Theoretical Studies of The Contraction and Extension Effect in The B-Ring of TIBO Derivatives

Y. Belmiloud¹,², A. Kadari², M. Brahimi², D. Cherquaoui³, D. Villemin⁴ and A. Schmitzer⁵

¹C. R. A. P. C., B. P. 248- Alger - 160 04 Alg?rie.

²L. P. C. T. C. I. Facult? de Chimie, U. S. T. H. B., BP 32 Al-alia ; Bab-Ezouar – Alger Algerie.

³Facult? des Sciences Semlalia, B. P. 2390,- Universit? Cadi Ayyad, Marrakech Maroc.

⁴ENSICAEN. LCMT, UMR CNRS, 6507, boulevard Mar?chal Juin, 14050 Caen France.

⁵2900 Edouard Mont petit CP 6128 Succursale. Universit? Montr?al, Qu?bec Canada.

ABSTRACT: Some new non-nucleoside reverse transcriptase inhibitors are designed by contraction and extension of the seven-membered ring of TIBO to six- and eight-membered rings respectively using PM3, HF and DFT methods. Independently of calculations level, contracted seven-membered ring in C15 position, showed great similarity between the 3D geometry and the molecular properties of the TIBO and 6MRC15. Otherwise, the same ring when extend between N4 and C15 atoms showed also a great similarity between TIBO and 8MR (N4-C15). The latter molecule can enter easily in the allosteric cavity of NNRTIs. These two TIBO derivating compounds conserve the butterfly-like conformation can constitute a new class of anti-HIV.

KEYWORDS: HIV; Reverse Transcriptase; 7 ring TIBO; contraction and extension ofTIBO, PM3; HF; DFT

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