The TosMIC approach to 3-(Oxazol-5-yl) indoles: application to the synthesis of indole-based IMPDH inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 12; no. 22; pp. 3305 - 3308
• Main Authors: Dhar, T.G.Murali, Shen, Zhongqi, Fleener, Catherine A., Rouleau, Katherine A., Barrish, Joel C., Hollenbaugh, Diane L., Iwanowicz, Edwin J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 18.11.2002; Elsevier
• Subjects: Binding Sites; Biological and medical sciences; Cyanides - chemistry; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Humans; Immunomodulators; IMP Dehydrogenase - antagonists & inhibitors; Indoles - chemical synthesis; Indoles - pharmacology; Lymphocyte Activation - drug effects; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; T-Lymphocytes - drug effects; Tumor Cells, Cultured; Enzyme; Nitrogen heterocycle; IMP dehydrogenase; Enzyme inhibitor; Cellular immunity; In vitro; Immunomodulator; Structure activity relation; T-Lymphocyte; Bicyclic compound; Carboxamide; Ureas; Aromatic compound; Oxidoreductases; Immunosuppressive agent; Indole derivatives; Chemical synthesis; Oxazole derivatives; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(02)00748-5

A modified approach to the synthesis of 3-(oxazolyl-5-yl) indoles is reported. This method was applied to the synthesis of series of novel indole based inhibitors of inosine monophosphate dehydrogenase (IMPDH). The synthesis and the structure–activity relationships (SARs), derived from in vitro studies, for this new series of inhibitors is given. A modified approach to the synthesis of 3-(oxazolyl-5-yl) indoles is reported. This method was applied to the synthesis of series of novel indole based inhibitors of inosine monophosphate dehydrogenase (IMPDH).