ZA200304671B - Pyridaxinone aldose reductase inhibitors. - Google Patents
Pyridaxinone aldose reductase inhibitors. Download PDFInfo
- Publication number
- ZA200304671B ZA200304671B ZA200304671A ZA200304671A ZA200304671B ZA 200304671 B ZA200304671 B ZA 200304671B ZA 200304671 A ZA200304671 A ZA 200304671A ZA 200304671 A ZA200304671 A ZA 200304671A ZA 200304671 B ZA200304671 B ZA 200304671B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyridazin
- sulfonyl
- benzofuran
- chloro
- het
- Prior art date
Links
- 239000003288 aldose reductase inhibitor Substances 0.000 title description 6
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 title description 4
- -1 pyrazinopyrazinyl Chemical group 0.000 claims description 205
- 150000001875 compounds Chemical class 0.000 claims description 171
- 229940002612 prodrug Drugs 0.000 claims description 85
- 239000000651 prodrug Substances 0.000 claims description 85
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 150000003839 salts Chemical class 0.000 claims description 64
- 125000001424 substituent group Chemical group 0.000 claims description 59
- 125000001153 fluoro group Chemical group F* 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 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 125000002883 imidazolyl group Chemical group 0.000 claims description 23
- 125000002971 oxazolyl group Chemical group 0.000 claims description 23
- 125000000335 thiazolyl group Chemical group 0.000 claims description 23
- 241000124008 Mammalia Species 0.000 claims description 22
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 22
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 21
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 21
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
- 125000002541 furyl group Chemical group 0.000 claims description 17
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 17
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 17
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 17
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
- 125000005493 quinolyl group Chemical group 0.000 claims description 17
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 17
- 125000001544 thienyl group Chemical group 0.000 claims description 17
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 16
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 16
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 16
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 16
- 125000001425 triazolyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
- 125000001246 bromo group Chemical group Br* 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 14
- 208000002249 Diabetes Complications Diseases 0.000 claims description 13
- 206010012655 Diabetic complications Diseases 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 7
- 125000004536 indazol-1-yl group Chemical group N1(N=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- BVGVSUYAYNIIGE-UHFFFAOYSA-N 3-[(5-fluoro-3-methyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(F)C=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 BVGVSUYAYNIIGE-UHFFFAOYSA-N 0.000 claims description 5
- FXFPQPNUMWQRAO-UHFFFAOYSA-N 6-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]pyridazin-3(2h)-one Chemical compound O1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 FXFPQPNUMWQRAO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 210000005003 heart tissue Anatomy 0.000 claims description 5
