Catechol-O-methyltransferase-inhibiting pyrocatechol derivatives: synthesis and structure-activity studies

3-Nitro- and 3-cyanopyrocatechols bearing electron-withdrawing substituents at C(5) have been found to inhibit the enzyme catechol-O-methyltransferase. Structure-activity studies are discussed on the basis of the pharmocological data of 50 compounds (cf, Chapt. 4, Tables 1–7). Some 3-nitro-5-aroylpyrocatechols (Type A2, Table 1) fulfil the requirements for a clinical candidate, being orally active, specific, reversible, and relatively short-acting. The chemical work involved is illustrated by describing a choice of exemplary syntheses, dealing with compounds 9, 11, 14, 18, 22, 24, 25, 35, 41, and 42(Chapt. 5, Schemes 1–10).

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