4521-22-6Relevant articles and documents
Identification of First-in-Class Inhibitors of Kallikrein-Related Peptidase 6 That Promote Oligodendrocyte Differentiation
A?t Amiri, Sabrina,Deboux, Cyrille,Soualmia, Feryel,Chaaya, Nancy,Louet, Maxime,Duplus, Eric,Betuing, Sandrine,Nait Oumesmar, Brahim,Masurier, Nicolas,El Amri, Chahrazade
, p. 5667 - 5688 (2021/05/29)
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that causes severe motor, sensory, and cognitive impairments. Kallikrein-related peptidase (KLK)6 is the most abundant serine protease secreted in the CNS, mainly by oligodendrocytes, the myelin-producing cells of the CNS, and KLK6 is assumed to be a robust biomarker of MS, since it is highly increased in the cerebrospinal fluid (CSF) of MS patients. Here, we report the design and biological evaluation of KLK6's low-molecular-weight inhibitors, para-aminobenzyl derivatives. Interestingly, selected hit compounds were selective of the KLK6 proteolytic network encompassing KLK1 and plasmin that also participate in the development of MS physiopathology. Moreover, hits were found noncytotoxic on primary cultures of murine neurons and oligodendrocyte precursor cells (OPCs). Among them, two compounds (32 and 42) were shown to promote the differentiation of OPCs into mature oligodendrocytes in vitro constituting thus emerging leads for the development of regenerative therapies.
Directed palladium(II)-catalyzed intermolecular anti-markovnikov hydroarylation of unactivated alkenes with (hetero)arylsilanes
Lu, Ming-Zhu,Loh, Teck-Peng,Luo, Haiqing,Hu, Zhengsong,Shao, Changdong,Kan, Yuhe
, p. 9022 - 9028 (2020/12/02)
We describe herein a regioselective palladium(II)catalyzed intermolecular hydroarylation of unactivated aliphatic alkenes with electronically and sterically diverse (hetero)arylsilanes under redox-neutral conditions. A removable bidentate 8-amino-quinoline auxiliary was readily employed to dictate the regioselectivity, prevent β-hydride elimination, and facilitate protodepalladation. This silicon-based protocol features a broad substrate scope with excellent functional group compatibility and enables an expeditious route to a variety of γ-aryl butyric acid derivatives in good yields with exclusive anti-Markovnikov selectivity.
Synthesis of Novel Pterocarpen Analogues via [3?+?2] Coupling-Elimination Cascade of α,α-Dicyanoolefins with Quinone Monoimines
Chen, Hui,Zhao, Sihan,Cheng, Shaobing,Dai, Xingjie,Xu, Xiaoying,Yuan, Weicheng,Zhang, Xiaomei
, p. 1672 - 1683 (2019/04/08)
By employing triethylamine as a catalyst, [3?+?2] coupling-elimination cascade of α,α-dicyanoolefins with quinone monoimines was realized. The reactions afforded various novel pterocarpen analogues with generally moderate yields (up to 75%). In addition, a plausible reaction mechanism was proposed.