Photoinduced Aromatization of Asymmetrically Substituted 1,4-Dihydropyridine Derivative Drug Cilnidipine

The antihypertensive drug Cilnidipine (1) is photolabile under UV-A light. Irradiation of a chloroform solution of Cilnidipine under aerobic and anaerobic conditions produces a common photoproduct which was isolated as 2-methoxyethyl-3-phenyl-2-propenyl pyridine dihydro-2,6-dimethyl-4-(3-nitrophenyl) pyridine-3,5-dicarboxylate (2). The formation of products was explained by photochemical aromatization of Cilnidipine. 1. Introduction The last few years have witnessed a growing interest of the scientific community in photoinitiated reactions of drugs [1]. This has been motivated by photobiological reasons, connected to the increasing number of cases of drug-photoinduced disorders but it has also attracted considerable attention from a more fundamental photochemical standpoint [2]. Thus it is worthy to stress that studies performed on drugs bearing either simple or complex chromophoric structures have provided remarkable contributions to the broad area of the molecular mechanisms of photoinitiated reactions [3, 4]. Derivatives of 1,4-dihydropyridines (DHPs) are drugs belonging to the class of pharmacological agents known as calcium channel blockers [5]. They inhibit calcium ion penetration inside cells and weaken the contractility of the cardiac muscle [6]. These compounds have been shown to be very effective vasodilators and are useful in the treatment of hypertension, ischemic heart disease, and other cardiovascular disorders [7, 8]. The 1,4-dihydropyridines show fast photochemical decomposition, which lead to chemical changes responsible for weakening the therapeutic effect [9, 10]. During the use of the DHPs, some side effects have been reported, of which the most common are associated with the vasodilatory action. But recently, besides these phenomena, more and more phototoxic effects on the skin are observed, indicating that they can cause skin photosensitivity reactions [11, 12]. Cilnidipine is a newly synthesized dihydropyridine calcium antagonist that has a slow onset and long duration of action. It can regulate the catecholamine secretion closely linked to intracellular Ca2+ levels [13, 14]. Comparing with other calcium antagonists, it has a slow onset, long-lasting antihypertensive effect, and unique inhibitory actions on sympathetic neurotransmission [15]. It shifts the lower limits for autoregulation of the cerebral blood flow downward, which may remain intact even if excessive hypotension is induced by Cilnidipine [16]. Hence, Cilnidipine has high potentials in the therapy of hypertension. Cilnidipine also exhibits photosensitive reaction