141171-72-4

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 
• 62023-59-0 (2S,3S)-3-benzyloxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 
• 172696-23-0 (2S,3S)-N-(benzyloxycarbonyl)-AHAP-(3-amino-2-hydroxy-4-phenylbutanoic acid) ethyl ester 
• 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 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 128018-17-7 Z-Pro-NH^tBu 

Downstream Products

• 207444-88-0 ((S)-1-{(S)-1-[(1S,2S)-1-Benzyl-3-((S)-2-tert-butylcarbamoyl-pyrrolidin-1-yl)-2-hydroxy-3-oxo-propylcarbamoyl]-2-carbamoyl-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid benzyl ester 
• 207444-87-9 ((R)-1-{(S)-1-[(1S,2S)-1-Benzyl-3-((S)-2-tert-butylcarbamoyl-pyrrolidin-1-yl)-2-hydroxy-3-oxo-propylcarbamoyl]-2-carbamoyl-ethylcarbamoyl}-2-phenyl-ethyl)-carbamic acid benzyl ester 

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.

Syntheses of HIV-protease inhibitors having a peptide moiety which binds to GP120

Some HIV-protease inhibitor derivatives having an N- carbomethoxycarbonyl-prolyl-phenylalanine benzyl ester (CPF) moiety as a binding site to gp120 were designed and synthesized. Almost all the compounds bearing CPF on the phenoxyacetyl group showed protease-inhibitory activity. Compounds 25a and 25b, which have the CPF moiety at the ortho- and meta- positions of the phenoxyacetyl group, respectively, had anti-HIV activity, although the others showed only protease-inhibitory activity. These results suggest that 25b binds to gp120 and inhibits HIV protease.

Synthesis of dipeptide-type human immunodeficiency virus (HIV) protease inhibitors with a binding unit to GP120

Some dipeptide-type human immunodeficiency virus (HIV) protease inhibitors derived from KNI-102, with a N-carbomethoxycarbonylprolyl- phenylalanine benzyl ester (CPF) moiety as a binding site to gp120, were synthesized. Compounds 11a showed 7 - 100 times higher HIV protease- inhibitory activity (11a; IC50 = 0.90 μg/ml, 1.1 μM) than the standard compound 3 or 4 (3; IC50 = 3.7 μg/ml, 7.7 μM, 4; IC50 = 75 μg/ml, 155 μM). Generally, the compounds substituted at the o-position of the phenoxyacetyl group 7a, 11a, 16a and 21a showed several times higher inhibitory activity than 3.

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.