| 摘要 |
Pyridazinone derivatives (I) are new. Pyridazinone derivatives of formula (I) and their prodrugs and salts are new. [Image] A : S, SO or SO 2; R 1>, R 2>H or Me; R 3>Het 1>, CHR 4>Het 1> or NR 6>R 7>; R 4>H or 1-3C alkyl; R 6>1-6C alkyl, aryl or Het 2>; R 7>Het 3>; Het 1>pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, phthalazinyl, cinnolinyl, naphthyridinyl, pteridinyl, pyrazinopyrazinyl, pyrazinopyridazinyl, pyrimidopyridazinyl, pyrimidopyrimidyl, pyridopyrimidyl, pyridopyrazinyl, pyridopyridazinyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzisothiazolyl, pyrrolopyridyl, furopyridyl, thienopyridyl, imidazolopyridyl, oxazolopyridyl, thiazolopyridyl, pyrazolopyridyl, isoxazolopyridyl, isothiazolopyridyl, pyrrolopyrimidyl, furopyrimidyl, thienopyrimidyl, imidazolopyrimidyl, oxazolopyrimidyl, thiazolopyrimidyl, pyrazolopyrimidyl, isoxazolopyrimidyl, isothiazolopyrimidyl, pyrrolopyrazinyl, furopyrazinyl, thienopyrazinyl, imidazolopyrazinyl, oxazolopyrazinyl, thiazolopyrazinyl, pyrazolopyrazinyl, isoxazolopyrazinyl, isothiazolopyrazinyl, pyrrolopyridazinyl, furopyridazinyl, thienopyridazinyl, imidazolopyridazinyl, oxazolopyridazinyl, thiazolopyridazinyl, pyrazolopyridazinyl, isoxazolopyridazinyl or isothiazolopyridazinyl (all optionally substituted by 1-4 halo, formyl, 1-6C alkoxycarbonyl, 1-6C alkenyloxycarbonyl, 1-4C alkoxy-(1-4C alkyl), C(OH)R 12>R 13>, 1-4C alkylcarbonylamido, 3-7C cycloalkylcarbonylamido, phenylcarbonylamido, benzyl, T, T 1>, 1-4C alkylsulfenyl, 1-4C alkylsulfonyl, 3-7C cycloalkyl, 1-6C alkyl (optionally substituted by 1-3 F) or 1-4C alkoxy (optionally substituted by 1-5 F) and in which benzyl, T and T 1> are optionally substituted by 1-3 OH, halo, 1-4C hydroxyalkyl, 1-4C alkoxy-(1-4C alkyl), 1-6C alkylsulfenyl, 1-6C alkylsulfinyl, 1-6C alkylsulfonyl, 1-6C alkyl (optionally substituted by 1-5 F) or 1-4C alkoxy (optionally substituted by 1-5 of F) and in which T 1> is optionally substituted by 1 or 2 OH, halo, 1-4C alkyl, 1-4C hydroxyalkyl, 1-4C alkoxy-(1-4C alkyl), 1-4C alkylphenyl (optionally substituted by Cl, Br, OMe, Me or SO 2-phenyl (optionally substituted by Cl, Br, OMe, Me, 1-4C alkyl (optionally substituted by 1-5 F) or 1-4C alkoxy (optionally substituted by 1-3 F))); T : phenyl, naphthyl, pyridyl, triazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, thienyl, benzothiazolyl, pyrrolyl, quinolyl, isoquinolyl, benzoxazolyl, pyridazinyl, pyridyloxy, pyridylsulfonyl, furanyl, phenoxy, thiophenoxy; T 1>imidazolyl, oxazolyl, isoxazolyl, thiazolyl or pyrazolyl; R 12>, R 13>H or 1-4C alkyl; Het 2>, Het 3>T 1>, pyridyl, triazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, thienyl, benzothiazolyl, pyrrolyl, quinolyl, isoquinolyl, benzoxazolyl, pyridazinyl, pyridyloxy, pyridylsulfonyl, furanyl, phenoxy or thiophenoxy (all optionally substituted by 1-4 halo, formyl, 1-6C alkoxycarbonyl, 1-6C alkenyloxycarbonyl, 1-4C alkoxy-(1-4C alkyl), C(OH)R 18>R 19>, 1-4C alkylcarbonylamido, 3-7C cycloalkylcarbonylamido, phenylcarbonylamido, phenyl, naphthyl, imidazolyl, pyridyl, triazolyl, benzimidazolyl, oxazolyl, isoxazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, thienyl, benzothiazolyl, pyrrolyl, pyrazolyl, quinolyl, isoquinolyl, benzoxazolyl, pyridazinyl, pyridyloxy, pyridylsulfonyl, furanyl, phenoxy, thiophenoxy, 1-4C alkylsulfenyl, 1-4C alkylsulfonyl, 3-7C cycloalkyl, 1-4C alkyl (optionally substituted by up to 3 of F) or 1-4C alkoxy (optionally substituted by up to 5 of F) and in which T and T 1> are optionally substituted by 1-3 OH, halo, 1-4C hydroxyalkyl, 1-4C alkoxy-(1-4C alkyl), 1-4C alkyl (optionally substituted by 1-51 F) or 1-4C alkoxy (optionally substituted by 1-5 F) and in which T 1> is optionally substituted by 1 or 2 OH, halo, 1-4C hydroxyalkyl, 1-4C alkoxy-(1-4C alkyl), 1-4C alkyl (optionally substituted by 1-5 F) or 1-4C alkoxy (optionally substituted by 1-3 F), and R 18>, R 19>H or 1-4C alkyl, provided that when R 3> = NR 6>R 7>, then A = SO 2. Independent claims are also included for the following: (1) a composition comprising (I) and a compound (III) comprising a sorbitol dehydrogenase inhibitor (SDI), glycogen phosphorylase inhibitor (GPI), selective serotonin reuptake inhibitor (SSRI), 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (a vastatin), a thiazolidinedione antidiabetic agent (a glitazone), a gamma -aminobutyric acid (GABA) agonist, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin-II (A-II) receptor antagonist or a phosphodiesterase type 5 (PDE-5) inhibitor; (2) a kit comprising a unit dose of (I) and a second unit dose comprising (III); (3) new pyridazine derivatives of formula (II), and (4) 5-chloro-2-mercapto-3-methylbenzofuran. [Image] Z : 1-6C alkyl or phenyl or benzyl (both optionally substituted by 1 or 2 Cl or Me), and R 3a>.Het 1> or CHR 4>Het 1>. ACTIVITY : Vasotropic; Antidiabetic; Neuroprotective; Nephrotropic; Ophthalmological; Antiulcer. Tests are described but no results are given. MECHANISM OF ACTION : Aldose reductase inhibition. |
