SK2592003A3 - Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors - Google Patents

Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors Download PDF

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Publication number: SK2592003A3
Authority: SK; Slovakia
Prior art keywords: carbamoyl; pyrrole; thieno; alkyl; carbon atoms
Prior art date: 2000-09-06

Application number

SK259-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Julie B Bartlett

Sue Freeman

Peter Kenny

Andrew Morley

Paul Whittamore

Original Assignee

Astrazeneca Ab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-09-06

Filing date

2001-08-31

Publication date

2003-08-05

2001-08-31 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2003-08-05 Publication of SK2592003A3 publication Critical patent/SK2592003A3/sk

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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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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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Child & Adolescent Psychology (AREA)
Cardiology (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)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Enzymes And Modification Thereof (AREA)

SK259-2003A 2000-09-06 2001-08-31 Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors SK2592003A3 (en)

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

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ID=9898927

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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 (30)

Country	Link
US (1)	US20030232875A1 (pl)
EP (1)	EP1317459B1 (pl)
JP (1)	JP2004508376A (pl)
KR (1)	KR100802369B1 (pl)
CN (2)	CN1264846C (pl)
AT (1)	ATE263772T1 (pl)
AU (2)	AU8283301A (pl)
BG (1)	BG107624A (pl)
BR (1)	BR0113606A (pl)
CA (1)	CA2417594A1 (pl)
CZ (1)	CZ2003616A3 (pl)
DE (1)	DE60102710T2 (pl)
DK (1)	DK1317459T3 (pl)
EE (1)	EE200300083A (pl)
ES (1)	ES2217183T3 (pl)
GB (1)	GB0021831D0 (pl)
HU (1)	HUP0400784A3 (pl)
IL (1)	IL154291A0 (pl)
IS (1)	IS2110B (pl)
MX (1)	MXPA03001512A (pl)
NO (1)	NO20031024D0 (pl)
NZ (1)	NZ524011A (pl)
PL (1)	PL361024A1 (pl)
PT (1)	PT1317459E (pl)
RU (1)	RU2003104013A (pl)
SK (1)	SK2592003A3 (pl)
TR (1)	TR200401659T4 (pl)
UA (1)	UA73781C2 (pl)
WO (1)	WO2002020530A1 (pl)
ZA (1)	ZA200301013B (pl)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
GB0205166D0 (en) *	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205175D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205162D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205165D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205176D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205170D0 (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
DE10215907A1 (de) *	2002-04-11	2003-11-06	Aventis Pharma Gmbh	Acyl-4-carboxyphenyl-harnstoffderivate, Verfahren zu deren Herstellung und deren Verwendung
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
EP1375477B1 (de) *	2002-06-17	2009-09-30	Saltigo GmbH	Verfahren zur Herstellung von mono-N-sulfonylierten Diaminen
BR0312593A (pt) *	2002-07-11	2005-04-12	Aventis Pharma Gmbh	Aciluréias substituìdas por uréia e uretano, processo para a sua produção e sua aplicação
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
MXPA05012547A (es) *	2003-05-21	2006-05-25	Prosidion Ltd	Inhibidores de amida de acido pirrolopiridina-2-carboxilico de fosforilasa de glucogeno.
US7405210B2 (en)	2003-05-21	2008-07-29	Osi Pharmaceuticals, Inc.	Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase
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
GB0319759D0 (en) *	2003-08-22	2003-09-24	Astrazeneca Ab	Chemical compounds
GB0319690D0 (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
JP2007517056A (ja)	2003-12-29	2007-06-28	セプラコアインコーポレーテッド	ピロール及びピラゾールｄａａｏ阻害剤
US7453002B2 (en)	2004-06-15	2008-11-18	Bristol-Myers Squibb Company	Five-membered heterocycles useful as serine protease inhibitors
WO2006055462A1 (en) *	2004-11-15	2006-05-26	Bristol-Myers Squibb Company	2-amino-4-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
WO2006053274A2 (en) *	2004-11-15	2006-05-18	Bristol-Myers Squibb Company	2-amino-1-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
PL1819704T3 (pl)	2004-12-02	2008-12-31	Prosidion Ltd	Amidowe pochodne kwasu pirolopirydyno-2-karboksylowego użyteczne jako inhibitory fosforylazy glikogenowej
CA2594946A1 (en) *	2005-01-19	2006-07-27	Merck & Co., Inc	Tertiary carbinamines having substituted heterocycles, which are active as inhibitors of beta-secretase, for the treatment of alzheimer's disease
US20100137397A1 (en) *	2005-02-05	2010-06-03	Astrazeneca Ab	Chemical Compounds
US20090124682A1 (en) *	2005-02-05	2009-05-14	Alan Martin Birch	Indan-Amide Derivatives with Glycogen Phosphorylase Inhibitory Activity
US20070203111A1 (en)	2006-01-06	2007-08-30	Sepracor Inc.	Cycloalkylamines as monoamine reuptake inhibitors
NZ569608A (en)	2006-01-06	2011-09-30	Sepracor Inc	Tetralone-based monoamine reuptake inhibitors
CN101421228B (zh)	2006-03-31	2014-05-21	塞普拉柯公司	手性酰胺和胺的制备
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
EP2077267A4 (en) *	2006-10-18	2010-04-07	Takeda Pharmaceutical	CONDENSED HETEROCYCLIC COMPOUND
US7902252B2 (en)	2007-01-18	2011-03-08	Sepracor, Inc.	Inhibitors of D-amino acid oxidase
CA2688493C (en)	2007-05-31	2016-04-19	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
SI3004138T1 (sl)	2013-06-05	2024-07-31	Bausch Health Ireland Limited	Ultra čisti agonisti gvanilat ciklaze C, postopek za njihovo pripravo in uporabo
CN111978319B (zh)	2014-06-27	2023-08-11	诺格拉制药有限公司	芳基受体调制剂及其制备和使用方法
KR102431436B1 (ko)	2014-08-29	2022-08-10	테스 파마 에스.알.엘.	α-아미노-β-카복시뮤콘산 세미알데히드 데카복실라제의 억제제
TWI763630B (zh) *	2015-07-02	2022-05-11	瑞士商赫孚孟拉羅股份公司	雙環內醯胺及其使用方法
MA44007A (fr) *	2016-02-05	2018-12-19	Denali Therapeutics Inc	Inhibiteurs du récepteur interagissant avec protéine kinase 1
AR109950A1 (es)	2016-10-14	2019-02-06	Tes Pharma S R L	INHIBIDORES DE LA ÁCIDO a-AMINO-b-CARBOXIMUCÓNICO SEMIALDEHÍDO DESCARBOXILASA
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
TW202115086A (zh) *	2019-06-28	2021-04-16	美商輝瑞大藥廠	Bckdk抑制劑
EP4066896A4 (en) *	2019-11-27	2024-03-27	Riken	G9A INHIBITOR

