Issue 4, 2013

Increasing small molecule drug developability in sub-optimal chemical space

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

Supplementary files

Article information

Article type
Concise Article
Submitted
02 Jan 2013
Accepted
14 Feb 2013
First published
19 Feb 2013

Med. Chem. Commun., 2013,4, 673-680

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements