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CHEMICAL DESIGN OF PERIPHERALLY ACTING COMPOUNDS
Author(s) -
Jackson W. Roy,
Copp Fred C.,
Cullen John D.,
Guyett Frances J.,
Rae Ian D.,
Robinson Andrea J.,
Pothoulackis Helen,
Serelis Algirdas K.,
Wong Margaret
Publication year - 1992
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1992.tb00392.x
Subject(s) - chemistry , pharmacology , biophysics , medicine , biology
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‐HT 2 antagonists. 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‐HT 2 pharmacophore. 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.