BG107624A - Бициклени пиролил амиди като гликоген фосфорилазни инхибитори - Google Patents

Бициклени пиролил амиди като гликоген фосфорилазни инхибитори Download PDF

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Publication number: BG107624A
Authority: BG; Bulgaria
Prior art keywords: carbamoyl; pyrrole; thieno; dichloro; alkyl
Prior art date: 2000-09-06

Application number

BG107624A

Other languages

Bulgarian (bg)

English (en)

Inventor

Julie B. Bartlet

Sue Freeman

Peter Kenny

Andrew Morley

Raul 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

2003-03-10

Publication date

2004-01-30

2003-03-10 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-01-30 Publication of BG107624A publication Critical patent/BG107624A/bg

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-1 Bicyclic pyrrolyl amides Chemical class 0.000 title claims abstract description 728
239000003112 inhibitor Substances 0.000 title description 7
102000009097 Phosphorylases Human genes 0.000 title description 2
108010073135 Phosphorylases Proteins 0.000 title description 2
150000003839 salts Chemical class 0.000 claims abstract description 39
150000002148 esters Chemical class 0.000 claims abstract description 30
238000001727 in vivo Methods 0.000 claims abstract description 28
108010046163 Glycogen Phosphorylase Proteins 0.000 claims abstract description 17
102000007390 Glycogen Phosphorylase Human genes 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract description 12
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 374
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 320
125000000217 alkyl group Chemical group 0.000 claims description 318
150000001875 compounds Chemical class 0.000 claims description 174
229910052757 nitrogen Inorganic materials 0.000 claims description 100
229910052739 hydrogen Inorganic materials 0.000 claims description 98
239000001257 hydrogen Substances 0.000 claims description 95
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 93
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
125000000623 heterocyclic group Chemical group 0.000 claims description 61
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
125000005843 halogen group Chemical group 0.000 claims description 52
125000003545 alkoxy group Chemical group 0.000 claims description 51
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
229910052799 carbon Inorganic materials 0.000 claims description 44
125000003118 aryl group Chemical group 0.000 claims description 40
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
150000001721 carbon Chemical group 0.000 claims description 37
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 30
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 30
125000005236 alkanoylamino group Chemical group 0.000 claims description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
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
125000000753 cycloalkyl group Chemical group 0.000 claims description 25
125000004423 acyloxy group Chemical group 0.000 claims description 24
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 24
125000003342 alkenyl group Chemical group 0.000 claims description 23
125000000304 alkynyl group Chemical group 0.000 claims description 21
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 20
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 20
229910052717 sulfur Inorganic materials 0.000 claims description 20
DWAIOCIOSRZZHO-UHFFFAOYSA-N 4h-thieno[3,2-b]pyrrole Chemical compound S1C=CC2=C1C=CN2 DWAIOCIOSRZZHO-UHFFFAOYSA-N 0.000 claims description 19
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 19
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 19
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 18
241001465754 Metazoa Species 0.000 claims description 17
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 17
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
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 15
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 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
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 14
125000005002 aryl methyl group Chemical group 0.000 claims description 14
125000001072 heteroaryl group Chemical group 0.000 claims description 14
230000002401 inhibitory effect Effects 0.000 claims description 13
125000005505 thiomorpholino group Chemical group 0.000 claims description 13
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 12
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 11
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
125000001589 carboacyl group Chemical group 0.000 claims description 11
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 11
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 10
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 10
125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
241000282414 Homo sapiens Species 0.000 claims description 9
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
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
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 8
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 7
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 7
125000003107 substituted aryl group Chemical group 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims description 6
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 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
