2.Endothelin antagonists: Evaluation of 2,1,3-benzothiadiazole as a methylendioxyphenyl bioisoster
- 1 January 1998
- journal article
- Published by Elsevier BV in Bioorganic & Medicinal Chemistry Letters
- Vol. 8 (1), 17-22
- https://doi.org/10.1016/s0960-894x(97)10151-2
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.Keywords
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