METHOD AND INTERMEDIATE COMPOUNDS FOR PREPARING PYRIDAZINONE ANTIDIABETIC AGENTS Russian patent published in 2006 - IPC C07D405/12 

FIELD: organic chemistry, chemical technology, medicine, endocrinology, biochemistry.

SUBSTANCE: invention relates to a method for preparing compound of the formula (I) wherein R¹ and R² represent independently of one another hydrogen atom or methyl; R³, R⁴, R⁵ and R⁶ represent independently of one another hydrogen atom (H), halogen atom, formyl group, (C₁-C₆)-alkyl substituted optionally with fluorine atoms in amount up to three, (C₁-C₆)-alkoxy-group substituted optionally with fluorine atoms in amount up to three, (C₁-C₆)-alkylenyloxycarbonyl, (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl, (C₁-C₄)-alkylcarbonylamido-group, (C₃-C₇)-cycloalkylcarbonylamido-group, phenylcarbonylamido-group, benzyl, phenyl or naphthyl wherein benzyl, phenyl and naphthyl are substituted optionally and independently of one another with substitutes in amount up to two and chosen independently from halogen atom, (C₁-C₆)-alkyl substituted optionally with fluorine atoms in amount up to three, (C₁-C₆)-alkoxy-group substituted optionally with fluorine atoms in amount up to three and (C₁-C₄)-alkoxy-(C₁-C₄)-alkyl. Proposed method involves the following successive stages: (a) interaction of compound of the formula (II) wherein R³, R⁴, R⁵ and R⁶ are determined independently as given above with lithium-organic compound in the presence of sulfur source in medium of the first reactively inert solvent to form the reactive intermediate compound of the formula (IIa) (b) interaction of indicated reactive intermediate compound of the formula (IIa) with compound of the formula (III) to form compound of the formula (IV) (c) interaction of indicated compound of the formula (IV) with alkaline (C₁-C₂)-alkoxide in (C₁-C₂)-alkanol medium to form derivative of simple ether of the formula (V) wherein Alk represents (C₁-C₂)-alkyl; (d) interaction of indicated compound of the formula (V) with mineral acid to form compound of the formula (VI) and (e) oxidation of compound of the formula (VI) in the second reactively inert solvent to form compound of the formula (I). Prepared pyridazinone compounds are effective inhibitors of aldose reductase activity and can be used in prophylaxis and/or treatment of diabetes mellitus complications, such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. Also, invention relates to new intermediate compounds of the formula (IV) used in synthesis of indicated inhibitors of aldose reductase, to a method for synthesis of compound of the formula (IV) and a method for synthesis of preferable pyridazinone compound of the formula (XI) .

EFFECT: improved preparing method, valuable medicinal properties of compounds and agents.

10 cl, 3 ex