1.4- Dihydropyridine calcium

H. Fujimoto, I. Nishino, K. Ueno and T. Umeda, Determination of the enantiomers of a new 1,4-dihydropyridine calcium antagonist in dog plasma achiral / chiral coupled high performance liquid cliromatography with electrochemical detection , 7. Pharm. Sci. 82 319-322(1993). 

Mason, R. R Campbell, S. F. Wang, S.-D. Herbette, L. G., Comparison of location and binding for the positively charged 1,4-dihydropyridine calcium channel antagonist amlopidine with uncharged drugs of this class in cardiac membranes, Molec. Pharmacol. 36, 634—640 (1989). 

Dihydropyridine calcium antagonist RP Ion exchange (Nucleosil SA) Ovamucoid Fujitomo et al., 1993... 

Katoh M, Nakajima M, Shimada N, et al. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol 2000 55 843-852. 

A quantitative structure-activity relationship of 1,4-dihydropyridine calcium channel blockers with electronic descriptors produced by quantum chemical topology... 

Dihydropyridine calcium channel blockers (CCBs) have been used for many years in the treatment of angina pectoris and hypertension (81). Their mechanism of action is based on inhibition of the smooth muscle L-type calcium current, thereby... 

Mager PP, Coburn RA, Solo AJ, Triggle DJ, Rothe H. QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists A difficult road ahead. Drug Des Discov 1992 8 273-89. 

Hemmateenejad B, Akhond M, Miri R, Shamsipur M. Quantitative structure-activity relationship study of recently synthesized 1,4-dihydropyridine calcium channel antagonists. In Application of the Hansch analysis method. Weinheim Arch Pharm, 2002. p. 472-80. 

Takahata Y, Costa MC, Gaudio AC. Comparison between neural networks (NN) and principal component analysis (PCA) Structure activity relationships of 1,4-dihydropyridine calcium channel antagonists (nifedipine analogues). J Chern Inf Comput Sci 2003 43 540-4. 

Si HZ, Wang T, Zhang KJ, Hu ZD, Fan BT. QSAR study of 1,4-dihydropyridine calcium channel antagonists based on gene expression programming. Bioorg Med Chem 2006 Mar 29 published on the Web. 

Yao X, Liu H, Zhang R, Liu M, Hu Z, Panaye A, et al. QSAR and classification study of 1,4-dihydropyridine calcium channel antagonists based on least squares support vector machines. Mol Pharm 2005 2 348-56. 

Triggle DJ, Structure-Function Correlations of 1,4-Dihydropyridine Calcium channel Antagonists and Activators, In Molecular and Cellular Mechanisms of Antiarrhythmic Agents [ Hondeghem LM, Ed ] pp. 269-291, Futura Press, Mt. Kiscoe, NY 1989. 

Andreazza Costa, M.C., Gaudio, A.C. and Takahata, Y. (1997) A comparative study of principal component and linear multiple regression analysis in SAR and QSAR applied to 1,4-dihydropyridine calcium channel antagonists (nifedipine analogues). ]. Mol. Struct. (Theochem), 394, 291-300. 

Safarpour, M.A., Hemmateenejad, B., Min, R. and Jamali, M. (2003) Quantum chemical-QSAR study of some newly synthesized 1,4-dihydropyridine calcium channel blockers. QSAR Comb. Sci., 22, 997-1005. 

Several 1,4-dihydropyridine calcium channel blockers have been tritiated and used to investigate binding of this class of drugs. The majority of studies utilized [3H]nitrendipine [26, 87-115], but [3H]nimodipine [ 115-123], [3H]nifedipine [124] and [3H]PN 200-110 [97,106,125,126] have also been employed in some studies. Drug binding has been shown to be specific, saturable, rapid and reversible. Scatchard plots of the specific binding at equilibrium are linear, consistent with mass action behaviour. The apparent dissociation constant (A d) and the number of binding sites (Bmax) may be determined from the Scatchard plot. 

Gaudio AC, Korolkovas A, Takahata Y. Quantitative structure-activity relationships for 1,4-dihydropyridine calcium channel antagonists (nifedipine analogs) a quantum/ classical approach. J Pharm Sci 1994 83 1110-1115. 

Figure 9 Structures of chiral 1,4-dihydropyridine calcium channel blocking agents.

Eltze, M. Boer, R. Sanders, K.H. Boss, H. Ulrich, W.-R. Flockerzi, D. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists. Chirality 1990,2,233-240. 

A number of the 1,4-dihydropyridine calcium channel antagonists are chiral and are used as the racemate for the treatment of hypertension and angina. 

When planning a biotransformation, identification of a bifunctional pro-chiral substrate provides a clear benefit over conventional resolution since up to 100% of a desired enantiomer can be obtained by enzymatic desymme-trization. This feature is exemplified in the work of Achiwa and coworkers [37] in the area of 1,4-dihydropyridine calcium channel blockers (Scheme 5.11). Hydrolysis of the bis(pivaloyloxymethyl)ester (15) gave enantiopure monoacid (16) which was used to correlate the absolute configuration of the novel agent (17) with that of (5)-(-)-felodipine (18). 

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