91646-69-4Relevant academic research and scientific papers
Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists
Sasmal, Pradip K.,Krishna, C. Vamsee,Adabala, S. Sudheerkumar,Roshaiah,Rawoof, Khaji Abdul,Thadi, Emima,Sukumar, K. Pavan,Cheera, Srisailam,Abbineni, Chandrasekhar,Rao, K.V.L. Narasimha,Prasanthi,Nijhawan, Kamal,Jaleel, Mahaboobi,Iyer, Lakshmi Ramachandran,Chaitanya, T. Krishna,Tiwari, Nirbhay Kumar,Krishna, N. Lavanya,Potluri, Vijay,Khanna, Ish,Frimurer, Thomas M.,Lückmann, Michael,Rist, ystein,Elster, Lisbeth,H?gberg, Thomas
, p. 887 - 892 (2015)
Kappa opioid receptor (KOR) is an important mediator of pain signaling and it is targeted for the treatment of various pains. Pharmacophore based mining of databases led to the identification of 2-aminobenzimidazole derivative as KOR agonists with selectivity over the other opioid receptors DOR and MOR. A short SAR exploration with the objective of identifying more polar and hence less brain penetrant agonists is described herewith. Modeling studies of the recently published structures of KOR, DOR and MOR are used to explain the receptor selectivity. The synthesis, biological evaluation and SAR of novel benzimidazole derivatives as KOR agonists are described. The in vivo proof of principle for anti-nociceptive effect with a lead compound from this series is exemplified.
Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity
Bressi, Jerome C.,Jong, Ron de,Wu, Yiqin,Jennings, Andy J.,Brown, Jason W.,O'Connell, Shawn,Tari, Leslie W.,Skene, Robert J.,Vu, Phong,Navre, Marc,Cao, Xiaodong,Gangloff, Anthony R.
scheme or table, p. 3138 - 3141 (2010/09/03)
A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[3-(1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC50s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21waf. Compound 5x displays efficacy in human tumor xenograft models.
