title: QSAR for non-nucleoside inhibitors of HIV-1 reverse transcriptase.
abstract: By means of QSAR algorithms we model the potency pIC(90) [mM] of 154 non-nucleoside reverse transcriptase inhibitors (NNRTI) of the wild-type HIV-1 virus, considered as the second generation analogues of Efavirenz. In addition, 56 inhibitors of the K-103N viral mutant form are also investigated. A pool of 1494 theoretical molecular descriptors provided mainly by the Dragon 5 software is explored by several methods of variable selection: forward stepwise regression, the replacement method, and the genetic algorithm approach. The optimal models found include up to seven parameters: R = 0.7991, R(l-20%-o) = 0.7233 for the case of wild-type, and R = 0.9261, R(l-5%-o) = 0.8802 for the K-103N mutation.
authors.affiliation: INIFTA, División Química Teórica, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Diag. 113 y 64, Suc. 4 C. C. 16, (1900) La Plata, Argentina. pabloducho@yahoo.com.ar
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Duchowicz
authors.forename: Michael
authors.initials: M
authors.lastname: Fernández
authors.forename: Julio
authors.initials: J
authors.lastname: Caballero
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Castro
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D000480:Alkynes; D048588:Benzoxazines; D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics; D015394:Molecular Structure; D009154:Mutation; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D052999:Quinazolinones; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; C430648:DPC 083; C413505:DPC 961; C514201:GW 620867X; D010078:Oxazines; D011799:Quinazolines; D052999:Quinazolinones; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz