title: Endothelin antagonists: evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster.
abstract: The methylendioxyphenyl group is present in a number of endothelin receptor antagonists thus far reported. By means of a Kohonen neural network we discovered with a benzothiadiazole a bioisosteric replacement instead. This group should be devoid of the negative metabolic interactions with cytochrome P450 ascribed to methylendioxyphenyl in vivo. The synthesis of a potent benzothiadiazole analogue EMD 122801 together with in vitro studies of different methylendioxyphenyl, benzothiadiazole and benzofurazan derivatives is described.
authors.affiliation: Merck KGaA, Preclinical Pharmaceutical Research, Darmstadt, Germany. mederski@merck.de
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
authors.forename: S
authors.initials: S
authors.lastname: Anzali
authors.forename: M
authors.initials: M
authors.lastname: Christadler
authors.forename: C J
authors.initials: CJ
authors.lastname: Schmitges
authors.forename: C
authors.initials: C
authors.lastname: Wilm
mesh_terms: D004149:Dioxoles / Q000737:chemistry* / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004149:Dioxoles; D016232:Endothelins; D013830:Thiadiazoles; C116437:methylendioxyphenyl; C015700:benzo-1,2,3-thiadiazole