Family Cites Families (19)

* Cited by examiner, † Cited by third party
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
JP2002506073A (ja) *	1998-03-12	2002-02-26	ノボノルディスクアクティーゼルスカブ	プロテイン・チロシン・ホスファターゼ（ＰＴＰａｓｅｓ）のモジュレーター
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

2000
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2001
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- 2001-08-31 AU AU8283301A patent/AU8283301A/xx active Pending
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- 2001-08-31 JP JP2002525151A patent/JP2004508376A/ja not_active Withdrawn
- 2001-08-31 SK SK259-2003A patent/SK2592003A3/sk unknown
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- 2001-08-31 KR KR1020037003265A patent/KR100802369B1/ko not_active Expired - Fee Related
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- 2001-08-31 CN CNA2006100818966A patent/CN1896078A/zh active Pending
- 2001-08-31 AT AT01961577T patent/ATE263772T1/de not_active IP Right Cessation
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HUP0400784A2 (hu)	2004-07-28
TR200401659T4 (tr)	2004-09-21
HK1055299A1 (en)	2004-01-02
EP1317459A1 (en)	2003-06-11
ES2217183T3 (es)	2004-11-01
JP2004508376A (ja)	2004-03-18
KR100802369B1 (ko)	2008-02-14
PT1317459E (pt)	2004-08-31
AU2001282833B2 (en)	2006-07-06
GB0021831D0 (en)	2000-10-18
DK1317459T3 (da)	2004-07-12
BR0113606A (pt)	2003-06-24
CN1264846C (zh)	2006-07-19
CZ2003616A3 (cs)	2003-05-14
NO20031024L (no)	2003-03-05
KR20030025305A (ko)	2003-03-28
US20030232875A1 (en)	2003-12-18
ZA200301013B (en)	2004-05-05
AU8283301A (en)	2002-03-22
RU2003104013A (ru)	2004-08-20
HUP0400784A3 (en)	2007-09-28
EE200300083A (et)	2004-12-15
DE60102710D1 (de)	2004-05-13
UA73781C2 (en)	2005-09-15
IL154291A0 (en)	2003-09-17
DE60102710T2 (de)	2005-04-14
CA2417594A1 (en)	2002-03-14
CN1473163A (zh)	2004-02-04
IS2110B (is)	2006-05-15
CN1896078A (zh)	2007-01-17
WO2002020530A1 (en)	2002-03-14
ATE263772T1 (de)	2004-04-15
BG107624A (bg)	2004-01-30
EP1317459B1 (en)	2004-04-07
IS6727A (is)	2003-02-24
MXPA03001512A (es)	2003-06-09
PL361024A1 (pl)	2004-09-20
NO20031024D0 (no)	2003-03-05
NZ524011A (en)	2004-08-27

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Publication	Publication Date	Title
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WO2007070796A1 (en)	2007-06-21	Azepinoindole derivatives as pharmaceutical agents
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JP2007503420A (ja)	2007-02-22	グリコーゲンホスホリラーゼ阻害活性を保有する複素環式アミド誘導体
EP0008950A2 (en)	1980-03-19	Pyrimido(1,6-a)indole derivatives and intermediates therefor, processes for their preparation, pharmaceutical compositions containing the derivatives and their use
HK1055299B (en)	2004-10-21	Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
JP2008528667A (ja)	2008-07-31	化合物