Synthesis of Dialkyl 1,4-Dihydro-2,6-dimethyl-4-(heteroaryl)-pyridine-3,5-dicarboxylates as Calcium Channel Antagonists

✍ Scribed by Raymond D. Anana; Edward E. Knaus

• Publisher: Journal of Heterocyclic Chemistry
• Year: 1997
• Tongue: English
• Weight: 263 KB
• Volume: 34
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570340240

✦ Synopsis

Abstract

The Hantzsch condensation of the heteroarylcarboxaldehydes 3a‐c with alkyl acetoacetates 4a‐c and alkyl 3‐aminocrotonates 5a‐b afforded the respective dialkyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(heteroaryl)‐pyridine‐3,5‐dicarboxylates 6a‐f possessing a C‐4 4‐quinolinyl, 8‐quinolinyl or 1‐oxido‐4‐pyridinyl substituent Calcium channel antagonist structure‐activity relationships acquired indicate that i) the position of the quinolyl nitrogen atom was not a determinant of activity, ii) increasing the size of the C‐3 and C‐S alkyl ester substituents decreases potency and iii) a C‐4 1‐oxido‐4‐pyridinyl substituent abolishes activity. The most active, and equipotent C‐4 4‐quinolinyl 6a and 8‐quinolinyl 6b analogs, were approximately 8‐fold less potent calcium channel antagonists than the reference drug nifedipine.