- 208000028867 ischemia Diseases 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- ZCHJRGKQXZDDOT-UHFFFAOYSA-N 3-(1h-indol-3-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2C3=CC=CC=C3NC=2)=N1 ZCHJRGKQXZDDOT-UHFFFAOYSA-N 0.000 claims description 4
- HTJQFBOZQJFYDR-UHFFFAOYSA-N 3-[(3-methyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=CC=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 HTJQFBOZQJFYDR-UHFFFAOYSA-N 0.000 claims description 4
- ZDIDXSOYTUCPQE-UHFFFAOYSA-N 3-[(5-chloro-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(Cl)=CC=C2OC=1S(=O)(=O)C=1C=CC(=O)NN=1 ZDIDXSOYTUCPQE-UHFFFAOYSA-N 0.000 claims description 4
- JOGGJDKLNQCAQJ-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzothiophen-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound S1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 JOGGJDKLNQCAQJ-UHFFFAOYSA-N 0.000 claims description 4
- HXNAGYMCTAINEA-UHFFFAOYSA-N 3-(1h-indol-2-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2NC3=CC=CC=C3C=2)=N1 HXNAGYMCTAINEA-UHFFFAOYSA-N 0.000 claims description 3
- CABVMWOKBSURKS-UHFFFAOYSA-N 3-[(3-hydroxy-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=CC=C2C(O)=C1S(=O)(=O)C=1C=CC(=O)NN=1 CABVMWOKBSURKS-UHFFFAOYSA-N 0.000 claims description 3
- OLKIXQGJDUXXTC-UHFFFAOYSA-N 3-[(5,7-dichloro-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(Cl)=CC(Cl)=C2OC=1S(=O)(=O)C=1C=CC(=O)NN=1 OLKIXQGJDUXXTC-UHFFFAOYSA-N 0.000 claims description 3
- WGSUFIBFKNDTGJ-UHFFFAOYSA-N 3-[(5-chloro-1h-indol-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(Cl)=CC=C2NC=1S(=O)(=O)C=1C=CC(=O)NN=1 WGSUFIBFKNDTGJ-UHFFFAOYSA-N 0.000 claims description 3
- DDADXEQGUNIKPT-UHFFFAOYSA-N 3-[(5-chloro-3-ethyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(CC)=C1S(=O)(=O)C=1C=CC(=O)NN=1 DDADXEQGUNIKPT-UHFFFAOYSA-N 0.000 claims description 3
- DXMRTFOZJATGPZ-UHFFFAOYSA-N 3-[[3-methyl-5-(trifluoromethyl)-1-benzofuran-2-yl]sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(C(F)(F)F)C=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 DXMRTFOZJATGPZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 3
- UIJXWCKFKVXTRU-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)sulfonyl]-5h-furo[3,2-c]pyridin-4-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2OC3=C(C(NC=C3)=O)C=2)=N1 UIJXWCKFKVXTRU-UHFFFAOYSA-N 0.000 claims description 2
- YVEUDWZQMUISKP-UHFFFAOYSA-N 3-(1-methylindol-2-yl)sulfonyl-1h-pyridazin-6-one Chemical compound C=1C2=CC=CC=C2N(C)C=1S(=O)(=O)C=1C=CC(=O)NN=1 YVEUDWZQMUISKP-UHFFFAOYSA-N 0.000 claims description 2
- MUEYUVJYJZJUIE-UHFFFAOYSA-N 3-(3-chloroindol-1-yl)sulfonyl-1h-pyridazin-6-one Chemical compound C12=CC=CC=C2C(Cl)=CN1S(=O)(=O)C=1C=CC(=O)NN=1 MUEYUVJYJZJUIE-UHFFFAOYSA-N 0.000 claims description 2
- LCVXWZKNHISEPA-UHFFFAOYSA-N 3-(5h-[1,3]dioxolo[4,5-f]indol-6-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2NC3=CC=4OCOC=4C=C3C=2)=N1 LCVXWZKNHISEPA-UHFFFAOYSA-N 0.000 claims description 2
- NTJWJLZMOKBOFA-UHFFFAOYSA-N 3-[(3,5-dimethyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(C)C=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 NTJWJLZMOKBOFA-UHFFFAOYSA-N 0.000 claims description 2
- SOVXTIRUOWJZSS-UHFFFAOYSA-N 3-[(3-chloro-1h-indol-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound N1C2=CC=CC=C2C(Cl)=C1S(=O)(=O)C=1C=CC(=O)NN=1 SOVXTIRUOWJZSS-UHFFFAOYSA-N 0.000 claims description 2
