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Structural simplification: an efficient strategy in lead optimization

The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoidi...

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Detalles Bibliográficos
Autores principales: Wang, Shengzheng, Dong, Guoqiang, Sheng, Chunquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804494/
https://www.ncbi.nlm.nih.gov/pubmed/31649841
http://dx.doi.org/10.1016/j.apsb.2019.05.004
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author Wang, Shengzheng
Dong, Guoqiang
Sheng, Chunquan
author_facet Wang, Shengzheng
Dong, Guoqiang
Sheng, Chunquan
author_sort Wang, Shengzheng
collection PubMed
description The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding “molecular obesity”. The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility but also improve their pharmacokinetic profiles, reduce side effects and so on. This review will summarize the application of structural simplification in lead optimization. Numerous case studies, particularly those involving successful examples leading to marketed drugs or drug-like candidates, will be introduced and analyzed to illustrate the design strategies and guidelines for structural simplification.
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spelling pubmed-68044942019-10-24 Structural simplification: an efficient strategy in lead optimization Wang, Shengzheng Dong, Guoqiang Sheng, Chunquan Acta Pharm Sin B Review The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding “molecular obesity”. The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility but also improve their pharmacokinetic profiles, reduce side effects and so on. This review will summarize the application of structural simplification in lead optimization. Numerous case studies, particularly those involving successful examples leading to marketed drugs or drug-like candidates, will be introduced and analyzed to illustrate the design strategies and guidelines for structural simplification. Elsevier 2019-09 2019-06-06 /pmc/articles/PMC6804494/ /pubmed/31649841 http://dx.doi.org/10.1016/j.apsb.2019.05.004 Text en © 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Wang, Shengzheng
Dong, Guoqiang
Sheng, Chunquan
Structural simplification: an efficient strategy in lead optimization
title Structural simplification: an efficient strategy in lead optimization
title_full Structural simplification: an efficient strategy in lead optimization
title_fullStr Structural simplification: an efficient strategy in lead optimization
title_full_unstemmed Structural simplification: an efficient strategy in lead optimization
title_short Structural simplification: an efficient strategy in lead optimization
title_sort structural simplification: an efficient strategy in lead optimization
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804494/
https://www.ncbi.nlm.nih.gov/pubmed/31649841
http://dx.doi.org/10.1016/j.apsb.2019.05.004
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