103322-58-3

Upstream product

• 667-27-6 Ethyl bromodifluoroacetate 
• 98105-42-1 (S)-2-(t-butoxycarbonylamino)-3-cyclohexyl-1-propanal 
• 115766-13-7 (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-N-methoxy-N-methylcyclohexanepropanamide 
• 37736-82-6 (S)-2-tert-butoxycarbonylamino-3-cyclohexylpropionic acid 

Downstream Products

• 118233-29-7 Boc-(3R,4S)-4-amino-5-cyclohexyl-2,2-difluoro-3-oxopentanoic acid (S)-2-methylbutylamide 
• 130466-62-5 Sodium; (3R,4S)-4-tert-butoxycarbonylamino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoate 
• 776256-23-6 (3R,4S)-4-Amino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester 
• 118233-28-6 (3R,4S)-4-tert-Butoxycarbonylamino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoic acid 
• 300865-77-4 [[4(S)-[(N-tert-butoxycarbonyl)amino]-2,2-difluoro-5-cyclohexyl-3(R)-hydroxypentanoyl]-L-valyl]-L-isoleucine methyl ester 
• 300865-81-0 [[4(S)-[(N-tert-butoxycarbonyl)amino]-2,2-difluoro-5-cyclohexyl-3(R)-hydroxypentanoyl]-L-valyl]-L-isoleucine benzyl ester 
• 300865-86-5 [4(S)-[[(N-tert-butoxycarbonyl)-L-valyl]amino-2,2-difluoro-5-cyclohexyl-3(R)-hydroxypentanoyl]-L-valyl]-L-isoleucine methyl ester 
• 300865-91-2 [4(S)-[[(N-tert-butoxycarbonyl)-L-valyl]amino-2,2-difluoro-5-cyclohexyl-3(R)-hydroxypentanoyl]-L-valyl]-L-isoleucine benzyl ester 
• 130694-46-1 [(S)-2-Cyclohexyl-1-((4S,6R)-5,5-difluoro-6-isopropyl-2,2-dimethyl-[1,3]dioxan-4-yl)-ethyl]-carbamic acid benzyl ester 
• 130581-98-5 [(S)-2-Cyclohexyl-1-((4S,6S)-5,5-difluoro-6-isopropyl-2,2-dimethyl-[1,3]dioxan-4-yl)-ethyl]-carbamic acid benzyl ester 
• 130694-45-0 ((1S,2R,4S)-1-Cyclohexylmethyl-3,3-difluoro-2,4-dihydroxy-5-methyl-hexyl)-carbamic acid benzyl ester 
• 130317-25-8 ((1S,2R,4R)-1-Cyclohexylmethyl-3,3-difluoro-2,4-dihydroxy-5-methyl-hexyl)-carbamic acid benzyl ester 
• 130645-56-6 {(S)-1-[(S)-1-((1S,2R,4R)-1-Cyclohexylmethyl-3,3-difluoro-2,4-dihydroxy-5-methyl-hexylcarbamoyl)-3-methyl-butylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester 
• 130317-23-6 (4S,5R)-4-Cyclohexylmethyl-5-(1,1-difluoro-3-methyl-2-oxo-butyl)-oxazolidin-2-one 

Relevant academic research and scientific papers

Difluoro ketone peptidomimetics suggest a large S1 pocket for Alzheimer's γ-secretase: Implications for inhibitor design

The final step in the generation of the amyloid-β protein (Aβ), implicated in the etiology of Alzheimer's disease, is proteolysis within the transmembrane region of the amyloid precursor protein (APP) by γ-secretase. Although considered an important target for therapeutic design, γ-secretase has been neither well-characterized nor definitively identified. Previous studies in our laboratory using substrate-based difluoro ketone and difluoro alcohol transition-state analogue inhibitors suggest that γ-secretase is an aspartyl protease with loose sequence specificity. To further characterize the active site of γ-secretase, we prepared a series of difluoro ketone peptide analogues with varying steric bulkiness in the P1 position and tested the ability of these compounds to inhibit Aβ production in APP-transfected cells. Incorporation of bulky, aliphatic P1 side chains, such as sec-butyl or cyclohexylmethyl, led to increased α-secretase inhibitory potency, suggesting a large S1 pocket to accommodate these substituents and providing further evidence for loose sequence specificity. The cyclohexylmethyl P1 substituent allowed N-terminal truncation to a low-molecular-weight compound (50 ~ 5 μM). This finding suggests that optimal S1 binding may allow the development of potent inhibitors with ideal pharmaceutical properties. Moreover, a difluoro alcohol analogue with a cyclohexylmethyl P1 substituent was equipotent with its difluoro ketone counterpart, providing strong evidence that γ-secretase is an aspartyl protease. All new analogues inhibited total Aβ and Aβ42 production with the same rank order of potency and increased Aβ42 production at low concentrations, providing further evidence for distinct γ-secretases that are nevertheless closely similar with respect to active site topology and mechanism.

Design and Synthesis of Potent, Selective, and Orally Active Fluorine-Containing Renin Inhibitors

A series of primate renin inhibitors containing difluorocarbinol and difluoroketone groups at the P1 - P1' position have been synthesized and studied both in vitro and in vivo.In vitro, the compounds were evaluated as inhibitors of m

Synthesis of 6(S)-Amino-7-cyclohexyl-4,4-difluoro-3(R),5(R)-dihydroxy-2-methylheptane, a Novel Dipeptide Mimic

The incorporation of the novel dipeptide mimic (1), synthesized via Boc-L-cyclohexylalaninol (Boc = t-butoxycarbonyl), into a dipeptide sequence has led to a very potent renin inhibitor.

Angiotensinogen analogs

The invention relates to renin inhibiting compounds of the formula STR1 wherein A is hydrogen; loweralkyl; arylalkyl; OR10 or SR10 wherein R10 is hydrogen, loweralkyl or aminoalkyl; NR11 R12 wherein R11 and R12 are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; STR2 wherein B is NH, alkylamino, S, O, CH2 or CHOH and R13 is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxyalkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl)(alkyl)amino, (dihydroxyalkyl)(alkyl)amino, aminoalkyl, alkoxycarbonylalkyl, carboxyalkyl, N-protected aminoalkyl, alkylaminoalkyl, (N-protected)(alkyl)aminoalkyl, dialkylaminoalkyl, (heterocyclic) alkyl or a substituted or unsubstituted heterocyclic; W is CO or CHOH and U is CH2 or NR2 with the proviso that when W is CHOH then U is CH2 ; R1 is loweralkyl, cycloaklylmethyl, benzyl, α,α-dimethylbenzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)-methyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R1 is phenoxy, thiophenoxy or anilino, B is CH2 or CHOH or A is hydrogen, R3 is loweralkyl, vinylloweralkyl, benzyl or heterocyclic ring substituted methyl, R5 is loweralkyl, cycloalkylmethyl or benzyl; R2 and R4 are independently selected from hydrogen and loweralkyl; R6 is CHOH or CO; R7 is CH2, CF2 or CF with the proviso that when R6 is CO, R7 is CF2 ; R8 is CH2, CHR14 wherein R14 is lower-alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or R7 and R8 taken together can be STR3 with the proviso that when R7 is CF2, R8 is CH2 ; E is O, S, SO, SO2, NR15 wherein R15 is hydrogen or loweralkyl or NR16 CO wherein R16 is hydrogen or loweralkyl; R9 is loweralkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or an N-protected group, or E and R9 taken together can be N3, with the proviso that when E is NH, R9 is an N-protecting group; and pharmaceutically acceptable salts thereof.