870153-29-0

Upstream product

• 103260-65-7 4-methoxy-1H-indole-2-carboxylic acid 
• 328086-60-8 (2S)-2-(tert-butoxycarbonylamino)-3-[(3'S)-2'-oxo-3'-pyrrolidinyl]propanoic acid methy ester 
• 1471484-96-4 tert-butyl (2S)-2-[(4-methoxy-1H-indole-2-carbonyl)amino]-4-methyl-pentanoate 
• 2748-02-9 L-leucine tert-butyl ester hydrochloride 
• 741267-61-8 tert-butyl ((1S)-3-diazo-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)carbamate 
• 741267-75-4 (2S)-2-(tert-butoxycarbonylamino)-3-[(3S)-2-oxopyrrolidin-3-yl]propanoic acid 

Relevant academic research and scientific papers

Inhibitors of cysteine proteases and methods of use thereof

The disclosure provides compounds with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease. Exemplary compounds provided include Formula II-I, where R3, RB are provided herein:

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.

METHODS OF INHIBITING SARS-COV-2 REPLICATION AND TREATING CORONAVIRUS DISEASE 2019

The invention relates to methods of treating COVID-19 in a patient by administering therapeutically effective amounts of certain SARS-CoV-2 inhibitor compounds or pharmaceutical compositions containing them to a patient in need thereof. The invention also relates to inhibiting SARS-CoV-2 coronavirus viral replication activity comprising contacting SARS-CoV-2-related coronavirus protease with a therapeutically effective amount of a SARS-Cov-2 protease inhibitor, such as a SARS-Cov-2 3CL protease inhibitor and compositions comprising the same

Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19

The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CLpro) in a post-Translational processing step that is critical for coronavirus replication. The 3CLpro sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CLpro employing ligand-protease structures solved by X-ray crystallography led to the identification of 3 and 4. Preclinical experiments reveal 4 (PF-00835231) as a potent inhibitor of CoV-2 3CLpro with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19.