NG-Aminoguanidines from Primary Amines and the Preparation of Nitric Oxide Synthase Inhibitors

详细信息    查看全文

• 作者：Nathaniel I. Martin ; William T. Beeson ; Joshua J. Woodward ; Michael A. Marletta
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：February 28, 2008
• 年：2008
• 卷：51
• 期：4
• 页码：924 - 931
• 全文大小：182K
• 年卷期：v.51,no.4(February 28, 2008)
• ISSN：1520-4804

文摘

A concise, general, and high-yielding method for the preparation of N^G-aminoguanidines from primary amines is reported. Using available and readily prepared materials, primary amines are converted to protected N^G-aminoguanidines in a one-pot procedure. The method has been successfully applied to a number of examples including the syntheses of four nitric oxide synthase (NOS) inhibitors. The inhibitors prepared were investigated as competitive inhibitors and as mechanistic inactivators of the inducible isoform of NOS (iNOS). In addition, one of the four inhibitors prepared, N^G-amino-N^G-2,2,2-trifluoroethyl-L-arginine 19, displays the unique ability to both inhibit NO formation and prevent NADPH consumption by iNOS without irreversible inactivation of the enzyme.