1 - ENDOTHELIN ANTAGONISTS - SEARCH FOR SURROGATES OF METHYLENDIOXYPHENYL BY MEANS OF A KOHONEN NEURAL-NETWORK

The methylendioxyphenyl group, present in a number of potent endotheli n receptor antagonists, could have undesirable metabolic interactions with cytochrome P450 in vivo. Using a self-organizing neural network w e analysed the features of molecular electrostatic potentials of sever al endothelin receptor ligands. A library of small ''fragments and fun ctional groups'' together with their corresponding Kohonen maps was ge nerated. By means of this Kohonen map library we discovered the benzot hiadiazole group as a surrogate for methylendioxyphenyl. (C) 1997 Else vier Science Ltd. All rights reserved.