- YWFVMRGAGDNRMA-UHFFFAOYSA-N 3-[(3-phenyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C2=C(C3=CC=CC=C3O2)C=2C=CC=CC=2)=N1 YWFVMRGAGDNRMA-UHFFFAOYSA-N 0.000 claims description 2
- GTSQOJISPPCBEE-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfinyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)C1=C(C)C2=CC(Cl)=CC=C2O1 GTSQOJISPPCBEE-UHFFFAOYSA-N 0.000 claims description 2
- PESVWIXUZNFVOB-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]-6-methoxypyridazine Chemical compound N1=NC(OC)=CC=C1S(=O)(=O)C1=C(C)C2=CC(Cl)=CC=C2O1 PESVWIXUZNFVOB-UHFFFAOYSA-N 0.000 claims description 2
- MVDAJCXOQBRPQC-UHFFFAOYSA-N 3-[(5-chloro-3-propan-2-yl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(C(C)C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 MVDAJCXOQBRPQC-UHFFFAOYSA-N 0.000 claims description 2
- YCAYZFGZUUVLMY-UHFFFAOYSA-N 3-[(6-chloro-1h-indol-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound N1C2=CC(Cl)=CC=C2C=C1S(=O)(=O)C=1C=CC(=O)NN=1 YCAYZFGZUUVLMY-UHFFFAOYSA-N 0.000 claims description 2
- PGWALDLWZWXTRU-UHFFFAOYSA-N 3-[(6-fluoro-1h-indol-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound N1C2=CC(F)=CC=C2C=C1S(=O)(=O)C=1C=CC(=O)NN=1 PGWALDLWZWXTRU-UHFFFAOYSA-N 0.000 claims description 2
- UGTGRHZJGQIRBG-UHFFFAOYSA-N 3-imidazol-1-ylsulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)N2C=NC=C2)=N1 UGTGRHZJGQIRBG-UHFFFAOYSA-N 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
- TVPRCLHSULCNLV-UHFFFAOYSA-N pyridazin-3-one Chemical compound O=C1C=CC=N[N]1 TVPRCLHSULCNLV-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- WFJJYKJYGCGPFS-UHFFFAOYSA-N 3-(1-benzylindol-5-yl)sulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2C=C3C=CN(CC=4C=CC=CC=4)C3=CC=2)=N1 WFJJYKJYGCGPFS-UHFFFAOYSA-N 0.000 claims 1
- ULUKHVCKTFCDRT-UHFFFAOYSA-N 3-(3-chloroindazol-1-yl)sulfonyl-1h-pyridazin-6-one Chemical compound C12=CC=CC=C2C(Cl)=NN1S(=O)(=O)C=1C=CC(=O)NN=1 ULUKHVCKTFCDRT-UHFFFAOYSA-N 0.000 claims 1
- MDZSNXLRKIMZRY-UHFFFAOYSA-N 3-[(5-chloro-3-hydroxy-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(O)=C1S(=O)(=O)C=1C=CC(=O)NN=1 MDZSNXLRKIMZRY-UHFFFAOYSA-N 0.000 claims 1
- BRGJYGOQKYCMGP-UHFFFAOYSA-N 3-[(5-methoxy-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(OC)=CC=C2OC=1S(=O)(=O)C=1C=CC(=O)NN=1 BRGJYGOQKYCMGP-UHFFFAOYSA-N 0.000 claims 1
- IIWJPLYZNNZNGB-UHFFFAOYSA-N 3-[(5-methoxy-1h-indol-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(OC)=CC=C2NC=1S(=O)(=O)C=1C=CC(=O)NN=1 IIWJPLYZNNZNGB-UHFFFAOYSA-N 0.000 claims 1
- GJSIXQDXGNTUSN-UHFFFAOYSA-N 3-[[3-(4-fluorophenyl)-1-benzofuran-2-yl]sulfonyl]-1h-pyridazin-6-one Chemical compound C1=CC(F)=CC=C1C1=C(S(=O)(=O)C2=NNC(=O)C=C2)OC2=CC=CC=C12 GJSIXQDXGNTUSN-UHFFFAOYSA-N 0.000 claims 1
- BCXKKVQJDYCMAD-UHFFFAOYSA-N 3-indol-1-ylsulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)N2C3=CC=CC=C3C=C2)=N1 BCXKKVQJDYCMAD-UHFFFAOYSA-N 0.000 claims 1
- NTGNYOSDAOGFDV-UHFFFAOYSA-N 3-pyridin-2-ylsulfinyl-1H-pyridazin-6-one Chemical compound N1=C(C=CC=C1)S(=O)C=1C=CC(NN=1)=O NTGNYOSDAOGFDV-UHFFFAOYSA-N 0.000 claims 1
- TWBJWMKHMNWGNT-UHFFFAOYSA-N 3-pyrrol-1-ylsulfonyl-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)N2C=CC=C2)=N1 TWBJWMKHMNWGNT-UHFFFAOYSA-N 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 10
- 102000016912 Aldehyde Reductase Human genes 0.000 description 9
- 108010053754 Aldehyde reductase Proteins 0.000 description 9
