Selection of heterocycles for drug design

Journal of Molecular Graphics & Modelling
Howard B Broughton, Ian Watson

Abstract

A method has been devised to obtain heterocyclic ring systems suitable for use in drug design and library design, with an emphasis on the selection of systems with good absorption, distribution, metabolism, excretion and toxicity (ADMET) properties in man. This has been achieved by extraction of the ring systems found in drugs that have reached Phase II or later stages of drug development and launch. Properties have been calculated for these ring systems to enable them to be rationally selected from the database, including descriptors based on molecular size, shape, hydrogen bonding and orbital properties. In many cases, the properties have been calculated for different attachment points of the same heterocycle. Principal components analysis has been used to enable visualization of the set of heterocycles in a useful "chemical space". Using this space, it is possible to select heterocycles for drug design to explore specific aspects of the properties of the heterocycle, such as size or hydrogen bonding, while maintaining other parameters near constant, or to select heterocycles with extreme values of these properties but which are nonetheless likely to be acceptable in a drug. The differences between the properties calculated f...Continue Reading

References

Jul 19, 1996·Journal of Medicinal Chemistry·G W Bemis, M A Murcko
Mar 13, 2003·Chemical Reviews·Douglas A HortonMark L Smythe
May 28, 2003·Journal of Chemical Information and Computer Sciences·Wolfgang H B Sauer, Matthias K Schwarz

❮ Previous
Next ❯

Citations

Jun 6, 2009·Journal of Computer-aided Molecular Design·I-Jen Chen, Roderick E Hubbard
Mar 25, 2011·Environmental Science and Pollution Research International·Gunnar HingerHenner Hollert
Sep 22, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pedro MartinsAlexandra R Fernandes
Feb 4, 2016·Journal of Medicinal Chemistry·Ye HuJürgen Bajorath
Aug 22, 2009·Bioorganic & Medicinal Chemistry·Roger J GillespieIan A Yule
Aug 12, 2006·ChemMedChem·Jörg Degen, Matthias Rarey
May 20, 2015·European Journal of Medicinal Chemistry·Hengyuan ZhangJinyi Xu
Sep 15, 2006·Bioorganic & Medicinal Chemistry Letters·Christine M RichardsonAnil Misra
Jan 7, 2015·Journal of Chemical Information and Modeling·Obdulia RabalJulen Oyarzabal
Dec 23, 2014·Bioorganic & Medicinal Chemistry Letters·Hengyuan ZhangJinyi Xu
Apr 14, 2016·Journal of Chemical Information and Modeling·Yi AnSteven E Wheeler
Feb 17, 2018·ChemMedChem·Andrea N Bootsma, Steven E Wheeler
Sep 20, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Antonio MartínezFernando Carrillo-Hermosilla
Feb 2, 2018·Molecular Diversity·Bakr F Abdel-WahabGamal A El-Hiti
Sep 21, 2016·Antimicrobial Agents and Chemotherapy·Vanessa M HowiesonKevin J Saliba
Jul 20, 2007·Nature Chemical Biology·Anang A Shelat, R Kiplin Guy
May 17, 2010·Molecular Informatics·Sarah R LangdonNathan Brown
Nov 22, 2019·Intellectual and Developmental Disabilities·Thomas L Boehm, Erik W Carter
Sep 1, 2015·American Journal on Intellectual and Developmental Disabilities·Thomas L BoehmJulie Lounds Taylor
Dec 15, 2010·Journal of Biomolecular Screening·Malin ElinderU Helena Danielson
Sep 12, 2014·Chemical Communications : Chem Comm·Merle ArrowsmithGabriele Kociok-Köhn
Apr 10, 2020·Molecular Diversity·Masoud Mohammadi ValaYadollah Bayat
Feb 20, 2021·Faraday Discussions·Andrés Moreno CarrascosaKenneth Lopata
Aug 20, 2020·Current Pharmaceutical Design·Marta Marín-LunaIbon Alkorta
May 15, 2010·Organic Letters·Graham R DickMartin D Burke
Jan 8, 2020·Journal of Medicinal Chemistry·Jessica A RowleyDavid P Fairlie
Jul 16, 2011·Journal of Chemical Information and Modeling·Ye HuJürgen Bajorath
Dec 7, 2018·Journal of Chemical Information and Modeling·Andrea N Bootsma, Steven E Wheeler
Aug 21, 2014·The Journal of Organic Chemistry·Jiajing TanNobuyoshi Yasuda
Jul 4, 2019·Journal of the American Chemical Society·Andrea N BootsmaSteven E Wheeler

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of Chemical Information and Modeling
Junmei Wang, Tingjun Hou
Journal of Medicinal Chemistry
G W Bemis, M A Murcko
Mini Reviews in Medicinal Chemistry
Nathan Brown, Edgar Jacoby
Journal of Chemical Information and Modeling
Ye HuJürgen Bajorath
© 2021 Meta ULC. All rights reserved