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Issue 4, 2013
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Increasing small molecule drug developability in sub-optimal chemical space

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Abstract

Using compounds occupying four distinct clog P/molecular weight regions that define optimal and sub-optimal chemical space, and a developability score derived from solubility, permeability, protein binding and 3A4 inhibition screening data, OPLS regression models were constructed to determine which physico-chemical properties were most correlated with developability. The results suggested that whilst certain molecule properties were important for developability across all chemical space, such as [clog D + aromatic ring count], [clog D + (aromatic atom count – sp3 carbon count)] and [sp3 carbon count/total carbon count], others such as heteroaliphatic ring count, positive ionisable group count and H-bond donor character exhibited varying degrees of importance depending on the clog P/Mw region.

Graphical abstract: Increasing small molecule drug developability in sub-optimal chemical space

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Supplementary files

Article information


Submitted
02 Jan 2013
Accepted
14 Feb 2013
First published
19 Feb 2013

Med. Chem. Commun., 2013,4, 673-680
Article type
Concise Article

Increasing small molecule drug developability in sub-optimal chemical space

T. J. Ritchie, S. J. F. Macdonald, S. Peace, S. D. Pickett and C. N. Luscombe, Med. Chem. Commun., 2013, 4, 673
DOI: 10.1039/C3MD00003F

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