A very large diversity space of synthetically accessible compounds for use with drug design programs

Sergey Nikitin, Natalia Zaitseva, Olga Demina, Vera Solovieva, Evgeny Mazin, Sergey Mikhalev, Maxim Smolov, Anatoly Rubinov, Peter Vlasov, Dmitry Lepikhin, Denis Khachko, Valery Fokin, Cary Queen, Viktor Zosimov

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We have constructed a very large virtual diversity space containing more than 1013 chemical compounds. The diversity space is built from about 400 combinatorial libraries, which have been expanded by choosing sizeable collections of suitable R-groups that can be attached to each link point of their scaffolds. These R-group collections have been created by selecting reagents that have drug-like properties from catalogs of available chemicals. As members of known combinatorial libraries, the compounds in the diversity space are in general synthetically accessible and useful as potential drug leads. Hence, the diversity space can be used as a vast source of compounds by a de novo drug design program. For example, we have used such a program to generate inhibitors of HIV integrase enzyme that exhibited activity in the micromolar range.

Original languageEnglish
Pages (from-to)47-63
Number of pages17
JournalJournal of Computer-Aided Molecular Design
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2005
Externally publishedYes

Fingerprint

reception diversity
Chemical compounds
Drug Design
Scaffolds
drugs
HIV Integrase Inhibitors
Enzymes
Pharmaceutical Preparations
chemical compounds
human immunodeficiency virus
inhibitors
catalogs
reagents
enzymes

Keywords

  • Combinatorial library
  • de novo drug design

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

A very large diversity space of synthetically accessible compounds for use with drug design programs. / Nikitin, Sergey; Zaitseva, Natalia; Demina, Olga; Solovieva, Vera; Mazin, Evgeny; Mikhalev, Sergey; Smolov, Maxim; Rubinov, Anatoly; Vlasov, Peter; Lepikhin, Dmitry; Khachko, Denis; Fokin, Valery; Queen, Cary; Zosimov, Viktor.

In: Journal of Computer-Aided Molecular Design, Vol. 19, No. 1, 01.2005, p. 47-63.

Research output: Contribution to journalArticle

Nikitin, S, Zaitseva, N, Demina, O, Solovieva, V, Mazin, E, Mikhalev, S, Smolov, M, Rubinov, A, Vlasov, P, Lepikhin, D, Khachko, D, Fokin, V, Queen, C & Zosimov, V 2005, 'A very large diversity space of synthetically accessible compounds for use with drug design programs', Journal of Computer-Aided Molecular Design, vol. 19, no. 1, pp. 47-63. https://doi.org/10.1007/s10822-005-0097-6
Nikitin, Sergey ; Zaitseva, Natalia ; Demina, Olga ; Solovieva, Vera ; Mazin, Evgeny ; Mikhalev, Sergey ; Smolov, Maxim ; Rubinov, Anatoly ; Vlasov, Peter ; Lepikhin, Dmitry ; Khachko, Denis ; Fokin, Valery ; Queen, Cary ; Zosimov, Viktor. / A very large diversity space of synthetically accessible compounds for use with drug design programs. In: Journal of Computer-Aided Molecular Design. 2005 ; Vol. 19, No. 1. pp. 47-63.
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