Catechol‐<i>O</i>‐methyltransferase‐Inhibiting Pyrocatechol Derivatives: Synthesis and Structure‐Activity Studies

Abstract

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 A 2 , 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) .