Compounds for inhibiting drug-resistant strains of HIV-1 integrase

US10208035B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Xue Zhi Zhao · Frederick, US
• Steven A. Smith · Tulsa, US
• Mathieu Metifiot · Ambarès-et-Lagrave, FR
• Barry Johnson · Castle Rock, US
• Christophe Marchand · Gaithersburg, US
• Stephen H. Hughes · Smithsburg, US
• Yves Pommier · Bethesda, US
• Terrence R. Burke, Jr. · Kirkwood, US

Key dates

• Filing date: May 8, 2017
• Grant date: Feb 19, 2019
• Expiry date: May 27, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D491/147
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of: wherein X is N, C(OH), or CH; Y is H or OH; each of Z1-Z5 is independently H or halogen; R4 is H, OH, NH2, NHR8, NR8R9 or R8; R5, R6, and R7 is each independently H, halogen, OR8, R8, NHR8, NR8R9, CO2R8, CONR8R9, SO2NR8R9, or R5 and R6 together with the carbon atoms to which R5 and R6 are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and R8 and R9 is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R8 and R9 together with the nitrogen to which R8 and R9 are attached form an optionally-substituted heterocycle.