مشخصات پژوهش

Hypertension is a common medical and social problem leading to cardiovascular diseases worldwide.[1] The five major classes of antihypertensive drugs- diuretics, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs), including dihydropyridines (DHPs) and non-dihydropyridines- are clinically applied to decrease the morbidity and mortality induced by hypertension itself and its complications.[2] 1,4-Dihydropyridine drugs are nowadays the most used drugs in the treatment of hypertension. As of now, there are four generations of DHPs clinically available.[3] The first-generation nicardipine and nifedipine have proven efficacy against hypertension, but due to their short half-life time and rapid onset of vasodilator action, these drugs were more likely to be associated with adverse effects. The second generation benidipine, and efonidipine with slow-release and short-acting preparations allowed better control of the therapeutic effect and a reduction in some adverse effects. The third-generation amlodipine and azelnidipine are more lipophilic with stable pharmacokinetics and long-term actions, and less cardio-selective and well tolerated in patients with heart failure. The fourth-generation lercanidipine and lacidipine (L/N-type CCB) are highly lipophilic with a real degree of therapeutic comfort in terms of stable activity, a reduction in adverse effects and a broad therapeutic spectrum, especially in myocardial ischemia and potentially in congestive heart failure. As can be seen, the higher generations of DHPs with more lipophilicity are much more potent drugs. Adamantne, the smallest diamondoid, is often viewed as providing just the critical lipophilicity, and it is used as a “lipophilic bullet” for modification of known drugs.[4,5] In this study, we wish to combine the remarkable structure and chemical properties of bulky and lipophilic adamantane with privileged 1,4-DHP scaffold and synt