176504-90-8

Usage

Chemical Properties

White powder

Upstream product

• 51987-73-6 (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester 
• 756-79-6 dimethyl methane phosphonate 
• 34939-91-8 dimethyl lithiomethylphosphonate 
• 63-91-2 L-phenylalanine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Downstream Products

• 176504-94-2 benzyl (E)-(5S)-6-phenyl-5-<(tert-butoxycarbonyl)amino>-4-oxo-2-hexenoate 
• 198208-03-6 (5S)-5-[N-(tert-butyloxycarbonyl)amino]-6-phenyl-2-hexen-4-one 
• 207222-80-8 (Z)-(S)-2-Benzyl-5-tert-butoxycarbonylamino-4-oxo-6-phenyl-hex-2-enoic acid methyl ester 
• 488760-73-2 tert-butyl (5S)-5-[N-(tert-butoxycarbonyl)amino]-4-oxo-6-phenyl-(E)-2-hexenoate 
• 742107-29-5 (1E,4S)-4-[N-(tert-butyloxycarbonyl)amino]-1-(4-nitrophenyl)-5-phenylpent-1-en-3-one 
• 637024-71-6 ethyl (5S,2Z)-2-methyl-[5-(tert-butoxycarbonyl)amino]-4-oxo-6-phenylhex-2-enoate 
• 152359-60-9 ethyl (E)-(5S)-6-phenyl-5-[(tert-butyloxycarbonyl)amino]-4-oxo-2-hexenoate 
• 488760-74-3 tert-butyl (4R,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-(E)-2-hexenoate 
• 668436-17-7 tert-butyl (4R,5S)-5-[N-(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenyl-hexanoate 
• 872033-26-6 (E,2S)-8-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)-3-oxo-1-phenyloct-4-ene 
• 872033-04-0 methyl (5E,8S)-8-[(tert-butoxycarbonyl)amino]-7-oxo-9-phenyl-non-5-enoate 
• 1372138-81-2 (1R,2R,3S)-3-tert-butoxycarbonylamino-4-phenyl-1-((R)-pyrrolidin-2-yl)butane-1,2-diol 
• 872033-11-9 (1S,2S,3S)-3-tert-butoxycarbonylamino-4-phenyl-1-((S)-pyrrolidin-2-yl)butane-1,2-diol 
• 1372138-76-5 C₅₁H₆₆N₈O₈ 

Relevant academic research and scientific papers

Impact of stereochemistry on ligand binding: X-ray crystallographic analysis of an epoxide-based HIV protease inhibitor

A new pseudopeptide epoxide inhibitor, designed for irreversible binding to HIV protease (HIV-PR), has been synthesized and characterized in solution and in the solid state. However, the crystal structure of the complex obtained by inhibitor-enzyme cocrys

Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors

Pyridazine and pyridazinone derivatives were designed and synthesized as coagulation factor XIa inhibitors. Potent and selective inhibitors with single digit nanomolar affinity for factor XIa were discovered. Selected inhibitors demonstrated moderate oral bioavailability.

Synthesis and biological activity of potent HIV-1 protease inhibitors based on Phe-Pro dihydroxyethylene isosteres

Peptidomimetic inhibitors of HIV-1 PR are still a key resource in the fight against AIDS. Here we describe the synthesis and biological activity of HIV-1 PR inhibitors based on four novel dihydroxyethylene isosteres of the Phe-Pro and Pro-Pro dipeptides. The isosteres, containing four stereogenic centers, were synthesized in high yield and excellent stereoselectivity via the cyclization of epoxy amines derived from α-amino acids. The inhibitors were assembled by coupling the isosteres with suitable flanking groups and were screened against recombinant HIV PR showing activities in the subnanomolar to micromolar range. Two Phe-Pro-based inhibitors active at the nanomolar level were further investigated: both inhibitors combine the ability to suppress HIV-1 replication in infected MT-2 cells with low cytotoxicity against the same cells, thereby displaying a high therapeutic index. These results demonstrate the potential of the new Phe-Pro dihydroxyethylene isostere as a core unit of powerful HIV-1 PR inhibitors.

Amino acid-based synthesis of trifluoromethylalkene dipeptide isosteres by alcohol-assisted nucleophilic trifluoromethylation and organozinc-copper- mediated SN2′ alkylation

(Chemical Equation Presented) A novel synthetic approach to Xaa-Yaa-type (Z)-trifluoromethylalkene dipeptide isostere (CF3-ADI) has been developed. Starting from readily available L-phenylalanine and L-alanine, several CF3-ADIs were obtained through nucleophilic trifluoromethylation of γ-keto esters and SN2′ alkylation of trifluoromethylated mesylates. The influence of a trifluoromethyl group on the diastereoselectivity of the SN2′ reaction is also discussed.

Angiotensin I-converting enzyme (ace) inhibitors

This invention relates to a process for the synthesis of ketomethylene derivatives of the tripeptide Phe-Gly-Pro (“keto-ACE”, compound 5a) and analogues thereof. The synthesis process proceeds via an α,β-unsaturated keto intermediate. A key feature of the process involves a Horner-Emmons olefination of the, -unsaturated keto-phosphonate with ethyl glyoxylate. Keto-ACE analogues produced by the process of the invention display C-domain selectivity.

Aminoethylenes: A tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1

A series of novel β-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to corresponding hydroxyethylene (HE) compounds. Enzymat

Synthesis of novel keto-ACE analogues as domain-selective angiotensin I-converting enzyme inhibitors

Novel analogues of the angiotensin I-converting enzyme (ACE) inhibitor keto-ACE were synthesized via a facile Horner-Emmons olefination of a phosphonoketone precursor with ethyl glyoxylate. Introduction of a bulky aromatic tryptophan at the P2

Stereoselective synthesis of photoreactive peptidomimetic γ-secretase inhibitors

The first asymmetric synthesis of novel, potent photoreactive γ-secretase inhibitors 2 and 3 has been accomplished. Two Stereoselective methods for the preparation of lactone 9 are described. Protected benzophenone intermediate 19 is prepared via an aldol-elimination reaction followed by a PtO2-catalyzed asymmetric hydrogenation. Two routes leading from 19 to compounds 2 and 3 are evaluated. The application of 3 as an activity-based probe has been demonstrated by localizing γ-secretase activity in the plasma membrane of intact cells.

Stereoselective synthesis of a novel pseudopeptide hapten for the generation of hydrolytic catalytic antibodies

The synthesis of a novel hapten containing a 1,4-diamino-2,3-diolbutane core unit is described. The molecule contains four stereogenic centres and has been synthesised via a stereoselective route. The absolute stereochemistry of each stereogenic carbon at

Aspartyl protease inhibitors

The present invention provides compounds having the formula: wherein R1, R′, R2, R3, R3′, R4, X1, X2 and X3 are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer's Disease). The present invention also provides methods for preparing compounds of the invention.