Aranidipine (MPC‐1304), a New Dihydropyridine Calcium Antagonist: A Review of Its Antihypertensive Action

Abstract

Key Words: Aranidipine-Antihypertensive agentxalcium channel antagonist.Calcium antagonists play an important role in the treatment of patients with cardiovascular diseases such as ischemic heart disease, heart failure, and hypertension. The dihydropyridine-type calcium antagonists are widely used to treat hypertension, because of their potent vasodilating activity and weak cardiodepressant action (9,38,11). Aranidipine (MPC-1304) is a novel dihydropyridine-type calcium antagonist, which is characterized by its active metabolites, once daily administration to facilitate patient compliance, and the prospect of good efficacy and safety. In experimental animal models aranidipine had more potent antihypertensive effects than did other dihydropyridines. Administration of aranidipine once daily had a highly potent antihypertensive effect and clinical utility in all of the clinical trials conducted in Japan. Aranidipine is now under registration. In this article, the pharmacological, toxicological, pharmacokinetic profiles, and clinical findings of aranidipine are reviewed. CHEMISTRY Aranidipine was first synthesized by Ohno et al. (24,25). The chemical structures of aranidipine [(+)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate] and its active metabolite, M-1 [2-hydroxypropyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate] , are shown in Fig. 1. Aranidipine has an asymmetric carbon at the C-4 position of the dihydropyridine ring. M-1 has two asymmetric carbons in its structure, and there exist four enantiomers: (S,S)-and (R,R)-M-1 (their mixture is M-l(a)), and (S,R)-and (R,S)-M-1 (their mixture is M-l(P)). The molecular weight of aranidipine (C19Hz,Nz0,) is 388.38, and its melting point is 149-150°C. Aranidipine is freely soluble in acetone and insoluble in water.

Hantzsch-Type Dihydropyridines and Biginelli-Type Tetra-hydropyrimidines: A Review of their Chemotherapeutic Activities

“…1,2,3,4-Tetrahydropyrimidines have also been evaluated as calcium channel modulating agents due to their structural similarity to 1,4dihydropyridines (20), and several reviews have been devoted to the chemistry and synthesis of these two chemical scaffolds (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The calcium channel modulating activity of both scaffolds has also led to numerous reviews dedicated to biological responses initiated by this property (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). However, little is about other biological capacities of 1,4-DHPs and 1,2,3,4-THPMs (52)(53)(54)(55)(56)(57).…”

Synthesis of α‐Acyloxy‐α′‐hydroxy Ketones via Cyclic Carbonate Intermediates Generated from Tertiary Bromopropargylic Alcohols and Cs2CO3

“…The α‐acyloxy carbonyl motifs are the key structural units, which are met in natural products and pharmaceuticals such as cortisone acetate, valrubicin,[1a], cortivazol,[1a], bendacort,[1a], aranidipine,[1a], and others that exhibit anti‐inflammatory, anticancer, antiallergic, hypotensive properties, etc. (Figure ).…”

The Multicomponent Hantzsch Reaction: Comprehensive Mass Spectrometry Monitoring Using Charge‐Tagged Reagents

“…Depending upon the reagents and or reaction conditions, low yields or unexpected products can be obtained, [3] including isomeric 1,2-DHP, [4] hence the need to fully understand its intricate mechanism. The 1,4-DHP have been found to posses many pharmacological activities, such as: [5] antitumorals for multidrug resistant (MDR) tumours, [6] bronchodilating, [7] antidiabetic, [8] neurotropic, [9] HIV protease inhibitors; [10] although they are perhaps best known as calcium channel blockers, [11] for example: aranidipine, [12] lercanidipine, [13] nifedipine [14] and the multibillion dollar drug amlodipine. [15] Additionally, the 1,4-DHP have great potential as hydride (or hydrogen) transfer reagents due to their similarity with the natural product enzyme co-factors NAD(P)H and the oxidized form NAD(P).…”