The prevalence of solvent effects in heterogeneous catalysis in condensed media has motivated developing quantitative kinetic, spectroscopic, and theoretical assessments of solvent structures and their interactions with reaction intermediates. 1588-83-6, Name is 4-Amino-3-nitrobenzoic acid, SMILES is C1=C([N+]([O-])=O)C(=CC=C1C(=O)O)N, belongs to naphthyridine compound. In a document, author is Madak, Joseph T., introduce the new discover, Formula: https://www.ambeed.com/products/1588-83-6.html.
We pursued a structure-guided approach toward the development of improved dihydroorotate dehydrogenase (DHODH) inhibitors with the goal of forming new interactions between DHODH and the brequinar class of inhibitors. Two potential residues, T63 and Y356, suitable for novel H-bonding interactions, were identified in the brequinar-binding pocket. Analogues were designed to maintain the essential pharmacophore and form new electrostatic interactions through strategically positioned H-bond accepting groups. This effort led to the discovery of potent quinoline-based analogues 41 (DHODH IC50 = 9.71 +/- 1.4 nM) and 43 (DHODH IC50 = 26.2 +/- 1.8 nM). A cocrystal structure between 43 and DHODH depicts a novel water mediated H-bond interaction with T63. Additional optimization led to the 1,7-naphthyridine 46 (DHODH IC50 = 28.3 +/- 3.3 nM) that forms a novel H-bond with Y356. Importantly, compound 41 possesses significant oral bioavailability (F = 56%) and an elimination t(1/2) = 2.78 h (PO dosing). In conclusion, the data supports further preclinical studies of our lead compounds toward selection of a candidate for early-stage clinical development.
The dynamic chemical diversity of the numerous elements, ions and molecules that constitute the basis of life provides wide challenges and opportunities for research. In my other articles, you can also check out more blogs about 1588-83-6. Formula: https://www.ambeed.com/products/1588-83-6.html.
Reference:
1,8-Naphthyridine – Wikipedia,
,1,8-Naphthyridine | C8H6N2 – PubChem