Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques

被引：35

作者：

Afantitis, Antreas

Melagraki, Georgia

Sarimveis, Haralambos ^{[1
]}

Koutentis, Panayiotis A.

Markopoulos, John

Igglessi-Markopoulou, Olga

机构：

[1] Natl Tech Univ Athens, Sch Chem Engn, Athens, Greece

[2] Univ Cyprus, Dept Chem, CY-1678 Nicosia, Cyprus

[3] NovaMech Ltd, Dept ChemoInformat, Larnax, Cyprus

[4] Univ Athens, Dept Chem, GR-10680 Athens, Greece

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 2006年 / 20卷 / 02期

关键词：

CCR5; binding affinity; QSAR; virtual screening;

D O I：

10.1007/s10822-006-9038-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A linear quantitative-structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Stepwise Regression Method (ES-SWR) is utilized. The predictive ability of the model is evaluated against a set of 13 compounds. Based on the produced QSAR model and an analysis on the domain of its applicability, the effects of various structural modifications on biological activity are investigated. The study leads to a number of guanidine derivatives with significantly improved predicted activities.

引用

页码：83 / 95

页数：13

共 29 条

[1] A novel simple QSAR model for the prediction of anti-HIV activity using multiple linear regression analysis
Afantitis, Antreas
Melagraki, Georgia
Sarimveis, Haralambos
Koutentis, Panayiotis A.
Markopoulos, John
Igglessi-Markopoulou, Olga
[J]. MOLECULAR DIVERSITY, 2006, 10 (03) : 405 - 414
[2] Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis:: Lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine
Andres, PG
Beck, PL
Mizoguchi, E
Mizoguchi, A
Bhan, AK
Dawson, T
Kuziel, WA
Maeda, N
MacDermott, RP
Podolsky, DK
Reinecker, HC
[J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (12) : 6303 - 6312
[3] [Anonymous], COMP QSAR
[4] The better predictive model:: High q2 for the training set or low root mean square error of prediction for the test set?
Aptula, AO
Jeliazkova, NG
Schultz, TW
Cronin, MTD
[J]. QSAR & COMBINATORIAL SCIENCE, 2005, 24 (03): : 385 - 396
[5] Atkinson AC., 1985, Plots, transformations and regression
[6] an introduction to graphical methods of diagnostic regression analysis
[7] Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1-(3,3-diphenylpropyl)-piperidinyl amides and ureas
Burrows, JN
Cumming, JG
Fillery, SM
Hamlin, GA
Hudson, JA
Jackson, RJ
McLaughlin, S
Shaw, JS
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (01) : 25 - 28
[8] Generation of predictive pharmacophore models for CCR5 antagonists: Study with piperidine- and piperazine-based compounds as a new class of HIV-1 entry inhibitors
Debnath, AK
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (21) : 4501 - 4515
[9] ESTIMATING THE ERROR RATE OF A PREDICTION RULE - IMPROVEMENT ON CROSS-VALIDATION
EFRON, B
[J]. JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1983, 78 (382) : 316 - 331
[10] Efroymson M. A., 1960, Mathematical Methods for Digital Computers, P191, DOI DOI 10.1177/1753193411414639

← 1 2 3 →