124682A1 (en) * | 2005-02-05 | 2009-05-14 | Alan Martin Birch | Indan-Amide Derivatives with Glycogen Phosphorylase Inhibitory Activity |
BRPI0606838A2 (pt) * | 2005-02-05 | 2010-02-09 | Astrazeneca Ab | composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, e, processo para preparação de um composto ou um sal farmaceuticamente aceitável do mesmo |
ES2594156T3 (es) | 2006-01-06 | 2016-12-16 | Sunovion Pharmaceuticals Inc. | Cicloalquilaminas como inhibidores de la recaptación de monoaminas |
JP5438975B2 (ja) | 2006-01-06 | 2014-03-12 | サノビオン ファーマシューティカルズ インク | テトラロン系モノアミン再取り込み阻害剤 |
WO2007115185A2 (en) | 2006-03-31 | 2007-10-11 | Sepracor Inc. | Preparation of chiral amides and amines |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
EP2298772A1 (en) * | 2006-10-18 | 2011-03-23 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compounds |
US7902252B2 (en) | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
NZ580429A (en) | 2007-05-31 | 2012-04-27 | Sepracor Inc | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
US20100152200A1 (en) * | 2008-11-17 | 2010-06-17 | The Regents Of The University Of Michigan | Alphavirus inhibitors and uses thereof |
US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
KR102272746B1 (ko) | 2013-06-05 | 2021-07-08 | 보슈 헬스 아일랜드 리미티드 | 구아닐레이트 사이클라제 c의 초순수 작용제, 및 이의 제조 및 사용 방법 |
DK3186242T3 (da) | 2014-08-29 | 2021-12-20 | Tes Pharma S R L | Alfa-amino-beta-carboxymuconsyre-semialdehyd-decarboxylasehæmmere |
CN111269221B (zh) * | 2015-07-02 | 2023-09-26 | 豪夫迈·罗氏有限公司 | 二环内酰胺和其应用方法 |
WO2017136727A2 (en) * | 2016-02-05 | 2017-08-10 | Denali Therapeutics Inc. | Compounds, compositions and methods |
EP3526199B1 (en) | 2016-10-14 | 2022-04-13 | Tes Pharma S.r.l. | Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase |
EP3526219B1 (en) | 2016-10-17 | 2021-12-15 | F. Hoffmann-La Roche AG | Bicyclic pyridone lactams and methods of use thereof |
US11072607B2 (en) | 2016-12-16 | 2021-07-27 | Genentech, Inc. | Inhibitors of RIP1 kinase and methods of use thereof |
WO2019204537A1 (en) | 2018-04-20 | 2019-10-24 | Genentech, Inc. | N-[4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol e-2-carboxamide derivatives and related compounds as rip1 kinase inhibitors for treating e.g. irritable bowel syndrome (ibs) |
AR117122A1 (es) | 2018-11-20 | 2021-07-14 | Tes Pharma S R L | INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA |
JPWO2021106988A1 (ru) * | 2019-11-27 | 2021-06-03 |
Family Cites Families (19)
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 |
US4692522A (en) * | 1985-04-01 | 1987-09-08 | Merck & Co., Inc. | Benzofused lactams useful as cholecystokinin antagonists |
US4668769A (en) * | 1985-08-02 | 1987-05-26 | Hoover Dennis J | Oxa- and azahomocyclostatine polypeptides |
US4720503A (en) * | 1985-08-02 | 1988-01-19 | Merck & Co., Inc. | N-substituted fused-heterocyclic carboxamide derivatives as dual cyclooxygenase and lipoxygenase inhibitors |
US4599198A (en) * | 1985-08-02 | 1986-07-08 | Pfizer Inc. | Intermediates in polypeptide synthesis |
FR2601368B1 (fr) * | 1986-07-08 | 1989-04-07 | Synthelabo | Derives de nitrofuranne, leur preparation et leur application en therapeutique. |
DE3629545A1 (de) * | 1986-08-30 | 1988-03-10 | Bayer Ag | Dihydropyridinverbindungen, verfahren zu ihrer herstellung und ihre verwendung |
US4751231A (en) * | 1987-09-16 | 1988-06-14 | Merck & Co., Inc. | Substituted thieno[2,3-b]pyrrole-5-sulfonamides as antiglaucoma agents |
ES2081747B1 (es) * | 1993-09-07 | 1997-01-16 | Esteve Labor Dr | Amidas derivadas de tienopirroles, su preparacion y su aplicacion como medicamentos. |
US5863903A (en) * | 1994-03-09 | 1999-01-26 | Novo Nordisk A/S | Use of hydroxy alkyl piperidine and pyrrolidine compounds to treat diabetes |
FR2723739B1 (fr) * | 1994-08-19 | 1997-02-14 | Sanofi Sa | Derives de glycinamide, procedes pour leur preparation et medicaments les contenant. |
CA2224062C (en) * | 1995-06-06 | 2001-09-04 | Pfizer Limited | Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors |
US5952322A (en) * | 1996-12-05 | 1999-09-14 | Pfizer Inc. | Method of reducing tissue damage associated with non-cardiac ischemia using glycogen phosphorylase inhibitors |
US5998463A (en) * | 1998-02-27 | 1999-12-07 | Pfizer Inc | Glycogen phosphorylase inhibitors |
WO1999046268A1 (en) * | 1998-03-12 | 1999-09-16 | Novo Nordisk A/S | MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPases) |
DE60007592T2 (de) * | 1999-09-30 | 2004-09-16 | Pfizer Products Inc., Groton | Bicyclische Pyrrolylamide als Glycogenphosphorylase-Inhibitoren |
CO5271699A1 (es) * | 2000-01-24 | 2003-04-30 | Pfizer Prod Inc | Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa |
US6555569B2 (en) * | 2000-03-07 | 2003-04-29 | Pfizer Inc. | Use of heteroaryl substituted N-(indole-2-carbonyl-) amides for treatment of infection |
US7057046B2 (en) * | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
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