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 9
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 8
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 8
- ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 229940123659 Sorbitol dehydrogenase inhibitor Drugs 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 4
- 102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 description 4
- 102400001190 Vastatin Human genes 0.000 description 4
- 101800000422 Vastatin Proteins 0.000 description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 4
- 239000003472 antidiabetic agent Substances 0.000 description 4
- 229940125708 antidiabetic agent Drugs 0.000 description 4
- 108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 4
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 3
- RBZSSTPBYFHRSR-UHFFFAOYSA-N 3-(1-benzofuran-2-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2OC3=CC=CC=C3C=2)=N1 RBZSSTPBYFHRSR-UHFFFAOYSA-N 0.000 description 3
- UUAVJCDYOHIIQW-UHFFFAOYSA-N 4-sulfonylpyridazin-3-one Chemical class O=C1N=NC=CC1=S(=O)=O UUAVJCDYOHIIQW-UHFFFAOYSA-N 0.000 description 3
- 229940123464 Thiazolidinedione Drugs 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 229940118148 Aldose reductase inhibitor Drugs 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- 208000032781 Diabetic cardiomyopathy Diseases 0.000 description 2
- 206010054044 Diabetic microangiopathy Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 229940123934 Reductase inhibitor Drugs 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 125000000218 acetic acid group Chemical class C(C)(=O)* 0.000 description 2
- 150000001323 aldoses Chemical class 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 201000009101 diabetic angiopathy Diseases 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- UTFQZXGZRNBLOH-UHFFFAOYSA-N 3-(1-benzothiophen-3-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)C=2C3=CC=CC=C3SC=2)=N1 UTFQZXGZRNBLOH-UHFFFAOYSA-N 0.000 description 1
- NQJFBHVHPOEWLC-UHFFFAOYSA-N 3-(3,4,4a,5-tetrahydro-2h-quinolin-1-ylsulfonyl)-1h-pyridazin-6-one Chemical compound N1C(=O)C=CC(S(=O)(=O)N2C3=CC=CCC3CCC2)=N1 NQJFBHVHPOEWLC-UHFFFAOYSA-N 0.000 description 1
- FFQYWMOJPDVLPU-UHFFFAOYSA-N 3-(3-methylindol-1-yl)sulfonyl-1h-pyridazin-6-one Chemical compound C12=CC=CC=C2C(C)=CN1S(=O)(=O)C=1C=CC(=O)NN=1 FFQYWMOJPDVLPU-UHFFFAOYSA-N 0.000 description 1
- SGOLLMYWJZAGJJ-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfanyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(C)=C1SC1=CC=C(O)N=N1 SGOLLMYWJZAGJJ-UHFFFAOYSA-N 0.000 description 1
- AMAQYLPFCRGWRB-UHFFFAOYSA-N 3-[(5-chloro-3-methyl-1-benzofuran-2-yl)sulfinyl]-1h-pyridazin-6-one Chemical compound O1C2=CC=C(Cl)C=C2C(C)=C1S(=O)C=1C=CC(=O)NN=1 AMAQYLPFCRGWRB-UHFFFAOYSA-N 0.000 description 1
- ACIIXSSSNZJFAG-UHFFFAOYSA-N 3-[(5-methyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(C)=CC=C2OC=1S(=O)(=O)C=1C=CC(=O)NN=1 ACIIXSSSNZJFAG-UHFFFAOYSA-N 0.000 description 1
- QSROOXVEHSOUBU-UHFFFAOYSA-N 3-[(5-methyl-1-benzothiophen-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound C=1C2=CC(C)=CC=C2SC=1S(=O)(=O)C=1C=CC(=O)NN=1 QSROOXVEHSOUBU-UHFFFAOYSA-N 0.000 description 1
- VTAPFQFGVVPFNM-UHFFFAOYSA-N 3-[(6-chloro-3-methyl-1-benzofuran-2-yl)sulfonyl]-1h-pyridazin-6-one Chemical compound O1C2=CC(Cl)=CC=C2C(C)=C1S(=O)(=O)C=1C=CC(=O)NN=1 VTAPFQFGVVPFNM-UHFFFAOYSA-N 0.000 description 1
