1571-89-7Relevant academic research and scientific papers
Fragment-based lead discovery of a novel class of small molecule antagonists of neuropeptide B/W receptor subtype 1 (GPR7)
Moningka, Remond,Romero, F. Anthony,Hastings, Nicholas B.,Guo, Zhiqiang,Wang, Ming,Di Salvo, Jerry,Li, Ying,Trusca, Dorina,Deng, Qiaoling,Tong, Vincent,Terebetski, Jenna L.,Ball, Richard G.,Ujjainwalla, Feroze
, (2020/10/02)
Here, we report the discovery of a new class of NPBWR1 antagonists identified from a fragment-based screen. Compound 1 (cAMP IC50 = 250 μM; LE = 0.29) emerged as an initial hit. Further optimization of 1 by SAR-by-catalogue and chemical modification produced 21a (cAMP IC50 = 30 nM; LE = 0.39) with a 6700-fold increase in potency from fragment 1. Somewhat surprisingly, Schild analysis of compound 21a suggested that in vitro inhibition of NPW-mediated effects on upon cAMP accumulation were saturable, and that compound 21a dose-dependently increased [125I]-hNPW23 dissociation rate constants from NPBWR1 in kinetic binding studies. Collectively, these data are inconsistent with a classic surmountable, orthosteric mechanism of inhibition. The benzimidazole inhibitors reported herein may therefore represent a mechanistically differentiated class of compounds with which to form a better appreciation of the pharmacology and physiological roles of this central neuropeptide system.
Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as novel VEGFR-2 kinase inhibitors
Shi, Lei,Wu, Ting-Ting,Wang, Zhi,Xue, Jia-Yu,Xu, Yun-Gen
, p. 698 - 707 (2014/08/18)
Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. In this work, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives were designed and identified as potent inhibitors of VEGFR-2 (
Discovery of quinazolin-4-amines bearing benzimidazole fragments as dual inhibitors of c-Met and VEGFR-2
Shi, Lei,Wu, Ting-Ting,Wang, Zhi,Xue, Jia-Yu,Xu, Yun-Gen
, p. 4735 - 4744 (2014/10/15)
Both c-Met and VEGFR-2 are important targets for the treatment of cancers. In this study, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinazolin-4- amine derivatives were designed and identified as dual c-Met and VEGFR-2 inhibitors. Among these compounds bearing quinazoline and benzimidazole fragments, compound 7j exhibited the most potent inhibitory activity against c-Met and VEGFR-2 with IC50 of 0.05 μM and 0.02 μM, respectively. It also showed the highest anticancer activity against the tested cancer cell lines with IC50 of 1.5 μM against MCF-7 and 8.7 μM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, which demonstrates that compound 7j is a potential agent for cancer therapy deserving further researching.
6-Nitrobenzimidazole derivatives: Potential phosphodiesterase inhibitors: Synthesis and structure-activity relationship
Khan,Shah, Zarbad,Ahmad,Ambreen,Khan,Taha,Rahim,Noreen,Perveen,Choudhary,Voelter
experimental part, p. 1521 - 1526 (2012/04/23)
6-Nitrobenzimidazole derivatives (1-30) synthesized and their phosphodiesterase inhibitory activities determined. Out of thirty tested compounds, ten showed a varying degrees of phosphodiesterase inhibition with IC50 values between 1.5 ± 0.043 and 294.0 ± 16.7 μM. Compounds 30 (IC50 = 1.5 ± 0.043 μM), 1 (IC50 = 2.4 ± 0.049 μM), 11 (IC50 = 5.7 ± 0.113 μM), 13 (IC50 = 6.4 ± 0.148 μM), 14 (IC50 = 10.5 ± 0.51 μM), 9 (IC50 = 11.49 ± 0.08 μM), 3 (IC50 = 63.1 ± 1.48 μM), 10 (IC50 = 120.0 ± 4.47 μM), and 6 (IC50 = 153.2 ± 5.6 μM) showed excellent phosphodiesterase inhibitory activity, much superior to the standard EDTA (IC50 = 274 ± 0.007 μM), and thus are potential molecules for the development of a new class of phosphodiesterase inhibitors. A structure-activity relationship is evaluated. All compounds are characterized by spectroscopic parameters.
