- Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents
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Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.
- Chen, Rui,Cheng, Fei,Cui, Xing,Du, Yao,Fan, Ling-Ling,Guo, Bing,Li, Shu-Min,Tang, Lei,Wang, Jian-Ta,Wang, Li-Li,Wu, Hao-Shu,Yang, Sheng-Gang,Zhang, Ji-Quan,Zhang, Na-Na
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- Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
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The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
- Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
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supporting information
p. 4567 - 4587
(2021/05/06)
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- Synthesis of a new series of aminomethylated 5-nitro-1H-benzo [d] imidazoles, 6-nitrobenzo [d] oxazol-2(3H)-ones and 4-nitroisoindoline-1,3-diones as antileishmanial and antimicrobial agents
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4-(Chlorobenzyloxy) anilines were incorporated into 5-nitro-1H-benzo [d] imidazole, 6-nitrobenzo [d] oxazol-2(3H)-one and 4-nitroisoindoline-1,3-dione in the presence of 40% aq formaldehyde to furnish a new series of 5-nitro-1-(4-chlorobenzyloxy)-anilinomethyl-1 H-benzo [d] imidazoles /6-nitro-3-(4-(chlorobenzyloxy)-anilinomethyl)-benzo [d] oxazol-2(3H)-ones and 4-nitro-2-(4-chlorobenzyloxy)-anilinomethyl) isoindoline-1,3-diones (11-25). The structures of the compounds were established by means of elemental analysis and spectral data (IR & PMR). Compounds were screened for their antileishmanial and antimicrobial potential.
- Rastogi, Nisheeth,Kant, Padam,Sethi, Rakesh,Shukla, Sarveshwar,Harrison, Darwin Anil
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p. 149 - 152
(2013/09/23)
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- Highly chemo- and regioselective reduction of aromatic nitro compounds using the system silane/oxo-rhenium complexes
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(Chemical Equation Presented) The reduction of aromatic nitro compounds to the corresponding amines with silanes catalyzed by high valent oxo-rhenium complexes is reported. The catalytic systems PhMe2SiH/ReIO 2(PPh3)2 (5 mol %) and PhMe2SiH/ ReOCl3(PPh3)2 (5 mol %) reduced efficiently a series of aromatic nitro compounds in the presence of a wide range of functional groups such as ester, halo, amide, sulfone, lactone, and benzyl. This methodology also allowed the regioselective reduction of dinitrobenzenes to the corresponding nitroanilines and the reduction of an aromatic nitro group in presence of an aliphatic nitro group. 2009 American Chemical Society.
- De Noronha, Rita G.,Romao, Carlos C.,Fernandes, Ana C.
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supporting information; experimental part
p. 6960 - 6964
(2010/03/03)
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- Amine derivatives and process for producing the same
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An amine derivative having a liquid crystal property over a wide temperature range and a process for production thereof are disclosed, the amine derivative being represented by formula (I) STR1 wherein A represents STR2 X1 and X2, which may be the same or different, each represents STR3 Y represents --O-- or STR4 R1 and R3, which may be the same or different, each represents a straight chain or branched chain alkyl group having 1 to 18 carbon atoms; R2 represents a hydrogen atom or a methyl group; m and n each represents 0 or 1; and p and q each represents 1 or 2, provided that p and q are 1 when n is 0, and p and q are not 2 at the same time when n is 1.
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