PMID: 7543577Jul 21, 1995Paper

Syntheses, calcium channel agonist-antagonist modulation activities, and voltage-clamp studies of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate racemates and enantiomers

Journal of Medicinal Chemistry
D VoEdward E Knaus

Abstract

A novel group of racemic isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate isomers [(+/-)-12-14] were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with isopropyl 3-aminocrotonate and 2-, 3-, or 4-pyridinecarboxaldehyde. Determination of their in vitro calcium channel-modulating activities using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays showed that the 2-pyridinyl isomer (+/-)-12 acted as a dual cardioselective calcium channel agonist (GPLA)/smooth muscle selective calcium channel antagonist (GPILSM). In contrast, the 3-pyridinyl [(+/-)-13] and 4-pyridinyl [(+/-)-14] isomers acted as calcium channel agonists on both GPLA and GPILSM. The agonist effect exhibited by (+/-)-12 on GPLA was inhibited by nifedipine and partially reversed by addition of extracellular Ca2+. In anesthetized rabbits, the 4-pyridinyl isomer (+/-)-14 exhibited a hypertensive effect that was qualitatively similar to that exhibited by the nonselective agonist Bay K 8644 and the 3-pyridinyl isomer (+/)-13, whereas the 2-pyridinyl isomer (+/-)-12 induced a hypotensive effect similar to that of the calcium channel antagonist nifedipine. Sim...Continue Reading

Citations

Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunV Vijayakumar
Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunV Vijayakumar
Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunV Vijayakumar
Jan 1, 2009·Acta Crystallographica. Section E, Structure Reports Online·B Palakshi ReddyP L Nilantha Lakshman
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Wan-Sin LohS Sarveswari
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Palakshi B ReddyEdward R T Tiekink
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Tara ShahaniS Sarveswari
May 17, 2012·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunShridhar Malladi
Jan 4, 2013·Acta Crystallographica. Section E, Structure Reports Online·Arun M IslorRichard Betz
Mar 8, 2013·Acta Crystallographica. Section E, Structure Reports Online·Arun M IslorRichard Betz
Mar 8, 2013·Acta Crystallographica. Section E, Structure Reports Online·Arun M IslorRichard Betz
Sep 5, 2009·Drug Discovery Today·Najmeh EdrakiRamin Miri
May 5, 2017·The Journal of Organic Chemistry·Fernando Auria-LunaRaquel P Herrera
Dec 13, 2002·Rapid Communications in Mass Spectrometry : RCM·C López-AlarcónCristián Camargo
Dec 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bimal Krishna BanikRajat Kumar
Jun 12, 2008·Chemical Reviews·Marcos A P MartinsHelio G Bonacorso
Sep 17, 2014·Chemical Reviews·Marcos A P MartinsHelio G Bonacorso

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.