139200-36-5Relevant articles and documents
Vinyl Sulfone-Based Inhibitors of Nonstructural Protein 2 Block the Replication of Venezuelan Equine Encephalitis Virus
Zhang, Huaisheng,Harmon, Moeshia,Radoshitzky, Sheli R.,Soloveva, Veronica,Kane, Christopher D.,Duplantier, Allen J.,Ogungbe, Ifedayo Victor
, p. 2139 - 2145 (2020/12/17)
Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2). Primary screen and dose response studies were performed to evaluate the potency and cytotoxicity of the compounds. The results provide structural insights into a new class of potent nonpeptidic covalent inhibitors of nsP2 cysteine protease represented by compound 11 (VEEV TrD, EC50= 2.4 μM (HeLa), 1.6 μM (Vero E6)). These results may facilitate the evolution of the compounds into selective and broad-spectrum anti-alphaviral drug leads.
Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain
McShan, Danielle,Kathman, Stefan,Lowe, Brittiney,Xu, Ziyang,Zhan, Jennifer,Statsyuk, Alexander,Ogungbe, Ifedayo Victor
, p. 4509 - 4512 (2015/10/12)
Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads.
A novel synthesis of 1,3-benzodiazepin-2-ones using intramolecular heck reaction
Hayashi, Masahito,Sai, Hiroshi,Horikawa, Hiroshi
, p. 1331 - 1335 (2007/10/03)
The formation of the skeleton of 1,3-benzodiazepin-2-one could be efficiently achieved by intramolecular Heck reaction. This methodology was well applicable to the preparation of optically pure 4-substituted 1,3-benzodiazepin-2-ones starting from easily available α-amino acids.
