134848-75-2

Upstream product

• 65710-57-8 3-{[(benzyloxy)carbonyl]amino}-N-(tert-butoxycarbonyl)-L-alanine 
• 91970-62-6 benzyl 4-hydroxybutanoate 
• 134879-38-2 4-oxo-4-(phenylmethoxy)butyl (4S,5R)-4-(cyclohexylmethyl)-2,2-dimethyl-3-<(1,1-dimethylethoxy)carbonyl>-5-oxazolidinecarboxylate 

Downstream Products

• 134848-67-2 (3R,4S,7S)-4-(cyclohexylmethyl)-7-<-L-phenylalanyl>amino>-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridecane 
• 134848-76-3 (3R,4S,7S)-4-(cyclohexylmethyl)-7-<<(1,1-dimethylethoxy)carbonyl>amino>-3-hydroxy-2,6,10-trioxo-1-oxa-5,9-diazacyclotridecane 

Relevant academic research and scientific papers

Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65 μM, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.