166382-65-6

Upstream product

• 143978-10-3 Z-Asn-(2S,3S)-AHPBA-OH 
• 246877-27-0 4(S)-Cl-Pro-tert-butylamide 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 143978-73-8 1-tert-butoxycarbonyl-4(R)-hydroxy-L-proline tert-butylamide 
• 166383-59-1 (4S)-1-t-butoxycarbonyl-N-t-butyl-4-chloro-L-prolinamide 
• 166383-85-3 (4S)-N-t-butyl-4-chloro-L-prolinamide hydrochloride 
• 2942-58-7 diethyl cyanophosphonate 

Downstream Products

• 785024-25-1 (S)-2-Amino-N¹-[(1S,2S)-1-benzyl-3-((2S,4S)-2-tert-butylcarbamoyl-4-chloro-pyrrolidin-1-yl)-2-hydroxy-3-oxo-propyl]-succinamide 

Relevant academic research and scientific papers

Inhibitors of HIV protease

Compounds of formula (I): STR1 wherein: R1 is hydrogen, alkyl, aralkyl, --CORa, --CORb, --CSRa, --CSRb, --SO2 Rb, --CONHRb, --CSNHRb, --CONRb Rb or --CSNRb Rb ; R2 is hydrogen or alkyl; R3 is hydrogen, alkylidene, substituted alkyl, or Rb ; R4 is optionally substituted alkyl, cycloalkyl, or aryl; R5 is Rb O--, Rb Rb N--, Rb HN--, aralkyloxycarbonyloxy or aralkyloxycarbonylamino, or R5 is --(CH2)p --D--(CH2)r --, where D is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH2 =CH2)-- or --NHCO--; and p and r are each 0 or an integer from 1 to 5; A is --(CH2)m --B--(CH2)n -- where B is a single bond, carbonyl, oxygen, sulfur, --NH--, --(CH2 =CH2)-- or --NHCO--; and m and n are each 0 or an integer from 1 to 5; Ra is alkoxy, aralkyloxy, aryloxy or alkoxycarbonyl; Rb is optionally substituted alkyl, cycloalkyl, heterocyclic, aryl or arylalkenyl; and pharmaceutically acceptable salts and esters thereof and pro-drugs therefor, have the ability to inhibit the activity of HIV protease and may thus be used for the treatment and prophylaxis of AIDS.

Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA - II. Modification of pyrrolidine ring at P1' proline

Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with five- or six-membered fused aromatic heterocycle carbonyl groups produced more potent inhibitors. 7-Methoxybenzofuran-2-carbonyl derivative (44) was the best of these and showed K(i) = 4.5 nM against HIV PR and IC90s 0.58 μM and 0.06 μM in chronic and acute infections, respectively. These results suggest that the combination of the 4(S)-Cl atom and fused bicyclic heterocycles may be effective in improving their cellular penetration.