Work

Synthetic Approaches to a Key Pyridone-carboxylic Acid Precursor Common to the HIV-1 Integrase Strand Transfer Inhibitors Dolutegravir, Bictegravir, and Cabotegravir

Year: 2023

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Dolutegravir (DTG), Bictegravir (BIC), and Cabotegravir (CAB) are the second-generation integrase strand transfer inhibitors (INSTIs) that have been FDA-approved for the treatment of HIV-1 infection. Preparation of these INSTIs utilizes the common intermediate 1-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid ( 6 ). Presented herein is a literature and patent review of synthetic routes used to access the pharmaceutically important intermediate 6 . The review highlights the ways in which small fine-tuned synthetic modifications have been used to achieve good yields and regioselectivity of ester hydrolysis.

Source: Organic Process Research & Development

DOI: 10.1021/acs.oprd.3c00063

Authors: Pankaj S. Mahajan, Terrence R. Burke

Institutions: National Institutes of Health, National Cancer Institute, Center for Cancer Research

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,000