Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity

Nhan, Bui Hoang Huu; Jeon, Seong Ho; Lee, Sujin; Son, Seung Hwan; Yang, Young Duk; Kim, Seok-Ho

doi:10.3390/molecules31183289

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Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity

by

Bui Hoang Huu Nhan

^1,†,

Seong Ho Jeon

^2,†,

Sujin Lee

^3,†

,

Seung Hwan Son

¹,

Young Duk Yang

^2,* and

Seok-Ho Kim

^1,*

¹

College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea

²

Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon 11160, Republic of Korea

³

College of Pharmacy, Daegu Catholic University, Gyungsan 38430, Republic of Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Molecules 2026, 31(18), 3289; https://doi.org/10.3390/molecules31183289

Submission received: 22 July 2026 / Revised: 10 September 2026 / Accepted: 11 September 2026 / Published: 16 September 2026

(This article belongs to the Section Medicinal Chemistry)

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Abstract

GPR119 is a promising target for the treatment of type 2 diabetes mellitus. Stimulating this receptor leads to the induction of glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which improves systemic glucose homeostasis. Encouraged by our previous research, we replaced 5-nitropyrimidine with 1,3,5-triazine to reduce hepatotoxicity. A new series of compounds with a 1,3,5-triazine scaffold was synthesized and evaluated for their agonistic activities against human GPR119. Thirty-three compounds were synthesized and evaluated for their potential GPR119 agonist activities. Analogs with a 4-cyano and a 4-methylsulfonyl group in the aryl ring exhibited more potent activation than those analogs with a 4-trifluoromethyl group. Compound 3c had the most favorable EC₅₀ value (hEC₅₀ = 2.39 µM) and significantly induced glucagon-like peptide-1 secretion. Furthermore, docking simulations showed that compound 3c stably binds to the active site of GPR119.

Keywords: diabetes; GPR119 agonist; 1,3,5-triazine; GLP-1; molecular docking

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MDPI and ACS Style

Nhan, B.H.H.; Jeon, S.H.; Lee, S.; Son, S.H.; Yang, Y.D.; Kim, S.-H. Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity. Molecules 2026, 31, 3289. https://doi.org/10.3390/molecules31183289

AMA Style

Nhan BHH, Jeon SH, Lee S, Son SH, Yang YD, Kim S-H. Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity. Molecules. 2026; 31(18):3289. https://doi.org/10.3390/molecules31183289

Chicago/Turabian Style

Nhan, Bui Hoang Huu, Seong Ho Jeon, Sujin Lee, Seung Hwan Son, Young Duk Yang, and Seok-Ho Kim. 2026. "Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity" Molecules 31, no. 18: 3289. https://doi.org/10.3390/molecules31183289

APA Style

Nhan, B. H. H., Jeon, S. H., Lee, S., Son, S. H., Yang, Y. D., & Kim, S.-H. (2026). Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity. Molecules, 31(18), 3289. https://doi.org/10.3390/molecules31183289

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Synthesis and Biological Evaluation of 1,3,5-Triazine Derivatives for GPR119 Agonistic Activity

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