2958-56-7Relevant academic research and scientific papers
Nickel-catalyzed hydrogen-borrowing strategy: Chemo-selective alkylation of nitriles with alcohols
Banerjee, Debasis,Bera, Atanu,Bera, Sourajit
supporting information, p. 6850 - 6853 (2020/07/04)
The first nickel-catalyzed hydrogen-borrowing alkylation of a series of aryl acetonitriles with a variety of aryl, heteroaryl, allylic and alkyl alcohols releasing water as the by-product (>33 examples, up to 90% yield) is reported.
Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design
Hoang, Van-Hai,Ngo, Van T.H.,Cui, Minghua,Manh, Nguyen Van,Tran, Phuong-Thao,Ann, Jihyae,Ha, Hee-Jin,Kim, Hee,Choi, Kwanghyun,Kim, Young-Ho,Chang, Hyerim,MacAlino, Stephani Joy Y.,Lee, Jiyoun,Choi, Sun
, p. 8011 - 8027 (2019/10/11)
Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of β-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor 1, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.
Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase
Bennett, Matthew R.,Thompson, Mark L.,Shepherd, Sarah A.,Dunstan, Mark S.,Herbert, Abigail J.,Smith, Duncan R. M.,Cronin, Victoria A.,Menon, Binuraj R. K.,Levy, Colin,Micklefield, Jason
supporting information, p. 10600 - 10604 (2018/08/17)
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.