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- FFJIULXBRJZUKP-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzofuran-2-thiol Chemical group C1=C(Cl)C=C2C(C)=C(S)OC2=C1 FFJIULXBRJZUKP-UHFFFAOYSA-N 0.000 description 1
- 101800000734 Angiotensin-1 Proteins 0.000 description 1
- 102400000344 Angiotensin-1 Human genes 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010063547 Diabetic macroangiopathy Diseases 0.000 description 1
- 102100038509 E3 ubiquitin-protein ligase ARIH1 Human genes 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000003790 Foot Ulcer Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 206010054805 Macroangiopathy Diseases 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QGAQQANQFMOQTQ-UHFFFAOYSA-N acetic acid;2h-pyrido[3,2-c]pyridazin-3-one Chemical class CC(O)=O.N1=CC=CC2=NNC(=O)C=C21 QGAQQANQFMOQTQ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 210000000695 crystalline len Anatomy 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000011737 fluorine Chemical group 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000010030 glucose lowering effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical group [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229950009116 mevastatin Drugs 0.000 description 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28005101P | 2001-03-30 | 2001-03-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200304671B true ZA200304671B (en) | 2004-06-25 |
Family
ID=23071435
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200304671A ZA200304671B (en) | 2001-03-30 | 2003-06-17 | Pyridaxinone aldose reductase inhibitors. |
Country Status (44)
Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ332762A (en) | 1996-07-24 | 2000-09-29 | Warner Lambert Co | Isobutylgaba and its derivatives for the treatment of pain |
ES2240657T3 (es) * | 2001-02-28 | 2005-10-16 | Pfizer Products Inc. | Compuestos de sulfonilpiridazinona utiles como inhibidores de aldosa reductasa. |
DE60216823T2 (de) * | 2001-03-30 | 2007-10-04 | Pfizer Products Inc., Groton | Zwischenprodukten für die Herstellung von Pyridazinon Aldose Reductase Inhibitoren. |
AU761191B2 (en) * | 2001-05-24 | 2003-05-29 | Pfizer Products Inc. | Therapies for tissue damage resulting from ischemia |
PT1463725E (pt) * | 2002-01-09 | 2005-10-31 | Pfizer Prod Inc | Processo e intermediarios para agentes antidiabeticos piridazinonas |
US7419981B2 (en) * | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
US20040092522A1 (en) * | 2002-08-15 | 2004-05-13 | Field Mark John | Synergistic combinations |
US6872833B2 (en) * | 2003-04-14 | 2005-03-29 | Hoffmann-La Roche Inc. | Adenosine receptor ligands |
US8017634B2 (en) | 2003-12-29 | 2011-09-13 | President And Fellows Of Harvard College | Compositions for treating obesity and insulin resistance disorders |
US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
PE20060272A1 (es) | 2004-05-24 | 2006-05-22 | Glaxo Group Ltd | (2r,3r,4s,5r,2'r,3'r,4's,5's)-2,2'-{trans-1,4-ciclohexanodiilbis-[imino(2-{[2-(1-metil-1h-imidazol-4-il)etil]amino}-9h-purin-6,9-diil)]}bis[5-(2-etil-2h-tetrazol-5-il)tetrahidro-3,4-furanodiol] como agonista a2a |
EP1750862B1 (en) | 2004-06-04 | 2011-01-05 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition containing irbesartan |
US20050288340A1 (en) * | 2004-06-29 | 2005-12-29 | Pfizer Inc | Substituted heteroaryl- and phenylsulfamoyl compounds |
