Design, synthesis and pharmacological evaluation of HIV-1 reverse transcriptase inhibition of new indolin-2-ones

Med Chem. 2007 Nov;3(6):533-42. doi: 10.2174/157340607782360326.

Abstract

The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2-ones, analogues of efavirenz (Sustivatrade mark), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzoxazinone ring of efavirenz was proven, since compound 15 presented a greater activity than efavirenz against HIV-1 replication and was not significantly cytotoxic.

MeSH terms

  • Alkynes
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology
  • Benzoxazines
  • Cell Line
  • Cell Survival / drug effects
  • Cyclopropanes
  • Drug Design
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Indoles
  • Reverse Transcriptase Inhibitors
  • indolin-2-one
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • efavirenz