3-Substituted indolizine-1-carbonitrile derivatives as phosphatase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 1; pp. 59 - 63
• Main Authors: Weide, Timo, Arve, Lars, Prinz, Heino, Waldmann, Herbert, Kessler, Horst
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: 3-Substituted indolizine-1-carbonitrile; Acetic Acid - chemistry; Animals; Biological and medical sciences; Carbon - chemistry; Chemistry, Pharmaceutical - methods; Combinatorial Chemistry Techniques; Drug Design; Electrons; Enzyme Inhibitors - pharmacology; Heterocyclic Compounds; Indoles - chemistry; Indolizines - chemistry; Inhibitory Concentration 50; Medical sciences; Mice; Miscellaneous; Models, Chemical; Molecular Conformation; Molecular Structure; Mycobacterium tuberculosis - metabolism; Nitriles - chemistry; Pharmacology. Drug treatments; Phosphatase; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphoric Monoester Hydrolases - chemistry; Protein Tyrosine Phosphatases - chemistry; Pyridines; Salmonella typhimurium - metabolism; Solid-phase; Structure-Activity Relationship; Yersinia pestis - metabolism; Phosphatase; Solid-phase; 3-Substituted indolizine-1-carbonitrile; Indolizine derivatives; Nitrile; Enzyme; Phosphoric monoester hydrolases; Enzyme inhibitor; Esterases; In vitro; Biological activity; 3-Substituted indolizine-1- carbonitrile; Aminoacid; Hydrolases; Solid phase; Chemical synthesis; Protein-tyrosine-phosphatase
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.09.051

The solid-phase supported synthesis and antiphosphatase activity of a series of indolizines are reported.
In the course of studies directed toward the discovery of novel scaffolds for medicinal application, we synthesized a series of 3-substituted indolizine-1-carbonitrile derivatives. Some of them displayed activity against MPtpA/MPtpB phosphatases which are involved in infectious diseases. We report here the solid-phase synthesis and antiphosphatase activity of a series of indolizines.