Effect of a calcium entry blocker NB-818 on renal blood flow in conscious spontaneously hypertensive rats.

Approaches to Combinatorial Synthesis of Heterocycles: A Solid-Phase Synthesis of 1,4-Dihydropyridines

“…1,4-Dihydro-4-(2-nitrophenyl)-2,6-dimethyl-3,5-bis(methoxycarbonyl)pyridine (7a, Nifedipine). Following method A, 50 mg (0.023 mmol) of the Rink-supported methyl aminocrotonate 2 yielded 5.6 mg (70%) of 7a 6a. Alternatively, 50 mg (0.045 mmol) of PAL-supported methyl aminocrotonate 2 with methyl 2-(2-nitrobenzylidene)acetoacetate (496 mg, 2 mmol) according to method B yielded 10.1 mg (65%) of 7a .…”

“…1,4-Dihydro-4-(3-nitrophenyl)-2,6-dimethyl-3-[(2-methoxyethoxy)carbonyl]-5-(isopropoxycarbonyl)pyridine (7c, Nimodipine). Following method A, 50 mg (0.023 mmol) of Rink-supported isopropyl aminocrotonate 2 yielded 7.5 mg (78%) of 7c 6c…”

“…The DHP nucleus is common to numerous bioactive compounds which include various vasodilator, antihypertensive, bronchodilator, antiatherosclerotic, hepatoprotective, antitumor, antimutagenic, geroprotective, and antidiabetic agents . DHPs have found commercial utility as calcium channel blockers, as exemplified by therapeutic agents such as Nifedipine ( 7a ),6a Nitrendipine ( 7b ),6b and Nimodipine ( 7c ) 6c. Second-generation calcium antagonists include DHP derivatives with improved bioavailability, tissue selectivity, and/or stability, such as the antihypertensive/antianginal drugs Elgodipine,6d Furnidipine, 6e,f Darodipine,6g Pranidipine,6h Lemildipine,6i Dexniguldipine,6j Lacidipine,6k and Benidipine,6l Following discovery of the compound Bay K 8644,6m a number of DHP calcium agonists have been introduced as potential drug candidates for treatment of congestive heart failure. 6n,o Among DHPs with other types of bioactivity, Cerebrocrast 6p has been recently introduced as a neuroprotectant and cognition enhancer lacking neuronal-specific calcium antagonist properties.…”

“…Second-generation calcium antagonists include DHP derivatives with improved bioavailability, tissue selectivity, and/or stability, such as the antihypertensive/antianginal drugs Elgodipine,6d Furnidipine, 6e,f Darodipine,6g Pranidipine,6h Lemildipine,6i Dexniguldipine,6j Lacidipine,6k and Benidipine,6l Following discovery of the compound Bay K 8644,6m a number of DHP calcium agonists have been introduced as potential drug candidates for treatment of congestive heart failure. 6n,o Among DHPs with other types of bioactivity, Cerebrocrast 6p has been recently introduced as a neuroprotectant and cognition enhancer lacking neuronal-specific calcium antagonist properties. In addition, a number of DHPs with platelet antiaggregatory activity have also been discovered 6r. These recent examples highlight the level of ongoing interest toward new DHP derivatives and have prompted us to explore this pharmacophoric scaffold in a combinatorial format as a fertile source of bioactive molecules.…”