Design and Synthesis of Regioisomeric Analogues of a Specific Anti-HIV-1 Agent 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)

Tanaka, Hiromichi; Baba, Masanori; Takahashi, Emiko; Matsumoto, K.; Kittaka, Atsushi; Walker, Richard; Clercq, Erik De; Miyasaka, Tadashi

doi:10.1080/15257779408013232

Cited by 16 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1 χ N (R2) index encodes information about the degree of branching or connectivity of the R2 substituents, and their high contribution in all models shows that the shape of R2 substituents has a strong effect on the activity. This is in agreement with the findings by other authors 17,37 who have shown that the differences of activity among the HEPT derivatives are strongly dependent on the positioning of the 6-phenylthio group, which is quite sensitive to the steric effects of the C-5 substituents. Thus, the 1 χ N (R2) index quantifies the effect of these substituents and shows that according to the 1 χ N (R2)/( 1 χ N (R2)) 2 relationship a maximum activity can be encountered when an optimum 1 χ N (R2) value is reached.…”

Section: Structural Interpretation Of the Models Analysis Of The Pls ...supporting

confidence: 93%

QSAR Based on Multiple Linear Regression and PLS Methods for the Anti-HIV Activity of a Large Group of HEPT Derivatives

Luco

Ferretti

1997

J. Chem. Inf. Comput. Sci.

152

120

View full text Add to dashboard Cite

Quantitative structure-activity relationships have been developed for a set of 107 inhibitors of the HIV-1 reverse transcriptase, derivatives of a recently reported HIV-1 specific lead: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The activity of these compounds was investigated by means of multiple linear regression (MLR) and PLS regression techniques and topological indexes as well as several tabulated physicochemical substituent constants were used as predictor variables. The results obtained indicate that the anti-HIV activity of the HEPT derivatives is strongly dependent on hydrophobic factors as expressed by the Hansch constant (sigma pi (R1+R2)), and especially dependent on the geometric factors mainly accounted for by the 1 chi N (R2) and 4 chi pN molecular connectivity indexes and also for the molecular volume (Vx), the Taft steric constant (Es(2R1)), and the Verloop parameter for the smallest width value (B1(3R1)). Besides, for this data set, comparison of the quality of MLR and PLS models show that PLS is a better approach to MLR for improving the interpretability of the data and also to exhibit models with a better predictive quality.

show abstract

Section: Structural Interpretation Of the Models Analysis Of The Pls ...supporting

confidence: 93%

QSAR Based on Multiple Linear Regression and PLS Methods for the Anti-HIV Activity of a Large Group of HEPT Derivatives

Luco

Ferretti

1997

J. Chem. Inf. Comput. Sci.

152

120

View full text Add to dashboard Cite

show abstract

“…This is in agreement with previously published results [2,23], which showed that the differences of the activity between the HEPT derivatives were strongly dependent on the positioning of the 6-phenylthio group, which is quite sensitive to the steric effect of the C-5 substituents (Table I).…”

Section: Regression Equationssupporting

confidence: 93%

QSAR for anti-HIV activity of HEPT derivatives

Bazoui

Zahouily

Boulajaaj

et al. 2002

SAR and QSAR in Environmental Research

View full text Add to dashboard Cite

QSARs were derived for 103 analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), a potent inhibitor of the HIV-1 reverse transcriptase (RT). The activity of these compounds was investigated by means of multiple linear regression (MLR) and artificial neural network (ANN) techniques. Considering the relevant descriptors obtained from the MLR, a correlation coefficient of 0.92 (n = 95) was obtained with a 4-5-1 ANN model. The contribution of each descriptor to the structure-activity relationships was evaluated. The results showed that the anti-HIV activity of HEPT derivatives was strongly dependent on hydrophobic character and also steric factors of substituents.

show abstract

“…52,53 The presence of an electron-donating alkyl group at the C-5 position may decrease the level of lithiation at C-6. 54 Attempts to benzylate the pyrimidine part using lithiation and benzyl bromide failed and gave the starting material and trans-stilbene, probably due to a-elimination, 54,55 as observed with other reactions involving benzyl bromide and lithiation. 56,57 Emivirine 53 (47) and other 6-benzyl analogues 58 of HEPT have been synthesized using lithiation and reaction with benzaldehyde.…”

Section: Synthesis Of Heptmentioning

confidence: 94%

The Flourishing Syntheses of Non-Nucleoside Reverse Transcriptase Inhibitors

Pedersen¹,

Pedersen²

2000

Synthesis

View full text Add to dashboard Cite

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are of increasing importance in the treatment of HIV-1 infected persons. In this review the focus is on the syntheses of the approved NNRTI drugs efavirenz, delavirdine, nevirapine, and their analogues. This review also deals with the syntheses of the most promising NNRTI candidates in clinical testing and with the syntheses of subclasses of NNRTIs with known crystal structures when complexed with the reverse transcriptase enzyme.

show abstract

Design and Synthesis of Regioisomeric Analogues of a Specific Anti-HIV-1 Agent 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)

Cited by 16 publications

References 22 publications

QSAR Based on Multiple Linear Regression and PLS Methods for the Anti-HIV Activity of a Large Group of HEPT Derivatives

QSAR Based on Multiple Linear Regression and PLS Methods for the Anti-HIV Activity of a Large Group of HEPT Derivatives

QSAR for anti-HIV activity of HEPT derivatives

The Flourishing Syntheses of Non-Nucleoside Reverse Transcriptase Inhibitors

Contact Info

Product

Resources

About