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 4
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 4
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
KSNOBMPPSWRYAR-UHFFFAOYSA-N 2-chloro-n-[2-[[3-(trifluoromethyl)pyridin-2-yl]amino]ethyl]-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound FC(F)(F)C1=CC=CN=C1NCCNC(=O)C(N1)=CC2=C1C=C(Cl)S2 KSNOBMPPSWRYAR-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
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000004432 carbon atom Chemical group C* 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
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
AZFSIXJWMGOBIS-UHFFFAOYSA-N 2-chloro-n-(2,3-dihydro-1h-inden-2-yl)-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound C1C2=CC=CC=C2CC1NC(=O)C1=CC(C=C(S2)Cl)=C2N1 AZFSIXJWMGOBIS-UHFFFAOYSA-N 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
VITUATBDFRQRIL-UHFFFAOYSA-N benzyl n-[3-[(2-chloro-4h-thieno[3,2-b]pyrrole-5-carbonyl)amino]propyl]carbamate Chemical compound C=1C=2SC(Cl)=CC=2NC=1C(=O)NCCCNC(=O)OCC1=CC=CC=C1 VITUATBDFRQRIL-UHFFFAOYSA-N 0.000 claims description 2
150000003950 cyclic amides Chemical class 0.000 claims description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
DWGKPIYUXLZLSG-UHFFFAOYSA-N n-(1,2-benzoxazol-3-ylmethyl)-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2C(CNC(=O)C3=CC=4SC(=C(C=4N3)Cl)Cl)=NOC2=C1 DWGKPIYUXLZLSG-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
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 1
RYZWHPXUBJROJE-UHFFFAOYSA-N 3-chloro-n-phenacyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=CSC=2C=C1C(=O)NCC(=O)C1=CC=CC=C1 RYZWHPXUBJROJE-UHFFFAOYSA-N 0.000 claims 1
MYTYHLDSYLKPSF-UHFFFAOYSA-N 6h-thieno[2,3-b]pyrrole Chemical compound C1=CSC2=C1C=CN2 MYTYHLDSYLKPSF-UHFFFAOYSA-N 0.000 claims 1
125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
125000004122 cyclic group Chemical group 0.000 claims 1
ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 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 claims 1
VKWIFFHOFWDMHE-UHFFFAOYSA-N n-benzyl-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=C(Cl)SC=2C=C1C(=O)NCC1=CC=CC=C1 VKWIFFHOFWDMHE-UHFFFAOYSA-N 0.000 claims 1
238000000034 method Methods 0.000 abstract description 171
230000008569 process Effects 0.000 abstract description 22
238000011282 treatment Methods 0.000 abstract description 17
230000000694 effects Effects 0.000 abstract description 13
230000005764 inhibitory process Effects 0.000 abstract description 8
230000002969 morbid Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 178
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 176
239000000243 solution Substances 0.000 description 132
239000000203 mixture Substances 0.000 description 122
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 118
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
238000005481 NMR spectroscopy Methods 0.000 description 92
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
239000007787 solid Substances 0.000 description 73
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
235000019439 ethyl acetate Nutrition 0.000 description 67
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 60
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 56
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 49
239000011541 reaction mixture Substances 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
230000002829 reductive effect Effects 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
150000002431 hydrogen Chemical class 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
229910052943 magnesium sulfate Inorganic materials 0.000 description 36
235000019341 magnesium sulphate Nutrition 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
125000002252 acyl group Chemical group 0.000 description 30
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 29
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 29
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 24
239000000377 silicon dioxide Substances 0.000 description 23
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
238000000451 chemical ionisation Methods 0.000 description 22
239000003480 eluent Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 20
150000001412 amines Chemical class 0.000 description 20
239000000706 filtrate Substances 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
238000004587 chromatography analysis Methods 0.000 description 17
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 16
229920006395 saturated elastomer Polymers 0.000 description 15
JFGOCNAOOLXIMV-UHFFFAOYSA-N 2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxylic acid Chemical compound S1C(Cl)=C(Cl)C2=C1C=C(C(=O)O)N2 JFGOCNAOOLXIMV-UHFFFAOYSA-N 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000000126 substance Substances 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
239000000284 extract Substances 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
238000005160 1H NMR spectroscopy Methods 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
239000000725 suspension Substances 0.000 description 11
208000001072 type 2 diabetes mellitus Diseases 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
229960001031 glucose Drugs 0.000 description 10
239000010410 layer Substances 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
239000000047 product Substances 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
