Conformational analysis of the 1,4-dihydropyridines linking the structural aspects to the biological binding event: a study of the receptor-site conformation

• Published in: Journal of molecular structure. Theochem 1994, Vol.303, p.255-263
• Main Authors: Gaudio, Anderson Coser, Korolkovas, Andrejus, Takahata, Yuji
• Format: Article
• Language: English
• Subjects: Atomic and molecular physics; Biological and medical sciences; Calculations and mathematical techniques in atomic and molecular physics (excluding electron correlation calculations); Electronic structure of atoms, molecules and their ions: theory; Exact sciences and technology; General pharmacology; Medical sciences; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Physics; Statistical model calculations (including Thomas-Fermi and Thomas-Fermi-Dirac models)
• ISSN: 0166-1280; 1872-7999
• DOI: 10.1016/0166-1280(94)80191-6

A conformational analysis involving a set of 45 2,6-dimethyl-3,5-dicarbomethoxy-4-X-phenyl-1,4-dihydropyridine derivatives was performed. The potential energy surfaces of the rotation of the phenyl ring around the pyridine ring were constructed for each compound. These were arranged in groups of five in descending order of biological activity. The energy level below 99% of the molecular population for each molecule was superimposed on those groups. The conformationally stable regions permitted to this molecular population were found and compared. The analysis of each group of potential energy surfaces thus constructed revealed that in the biologically active conformation the phenyl ring bisects the pyridine ring and the ortho/meta phenyl substituents are spatially away from the pyridine ring.