3,5-DISUBSTITUTED PYROCATECHOLE DERIVATIVES

摘要

RAN 4007/50 The catechol derivatives of the general formula Ia wherein Ra signifies nitro or cyano, Rb signifies hydrogen or halogen, Rc signifies halogen, nitro, cyano or the group -(A)n-(Q)m-R1 or -(A)n-Q-R2, A signifies vinylene optionally substituted by lower alkyl, n signifies the number O or 1, m signifies the number 0 or 1, R1 signifies the group -COR3, a carbocyclic, aromatic group or an aromatic or partially unsaturated, heterocyclic group attached via a carbon atom, R2 signifies hydrogen or an optionally substituted, saturated or partially unsaturated, lower hydrocarbon residue, R3 signifies hydroxy, amino, an optionally substituted, saturated or partially unsaturated, lower hydrocarbon residue ateached via an oxygen atom or an imino or lower alkylimino group or a saturated, N-containing heterocyclic group attached via a ring nitrogen atom, Q signifies the group -CO- or >C=N-(Z)p-R4, Z signifies an oxygen atom or an imino group, p signifies the number 0 or 1 and R4 signifies hydrogen or a saturated or partially unsaturated. lower hydrocarbon residue which is optionally substituted and which is optionally attached via a carbonyl group, the ester and ether derivatives which are hydrolyzable under physiological conditions and the pharmaceutically acceptable salts thereof posses valuable pharmacological ( cont'd) properties. In particular, they inhibit the enzyme catechol-O-methyltransferase (COMT), a soluble, magnesium dependent enzyme which catalyses the transference of the methyl group of S-adenosylmethionine to a catechol substrate, whereby the corresponding methyl ethers are formed. Suitable substrates which can be O-methylated by COMT and which can thus be deactivated are, for example, extraneuronal catecholamines and exogeneously-administered therapeutically active substances having a catechol structure. Formula Ia above embraces not only novel compounds, but also known compounds; the novel compounds can be manufactured according to methods known per se.