Cyclopropylamino acid amide

A particularly elegant example of the application of bioisosterism designed to avoid toxicity associated with the metabolic activation of a 2,3-diaminopyridine ring has been described in the context of the potent bradykinin B1 receptor antagonist 8, a compound explored for its potential to treat pain [10]. The iterations considered in identifying a replacement for the core heterocycle initially reduced the linker element to the simple ethylene diamine derivative 9 that was ultimately modified to the cyclopropylamino acid amide 12 through the intermediacy of compounds 10 and 11. 

Prueksaritanont, T, Detwiler, T.J., Hettrick, L.A., Landis, E.R., Leonard, Y.M., Krueger, J.A., Lewis, S.D., Pettibone, D.J., Freidinger, R.M., and Bock, M.G. (2006) Cyclopropylamino acid amide as a pharmacophoric replacement for 2,3-diaminopyridine. Application to the design of novel bradykinin Bj receptor antagonists, journal of Medicinal Chemistry, 49, 1231-1234. 

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