WO2006028565A2 (en) * | 2004-06-30 | 2006-03-16 | Whitehead Institute For Biomedical Research | Novel methods for high-throughput genome-wide location analysis |
GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
US7645752B2 (en) * | 2006-01-13 | 2010-01-12 | Wyeth Llc | Sulfonyl substituted 1H-indoles as ligands for the 5-hydroxytryptamine receptors |
ME00535B (me) | 2006-06-27 | 2011-10-10 | Takeda Pharmaceuticals Co | Fuzionisana ciklična jedinjenja |
CN101663262B (zh) | 2006-12-01 | 2014-03-26 | 百时美施贵宝公司 | 用于治疗动脉粥样硬化和心血管疾病的作为cetp抑制剂的n-(3-苄基)-2,2-(二苯基)-丙-1胺衍生物 |
US8173645B2 (en) * | 2007-03-21 | 2012-05-08 | Takeda San Diego, Inc. | Glucokinase activators |
JP2010043063A (ja) | 2008-05-09 | 2010-02-25 | Agency For Science Technology & Research | 川崎病の診断及び治療 |
WO2011071995A2 (en) | 2009-12-08 | 2011-06-16 | Case Western Reserve University | Compounds and methods of treating ocular disorders |
US8916563B2 (en) | 2010-07-16 | 2014-12-23 | The Trustees Of Columbia University In The City Of New York | Aldose reductase inhibitors and uses thereof |
CA2848877A1 (en) * | 2011-09-15 | 2013-03-21 | Taipei Medical University | Use of indolyl and indolinvl hvdroxamates for treating heart failure or neuronal injury |
US9339542B2 (en) * | 2013-04-16 | 2016-05-17 | John L Couvaras | Hypertension reducing composition |
MX2015014666A (es) | 2013-04-17 | 2016-03-01 | Pfizer | Derivados de n-piperidin-3-ilbenzamida para tratar enfermedades cardiovasculares. |
CN103739547B (zh) * | 2014-01-03 | 2015-09-02 | 沈阳药科大学 | 2-[6-甲氧基-3-(2,3-二氯苯基)甲基-4-氧代-1,4-二氢-1(4h)-喹啉基]乙酸的合成方法 |
WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
CA2982784A1 (en) * | 2015-04-14 | 2016-10-20 | Case Western Reserve University | Compositions and methods of modulating short-chain dehydrogenase activity |
WO2017168174A1 (en) | 2016-04-02 | 2017-10-05 | N4 Pharma Uk Limited | New pharmaceutical forms of sildenafil |
CN115160339B (zh) | 2016-06-21 | 2024-05-14 | 纽约市哥伦比亚大学理事会 | 醛糖还原酶抑制剂及其使用方法 |
WO2018002673A1 (en) | 2016-07-01 | 2018-01-04 | N4 Pharma Uk Limited | Novel formulations of angiotensin ii receptor antagonists |
WO2018058109A1 (en) * | 2016-09-26 | 2018-03-29 | Nusirt Sciences, Inc. | Compositions and methods for treating metabolic disorders |
US11690847B2 (en) | 2016-11-30 | 2023-07-04 | Case Western Reserve University | Combinations of 15-PGDH inhibitors with corticosteroids and/or TNF inhibitors and uses thereof |
WO2018145080A1 (en) | 2017-02-06 | 2018-08-09 | Case Western Reserve University | Compositions and methods of modulating short-chain dehydrogenase activity |
BR112020001755A2 (pt) | 2017-07-28 | 2020-07-21 | Applied Therapeutics Inc. | composições e métodos para o tratamento de galactosemia |
EP3911648A4 (en) | 2019-01-18 | 2022-10-26 | Astrazeneca AB | PCSK9 INHIBITORS AND METHODS OF USE THEREOF |
TW202108559A (zh) | 2019-05-31 | 2021-03-01 | 美商醫肯納腫瘤學公司 | Tead抑制劑及其用途 |
US11274082B2 (en) | 2019-05-31 | 2022-03-15 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
WO2022120353A1 (en) * | 2020-12-02 | 2022-06-09 | Ikena Oncology, Inc. | Tead inhibitors and uses thereof |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IE47592B1 (en) | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
US4939140A (en) | 1985-11-07 | 1990-07-03 | Pfizer Inc. | Heterocyclic oxophthalazinyl acetic acids |
US4996204A (en) | 1989-05-11 | 1991-02-26 | Pfizer Inc. | Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors |
