A novel method for the synthesis of carbon-14-labeled N-[3-(1-methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]propanamide and its use in quantitative whole-body autoradiography studies

✍ Scribed by William J. Wheeler; Sylvia H. Chay; Jennifer L. Herman; Douglas D. O'Bannon

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 183 KB
• Volume: 48
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.959

✦ Synopsis

Abstract

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.