Downs, Ryan P.; Xiao, Zhousheng; Ikedionwu, Munachi O.; Cleveland, Jacob W.; Chin, Ai Lin; Cafferty, Abigail E.; Darryl Quarles, L.; Carrick, Jesse D. published their research in Bioorganic & Medicinal Chemistry in 2021. The article was titled 《Design and development of FGF-23 antagonists: Definition of the pharmacophore and initial structure-activity relationships probed by synthetic analogues》.Reference of 2-Bromonicotinaldehyde The article contains the following contents:
Hereditary hypophosphatemic disorders, TIO, and CKD conditions are believed to be influenced by an excess of Fibroblast Growth Factor-23 (FGF-23) which activates a binary renal FGFRs/α-Klotho complex to regulate homeostatic metabolism of phosphate and vitamin D. Adaptive FGF-23 responses from CKD patients with excess FGF-23 frequently lead to increased mortality from cardiovascular disease. A reversibly binding small mol. therapeutic has yet to emerge from research and development in this area. Current outcomes described in this work highlight efforts related to lead identification and modification using organic synthesis of strategic analogs to probe structure-activity relationships and preliminarily define the pharmacophore of a computationally derived hit obtained from virtual high-throughput screening. Synthetic strategies for the initial hit and analog preparation, as well as preliminary cellular in vitro assay results highlighting sub micromolar inhibition of the FGF-23 signaling sequence at a concentration well below cytotoxicity are reported herein. In the experiment, the researchers used 2-Bromonicotinaldehyde(cas: 128071-75-0Reference of 2-Bromonicotinaldehyde)
2-Bromonicotinaldehyde(cas: 128071-75-0) belongs to pyridine. Pyridine is very deactivated towards electrophilic substitution with respect to benzene. For this reason classical formylation, using methods such as the Gattermann or Vilsmeier reactions, are not generally successful. Reference of 2-Bromonicotinaldehyde