Nifedipine structure-activity relationship

This section deals with the application of molecular orbital (MO) calculations in structure-activity relationship (SAR) analyses. Calcium channel-blocking 1,4-dihydropyridine (DHP) derivatives such as nifedipine (Fig. 9.10) are widely used in the therapy of cardiovascular disorders. 

Quantitative structure-activity relationship Phenylalkylamines - 1,4-Dihydropyridines Benzothiazepines Verapamil Nifedipine DUtiazem Dihydropyrimidines ... 

Three-Dimensional Quantitative Structure-Activity Relationship Approaches An early study by Seidel et al. showed that a certain 3D feature, such as a torsion angle, can be used to help explain calcium channel activity of a series of DHPs [123], For a set of rigid analogues of nifedipine, their calcium channel affinities (log A)) were correlated with the deviation from 90° of the torsion angle between the two rings (Aa) ... 

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. 

Structure activity relationships are available for verapamil and nifedipine but not, as yet, for diltiazem. 

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

Bossert and co-workers original three-component Hantzsch synthesis of nifedipine used 1 equiv of 2-ntirobenzaldehyde 181, 2 equiv of methyl acetoacetate 180, and ammonia to give nifedipine in 72% yield. Since their report, a number of variations on the Hantzsch 1,4-dihydropyridine synthesis have been reported. Many of the initial reports on the synthesis of 1,4-dihydropyridine derivatives were aimed at studying the structure activity relationships of these compounds with the goal of developing more potent and specific analogs of nifedipine. 

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