446284-68-0

Upstream product

• 67443-38-3 5-bromo-2-chloro-3-nitropyridine 

Downstream Products

• 446285-02-5 1-(4-benzoylpiperazin-1-yl)-2-(7-chloro-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701213-36-7 1-(4-benzoylpiperazin-1-yl)-2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione 
• 864953-39-9 1,3-dihydroxy-2-(hydroxymethyl)propan-2-aminium (3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl)methyl hydrogen phosphate 
• 701213-73-2 (R)-1-(4-benzoyl-3-methylpiperazin-1-yl)-2-(7-chloro-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 446289-32-3 N-(5-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-7-yl)thiazol-2-yl)acetamide 
• 446289-94-7 1-(7-(2-aminothiazol-5-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-benzoylpiperazin-1-yl)ethane-1,2-dione 
• 619330-81-3 1-(4-benzoylpiperazin-1-yl)-2-(4-methoxy-7-(1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701212-80-8 (R)-1-(4-benzoyl-3-methylpiperazin-1-yl)-2-(4-methoxy-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701212-70-6 (R)-1-(4-benzoyl-3-methylpiperazin-1-yl)-2-(4-methoxy-7-(1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701212-66-0 (R)-1-(4-benzoyl-3-methylpiperazin-1-yl)-2-(4-methoxy-7-(3-methyl-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701212-65-9 1-(4-benzoylpiperazin-1-yl)-2-(4-methoxy-7-(5-methyl-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione 
• 701212-76-2 1-(7-(3-amino-1H-pyrazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-benzoylpiperazin-1-yl)ethane-1,2-dione 
• 701212-78-4 (R)-1-(7-(3-amino-1H-pyrazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-benzoyl-3-methylpiperazin-1-yl)ethane-1,2-dione 
• 701212-79-5 (R)-1-(7-(5-amino-1H-pyrazol-1-yl)-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-benzoyl-3-methylpiperazin-1-yl)ethane-1,2-dione 

Relevant academic research and scientific papers

Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir

The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp2-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species. However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clinical trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.

Discovery and optimization of novel small-molecule HIV-1 entry inhibitors using field-based virtual screening and bioisosteric replacement

With the emergence of drug-resistant strains and the cumulative toxicities associated with current therapies, demand remains for new inhibitors of HIV-1 replication. The inhibition of HIV-1 entry is an attractive, yet underexploited therapeutic approach with implications for salvage and preexposure prophylactic regimens, as well as topical microbicides. Using the combination of a field-derived bioactive conformation template to perform virtual screening and iterative bioisosteric replacements, coupled with in silico predictions of absorption, distribution, metabolism, and excretion, we have identified new leads for HIV-1 entry inhibitors.