Design, Synthesis, and Biological Evaluation of Novel Matrix Metalloproteinase Inhibitors As Potent Antihemorrhagic Agents: From Hit Identification to an Optimized Lead was written by Orbe, Josune;Sanchez-Arias, Juan A.;Rabal, Obdulia;Rodriguez, Jose A.;Salicio, Agustina;Ugarte, Ana;Belzunce, Miriam;Xu, Musheng;Wu, Wei;Tan, Haizhong;Ma, Hongyu;Paramo, Jose A.;Oyarzabal, Julen. And the article was included in Journal of Medicinal Chemistry in 2015.Reference of 51834-97-0 This article mentions the following:
Growing evidence suggests that matrix metalloproteinases (MMP) are involved in thrombus dissolution; then, considering that new therapeutic strategies are required for controlling hemorrhage, we hypothesized that MMP inhibition may reduce bleeding by delaying fibrinolysis. Thus, we designed and synthesized a novel series of MMP inhibitors to identify potential candidates for acute treatment of bleeding. Structure-based and knowledge-based strategies were utilized to design this novel chem. series, α-spiropiperidine hydroxamates, of potent and soluble (>75 μg/mL) pan-MMP inhibitors. The initial hit was progressed to an optimal lead I. Racemic I showed a remarkable in vitro phenotypic response and outstanding in vivo efficacy; in fact, the mouse bleeding time at 1 mg/kg was 0.85 min compared to 29.28 min using saline. In addition, I displayed an optimal ADME and safety profile (e.g., no thrombus formation). Its corresponding enantiomers were separated, leading to the preclin. candidate (R)-I. In the experiment, the researchers used many compounds, for example, 5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0Reference of 51834-97-0).
5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Reference of 51834-97-0