239000002904 solvent Substances 0.000 description 10
SOGNHUJSAKAIRG-UHFFFAOYSA-N 2-chloro-6h-thieno[2,3-b]pyrrole-5-carboxylic acid Chemical compound C1=C(Cl)SC2=C1C=C(C(=O)O)N2 SOGNHUJSAKAIRG-UHFFFAOYSA-N 0.000 description 9
239000012131 assay buffer Substances 0.000 description 9
238000001035 drying Methods 0.000 description 9
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238000007796 conventional method Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000002993 cycloalkylene group Chemical group 0.000 description 1
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000000428 dust Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
KDGBBRFBCPCHDS-UHFFFAOYSA-N ethyl 2-[methyl(methylsulfonyl)amino]acetate Chemical compound CCOC(=O)CN(C)S(C)(=O)=O KDGBBRFBCPCHDS-UHFFFAOYSA-N 0.000 description 1
QXJAISFCHYMQPF-UHFFFAOYSA-N ethyl 4-phenyl-1,2-oxazole-3-carboxylate Chemical compound CCOC(=O)C1=NOC=C1C1=CC=CC=C1 QXJAISFCHYMQPF-UHFFFAOYSA-N 0.000 description 1
AGFXIDUOQOTKNO-AWEZNQCLSA-N ethyl 5-[(1s)-1-[(2-chloro-6h-thieno[2,3-b]pyrrole-5-carbonyl)amino]-2-phenylethyl]-1,3,4-oxadiazole-2-carboxylate Chemical compound O1C(C(=O)OCC)=NN=C1[C@@H](NC(=O)C=1NC=2SC(Cl)=CC=2C=1)CC1=CC=CC=C1 AGFXIDUOQOTKNO-AWEZNQCLSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
230000000855 fungicidal effect Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000001890 gluconeogenic effect Effects 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
229960002743 glutamine Drugs 0.000 description 1
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
238000001802 infusion Methods 0.000 description 1
150000002485 inorganic esters Chemical class 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
230000004410 intraocular pressure Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
150000002689 maleic acids Chemical class 0.000 description 1
239000002609 medium Substances 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
NVGZUFPJPZPJBW-UHFFFAOYSA-N methyl 2-[2-(2-aminoethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=CC=C1CCN NVGZUFPJPZPJBW-UHFFFAOYSA-N 0.000 description 1
RXYCUKSOYJWGPE-UHFFFAOYSA-N methyl 2-azidoacetate Chemical compound COC(=O)CN=[N+]=[N-] RXYCUKSOYJWGPE-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-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
150000007522 mineralic acids Chemical class 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
HYSMMFXCEYNSLA-UHFFFAOYSA-N n-(1,3-benzothiazol-2-ylmethyl)-2,3-dichloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC=C2SC(CNC(=O)C3=CC=4SC(=C(C=4N3)Cl)Cl)=NC2=C1 HYSMMFXCEYNSLA-UHFFFAOYSA-N 0.000 description 1
JZTLPJKMSMDRDT-UHFFFAOYSA-N n-(2-hydroxy-3-phenoxypropyl)acetamide Chemical compound CC(=O)NCC(O)COC1=CC=CC=C1 JZTLPJKMSMDRDT-UHFFFAOYSA-N 0.000 description 1
LGYMIWAYGWVTKU-UHFFFAOYSA-N n-[2-(benzylsulfonylamino)ethyl]-3-chloro-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound N1C=2C(Cl)=CSC=2C=C1C(=O)NCCNS(=O)(=O)CC1=CC=CC=C1 LGYMIWAYGWVTKU-UHFFFAOYSA-N 0.000 description 1
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 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
230000001537 neural effect Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910001120 nichrome Inorganic materials 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
239000002674 ointment Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
238000010979 pH adjustment Methods 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
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000002831 pharmacologic agent 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
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 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
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-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
239000002243 precursor Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
108090000765 processed proteins & peptides Proteins 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
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
150000003233 pyrroles Chemical class 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
229960000948 quinine Drugs 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
239000011435 rock Substances 0.000 description 1
230000028327 secretion Effects 0.000 description 1
235000012239 silicon dioxide Nutrition 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
SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000010561 standard procedure Methods 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
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ROUONLKDWVQKNB-NWDGAFQWSA-N tert-butyl n-[(1r,2s)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]carbamate Chemical compound C1=CC=C2[C@@H](NC(=O)OC(C)(C)C)[C@@H](O)CC2=C1 ROUONLKDWVQKNB-NWDGAFQWSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 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
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
208000019553 vascular disease Diseases 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
238000010792 warming Methods 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)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Emergency Medicine (AREA)
Oncology (AREA)
Communicable Diseases (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)
Enzymes And Modification Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

