title: The search for potent, small molecule NNRTIs: A review.
abstract: AIDS has become the leading pandemic disease, and is the cause of death worldwide. Presently, HAART treatment, a combination of reverse transcriptase (RT) and protease inhibitors is also unsuccessful due to the virus getting resistant to the drugs because of mutational changes. Two types of RT inhibitors exist namely nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The NNRTIs which bind to an allosteric site on RT are an important arsenal of drugs against HIV-1. The specificity of NNRTIs towards HIV-1 has led to extensive structural and molecular modelling studies of enzyme complexes and chemical synthesis of second and third-generation NNRTIs. The major drawbacks of NNRTIs are generation of resistance and pharmacokinetic problems. By mutational studies of non-nucleoside inhibitor binding pocket (NNIBP) some amino acids which were found to play an important role in proper binding resulted less prone to mutation. In this review we present a chronological history of NNRTI development, also highlighting the need for small molecules belonging to the NNRTI class for the management of AIDS.
authors.affiliation: Pharmacy Department, Kalabhavan, The M.S. University of Baroda, Vadodara, India.
authors.forename: Dhaval G
authors.initials: DG
authors.lastname: Prajapati
authors.forename: R
authors.initials: R
authors.lastname: Ramajayam
authors.forename: Mange Ram
authors.initials: MR
authors.lastname: Yadav
authors.forename: Rajani
authors.initials: R
authors.lastname: Giridhar
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000495:Allosteric Site; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology; D001577:Benzophenones / Q000737:chemistry / Q000494:pharmacology; D024882:Drug Resistance, Viral; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C476867:4,5,6,7-tetrahydroimidazo-(4,5,1- jk)(1,4)benzodiazepin-2 (1 H)-one; D019380:Anti-HIV Agents; D001577:Benzophenones; D007093:Imidazoles; D011728:Pyridones; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines