613656-89-6Relevant academic research and scientific papers
Rhodium-Catalyzed Synthesis of Amides from Functionalized Blocked Isocyanates
Beauchemin, André M.,Derasp, Joshua S.
, p. 8104 - 8109 (2019/08/26)
Isocyanates are useful building blocks for the synthesis of amides, although their widespread use has been limited by their high reactivity, which often results in poor functional group tolerance and a propensity to oligomerize. Herein, a rhodium-catalyzed synthesis of amides is described coupling boroxines with blocked (masked) isocyanates. The success of the reaction hinges on the ability to form both the isocyanate and the organorhodium intermediates in situ. Relying on masked isocyanate precursors and on the high reactivity of the organorhodium intermediate results in broad functional group tolerance, including protic nucleophilic groups such as amines, anilines, and alcohols.
Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking
Zhao, Yongqiang,Liu, Feifei,He, Guojing,Li, Ke,Zhu, Changcheng,Yu, Wei,Zhang, Conghai,Xie, Mingjin,Lin, Jun,Zhang, Jihong,Jin, Yi
supporting information, (2019/11/11)
Herein, we embarked on a structural optimization campaign aiming at the discovery of novel anticancer agents with our previously reported XL-6f as a lead compound. A library of 23 compounds has been synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2, which also displayed selective anti-proliferation potency against HepG2 cell. All synthesized compounds were evaluated for anti-angiogenesis capability. Compound 7o showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC and HepG2 cell lines with IC50 values of 0.58 and 0.23 μM, respectively). The molecular docking analysis revealed 7o is a Type-II inhibitor of VEGFR-2 kinase. In general, these results indicated these arylamide-5-anilinoquinazoline-8-nitro derivatives are promising inhibitors of VEGFR-2 for the potential treatment of anti-angiogenesis.
Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold
Flaherty, Daniel P.,Simpson, Denise S.,Miller, Melissa,Maki, Brooks E.,Zou, Beiyan,Shi, Jie,Wu, Meng,McManus, Owen B.,Aubé, Jeffrey,Li, Min,Golden, Jennifer E.
, p. 3968 - 3973 (2014/09/03)
TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC 50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay.
Elaborate ligand-based pharmacophore exploration and QSAR analysis guide the synthesis of novel pyridinium-based potent β-secretase inhibitory leads
Al-Nadaf, Afaf,Sheikha, Ghassan Abu,Taha, Mutasem O.
experimental part, p. 3088 - 3115 (2010/07/08)
β-Secretase (BACE) inhibitors have potential as anti-Alzheimer's disease treatments prompting us to explore the pharmacophoric space of 129 known BACE inhibitors. QSAR analysis was employed to select optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of explaining bioactivity variation (r2 = 0.88, F = 60.48, rLOO2 = 0.85, rPRESS2 against 25 external test inhibitors = 0.71). We were obliged to use ligand efficiency as the response variable because the logarithmic transformation of bioactivities failed to access self-consistent QSAR models. Three pharmacophoric models emerged in the successful QSAR equation suggesting at least three binding modes accessible to ligands within BACE binding pocket. QSAR equation and pharmacophoric models were validated through ROC curves and were employed to guide synthesis of novel pyridinium-based BACE inhibitors. The best inhibitor illustrated an IC50 value of 1.0 μM against BACE.
