668261-49-2Relevant academic research and scientific papers
Design, synthesis, and antiviral activity of phenylalanine derivatives as HIV-1 capsid inhibitors
Li, Jing,Jiang, Xiangyi,Dick, Alexej,Prakash Sharma, Prem,Chen, Chin-Ho,Rathi, Brijesh,Kang, Dongwei,Wang, Zhao,Ji, Xiangkai,Lee, Kuo-Hsiung,Cocklin, Simon,Liu, Xinyong,Zhan, Peng
, (2021/09/28)
The HIV-1 Capsid (CA) is considered as a promising target for the development of potent antiviral drugs, due to its multiple roles during the viral life cycle. Herein, we report the design, synthesis, and antiviral activity evaluation of series of novel phenylalanine derivatives as HIV-1 CA protein inhibitors. Among them, 4-methoxy-N-methylaniline substituted phenylalanine (II-13c) and indolin-5-amine substituted phenylalanine (V-25i) displayed exceptional anti-HIV-1 activity with the EC50 value of 5.14 and 2.57 μM respectively, which is slightly weaker than that of lead compound PF-74 (EC50 = 0.42 μM). Besides, surface plasmon resonance (SPR) binding assay demonstrated II-13c and V-25i prefer to combine with CA hexamer rather than monomer, which is similar to PF-74. Subsequently, molecular dynamics simulation (MD) revealed potential interactions between representative compounds with HIV-1 CA hexamer. Overall, this work laid a solid foundation for further structural optimization to discover novel promising HIV-1 CA inhibitors.
Synthesis and biological evaluation of novel N1-phenylsulphonyl indole derivatives as potent and selective 5-HT6R ligands for the treatment of cognitive disorders
Nirogi, Ramakrishna V. S.,Bandyala, Thrinath Reddy,Gangadasari, Pamuletinarasimha Reddy,Khagga, Mukkanti
, p. 1 - 15 (2016/12/03)
A series of 1-[3-(4-methyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole and 1-[3-(4-ethyl piperazin-1-ylmethyl) phenylsulfonyl]-1H-indole derivatives were designed and synthesized as 5-HT6 receptor (5-HT6R) ligands. The lead compound 1-[4-methyl-3-(4-methyl piperazin-1-yl methyl) phenylsulfonyl]-1H-indole dihydrochloride (6b), in this series, has shown potent in vitro binding affinity, selectivity, good pharmacokinetics (PK) profile and activity in the animal models of cognition.
Arylsulfonyl]-1H-indoles: Synthesis, SAR and biological evaluation as a novel class of 5-HT6 Receptor Antagonists
Nirogi, Ramakrishna V.S.,Badange, Rajesh Kumar,Kandukuri, Kiran Kumar,Khagga, Mukkanti
, p. 439 - 445 (2015/05/13)
In continuation to our efforts to develop better treatment options for cognitive decline, we have been focussing on 5-HT6 receptor (5-HT6R) antagonists, which are known to be involved in improving cognitive function in numerous animal models. In this paper, we report a novel series of [3-[(1-Methylpiperidin-4-yl) methyl] arylsulfonyl]-1H-indole derivatives as potent and selective 5-HT6R antagonists. The lead compound from this series shows potent in vitro binding affinity, functional antagonistic activity at 5-HT6R, good pharmacokinetic profile, excellent selectivity and no Cytochrome P450 liabilities. [Figure not available: see fulltext.]
