Issue 10, 2018, Issue in Progress

Computational method for estimating progression saturation of analog series

Abstract

In lead optimization, it is difficult to estimate when an analog series might be saturated and synthesis of additional compounds would be unlikely to yield further progress. Rather than terminating a series, one often continues to generate analogs hoping to reach the final optimization goal, even if obstacles that are faced ultimately prove to be unsurmountable. Clearly, methodologies to better understand series progression and saturation are highly desirable. However, only a few approaches are currently available to monitor series progression and aid in decision making. Herein, we introduce a new computational method to assess progression saturation of an analog series by relating the properties of existing compounds to those of synthetic candidates and comparing their distributions in chemical space. The neighborhoods of analogs are analyzed and the distance relationships between existing and candidate compounds quantified. An intuitive dual scoring scheme makes it possible to characterize analog series and their degree of progression saturation.

Graphical abstract: Computational method for estimating progression saturation of analog series

Supplementary files

Article information

Article type
Paper
Submitted
29 Dec 2017
Accepted
26 Jan 2018
First published
31 Jan 2018
This article is Open Access
Creative Commons BY license

RSC Adv., 2018,8, 5484-5492

Computational method for estimating progression saturation of analog series

R. Kunimoto, T. Miyao and J. Bajorath, RSC Adv., 2018, 8, 5484 DOI: 10.1039/C7RA13748F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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