AG-7088 Pfizer.

Abstract

Pfizer (formerly Agouron) is developing AG-7088, a peptide aldehyde that targets the human rhinovirus (HRV) 3C proteinase enzyme and has potential for the treatment of the common cold. A phase II efficacy study has been completed in healthy patients infected with the virus [318668] and in November 1999, Agouron initiated a large, double-blind, placebo-controlled trial in the US, in individuals within 36 h of experiencing cold symptoms [346362]. AG-7088 is derived from AG-6084, the development of which has been discontinued. In order to develop human rhinovirus 3C protease inhibitors with improved pharmacological properties, Agouron replaced the backbone amide moiety of the series which yielded AG-6084, with a ketomethylene isostere. Such compounds displayed slightly reduced anti-3CP inhibitory activity, but improved antiviral properties, due to increased cell membrane permeability [324627]. Compounds in which P1 lactam moieties were incorporated in lieu of an L-glutamine residue displayed significantly increased 3CP inhibition activity and improved antirhinoviral properties relative to the corresponding molecules. Of this series, AG-7088 was the most potent inhibitor [324635]. In May 2000, Merrill Lynch predicted that phase III trials would begin in the first half of 2000 and that US filing would take place in the second half of 2001 [375962].

• Authors: G Witherell
• Journal: Current opinion in investigational drugs (London, England : 2000) (Curr Opin Investig Drugs) Vol. 1 Issue 3 Pg. 297-302 (Nov 2000) ISSN: 1472-4472 [Print] England
• PMID: 11249711 (Publication Type: Journal Article, Review)

Chemical References

• Antiviral Agents
• Drugs, Investigational
• Isoxazoles
• Protease Inhibitors
• Pyrrolidinones
• Phenylalanine
• Valine
• rupintrivir

Topics

• Antiviral Agents (metabolism, pharmacology, therapeutic use, toxicity)
• Clinical Trials as Topic
• Contraindications
• Drugs, Investigational (metabolism, pharmacology, therapeutic use, toxicity)
• Humans
• Isoxazoles (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Phenylalanine (analogs & derivatives)
• Protease Inhibitors (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Pyrrolidinones (adverse effects, metabolism, pharmacology, therapeutic use, toxicity)
• Rhinovirus (drug effects, enzymology)
• Structure-Activity Relationship
• Valine (analogs & derivatives)