92126-72-2Relevant academic research and scientific papers
Synthesis, in-vitro antibacterial and anticancer screening of novel nicotinonitrile-coumarin hybrids utilizing piperazine citrate
Mekky, Ahmed E. M.,Sanad, Sherif M. H.
, (2020/04/01)
An efficient, low-cost, high yield% and eco-friendly synthetic procedure is designed for the synthesis of novel series of nicotinonitrile-coumarin hybrid molecules bearing several aryl and/or heteroaryl moieties. Our strategy includes the synthesis of a novel series of 2-hydroxybenzaldehydes, bearing nicotinonitrile moiety, followed by its Knoevenagel reaction with ethyl acetoacetate in the presence of an organo-base. The above reaction is studied in different reaction conditions. The optimized conditions are performing the reaction in ethanol at 80 °C in the presence of 10 mol% of piperazine citrate (1:1). The in-vitro antibacterial activities of the nicotinonitrile-coumarins were evaluated against different Gram-positive and negative bacterial strains. Moreover, the in-vitro cytotoxicity of nicotinonitrile-coumarins were estimated against different eukaryotic cell lines. Compounds 5a and 5b exhibited the most promising antibacterial agents among the novel series. The structures of novel series of the target nicotinonitrile-coumarin hybrid molecules were confirmed by considering their elemental analyses and spectral data.
Study the solvation effect on 6-phenyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile derivatives by TD- DFT calculations and molecular dynamics simulations
Abdel-Latif, Mahmoud K.,Abd El-Mageed,Mohamed, Hussein S.,Mustafa
, (2019/09/30)
The electronic structure of 6-phenyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile (2-mercapto-6-phenylpyridine-3-carbonitrile) and its some derivatives have been studied both theoretically and experimentally. The choice of these compounds was motivated by their biological importance and relevance. The corresponding proposed structures of all studied derivatives in this work were confirmed by FT-IR spectrophotometer, 1HNMR spectra and XRD patterns. The Density Functional Theory (DFT) has been used to investigate the effect of substituents with different strengths of all studied compounds on the geometry structures, natural bond orbital (NBO) properties, electrostatic potential (ESP) and the global properties such as (the chemical hardness (η), global softness (S), and electronegativity (χ) by analysis of the charge distribution and extent of charge transfer in the molecule in the gas phase. Non-linear optical properties (NLO) such as (static dipole moment (μ), polarizability (α), anisotropy polarizability (Δα), first order hyperpolarizability (β) and mean second order hyperpolarizability (γ)) also, were computed by DFT in the gas and solvent (benzene and ethanol) phases. The effect of the different substitutions and solvent polarity on the NLO properties were also investigated to show their ability to be used as NLO compounds. We find that all studied compounds exhibited higher NLO properties compared to urea (reference materials) in the gas phase and showed higher NLO properties in ethanol than in the benzene phase. The effect of solvent polarity on the electronic absorption spectra of the studied molecules was measured experimentally and calculated theoretically at the Time-Dependent Density Functional Theory (TD-DFT) level of theory. The interactions of different solvents (ethanol and benzene) with studied compounds were also studied by molecular dynamics (MD) simulations. The radial distribution functions (RDFs) and coordination numbers (CNs) of all studied compounds in the different solvent are computed. The diffusion coefficient (D) also was calculated to investigate the influence of substitutions on the mobility of the studied compounds in the surrounding solvent.
Discovery and structure-activity relationships study of thieno[2,3-b]pyridine analogues as hepatic gluconeogenesis inhibitors
Ma, Fei,Liu, Jian,Zhou, Tingting,Lei, Min,Chen, Jing,Wang, Xiachang,Zhang, Yinan,Shen, Xu,Hu, Lihong
, p. 307 - 317 (2018/05/22)
Type 2 diabetes mellitus (T2DM) is a chronic, complex and multifactorial metabolic disorder, and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. This study discovered a new class of thieno[2,3-b]pyridine derivatives as hepatic gluconeogenesis inhibitors. First, a hit compound (DMT: IC50 = 33.8 μM) characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. Structure activity relationships (SARs) study showed that replaced the CF3 in the thienopyridine core could improve the potency and led to the discovery of 8e (IC50 = 16.8 μM) and 9d (IC50 = 12.3 μM) with potent inhibition of hepatic glucose production and good drug-like properties. Furthermore, the mechanism of 8e for the inhibition of hepatic glucose production was also identified, which could be effective through the reductive expression of the mRNA transcription level of gluconeogenic genes, including glucose-6-phosphatase (G6Pase) and hepatic phosphoenolpyruvate carboxykinase (PEPCK). Additionally, 8e could also reduce the fasting blood glucose and improve the oral glucose tolerance and pyruvate tolerance in db/db mice. The optimization of this class of derivatives had provided us a start point to develop new anti-hepatic gluconeogenesis agents.
