CHEMICAL DESIGN OF PERIPHERALLY ACTING COMPOUNDS

Abstract
SUMMARY: 1. Some guanidines, related in structure to mianserin and to 2‐methyl‐1,2,9,13b‐tetrahydro‐3H‐dibenz[c,f]irnadazo[l,5a]azepin‐3‐imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5‐HT2antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity.2. Computer‐aided molecular modelling has been used to establish a 5‐HT2pharmacophore.3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.