271597-75-2Relevant articles and documents
Consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz syntheses of tri- and tetrasubstituted pyridines
Dohe, Janis,Müller, Thomas J. J.
, p. 705 - 718 (2016/07/06)
The concatenation of the modified Sonogashira alkynone synthesis and the Bagley-Bohlmann-Rahtz pyridine synthesis gives novel consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz (cBBR) syntheses of tri- and tetrasubstituted pyridines in a one-pot fashion. With these processes 15 differently substituted 3-ethoxycarbonyl 2-methylpyridines can be readily obtained in modest to moderate yields.
Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
Deng, Chang-Bo,Li, Juan,Li, Lu-Yi,Sun, Feng-Jie
supporting information, p. 3195 - 3201 (2016/06/13)
In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 ± 2.5 μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.
Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides
Eldehna, Wagdy M.,Fares, Mohamed,Abdel-Aziz, Marwa M,Abdel-Aziz, Hatem A
, p. 8800 - 8815 (2016/09/04)
Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents
Eldehna, Wagdy M.,Altoukhy, Ayman,Mahrous, Hoda,Abdel-Aziz, Hatem A.
, p. 684 - 694 (2015/02/02)
A hybrid pharmacophore approach was adopted to design and synthesize new series of isatin-pyridine hybrids. All the newly prepared hybrids (5a-o, 8 and 11a-d) were in vitro evaluated for their anti-proliferative activity against three human cancer cell lines, namely HepG2 hepatocellular carcinoma, A549 lung cancer and MCF-7 breast cancer. Compound 8 emerged as the most active member against HepG2 cell line (ICinf50/inf = 2.5 ± 0.39 μM), with 2.7-fold increased activity than the reference drug, doxorubicin (ICinf50/inf = 6.9 ± 2.05 μM). Whilst, compound 11c was found to be the most potent counterpart against A549 and MCF-7 cell lines with ICinf50/inf values of 10.8 ± 1.15 and 6.3 ± 0.79, respectively. The weightiness of the utilization of non-cleavable linker, as the chalcone linker, and simplification of the first group, was explored via the SAR study. Furthermore, a QSAR model was built to explore the structural requirements controlling the cytotoxic activities. Notably, the predicted activities by the QSAR model were very close to those experimentally observed, hinting that this model could be safely applied for prediction of more efficacious hits comprising the same skeletal framework. Finally, a theoretical kinetic study was established to predict the ADME of the active hybrids.
Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity
Abdel-Aziz, Hatem A.,Aboul-Fadl, Tarek,Al-Obaid, Abdul-Rahman M.,Ghazzali, Mohamed,Al-Dhfyan, Abdullah,Contini, Alessandro
, p. 1543 - 1552 (2013/03/13)
Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC 50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F3 and F4) and two Aromatic annotations (F1 and F2).
A highly efficient regioselective one-pot synthesis of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones using K5CoW12O40·3H2O as a heterogeneous recyclable catalyst
Kantevari, Srinivas,Chary, Mahankhali Venu,Vuppalapati, Srinivasu V.N.
, p. 13024 - 13031 (2008/03/14)
A systematic investigation into the regioselective one-pot, three-component condensation of enaminones 1a-g, β-dicarbonyl compounds 2a-c, and ammonium acetate in the presence of a catalytic amount of K5CoW12O40·3H2O (0.01 equiv or 1.0 mol %) under solvent free conditions, as well as in refluxing isopropanol, has been reported. The reaction was highly efficient to produce 2,3,6-trisubstituted pyridines 3a-g, 4a-g, and novel 2,7,7-trisubstituted-5,6,7,8-tetrahydroquinoline-5-ones 5a-g in excellent yields. The present procedure offers advantages of short reaction time, simple work-up, and the catalyst exhibited remarkable reusable activity.
A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support
Jagath Reddy,Latha,Thirupathaiah,Srinivasa Rao
, p. 301 - 302 (2007/10/03)
A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support is described. A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support is reported herein.
Enaminones in heterocyclic synthesis: A new regioselective synthesis of 2,3,6-trisubstituted pyridines, 6-substituted-3-aroylpyridines and 1,3,5-triaroylbenzenes
Al-Saleh, Balkis,Abdelkhalik, Mervat Mohammed,Eltoukhy, Afaf Mohammed,Elnagdi, Mohammed Hilmy
, p. 1035 - 1038 (2007/10/03)
1-Substituted-3-dimethylaminopropenones 1a-d reacted with acetylacetone and with ethyl acetoacetate to yield regioselectively 2,3,6-trisubstituted pyridines. Refluxing 1a-d in acetic acid/ammonium acetate resulted in the formation of 6-substituted-3-aroylpyridines, whereas refluxing in acetic acid alone afforded 1,3,5-triaroylbenzene.
Total synthesis of the thiopeptide promothiocin A
Bagley, Mark C.,Bashford, Katherine E.,Hesketh, Claire L.,Moody, Christopher J.
, p. 3301 - 3313 (2007/10/03)
The thiopeptide (or thiostrepton) antibiotics are a class of sulfur-containing highly modified cyclic peptides with interesting biological activity. Described herein is the total synthesis of the thiopeptide antibiotic promothiocin A, which utilizes a mod
