Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

Kuen-Da Wu; Grace Shiahuy Chen; Jia-Rong Liu; Chen-En Hsieh; Ji-Wang Chern

doi:10.1021/acsmedchemlett.8b00270

Acrylamide Functional Group Incorporation Improves Drug-like Properties: An Example with EGFR Inhibitors

ACS Med Chem Lett. 2018 Dec 6;10(1):22-26. doi: 10.1021/acsmedchemlett.8b00270. eCollection 2019 Jan 10.

Authors

Kuen-Da Wu¹, Grace Shiahuy Chen², Jia-Rong Liu¹, Chen-En Hsieh², Ji-Wang Chern¹

Affiliations

¹ School of Pharmacy and Center for Innovative Therapeutics Discovery, National Taiwan University, Taipei 10055, Taiwan.
² Department of Applied Chemistry, Providence University, Taichung 43301, Taiwan.

Abstract

We demonstrate that the acrylamide group can be used to improve the drug-like properties of potential drug candidates. In the EGFR inhibitor development, both the solubility and membrane permeability properties of compounds 6a and 7, each containing an acrylamide group, were substantially better than those of gefitinib (1) and AZD3759 (2), respectively. We demonstrated that incorporation of an acrylamide moiety could serve as a good strategy for improving drug-like properties.