Nonpeptide inhibitors of HIV

Yehia NAM, Antuch W, Beck B, Hess S, Schauer Vukasinovic V, Ahnstetter M, Eurer P, Herdtweck E, Domling A (2004) Novel nonpeptidic inhibitors of HIV-1 protease obtained via a new multicomponent chemistry strategy. Bioorg Med Chem Lett 14 3121-3125... 

Due to their substantial size and peptidic nature, inhibitors from this class were not suitable for clinical application. Nevertheless, the structural information derived from many crystal structures of peptidic inhibitors bound to the HIV PR active site was critical for subsequent modeling and design of the next generation of peptidomimetic and nonpeptidic inhibitors of HIV PR. 

Reich SH, Melnick M, Pino M, Fuhry MA, Trippe AJ, Appelt K, Davies JF, Wu B-W, Musick L. Structure-based design and synthesis of substituted 2-butanols as nonpeptidic inhibitors of HIV protease secondary amide series. J. Med. Chem. 1996 39 2781-2794. 

Tetrazole thioacetanilides 595 (HIV non-nucleoside reverse transcriptase inhibitors) <2006BML2748> and derivatives of cyclic ureas 596 (nonpeptide inhibitors of HIV protease) have been prepared <1998JME2019>. 

In the second example, we summarize our efforts to design highly focused virtual library subset of nonpeptidic inhibitors of HIV PR, using structure-based computational approach [20]. 

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