191849-91-9

Upstream product

• 222848-56-8 (3S)-N-(benzyloxycarbonyl)-3-amino-2-hydroxy-4-phenylbutanoic acid 
• 128018-18-8 L-proline tert-butylamide 
• 62023-60-3 (2R,3S)-N-(benzyloxycarbonyl)-3-amino-2-hydroxy-4-phenylbutanoic acid 
• 172696-22-9 (2R,3S)-N-(benzyloxycarbonyl)-AHAP-(3-amino-2-hydroxy-4-phenylbutanoic acid) ethyl ester 
• 62023-59-0 (2S,3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 
• 114744-85-3 [(S)-1-(methoxy-methyl-carbamoyl)-2-phenyl-ethyl]-carbamic acid benzyl ester 
• 121253-57-4 β-<<(phenylmethoxy)carbonyl>amino>-α-oxobenzenebutanoic acid ethyl ester 
• 121253-53-0 2-ethoxy-5-phenyl-4-<<(phenylmethoxy)carbonyl>amino>-3-oxo-1-pentene 

Downstream Products

• 141197-75-3 (3S)-3-(N-benzyloxycarbonyl)amino-2-keto-4-phenylbutyryl-L-prolyl-tert-butyl amide 
• 165522-26-9 1-<(2R,3S)-3-amino-2-hydroxy-4-phenylbutyryl>-N-tert-butyl-L-prolinamide 

Relevant academic research and scientific papers

HIV protease inhibitors

Combinatorial libraries of HIV and FIV protease inhibitors are characterized by alpha-keto amide or hydroxyethylamine core structures flanked by on one side by substituted pyrrolidines, piperidines, or azasugars and on the other side by phenylalanine, tyrosine, or substituted tyrosines. The libraries are synthesized via a one step coupling reaction. Highly efficacious drug candidates are identified by screening the libraries for binding and inhibitory activity against both HIV and FIV protease. Drug candidates displaying clinically useful activity against both HIV and FIV protease are identified as being potentially resistive against a loss of inhibitory activity due to development of resistant strains of HIV.

Selectivity in the inhibition of HIV and FIV protease: Inhibitory and mechanistic studies of pyrrolidine-containing α-keto amide and hydroxyethylamine core structures

This paper describes the development of new pyrrolidine-containing α-keto amide and hydroxyethylamine core structures as mechanism based inhibitors of the HIV and FIV proteases. It was found that the α-keto amide core structure 2 is approximately 300-fold better than the corresponding hydroxyethylamine isosteric structure and 1300-fold better than the corresponding phosphinic acid derivative as an inhibitor of the HIV protease. The α-keto amide is however not hydrated until it is bound to the HIV protease as indicated by the NMR study and the X-ray structural analysis. Further analysis of the inhibition activities of hydroxyethylamine isosteres containing modified pyrrolidine derivatives revealed that a cis-methoxy group at C-4 of the pyrrolidine would improve the binding 5- and 25-fold for the trans-isomer. When this strategy was applied to the α-keto amide isostere, a cis-benzyl ether at C-4 was found to enhance binding 3-fold. Of the core structures prepared as inhibitors of the HIV protease, none show significant inhibitory activity against the mechanistically identical FIV protease, and additional complementary groups are needed to improve inhibition.

Synthesis and human immunodeficiency virus (HIV-1 protease inhibitory activity of tripeptide analogues containing a dioxoethylene moiety

Tripeptide analogues 2 and 3 containing a dioxoethylene moiety were designed based on the characteristic structure of the naturally occurring human immunodeficiency virus (HIV)-I protease inhibitors RPI-856 A, B, C and D (1). The compounds (2, 3) prepared showed high inhibitory activity, comparable to that of RPI-856 A, against HIV-1 protease in vitro.