Endothelin antagonists: search for surrogates of methylendioxyphenyl by means of a Kohonen neural network.
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.
Anzali
S
S
Merck KGaA, Preclinical Pharmaceutical Research, Darmstadt, Germany. soheila.anzali@merck.de
Mederski
W W
WW
Osswald
M
M
Dorsch
D
D
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
D004149:Dioxoles; D016232:Endothelins; C116437:methylendioxyphenyl; D003577:Cytochrome P-450 Enzyme System