Microwave-Assisted Synthesis, Structure, and Preliminary Biological Evaluation of Novel 6-Methoxy-5,6-dihydro-5-azapurines

Alena I Siutkina; Svetlana Kalinina; Rongfang Liu; Laura H Heitman; Anna Junker; Constantin G Daniliuc; Dmitrii V Kalinin

doi:10.1021/acsomega.3c00765

Microwave-Assisted Synthesis, Structure, and Preliminary Biological Evaluation of Novel 6-Methoxy-5,6-dihydro-5-azapurines

ACS Omega. 2023 Apr 5;8(15):14097-14112. doi: 10.1021/acsomega.3c00765. eCollection 2023 Apr 18.

Authors

Alena I Siutkina¹, Svetlana Kalinina², Rongfang Liu³, Laura H Heitman³, Anna Junker⁴, Constantin G Daniliuc⁵, Dmitrii V Kalinin¹

Affiliations

¹ Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, 48149 Münster, Germany.
² Institute of Food Chemistry, University of Münster, 48149 Münster, Germany.
³ Leiden Academic Centre for Drug Research (LACDR), Division of Drug Discovery and Safety, Leiden University, 2333 CC Leiden, The Netherlands.
⁴ European Institute for Molecular Imaging (EIMI), University of Münster, 48149 Münster, Germany.
⁵ Institute for Organic Chemistry, University of Münster, 48149 Münster, Germany.

Abstract

We herein disclose the microwave-assisted synthesis of previously unreported 6-methoxy-5,6-dihydro-5-azapurines, whose purine-like scaffold is promising for drug discovery. The method is simple, fast, and relies on easily accessible reagents such as trimethyl orthoformate, acetic acid, and aminotriazole-derived N,N'-disubstituted formamidines. The preliminary biological evaluation revealed that selected representatives of synthesized 6-methoxy-5,6-dihydro-5-azapurines dose-dependently reduce the viability of HepG2 and A549 cancer cells having little to no influence on five tested purinergic receptors.