title: Small molecule HIV entry inhibitors: Part I. Chemokine receptor antagonists: 2004 - 2010.
abstract: BACKGROUND
  HIV/AIDS is one of the most devastating diseases in the world affecting > 40 million people worldwide. Morbidity and mortality from AIDS are significantly reduced due to the advent of highly active antiretroviral therapy (HAART). Long-term toxicity, emergence of drug resistant HIV strains and drug-drug interactions limit the effectiveness of HAART therapy. Chemokine receptor antagonists can provide drugs with lesser side effects and enhanced anti-HIV activity. Maraviroc, a chemokine co-receptor 5 (CCR5) antagonist from Pfizer, is already in clinical use.
  
  
  METHODS
  This review covers patents and patent applications for small molecule CCR5 and CXC chemokine receptor 4 (CXCR4) antagonists published between 2004 and 2010 and related literature with a focus on recent developments based on lead generation and lead modification. The reader will gain information about the development of small molecule CCR5 and CXCR4 antagonists from the major pharmaceutical and biopharmaceutical companies.
  
  
  CONCLUSIONS
  Several small lead molecules (CCR5 and CXCR4 antagonists) have been modified over this period for enhanced therapeutic activity and to obtain drug-like properties. CCR5 antagonists such as TBK-652 and TBK-220 from Tobira Therapeutics, and vicriviroc from Schering Plough showed a lot of promise in the developmental stage.
authors.affiliation: National Institute of Pharmaceutical Education and Research, Department of Natural Products, Sector-67, S.A.S. Nagar, Punjab 160062, India. ipsingh@niper.ac.in
authors.forename: Inder Pal
authors.initials: IP
authors.lastname: Singh
authors.forename: Siddheshwar K
authors.initials: SK
authors.lastname: Chauthe
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D010330:Patents as Topic; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D065100:CCR5 Receptor Antagonists; D023581:HIV Fusion Inhibitors; D019718:Receptors, CXCR4