BG107624A 2000-09-06 2003-03-10 Бициклени пиролил амиди като гликоген фосфорилазни инхибитори BG107624A (bg)

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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
BG107624A true BG107624A (bg)	2004-01-30

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Country Status (30)

Country	Link
US (1)	US20030232875A1 (et)
EP (1)	EP1317459B1 (et)
JP (1)	JP2004508376A (et)
KR (1)	KR100802369B1 (et)
CN (2)	CN1896078A (et)
AT (1)	ATE263772T1 (et)
AU (2)	AU8283301A (et)
BG (1)	BG107624A (et)
BR (1)	BR0113606A (et)
CA (1)	CA2417594A1 (et)
CZ (1)	CZ2003616A3 (et)
DE (1)	DE60102710T2 (et)
DK (1)	DK1317459T3 (et)
EE (1)	EE200300083A (et)
ES (1)	ES2217183T3 (et)
GB (1)	GB0021831D0 (et)
HU (1)	HUP0400784A3 (et)
IL (1)	IL154291A0 (et)
IS (1)	IS2110B (et)
MX (1)	MXPA03001512A (et)
NO (1)	NO20031024L (et)
NZ (1)	NZ524011A (et)
PL (1)	PL361024A1 (et)
PT (1)	PT1317459E (et)
RU (1)	RU2003104013A (et)
SK (1)	SK2592003A3 (et)
TR (1)	TR200401659T4 (et)
UA (1)	UA73781C2 (et)
WO (1)	WO2002020530A1 (et)
ZA (1)	ZA200301013B (et)