FR2647676A1 (fr) | 1989-06-05 | 1990-12-07 | Union Pharma Scient Appl | Nouveaux derives de pyridazinone, leurs procedes de preparation, medicaments les contenant, utiles notamment comme inhibiteurs de l'aldose reductase |
EP0516860A4 (en) * | 1990-11-30 | 1993-12-01 | Tsumura & Co. | Chromone derivative and aldose reductase inhibitor containing the same as active ingredient |
EP0582643A1 (en) | 1991-03-28 | 1994-02-16 | Pfizer Inc. | Pyridazinone acetic acids |
US5834466A (en) | 1994-12-22 | 1998-11-10 | The Regents Of The University Of California | Method for protecting of heart by limiting metabolic and ionic abnormalities developed during ischemia, following ischemia or resulting from ischemia |
TWI238064B (en) | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
WO1999015523A1 (en) * | 1997-09-24 | 1999-04-01 | Orion Corporation | Bisethers of 1-oxa, aza and thianaphthalen-2-ones as phospholamban inhibitors |
FR2822827B1 (fr) * | 2001-03-28 | 2003-05-16 | Sanofi Synthelabo | Nouveaux derives de n-(arylsulfonyl) beta-aminoacides comportant un groupe aminomethyle substitue, leur procede de preparation et les compositions pharmaceutiques en contenant |
DE60216823T2 (de) * | 2001-03-30 | 2007-10-04 | Pfizer Products Inc., Groton | Zwischenprodukten für die Herstellung von Pyridazinon Aldose Reductase Inhibitoren. |
AU2002236131B2 (en) * | 2001-04-30 | 2005-04-14 | Pfizer Products Inc. | Combinations of aldose reductase inhibitors and cyclooxygenase-2 inhibitors |
PT1463725E (pt) * | 2002-01-09 | 2005-10-31 | Pfizer Prod Inc | Processo e intermediarios para agentes antidiabeticos piridazinonas |
-
2002
- 2002-01-31 DE DE60216823T patent/DE60216823T2/de not_active Expired - Fee Related
- 2002-01-31 OA OA1200300222A patent/OA12453A/en unknown
- 2002-01-31 EP EP04023149A patent/EP1491540B1/en not_active Expired - Lifetime
- 2002-01-31 UA UA2003098846A patent/UA73236C2/uk unknown
- 2002-01-31 PL PL02365294A patent/PL365294A1/xx not_active Application Discontinuation
- 2002-01-31 AT AT04023149T patent/ATE348100T1/de not_active IP Right Cessation
- 2002-01-31 EP EP04023150A patent/EP1491541B1/en not_active Expired - Lifetime
- 2002-01-31 NZ NZ528406A patent/NZ528406A/en unknown
- 2002-01-31 AT AT02716247T patent/ATE286049T1/de active
- 2002-01-31 DE DE60202452T patent/DE60202452C5/de not_active Expired - Fee Related
- 2002-01-31 DK DK02716247T patent/DK1373259T3/da active
- 2002-01-31 CA CA002442476A patent/CA2442476A1/en not_active Abandoned
- 2002-01-31 GE GE5314A patent/GEP20053675B/en unknown
- 2002-01-31 MX MXPA03008850A patent/MXPA03008850A/es active IP Right Grant
- 2002-01-31 PT PT02716247T patent/PT1373259E/pt unknown
- 2002-01-31 HU HU0303644A patent/HUP0303644A3/hu unknown
- 2002-01-31 JP JP2002577823A patent/JP2004528319A/ja active Pending
- 2002-01-31 AU AU2002226634A patent/AU2002226634B2/en not_active Ceased
- 2002-01-31 AT AT04023150T patent/ATE352551T1/de not_active IP Right Cessation
- 2002-01-31 BR BR0208571-2A patent/BR0208571A/pt not_active IP Right Cessation
- 2002-01-31 EE EEP200300470A patent/EE200300470A/xx unknown
- 2002-01-31 EP EP02716247A patent/EP1373259B1/en not_active Expired - Lifetime
- 2002-01-31 DK DK04023149T patent/DK1491540T3/da active
- 2002-01-31 ES ES04023149T patent/ES2274369T3/es not_active Expired - Lifetime
- 2002-01-31 DE DE60217930T patent/DE60217930T2/de not_active Expired - Fee Related
- 2002-01-31 WO PCT/IB2002/000320 patent/WO2002079198A1/en active IP Right Grant
