Christopher Lipinski - Acidic isostere design: Synthetic strategies and recent progress in understanding electronic properties and metabolic stability

Version 1

      Publication Details (including relevant citation   information): Lipinski, Christopher A., Chenard, Bert   L., Pesticide Science, 1990,   29 (2), pp 227-240

      Abstract: The efficient synthesis of a family of   twelve acidic heterocycles of varying acidity from a single   common intermediate facilitates the search for new acidic   bioisosteres. An extension of this chemical approach led to a new   family of phosphonate replacements in prototypes related to the   N-methyl Dasparate (NMDA) antagonist 2-amino-7-phosphonoheptanoic   acid (AP7). Acidic isostere design may be facilitated by grouping   hydroxylic heterocyclic carboxylic isosteres into one of two   electronic classes based on the Gandour hypothesis. The   limitations of normal hydroxamic acids as carboxylic acid   surrogates suggest that the excellent metabolic stability of   reverse hydroxamic acids may be useful in prospective acidic   isostere design.

      Address (URL): http://onlinelibrary.wiley.com/doi/10.1002/ps.2780290211/pdf