154440-76-3Relevant academic research and scientific papers
Manganese-catalyzed oxidative azidation of cyclobutanols: Regiospecific synthesis of alkyl azides by C-C bond cleavage
Ren, Rongguo,Zhao, Huijun,Huan, Leitao,Zhu, Chen
, p. 12692 - 12696 (2015)
A novel, manganese-catalyzed oxidative azidation of cyclobutanols is described. A wide range of primary, secondary, and tertiary alkyl azides were generated in synthetically useful yields and exclusive regioselectivity. Aside from linear alkyl azides, oth
Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from: Mycobacterium tuberculosis to overcome kanamycin resistance
Garneau-Tsodikova, Sylvie,Garzan, Atefeh,Green, Keith D.,Holbrook, Selina Y. L.,Hou, Caixia,Krieger, Kyle,Pang, Allan H.,Parish, Tanya,Posey, James E.,Punetha, Ankita,Thamban Chandrika, Nishad,Tsodikov, Oleg V.,Willby, Melisa J.
supporting information, p. 1894 - 1909 (2022/01/12)
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly bacterial disease. Drug-resistant strains of Mtb make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by Mtb confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, 1), was a potent Eis inhibitor with IC50 = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (1), eight analogues, some of which were smaller than 1, potently inhibited Eis (IC50 ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant Mtb strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition. This journal is
Benzenesulfonamide Derivatives as Calcium/Calmodulin-Dependent Protein Kinase Inhibitors and Antiviral Agents against Dengue and Zika Virus Infections
Chen, Wei-Chia,Simanjuntak, Yogy,Chu, Li-Wei,Ping, Yueh-Hsin,Lee, Yi-Ling,Lin, Yi-Ling,Li, Wen-Shan
, p. 1313 - 1327 (2020/03/10)
Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIK
Discovery of selective imidazole-based inhibitors of mammalian 15-lipoxygenase: Highly potent against human enzyme within a cellular environment
Weinstein, David S.,Liu, Wen,Ngu, Khehyong,Langevine, Charles,Combs, Donald W.,Zhuang, Shaobin,Chen, Cindy,Madsen, Cort S.,Harper, Timothy W.,Robl, Jeffrey A.
, p. 5115 - 5120 (2008/12/20)
A series of 2,4,5-tri-substituted imidazoles has proven to be highly potent in inhibiting mammalian 15-lipoxygenase (15-LO) with excellent selectivity over human isozymes 5- and P-12-LO. Non-symmetrical sulfamides (e.g., 21a-n) were found to be suitable r
