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Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity

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Abstract

This paper describes an investigation of novel RAGE inhibitors with improved drug-like properties. To identify the improved drug-like RAGE inhibitor, we designed and synthesized pyrimidine-2-carboxamide analogs based on our previous work. Several potent analogs with improved hydrophilicity were identified by evaluation of RAGE inhibitory activity. In particular, one of the potent (diethylamino)ethoxymethoxy analogs did not exhibit undesired cytotoxicity in contrast with the parent RAGE inhibitors.

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Acknowledgments

This work was supported by National Research Foundation grant funded by the Korea government (MEST) as a part of Global Drug Candidate Development Program for Neurodegenerative Diseases (2011-0018334).

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Authors and Affiliations

  1. College of Pharmacy, CHA University, Pochen-Si, Gyeonggi-do, 487-010, Korea

    Seok-Ho Kim

  2. College of Pharmacy, Dankook University, Cheonan, 330-714, Korea

    Young Taek Han

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  1. Seok-Ho Kim
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Correspondence to Young Taek Han.

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Kim, SH., Han, Y.T. Design, synthesis, and biological evaluation of pyrimidine-2-carboxamide analogs: investigation for novel RAGE inhibitors with reduced hydrophobicity and toxicity. Arch. Pharm. Res. 38, 1952–1962 (2015). https://doi.org/10.1007/s12272-015-0596-5

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  • DOI: https://doi.org/10.1007/s12272-015-0596-5

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