Discovery and structure-activity relationships study of novel thieno[2,3-b]pyridine analogues as hepatitis C virus inhibitors
Wang, Ning-Yu,Zuo, Wei-Qiong,Xu, Ying,Gao, Chao,Zeng, Xiu-Xiu,Zhang, Li-Dan,You, Xin-Yu,Peng, Cui-Ting,Shen, Yang,Yang, Sheng-Yong,Wei, Yu-Quan,Yu, Luo-Ting
, p. 1581 - 1588 (2014/03/21)
Current treatment for hepatitis C is barely satisfactory, there is an urgent need to develop novel agents for combating hepatitis C virus infection. This study discovered a new class of thieno[2,3-b]pyridine derivatives as HCV inhibitors. First, a hit compound characterized by a thienopyridine core was identified in a cell-based screening of our privileged small molecule library. And then, structure activity relationship study of the hit compound led to the discovery of several potent compounds without obvious cytotoxicity in vitro (12c, EC50 = 3.3 μM, SI >30.3, 12b, EC50 = 3.5 μM, SI >28.6, 10l, EC50 = 3.9 μM, SI >25.6, 12o, EC 50 = 4.5 μM, SI >22.2, respectively). Although the mechanism of them had not been clearly elucidated, our preliminary optimization of this class of compounds had provided us a start point to develop new anti-HCV agents.
PYRIDO [3',2' :4,5] THIENO [3, 2-D] PYRIMIDIN- 4 - YLAMINE DERIVATIVES AND THEIR THERAPEUTICAL USE
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, (2012/10/18)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain fused triaryl amine compounds of the following formula (for convenience, collectively referred to herein as "FTA compounds"), which, inter alia, inhibit LIM kinase (LIMK) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit LIMK activity, and in the treatment of diseases and conditions that are mediated by LIMK, that are ameliorated by the inhibition of LIMK activity, etc., including proliferative conditions such as cancer (e.g., breast cancer, prostate cancer, melanoma, glioma, etc.), as well as vasodilation (including, e.g., hypertension, angina, cerebral vasospasm, and ischemia following subarachnoid hemorrhage), neurodegenerative disorders, atherosclerosis, fibrosis, and inflammatory diseases (including, e.g., Crohn's disease and chronic obstructive pulmonary disease (COPD)), and glaucoma (also known as ocular hypertension).
Facile synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones from aryl ketones
Zheng, Ren-Lin,Zeng, Xiu-Xiu,He, Hai-Yun,He, Jun,Yang, Sheng-Yong,Yu, Luo-Ting,Yang, Li
, p. 1521 - 1531 (2012/04/17)
An improved synthesis of 6-aryl-3-cyanopyridine-2-(1H)-thiones utilizing enaminones as starting materials catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) was described. Moreover, a convenient one-pot conversion of aryl ketones to 6-aryl-3-cyanopyridine-2-(1H)-thiones was also developed in moderate to good yields (up to 80%). Copyright Taylor & Francis Group, LLC.
Enaminones in heterocyclic synthesis: Synthesis and chemical reactivity of 3-anilino-1-substituted-2-propene-1- one
Al-Saleh, Balkis,El-Apasery, Morsy Ahmed,Abdel-Aziz, Rasha Safwat,Elnagdi, Mohamed Hilmy
, p. 563 - 566 (2007/10/03)
The 3-anilinoenones 3a,b were prepared from the corresponding 3-dimethyl-aminopropenones. The reactivity of 3a,b towards a variety of carbon and nitrogen nucleophiles as well as naphthoquinones is reported.
Synthesis of N-glycosylated pyridines as new antimetabolite agents
Hussain, Badria A.,Attia, Adel M.,Elgemeie, Galal E. H.
, p. 2335 - 2343 (2007/10/03)
Condensation of cyanoacetamide and cyanothioacetamide with the sodium salts of α-(hydroxymethylene)alkanones afforded the pyridine-2(1H)-ones and their corresponding thiones 3. Compounds 3 served as a key intermediates for the synthesis of N-glycosylated pyridines.