- 2002-01-31 CN CNB028076001A patent/CN1215067C/zh not_active Expired - Fee Related
- 2002-01-31 EA EA200300673A patent/EA006023B1/ru not_active IP Right Cessation
- 2002-01-31 ES ES02716247T patent/ES2231681T3/es not_active Expired - Lifetime
- 2002-01-31 SI SI200230071T patent/SI1373259T1/xx unknown
- 2002-01-31 YU YU71403A patent/YU71403A/sh unknown
- 2002-01-31 PT PT04023149T patent/PT1491540E/pt unknown
- 2002-01-31 KR KR1020037012753A patent/KR100586138B1/ko not_active IP Right Cessation
- 2002-01-31 SK SK1185-2003A patent/SK11852003A3/sk unknown
- 2002-01-31 IL IL15646202A patent/IL156462A0/xx unknown
- 2002-03-21 US US10/104,664 patent/US6579879B2/en not_active Expired - Fee Related
- 2002-03-22 PA PA20028541801A patent/PA8541801A1/es unknown
- 2002-03-27 PE PE2002000246A patent/PE20030007A1/es not_active Application Discontinuation
- 2002-03-27 AR ARP020101134A patent/AR035798A1/es unknown
- 2002-03-27 MY MYPI20021093A patent/MY134304A/en unknown
- 2002-03-27 UY UY27237A patent/UY27237A1/es not_active Application Discontinuation
- 2002-03-28 AP APAP/P/2002/002461A patent/AP2002002461A0/en unknown
- 2002-03-29 TW TW091106386A patent/TWI245762B/zh not_active IP Right Cessation
- 2002-03-29 TN TNTNSN02037A patent/TNSN02037A1/fr unknown
- 2002-03-31 CZ CZ20032563A patent/CZ20032563A3/cs unknown
-
2003
- 2003-02-20 US US10/370,895 patent/US6849629B2/en not_active Expired - Fee Related
- 2003-06-16 IS IS6845A patent/IS2205B/is unknown
- 2003-06-17 ZA ZA200304671A patent/ZA200304671B/en unknown
- 2003-06-25 EC EC2003004671A patent/ECSP034671A/es unknown
- 2003-09-17 MA MA27314A patent/MA27003A1/fr unknown
- 2003-09-17 BG BG108179A patent/BG108179A/xx unknown
- 2003-09-17 HR HR20030752A patent/HRP20030752A2/hr not_active Application Discontinuation
- 2003-09-29 NO NO20034345A patent/NO20034345D0/no unknown
-
2004
- 2004-06-24 HK HK04104538A patent/HK1061678A1/xx not_active IP Right Cessation
-
2006
- 2006-01-23 IS IS8250A patent/IS8250A/is unknown
- 2006-01-23 IS IS8251A patent/IS8251A/is unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200304671B (en) | Pyridaxinone aldose reductase inhibitors. | |
JP6097422B2 (ja) | 5−フェノキシ−3h−ピリミジン−4−オン誘導体およびhiv逆転写酵素阻害薬としてのそれらの使用 | |
WO2020146636A1 (en) | Compounds and methods for treating or preventing heart failure | |
US6936600B2 (en) | Sorbitol dehrydrogenase inhibitors | |
JP2004528319A5 (es) | ||
AU2002363176B2 (en) | Heteroaryl amines as glycogen synthase kinase 3Beta inhibitors (GSK3 inhibitors) | |
EP1753743B1 (en) | Pyridazinone derivatives, methods for producing them and their use as pharmaceuticals | |
CN101213189B (zh) | 4-(吡啶-3-基)-2-(吡啶-2-基)-1,2-二氢-3h-吡唑啉-3-酮衍生物作为用于治疗心血管和血液学疾病的转录因子-脯氨酰-4-羟化酶的特异性抑制剂 | |
DE60314603T2 (de) | Zusammensetzungen brauchbar als protein-kinase-inhibitoren | |
EP2683710B1 (en) | Soluble guanylate cyclase activators | |
US20100144738A1 (en) | Inhibitors of c-met and uses thereof | |
AU2002226634A1 (en) | Pyridazinone aldose reductase inhibitors | |
EP2518072A1 (en) | Imidazopyridazine compounds | |
JP2010070514A (ja) | ピラゾール誘導体及びその医薬用途 | |
CN115916756A (zh) | 砜衍生物 | |
ZA200307204B (en) | Combinations of aldose reductase inhibitors and cyclooxygenase-2-inhibitors. | |
US20050113381A1 (en) | Pyridazinone aldose reductase inhibitors | |
EP3068390B1 (en) | Piperazine-imidazole derivatives and methods of use thereof for improving the pharmacokinetics of a drug |