956035-15-7

Upstream product

• 172901-02-9 (1S,2S,4R,2'S)-(4-butylcarbamoyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3'-methyl-butyl}-pentyl)-carbamic acid tert-butyl ester 

Downstream Products

• 173336-39-5 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid 
• 173337-69-4 (1S,2S,4R,2'S)-(2-hydroxy-4-(3-hydroxy-propylcarbamoyl)-1-{2'-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3'-methyl-butyl}-pentyl)-carbamic acid tert-butyl ester 
• 173337-70-7 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(4-hydroxybutyl)] amide 
• 173337-68-3 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-(2-thiomorpholinoethyl) amide 
• 173337-84-3 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid N-[2-(1,1-dioxothiomorpholino)ethyl] amide 
• 173337-67-2 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid N-[2-(4-methoxypiperidino)-ethyl] amide 
• 173337-89-8 (2R,4S,5S,7S)-3-{5-tert-butoxycarbonylamino-4-hydroxy-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-2,8-dimethyl-nonanoylamino}-propionic acid ethyl ester 
• 173337-85-4 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid {N-[2-(N,N-dimethylsulfonyl)-ethyl]} amide 

Relevant academic research and scientific papers

Novel 2,7-dialkyl-substituted 5(S)-amino-4(S)-hydroxy-8-phenyl- octanecarboxamide transition state peptidomimetics are potent and orally active inhibitors of human renin

The action of renin is the rate-limiting step of the renin-angiotensin system (RAS), a key regulator of blood pressure. Effective renin inhibitors directly block the RAS entirely at source and, thus, may provide a vital weapon for hypertension therapy. Our efforts toward identifying novel small-molecule peptidomimetic renin inhibitors have resulted in the design of transition-state isosteres such as 1 bearing an all-carbon 8-phenyl-octanecarboxamide framework. Optimization of the extended P3 portion of 1 and extensive P2′ modifications provided analogues with improved in vitro potencies in the presence of plasma. X-ray resolution of rh-renin/38a in the course of SAR work surprisingly unveiled the exploitation of a previously unexplored pocket (S3sp) important for strong binding affinities. Several inhibitors demonstrated oral efficacy in sodium-depleted marmosets. The most potent, 38a, induced dose-dependently a pronounced reduction in mean arterial blood pressure, paralleled by complete blockade of active plasma renin, up to 8 h post-dose. Oral bioavailability of 38a was 16% in marmosets.