title: Endothelin antagonists: search for surrogates of methylendioxyphenyl by means of a Kohonen neural network.
abstract: The methylendioxyphenyl group, present in a number of potent endothelin receptor antagonists, could have undesirable metabolic interactions with cytochrome P450 in vivo. Using a self-organizing neural network we analysed the features of molecular electrostatic potentials of several endothelin receptor ligands. A library of small "fragments and functional groups" together with their corresponding Kohonen maps was generated. By means of this Kohonen map library we discovered the benzothiadiazole group as a surrogate for methylendioxyphenyl.
authors.affiliation: Merck KGaA, Preclinical Pharmaceutical Research, Darmstadt, Germany. soheila.anzali@merck.de
authors.forename: S
authors.initials: S
authors.lastname: Anzali
authors.forename: W W
authors.initials: WW
authors.lastname: Mederski
authors.forename: M
authors.initials: M
authors.lastname: Osswald
authors.forename: D
authors.initials: D
authors.lastname: Dorsch
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004149:Dioxoles / Q000737:chemistry* / Q000378:metabolism; D016232:Endothelins / Q000037:antagonists & inhibitors*; D016571:Neural Networks, Computer; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004149:Dioxoles; D016232:Endothelins; C116437:methylendioxyphenyl; D003577:Cytochrome P-450 Enzyme System