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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
TWI243164B (en)	2001-02-13	2005-11-11	Aventis Pharma Gmbh	Acylated indanyl amines and their use as pharmaceuticals
PE20020856A1 (es) *	2001-02-13	2002-11-11	Aventis Pharma Gmbh	1,2,3,4-tetrahidronaftil aminas aciladas
GB0205162D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205170D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205175D0 (en)	2002-03-06	2002-04-17	Astrazeneca Ab	Chemical compounds
GB0205166D0 (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
DE10215907A1 (de) *	2002-04-11	2003-11-06	Aventis Pharma Gmbh	Acyl-4-carboxyphenyl-harnstoffderivate, Verfahren zu deren Herstellung und deren Verwendung
DE10215908B4 (de) *	2002-04-11	2005-08-18	Aventis Pharma Deutschland Gmbh	Acyl-3-carboxyphenyl-harnstoffderivate und deren Verwendung als Arzneimittel
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
ATE444284T1 (de) *	2002-06-17	2009-10-15	Saltigo Gmbh	Verfahren zur herstellung von mono-n- sulfonylierten diaminen
MXPA05000055A (es) *	2002-07-11	2005-04-08	Aventis Pharma Gmbh	Acilureas sustituidas con urea y uretano, metodos para su produccion y su uso.
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
JP2006507294A (ja) *	2002-11-07	2006-03-02	ファイザー・プロダクツ・インク	抗糖尿病剤
EP1620427A1 (en)	2003-04-17	2006-02-01	Pfizer Products Inc.	Carboxamide derivatives as anti-diabetic agents
JP2006528702A (ja) *	2003-05-21	2006-12-21	プロシディオン・リミテッド	グリコーゲンホスホリラーゼのピロロピリジン−２−カルボン酸アミドインヒビター
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
GB0318463D0 (en) *	2003-08-07	2003-09-10	Astrazeneca Ab	Chemical compounds
GB0318464D0 (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
CN1922149A (zh)	2003-12-29	2007-02-28	塞普拉科公司	吡咯和吡唑daao抑制剂
US7453002B2 (en) *	2004-06-15	2008-11-18	Bristol-Myers Squibb Company	Five-membered heterocycles useful as serine protease inhibitors
WO2006053274A2 (en) *	2004-11-15	2006-05-18	Bristol-Myers Squibb Company	2-amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors
WO2006055462A1 (en) *	2004-11-15	2006-05-26	Bristol-Myers Squibb Company	2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors
WO2006055463A2 (en) *	2004-11-15	2006-05-26	Bristol-Myers Squibb Company	2-amino-3-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
PL1819704T3 (pl)	2004-12-02	2008-12-31	Prosidion Ltd	Amidowe pochodne kwasu pirolopirydyno-2-karboksylowego użyteczne jako inhibitory fosforylazy glikogenowej
WO2006059163A1 (en) *	2004-12-02	2006-06-08	Prosidion Limited	Treatment of diabetes with glycogen phosphorylase inhibitors
AU2006206654A1 (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
EP1848693A1 (en) *	2005-02-05	2007-10-31	AstraZeneca AB	Indan-amide derivatives with glycogen phosphorylase inhibitory activity
US20100137397A1 (en) *	2005-02-05	2010-06-03	Astrazeneca Ab	Chemical Compounds
KR101381768B1 (ko)	2006-01-06	2014-04-07	선오비온 파마슈티컬스 인코포레이티드	테트랄론-기재 모노아민 재흡수 저해제
EP1976513B1 (en)	2006-01-06	2016-08-24	Sunovion Pharmaceuticals Inc.	Cycloalkylamines as monoamine reuptake inhibitors
PT2816024T (pt)	2006-03-31	2017-10-20	Sunovion Pharmaceuticals Inc	Aminas quirais
PE20080251A1 (es)	2006-05-04	2008-04-25	Boehringer Ingelheim Int	Usos de inhibidores de dpp iv
US7884124B2 (en)	2006-06-30	2011-02-08	Sepracor Inc.	Fluoro-substituted inhibitors of D-amino acid oxidase
US8492405B2 (en)	2006-10-18	2013-07-23	Takeda Pharmaceutical Company Limited	Glucokinase-activating fused heterocyclic compounds and methods of treating diabetes and obesity
US7902252B2 (en)	2007-01-18	2011-03-08	Sepracor, Inc.	Inhibitors of D-amino acid oxidase
WO2008151156A1 (en)	2007-05-31	2008-12-11	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
EA201592263A1 (ru)	2013-06-05	2016-05-31	Синерджи Фармасьютикалз, Инк.	Ультрачистые агонисты гуанилатциклазы c, способ их получения и использования
BR112016030690B1 (pt)	2014-06-27	2023-11-14	Nogra Pharma Limited	Compostos moduladores do receptor de arila, composição farmacêutica compreendendo os mesmos e usos terapêuticos dos ditos compostos
EP3186242B1 (en)	2014-08-29	2021-10-06	Tes Pharma S.r.l.	Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase
TWI788830B (zh) *	2015-07-02	2023-01-01	瑞士商赫孚孟拉羅股份公司	雙環內醯胺及其使用方法
SG10201913587WA (en) *	2016-02-05	2020-02-27	Denali Therapeutics Inc	Inhibitors of receptor-interacting protein kinase 1
AU2017342083A1 (en)	2016-10-14	2019-04-11	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
JP7398391B2 (ja)	2018-04-20	2023-12-14	エフ．ホフマン－ラロシュアーゲー	Ｎ－［４－オキソ－２，３－ジヒドロ－１，５－ベンズオキサゼピン－３－イル］－５，６－ジヒドロ－４Ｈ－ピロロ［１，２－ｂ］ピラゾール－２－カルボキサミド誘導体及び例えば過敏性腸症候群（ＩＢＳ）を処置するためのＲＩＰ１キナーゼ阻害剤としての関連化合物
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
JP7805583B2 (ja) *	2019-11-27	2026-01-26	国立研究開発法人理化学研究所	Ｇ９ａ阻害剤

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
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
US4668769A (en) *	1985-08-02	1987-05-26	Hoover Dennis J	Oxa- and azahomocyclostatine polypeptides
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.
JP3314938B2 (ja) *	1995-06-06	2002-08-19	ファイザー・インコーポレーテッド	グリコーゲンホスホリラーゼ抑制剤としての置換されたｎ−（インドール−２−カルボニル）−グリシンアミド類および誘導体
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

