- Synthesis and evaluation of selected benzimidazole derivatives as potential antimicrobial agents
-
A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1Hbenzo[ d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.
- Alasmary, Fatmah A.S.,Snelling, Anna M.,Zain, Mohammed E.,Alafeefy, Ahmed M.,Awaad, Amani S.,Karodia, Nazira
-
p. 15206 - 15223
(2015/09/21)
-
- Molecular properties prediction and synthesis of new benzimidazole H4-receptor antagonists as anti-inflammatory agents
-
This investigation deals with the design and calculation of molecular properties, drug likeness, lipophilicity and solubility parameters of substituted benzimidazolyl carbonyl piperazines/piperidines using Mol inspiration, Mol soft, Software's and ALOPGPS 2.1 program. Toxicity parameters were calculated using Osiris Software. All compounds are non toxic; fulfill the solubility requirements and passing oral bioavailability criteria. The compounds were synthesized and characterized by IR, 1H NMR and Mass spectral analysis. Most of the compounds exhibited significant antiinflammatory activity.
- Anuradha Bai,Tangeda, Sarita Jyostna,Madhavi,Garlapati, Achaiah
-
-
- Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase
-
Dual-target-directed agents simultaneously inhibiting glycogen phosphorylase (GP) and activating glucokinase (GK) could decelerate the inflow of glucose from glycogenolysis and accelerate the outflow of glucose in the liver, therefore allow for a better control over hyperglycaemia in a synergetic manner. A series of hybrid compounds were designed by structure-assisted and ligand-based strategies. In vitro bioassays found two novel compounds (1j, 6g) worthy of further optimization on balance of dual action to GP and GK. In addition, for single-target activity, two compounds exhibited more potent GP inhibitory activity and four compounds showed better GK activation than their corresponding references.
- Zhang, Lei,Chen, Xiaojie,Liu, Jun,Zhu, Qingzhang,Leng, Ying,Luo, Xiaomin,Jiang, Hualiang,Liu, Hong
-
p. 624 - 639
(2013/02/21)
-
- NITROGEN HETEROCYCLIC COMPOUNDS USEFUL AS PDE10 INHIBITORS
-
Unsaturated nitrogen heterocyclic compounds of formula (I): (I), as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.
- -
-
Page/Page column 138
(2011/12/02)
-
- BENZIMIDAZOLE CARBOXAMIDES AS RAF KINASE INHIBITORS
-
The present invention relates to benzimidazole carboxamides of formula (I), the use of the compounds of formula (I) as inhibitors of as inhibitors of one or more kinases, the use of the compounds of formula (I) for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient. Accordingly, the compound of Formula (I) or a pharmaceutically acceptable salt thereof is administered for the treatment of diseases mediated by one or more kinase phathways, preferably by the raf kinase pathway, especially cancers.
- -
-
Page/Page column 135
(2008/06/13)
-
- Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H4 receptor antagonists
-
We describe the structure-activity relationships for a series of ligands structurally related to the recently identified (5-chloro-1H-indol-2-yl)-(4- methyl-piperazin-1-yl)-methanone (1) as histamine H4 receptor (H 4R) antagonists. Furthermore, we identified related benzimidazoles as novel lead compounds for the H4R. The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H3 and H4 receptors and exhibit pKi values up to 7.5 at the human H4R.
- Terzioglu, Nalan,Van Rijn, Richard M.,Bakker, Remko A.,De Esch, Iwan J.P.,Leurs, Rob
-
p. 5251 - 5256
(2007/10/03)
-
- HETEROCYCLIC COMPOUNDS
-
Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H4 receptor, including allergic rhinitis.
- -
-
Page/Page column 24
(2008/06/13)
-
- Benzimidazoles as NMDA glycine-site antagonists: Study on the structural requirements in 2-position of the ligand
-
A series of different substituted benzimidazole derivatives has been synthesized and evaluated for the ability to displace [3H]MDL-105,519 to rat cortical membranes. Two benzimidazole-2-carboxylic acids 9 b and 9 c, in this substitution pattern not yet described as glycine antagonists, showed IC50 values of 0.89 μM (9 b) and 38.0 μM (9 c). Replacement of the carboxylate function in 2-position by a sulfonic acid moiety appreciably increased solubility, but decreased the affinity giving evidence for the strong need of the carboxylate group within the ligand. Further structure-activity studies using benzimidazol-2-one derivatives with an acetic acid moiety adjacent to a ring nitrogen revealed new insights into the importance of amide functionalities within the heterocycle for the affinity of antagonist glycine-site ligands.
- Dannhardt, Gerd,Kohl, Beate K.
-
p. 123 - 129
(2007/10/03)
-
