Computational design of new molecular scaffolds for medicinal chemistry, part II: generalization of analog series-based scaffolds

被引：6

作者：

Dimova, Dilyana ^{[1
]}

Stumpfe, Dagmar ^{[1
]}

Bajorath, Juergen ^{[1
]}

机构：

[1] Rheinische Friedrich Wilhelms Univ, LIMES Program Unit Chem Biol & Med Chem, B IT, Dept Life Sci Informat, Dahlmannstr 2, D-53113 Bonn, Germany

来源：

FUTURE SCIENCE OA | 2018年 / 4卷 / 02期

关键词：

analog series; bioactive compounds; computationalmethods; medicinal chemistry; scaffolds; targets;

D O I：

10.4155/fsoa-2017-0102

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Aim: Extending and generalizing the computational concept of analog series-based (ASB) scaffolds. Materials & methods: Methodological modifications were introduced to further increase the coverage of analog series (ASs) and compounds by ASB scaffolds. From bioactive compounds, ASs were systematically extracted and second-generation ASB scaffolds isolated. Results: More than 20,000 second-generation ASB scaffolds with single or multiple substitution sites were extracted from active compounds, achieving more than 90% coverage of ASs. Conclusion: Generalization of the ASB scaffold approach has yielded a large knowledge base of scaffold-capturing compound series and target information.

引用

收藏

页数：17

相关论文

共 13 条

[1] The properties of known drugs .1. Molecular frameworks [J].

Bemis, GW ;

Murcko, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (15) :2887-2893

[2] KNIME:: The Konstanz Information Miner [J].

Berthold, Michael R. ;

Cebron, Nicolas ;

Dill, Fabian ;

Gabriel, Thomas R. ;

Koetter, Tobias ;

Meinl, Thorsten ;

Ohl, Peter ;

Sieb, Christoph ;

Thiel, Kilian ;

Wiswedel, Bernd .

DATA ANALYSIS, MACHINE LEARNING AND APPLICATIONS, 2008, :319-326

[3] Matched molecular pairs derived by retrosynthetic fragmentation [J].

de Leon, Antonio de la Vega ;

Bajorath, Juergen .

MEDCHEMCOMM, 2014, 5 (01) :64-67

[4] Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry [J].

Dimova, Dilyana ;

Stumpfe, Dagmar ;

Hu, Ye ;

Bajorath, Juergen .

FUTURE SCIENCE OA, 2016, 2 (04)

[5] ChEMBL: a large-scale bioactivity database for drug discovery [J].

Gaulton, Anna ;

Bellis, Louisa J. ;

Bento, A. Patricia ;

Chambers, Jon ;

Davies, Mark ;

Hersey, Anne ;

Light, Yvonne ;

McGlinchey, Shaun ;

Michalovich, David ;

Al-Lazikani, Bissan ;

Overington, John P. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (D1) :D1100-D1107

[6] MMP-Cliffs: Systematic Identification of Activity Cliffs on the Basis of Matched Molecular Pairs [J].

Hu, Xiaoying ;

Hu, Ye ;

Vogt, Martin ;

Stumpfe, Dagmar ;

Bajorath, Juergen .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2012, 52 (05) :1138-1145

[7] Computational Exploration of Molecular Scaffolds in Medicinal Chemistry [J].

Hu, Ye ;

Stumpfe, Dagmar ;

Bajorath, Juergen .

JOURNAL OF MEDICINAL CHEMISTRY, 2016, 59 (09) :4062-4076

[8] Lessons Learned from Molecular Scaffold Analysis [J].

Hu, Ye ;

Stumpfe, Dagmar ;

Bajorath, Juergen .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2011, 51 (08) :1742-1753

[9]

Kenny PW., 2004, CHEMOINFORMATICS DRU, P271, DOI DOI 10.1002/3527603743.CHLL

[10] Application of a New Scaffold Concept for Computational Target Deconvolution of Chemical Cancer Cell Line Screens [J].

Kunimoto, Ryo ;

Dimova, Dilyana ;

Bajorath, Juergen .

ACS OMEGA, 2017, 2 (04) :1463-1468