2. Academic Validation
  3. Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists

Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists

  • Bioorg Med Chem Lett. 2014 Sep 1;24(17):4271-5. doi: 10.1016/j.bmcl.2014.07.026.
Eun Ju Park 1,  Young Gil Ahn 2,  Seung Hyun Jung 2,  Hyo Jeong Bang 1,  Mira Kim 1,  Dong Jin Hong 1,  Jisook Kim 2,  Kwee Hyun Suh 2,  Young Jin Kim 3,  Doran Kim 3,  Eun-Yeong Kim 4,  Kiho Lee 4,  Kyung Hoon Min 5
Affiliations

Affiliations

  • 1 Hanmi Research Center, Hanmi Pharm. Co. Ltd, Gyeonggi-do 445-813, Republic of Korea; College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
  • 2 Hanmi Research Center, Hanmi Pharm. Co. Ltd, Gyeonggi-do 445-813, Republic of Korea.
  • 3 College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
  • 4 College of Pharmacy, Korea University, Sejong 339-700, Republic of Korea.
  • 5 College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea. Electronic address: khmin@cau.ac.kr.
PMID: 25082126 DOI: 10.1016/j.bmcl.2014.07.026
Abstract

Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate.

Keywords

Agonist; Bioisostere; Malonamide; Pyrimidine; TGR5.

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