Quantitative structure activity relationship studies of aryl heterocycle-based thrombin inhibitors

被引：39

作者：

Deswal, Sumit ^{[1
]}

Roy, Nilanjan ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res, Pharmacoinformat, Nagar 160062, Punjab, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 41卷 / 11期

关键词：

QSAR; thrombin inhibitors; genetic function approximation; aryl heterocyclic;

D O I：

10.1016/j.ejmech.2006.07.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A quantitative structure activity relationship (QSAR) analysis has been performed on a data set of 42 aryl heterocycle-based thrombin inhibitors. Several types of descriptors including topological, spatial, thermodynamic, information content and E-state indices were used to derive a quantitative relationship between the anti thrombin activity and structural properties. Genetic algorithm based genetic function approximation method of variable selection was used to generate the model. Best model was developed when number of descriptors in the equation was set to five. Highly statistically significant model was obtained with atom type logP descriptors, logP and Shadow_YZ. The model is not only able to predict the activity of new compounds but also explained the important regions in the molecules in a quantitative manner. (c) 2006 Elsevier Masson SAS. All rights reserved.

引用

页码：1339 / 1346

页数：8

共 27 条

[1]

Anand S, 1999, HAEMOSTASIS, V29, P76

[2]

QSAR modeling with the electrotopological state indices: Corticosteroids [J].

de Gregorio, C ;

Kier, LB ;

Hall, LH .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1998, 12 (06) :557-561

[3]

THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].

DEWAR, MJS ;

ZOEBISCH, EG ;

HEALY, EF ;

STEWART, JJP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909

[4]

Recent advances on the role of topological indices in drug discovery research [J].

Estrada, E ;

Uriarte, E .

CURRENT MEDICINAL CHEMISTRY, 2001, 8 (13) :1573-1588

[5]

NEW SUBSTITUENT CONSTANT PI DERIVED FROM PARTITION COEFFICIENTS [J].

FUJITA, T ;

HANSCH, C ;

IWASA, J .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (23) :5175-&

[6]

ATOMIC PHYSICOCHEMICAL PARAMETERS FOR 3-DIMENSIONAL STRUCTURE-DIRECTED QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS .1. PARTITION-COEFFICIENTS AS A MEASURE OF HYDROPHOBICITY [J].

GHOSE, AK ;

CRIPPEN, GM .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1986, 7 (04) :565-577

[7]

A QUANTITATIVE APPROACH TO BIOCHEMICAL STRUCTURE-ACTIVITY RELATIONSHIPS [J].

HANSCH, C .

ACCOUNTS OF CHEMICAL RESEARCH, 1969, 2 (08) :232-&

[8]

Chem-bioinformatics and QSAR: A review of QSAR lacking positive hydrophobic terms [J].

Hansch, C ;

Kurup, A ;

Garg, R ;

Gao, H .

CHEMICAL REVIEWS, 2001, 101 (03) :619-672

[9]

Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides [J].

Jaiswal, M ;

Khadikar, PV ;

Scozzafava, A ;

Supuran, CT .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (12) :3283-3290

[10]

AN ELECTROTOPOLOGICAL-STATE INDEX FOR ATOMS IN MOLECULES [J].

KIER, LB ;

HALL, LH .

PHARMACEUTICAL RESEARCH, 1990, 7 (08) :801-807

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