Synthesis and structural conformation studies of a potent unsymmetrical 1,4-dihydropyridine

Abstract 2,6-Dimethyl-5-(phenylcarbamoyl)-4-(3-nitro-phenyl)-1,4-dihydropyridine-2-carboxylatewassynthesizedin two steps and was characterized spectroscopically andconfirmed by X-ray diffraction studies. The molecule crys-tallizesinthemonocliniccrystalclassinthespacegroupP2 1 /cwith cell parameters a = 10.5960(6) A˚ , b = 10.2450(7) A˚ ,c = 19.5790(11) A˚, b = 107.448(3) and Z = 4. The 1,4-dihydropyridine ring in the structure adopts a flattened boatconformation.Keywords 1,4-Dihydropyridine Flat boat Hydrogen bondIntroductionCalcium channel blockers (Ca 2+ antagonists) are animportant class of drugs used for the management of anumber of cardiovascular diseases [1]. The 1,4-dihydro-pyridines (DHPs) are a class of compounds used in thetreatment of many cardio-vascular diseases like variant andexertional angina, certain types of cardial arrhythmias,hypertension and so on [2]. Their action is based onblocking the flow of calcium ions through a plasmamembrane channel into the muscle cell. The most potentclass of antagonists comprises prototype of 1,4-dihydro-pyridine derivatives of which nifedipine has been approvedas a clinical agent for anti-anginal and anti-hypertensivetherapy [3]. 1,4-Dihydropyridine (1,4-DHPs) was intro-duced by Hantzsch in a single step preparation [4].Very recently, 2D and 3D QSAR of the many sym-metrical 1,4-DHPs prompted us to design some moleculesfor the screening against antitubercular activity [5, 6]. Incontinuation of the earlier work [7–9], we introduced thecarbamoyl functionality and also the esteric part in the 3rdand 5th positions of 1,4-DHPs. In the present work, wereport the synthesis and structure conformation of the ref-erence molecule for the screening. The 2D and 3D QSARstudies have revealed some important points in drug design[10], but structure with the carbamoyl and esteric groupswere not synthesized. Very few compounds of this type arereported in literature [11]. This has prompted us to syn-thesize the unsymmetrical 1,4-DHP, where at C3, thecarbamoyl function is introduced and on the other handesteric group is present [12, 13]. The product obtained wascharacterized by spectroscopic techniques and the structurewas confirmed by X-ray diffraction method (Scheme 1).ExperimentalPreparation of 2,6-Dimethyl-4-(3-Nitrophenyl)-3-(Phenylcarbamoyl)-5-Carbameth-Oxy-1,4-DihydropyridineA mixture of 2-acetyl-N-(phenyl)-3-(3-nitrophenyl) acryl-amide (0.01 mol, 3.10 gm) and methyl-3-amino crotonate(0.01 mol, 1.15 gm) was taken in a flat bottom flask andmethanol (25 mL) was added, stirred and refluxed on astirring device for 7 h. A sticky mass was obtained on thereaction flask which was treated with diethyl ether and thefree solid product of was collected in the flask. The solid