Catechol‐O‐methyltransferase‐Inhibiting Pyrocatechol Derivatives: Synthesis and Structure‐Activity Studies

Abstract 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).