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A novel method for the synthesis of carbon‐14‐labeled N ‐[3‐(1‐methyl‐4‐piperidinyl)‐1 H ‐pyrrolo[3,2‐b]pyridin‐5‐yl]propanamide and its use in quantitative whole‐body autoradiography studies
Author(s) -
Wheeler William J.,
Chay Sylvia H.,
Herman Jennifer L.,
O'Ban Douglas D.
Publication year - 2005
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.959
Subject(s) - chemistry , agonist , selectivity , receptor , 5 ht receptor , serotonin , stereochemistry , indole test , chemical synthesis , bicyclic molecule , pharmacology , biochemistry , in vitro , medicine , catalysis
Sumitriptan ( 1 ), a non‐selective 5‐HT 1B/1D agonist is an effective therapeutic agent for the acute treatment of migraine, but it is contraindicated for use in patients with known heart disease. The first Selective Serotonin One F Receptor Agonist (SSOFRA), 5‐(4′‐fluorobenz‐amido)‐3‐( N ‐methyl‐piperidin‐4‐yl)‐1H‐indole ( 2 ) was demonstrated to be clinically useful in the treatment of migraine. Although 2 exhibited high affinity for the 5‐HT 1F receptor as well as high selectivity for the 5‐HT 1F receptor relative to 5‐HT 1B and 5‐HT 1D receptors, it demonstrated appreciable affinity for the 5‐HT 1A receptor. Subsequently, a program was launched to discover SSOFRA's with improved selectivity over other 5‐HT 1 receptor subtypes. As a result of these efforts, N ‐[3‐(1‐methyl‐4‐piperidinyl)‐1 H ‐pyrrolo[3,2‐b]pyridin‐5‐yl]propanamide ( 3 ) was found to possess greater than 100‐fold selectivity over 5‐HT 1A , 5‐HT 1B and 5‐HT 1D receptors. Pursuant to a potential clinical investigation of 3 , its carbon‐14‐labeled isotopomer has been prepared by a circuitous route from unlabeled 3 and used in quantitative whole‐body autoradiography studies in rats. The results of these efforts are reported herein. Copyright © 2005 John Wiley & Sons, Ltd.