883868-65-3Relevant academic research and scientific papers
Design, synthesis, and structure-activity relationship studies of novel 2,4,6-trisubstituted-5-pyrimidinecarboxylic acids as peroxisome proliferator-activated receptor γ (PPARγ) partial agonists with comparable antidiabetic efficacy to rosiglitazone
Seto, Shigeki,Okada, Kyoko,Kiyota, Koichi,Isogai, Shigeki,Iwago, Maki,Shinozaki, Takehiro,Kitamura, Yoshiaki,Kohno, Yasushi,Murakami, Koji
scheme or table, p. 5012 - 5024 (2010/09/05)
A series of novel 2,4,6-trisubstitutedpyrimidine-5-carboxylic acid derivatives were designed and synthesized with the intent of producing a peroxisome proliferator-activated receptor γ (PPARγ) partial agonist for antidiabetic agents. A pharmacophore-driven approach of in-house screening identified compound 7, which led to the identification of compound 9 featuring a 2,4,6-trisubstituted pyrimidine-5-carboxylic acid core. Structure-activity relationship studies of 9 resulted in identifying 4,6-bisbenzylthio-2- methylthiopyrimidine-5-carboxylic acid (50) as the most attractive of all the screened compounds. The X-ray cocrystal structure of 50 bound on PPARγ revealed that the key hydrogen bond interactions, which are not related to the activation function 2 (AF-2) site, are different from those of the full agonist. Compound 50 showed typical PPARγ partial agonist properties in the PPARγ-GAL4 functional assay and weaker differentiation of adipocytes in 3T3-L1 cells than observed with rosiglitazone. Furthermore, 50 displayed comparable antidiabetic efficacy with rosiglitazone in db/db mice, although its potency is 10-fold weaker than that of rosiglitazone.
Chemoselective displacement of methylsulfinyl group with amines to provide 2-alkylamino-4,6-disubstituted pyrimidine-5-carboxylic acid
Seto, Shigeki,Kohno, Yasushi
experimental part, p. 2263 - 2275 (2010/04/29)
An efficient and rapid method for introducing various kinds of alkylamines at C2 of methyl 6-(benzylamino)-4-chloro-2-(methylsulfinyl)pyrimidine-5-carboxylate using the chemoselective displacement of the methylsulfinyl group (SOMe) against a chlorine atom