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AU8283301A (en)	2002-03-22
HK1055299A1 (en)	2004-01-02
CZ2003616A3 (cs)	2003-05-14
IS6727A (is)	2003-02-24
SK2592003A3 (en)	2003-08-05
HUP0400784A2 (hu)	2004-07-28
GB0021831D0 (en)	2000-10-18
PL361024A1 (en)	2004-09-20
CN1896078A (zh)	2007-01-17
NO20031024D0 (no)	2003-03-05
EP1317459A1 (en)	2003-06-11
NO20031024L (no)	2003-03-05
UA73781C2 (en)	2005-09-15
IL154291A0 (en)	2003-09-17
DK1317459T3 (da)	2004-07-12
WO2002020530A1 (en)	2002-03-14
HUP0400784A3 (en)	2007-09-28
TR200401659T4 (tr)	2004-09-21
MXPA03001512A (es)	2003-06-09
NZ524011A (en)	2004-08-27
DE60102710T2 (de)	2005-04-14
AU2001282833B2 (en)	2006-07-06
US20030232875A1 (en)	2003-12-18
KR20030025305A (ko)	2003-03-28
CA2417594A1 (en)	2002-03-14
JP2004508376A (ja)	2004-03-18
EP1317459B1 (en)	2004-04-07
IS2110B (is)	2006-05-15
CN1264846C (zh)	2006-07-19
RU2003104013A (ru)	2004-08-20
CN1473163A (zh)	2004-02-04
BR0113606A (pt)	2003-06-24
DE60102710D1 (de)	2004-05-13
ZA200301013B (en)	2004-05-05
ATE263772T1 (de)	2004-04-15
ES2217183T3 (es)	2004-11-01
PT1317459E (pt)	2004-08-31
KR100802369B1 (ko)	2008-02-14
EE200300083A (et)	2004-12-15

Publication	Publication Date	Title
KR100802369B1 (ko)	2008-02-14	글루코겐 포스포릴라제 억제제로서의 비시클릭 피롤릴아미드
AU2001282833A1 (en)	2002-06-13	Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
CN100384852C (zh)	2008-04-30	作为糖原磷酸化酶抑制剂的杂环酰胺衍生物
KR101312993B1 (ko)	2013-11-25	히스톤 데아세틸라아제의 억제제
US9447100B2 (en)	2016-09-20	Substituted pyrazolo[1,5-A] pyrimidines as calcium receptor modulating agents
EA028991B1 (ru)	2018-01-31	Гетероциклические амиды в качестве ингибиторов киназы
ES2276092T3 (es)	2007-06-16	Derivados de amidas heterociclicas que poseen actividad inhibidora de glucogeno-fosforilasa.
JP2020519596A (ja)	2020-07-02	Ｉｒａｋ−４阻害剤として有用なチエノピリジンおよびベンゾチオフェン
ES2309537T3 (es)	2008-12-16	Derivados de amida heterociclica que poseen actividad inhibidora de la glucogeno fosforilasa.
ES2315676T3 (es)	2009-04-01	Derivados de indolamida que poseen actividad inhibidora de la glucogeno fosforilasa.
KR20030045187A (ko)	2003-06-09	도파민 ｄ₃수용체 조절제 (정신병 치료제)로서 유용한테트라히드로벤즈아제핀 유도체
PT1797099E (pt)	2010-11-18	Compostos de piperidinilamino-tieno[2,3-d]pirimidina
RS65543B1 (sr)	2024-06-28	Diazabiciklični supstituisani imidazopirimidini i njihova primena za lečenje poremećaja disanja
JP5377313B2 (ja)	2013-12-25	セリンヒドロラーゼ阻害剤
RU2238274C2 (ru)	2004-10-20	Тиенопиримидины, способ их получения, фармацевтический препарат и способ его получения
WO1988002370A1 (en)	1988-04-07	2-substituted-e-fused-[1,2,4]triazolo[1,5-c]pyrimidines pharmaceutical compositions and uses thereof
MX2007009784A (es)	2007-09-26	Compuestos moduladores de receptores de androgenos y metodos.
CN119192183A (zh)	2024-12-27	一类苯并二氮䓬类化合物及其用途
HK1055299B (en)	2004-10-21	Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
HUP9802585A2 (hu)	2000-08-28	Piridazino-oxazepin-,-tiazepin-, diazepin- és -tiazin-származékok, valamint az ezeket tartalmazó gyógyszerkészítmények
HK1070365B (en)	2007-04-27	Heterocyclic amide derivatives having glycogen phosphorylase inhibitory activity