328086-54-0

Usage

Uses

Used in Pharmaceutical Industry:
(2E,4S)-4-[(tert-Butyloxycarbonyl)aMino]-5-[(3S)-2-oxo-3-pyrrolidinyl]-2-pentenoic Acid Eethyl Ester is used as a key intermediate in the synthesis of Rhinovirus protease inhibitors. These inhibitors are crucial for the development of antiviral drugs targeting Rhinoviruses, which are responsible for causing the common cold and other respiratory illnesses. (2E,4S)-4-[(tert-Butyloxycarbonyl)aMino]-5-[(3S)-2-oxo-3-pyrrolidinyl]-2-pentenoic Acid Eethyl Ester's unique structure allows it to be a valuable building block in the design and synthesis of potent and selective protease inhibitors, potentially leading to more effective treatments for Rhinovirus infections.

Upstream product

• 1099-45-2 ethyl (triphenylphosphoranylidene)acetate 
• 1025451-28-8 tert-butyl ((S)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)carbamate 
• 223526-37-2 ethyl-3->-E-propenoate 
• 105-36-2 ethyl bromoacetate 
• 6525-53-7 L-glutamic acid dimethyl ester 
• 56-86-0 L-glutamic acid 
• 870154-03-3 tert-butyl ((1S)-2-[methoxy(methyl)amino]-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}ethyl)carbamate 
• 741267-75-4 (2S)-2-(tert-butoxycarbonylamino)-3-[(3S)-2-oxopyrrolidin-3-yl]propanoic acid 
• 95049-80-2 dimethyl (S)-2-((tert-butoxycarbonyl)amino)-4-methylenepentanedioate 
• 42809-80-3 P-(carboethoxymethyl)triphenylphosphonium cation 
• 249736-45-6 [2-hydroxy-1S-(2-oxopyrrolidin-3S-ylmethyl)ethyl]carbamic acid tert-butyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 112418-19-6 (R)-2-N-tert-butoxycarbonylamino-3-(tert-butyldimethylsilyloxy)propionic acid methyl ester 

Downstream Products

• 799270-24-9 (S,E)-ethyl 4-((2R,5S)-5-(tert-butoxycarbonylamino)-2-(4-fluorobenzyl)-6-methyl-4-oxoheptanamido)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate 
• 869494-42-8 (E)-(S)-4-{(2R,4S,5S)-2-Benzyl-4-(tert-butyl-dimethyl-silanyloxy)-6-methyl-5-[(5-methyl-isoxazole-3-carbonyl)-amino]-heptanoylamino}-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester 
• 869494-40-6 (E)-(S)-4-[(2R,4S,5S)-2-Benzyl-5-tert-butoxycarbonylamino-4-(tert-butyl-dimethyl-silanyloxy)-6-methyl-heptanoylamino]-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester 
• 869494-44-0 (E)-(S)-4-{(2R,4S,5S)-2-Benzyl-4-hydroxy-6-methyl-5-[(5-methyl-isoxazole-3-carbonyl)-amino]-heptanoylamino}-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester 
• 328086-61-9 ethyl (S,E)-4-((tert-butoxycarbonyl)amino)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate 

Relevant academic research and scientific papers

INHIBITORS OF NOROVIRUS AND CORONAVIRUS REPLICATION

Compounds of Formula (I) and methods of inhibiting the replication of viruses in a biological sample or patient, of reducing the amount of viruses in a biological sample or patient, and of treating a virus infection in a patient, comprising administering to said biological sample or patient an effective amount of a compound represented by Formula (I), a compound of Table A or B or a pharmaceutically acceptable salt thereof.

PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS

Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or Hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV- 2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.

PEPTIDOMIMETICS FOR THE TREATMENT OF NOROVIRUS INFECTION

The present invention is directed to compounds, compositions and methods for preventing, treating or curing Norovirus infection in human subjects or other animal hosts.

Improved synthesis of rupintrivir

An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (l-glutamic acid, d-4-fluorophenylalanine, and l-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.

Novel CADD-based peptidyl vinyl ester derivatives as potential proteasome inhibitors

A series of peptidyl vinyl ester derivatives bearing three different P1 substitutions as potential proteasome inhibitors were studied. The target molecules were designed based on CADD (computer aided drug design) protocol and synthesized. Their activities

Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide α,β-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 μM), the ketomethylene isosteres and tripeptide α,β-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 μM). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 μM is obtained by condensation of the Phe-Phe dipeptide α,β-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 μM.

Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors

Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.

Protease inhibitors

This invention relates to treating an infection with a virus using protease inhibitors. Examples of the protease inhibitors include compounds of formula (I). Each variable is defined in the specification.

Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 8. Pharmacological optimization of orally bioavailable 2-pyridone-containing peptidomimetics

The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an α,β-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P 2 substituent present in the peptidomimetic portion of the inhibitors. The pharmacokineties of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an α,β-unsaturated ethyl ester fragment and either an ethyl or propargyl P2 moiety displayed the most promising combination of 3C enzyme inhibition (kobs/[Il 170 000-223 000 M-1 s-1), antiviral activity (EC50 = 0.047-0.058 μM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 μM; 7 h CM-monkey plasma levels = 0.057-0.896 μM).

Structure-based design of a parallel synthetic array directed toward the discovery of irreversible inhibitors of human rhinovirus 3C protease

Utilizing the tools of parallel synthesis and structure-based design, a new class of Michael acceptor-containing, irreversible inhibitors of human rhinovirus 3C protease (HRV 3CP) was discovered. These inhibitors are shown to inhibit HRV-14 3CP with rates