Quantitative structure-activity relationship analysis of aryl alkanol piperazine derivatives with antidepressant activities

被引：20

作者：

Chen, Ke-Xian ^{[1
]}

Li, Zu-Guang ^{[1
]}

Xie, Hai-Ying ^{[1
]}

Gao, Jian-Rong ^{[1
]}

Zou, Jian-Wei ^{[2
]}

机构：

[1] Zhejiang Univ Technol, Coll Chem Engn & Mat Sci, Hangzhou 310014, Zhejiang, Peoples R China

[2] Zhejiang Univ, Ningbo Inst Technol, Key Lab Mol Design & Nutr Engn, Ningbo 315104, Zhejiang, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Aryl alkanol piperazine derivatives; Antidepressant activities; Genetic function approximation (GFA); Molecular field analysis (MFA); Genetic partial least squares (G/PLS); Quantitative structure-activity relationship (QSAR); GENETIC FUNCTION APPROXIMATION; INHIBITORS; ANALOGS; QSAR; DEPRESSION; SEROTONIN; ANTAGONISTS; DESIGN; COMFA;

D O I：

10.1016/j.ejmech.2009.05.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Quantitative structure-activity relationship analysis for recently synthesized aryl alkanol piperazine derivatives was studied for their antidepressant activities. The statistically significant 2D-QSAR models (r(2) > 0.924, r(-cv)(2) > 0.870, r(-pred)(2) > 0.890) were developed using genetic function approximation (GFA) when the number of descriptors in equation was set to four, indicating the descriptors of Atype_C_6, Dipole-mag, S_sssCH and Jurs-PNSA-3 mainly influence the 5-hydroxytryptamine (5-HT) reuptake inhibition activity while the descriptors of HOMO, PMI-mag, S_sssN and Shadow-XZ may chiefly control the noradrenaline (NA) reuptake inhibition activity. The results of the 2D-QSAR models were further compared with 3D-QSAR models generated by molecular field analysis (MFA), investigating the substitutional requirements for the favorable receptor-drug interaction and providing useful information in the characterization and differentiation of their binding sites. The results derived may be useful in further designing novel antidepressants prior to synthesis. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4367 / 4375

页数：9

共 34 条

[11]

GASTEIGER J, 1980, TETRAHEDRON, V36, P3291

[12] ATOMIC PHYSICOCHEMICAL PARAMETERS FOR 3-DIMENSIONAL-STRUCTURE-DIRECTED QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS .2. MODELING DISPERSIVE AND HYDROPHOBIC INTERACTIONS [J].

GHOSE, AK ;

CRIPPEN, GM .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1987, 27 (01) :21-35

[13] THE ELECTROTOPOLOGICAL STATE - AN ATOM INDEX FOR QSAR [J].

HALL, LH ;

MOHNEY, B ;

KIER, LB .

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS, 1991, 10 (01) :43-51

[14] 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

[15] Quantitative structure-activity relationship study of recently synthesized 1,4-dihydropyridine calcium channel antagonists. Application of the Hansch analysis method [J].

Hemmateenejad, B ;

Miri, R ;

Akhond, M ;

Shamsipur, M .

ARCHIV DER PHARMAZIE, 2002, 335 (10) :472-480

[16]

Henn F, 2004, DRUG DISCOV TODAY DI, V1, P407, DOI DOI 10.1016/J.DDMEC.2004.10.007

[17] Classification of dopamine, serotonin, and dual antagonists by decision trees [J].

Kim, HJ ;

Choo, H ;

Cho, YS ;

Koh, HY ;

No, KT ;

Pae, AN .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (08) :2763-2770

[18] Synthesis and antidepressant-like profile of novel 1-aryl-3-[(4-benzyl)piperidine-1-yl]propane derivatives [J].

Koksal, Meric ;

Bilge, S. Sirri .

ARCHIV DER PHARMAZIE, 2007, 340 (06) :299-303

[19] Exploring molecular shape analysis of styrylquinoline derivatives as HIV-1 integrase inhibitors [J].

Leonard, J. Thomas ;

Roy, Kunal .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2008, 43 (01) :81-92

[20]

[李建其 LI Jianqi], 2006, [中国药物化学杂志, Chinese Journal of Medicinal Chemistry], V16, P270

← 1 2 3 4 →