title: Structure activity relationship of organic nitrates: an exploratory hypothesis via molecular models.
abstract: An exploratory attempt to explain the structure/activity relationship of organic nitrates was initiated. In addition to the partition coefficient, a new empirical parameter, F(5.8A), was used in this correlation. This new parameter denotes the number of times that two oxygen atoms in the molecule can be arranged at a distance of 5.8A. Vasodilating potencies (EC50s) and partition coefficients of 11 organic nitrates were obtained from a literature report, while their corresponding F(5.8A) values were obtained from manual determination using two molecular models, viz: CPK and Drieding. Via linear regression comparisons, we showed that F(5.8A) was a better physicochemical parameter than the partition coefficient in explaining the differences in the observed pharmacologic activity. When the two parameters were combined, greater than 90% of the variability of the potency was accounted for. These results suggest that the pertinent protein (most likely the activating enzyme) for organic nitrate activity may contain at least two 'oxygen-philic' attachment sites which are separated by a distance of 5.8A.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.
authors.forename: T B
authors.initials: TB
authors.lastname: Tzeng
authors.forename: H L
authors.initials: HL
authors.lastname: Fung
mesh_terms: D000818:Animals; D001665:Binding Sites; D066298:In Vitro Techniques; D008958:Models, Molecular; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D011506:Proteins