Olson, Kirk L.; Holt, Melissa C.; Ciske, Fred L.; Kramer, James B.; Heiple, Paige E.; Collins, Margaret L.; Johnson, Carrie M.; Ho, Chi S.; Morano, M. Ines; Barrett, Stephen D. published their research in Bioorganic & Medicinal Chemistry Letters in 2021. The article was titled 《Novel amide and imidazole compounds as potent hematopoietic prostaglandin D2 synthase inhibitors》.Formula: C5H6BNO2 The article contains the following contents:
In seeking novel and potent small mol. hematopoietic prostaglandin D2 synthase (H-PGDS) inhibitors as potential therapies for PGD2-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole “”linker”” between the pyrimidine or pyridine “”core”” ring and the “”tail”” ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD2 stimulation. Amide analogs show ten-fold greater shift in the thermal shift assay in the presence of glutathione (GSH) vs. the same assay run in the absence of GSH. The imidazole analogs did not produce a significant change in thermal shift between the two assay conditions, suggesting a possible stabilization effect of the amide linker in the synthase-GSH-inhibitor complex. Imidazole analog 23, (KMN-010034) demonstrates superior potency across the in vitro assays and good in vitro metabolic stability in both human and guinea pig liver microsomes. The experimental process involved the reaction of 2-Pyridinylboronic acid(cas: 197958-29-5Formula: C5H6BNO2)
2-Pyridinylboronic acid(cas: 197958-29-5) belongs to pyridine. Pyridine is widely used in the precursor to agrochemicals and pharmaceuticals. Also, it is used as an important reagent and organic solvent.Formula: C5H6BNO2