124603-80-1Relevant articles and documents
A Unified Approach to Systematic Isoesteric Substitution for Acidic Groups and Application to NMDA Antagonists Related to 2-Amino-7-phosphonoheptanoate
Chenard, B. L.,Lipinski, C. A.,Dominy, B. W.,Mena, E. E.,Ronau, R. T.,et al.
, p. 1077 - 1083 (2007/10/02)
A systematic approach to the replacement of acidic groups with potential bioisoesteres is described.The strategy involves simple nucleophilic displacement of a common alkyl halide precursor with a variety of mercaptoazoles and related molecules.The mercaptoazoles and their oxidized derivatives (sulfinyl- and sulfonylazoles) represent a series of possible surrogates for acidic groups which span a pKa range from about 4.5-11.5.This simple strategy was extended to include 2-hydroxy- or 2-aminothiophenyl groups which function as relatively nonacidic isoesteres for a phosphonic acid.By replacing the phosphonic acid of 2-amino-7-phosphonoheptanoate (AP-7) with these groups, we have synthesized novel N-methyl-d-aspartate (NMDA) antagonists.
