- Phenothiazine and amide-ornamented novel nitrogen heterocyclic hybrids: synthesis, biological and molecular docking studies
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The synthesis of novel hybrids, namely, phenothiazine and amide-ornamented nitrogen heterocycles (25-34) has been accomplished utilizing a multi-step synthetic protocol and the structures have been established based on physical and spectral techniques. Of these, the hybrids possessing meta-nitro (26), para-fluoro (28), meta- and para-methyl (31), ortho-bromo (33) and ortho- and para-dimethyl (34) phenyl carboxamide scaffolds exhibited superior anti-inflammatory profiles over the standard diclofenac sodium. A hybrid integrated with a para-fluorophenyl carboxamide moiety (28) showed the highest DPPH radical scavenging activity among the chemical entities synthesized. Furthermore, the results of anticancer evaluations implied that the hybrid tethered with a phenyl carboxamide structural unit (29) exerted superior activity when compared with other hybrids against the pancreatic cancer cells SW1990 and AsPC1. Molecular docking between the hybrid 29 and B-cell lymphoma 2 reflects its appreciable binding affinity (-8.84 kcal mol-1). The results revealed that these chemical entities can serve as potent biological agents and/or efficient intermediates for the construction of potent biological agents.
- Iniyaval, Shunmugam,Karuppasamy, Ayyanar,Lim, Wei-Meng,Mai, Chun-Wai,Padmavathy, Krishnaraj,Ramalingan, Chennan,Sivaramakarthikeyan, Ramar
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p. 4049 - 4060
(2020/03/19)
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- Phenothiazine and amide-ornamented dihydropyridines: Via a molecular hybridization approach: Design, synthesis, biological evaluation and molecular docking studies
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A series of novel phenothiazinyldihydropyridine dicarboxamides 7a-7j was synthesized by adopting a multi-step synthetic strategy and characterized through physical and spectral techniques. Among them, the chemical entities with para-fluoro (7d), ortho-bromo and-fluoro (7f and 7i), ortho- A nd para-methyl (7e) and meta- A nd para-methoxy (7h) substituents exhibited either similar or superior anti-inflammatory activities with respect to the standard drug diclofenac sodium. Besides, the chemical entities with ortho-bromo and-fluoro substituents as well as meta-nitro substituents (7f, 7g and 7i) showed enhanced radical scavenging activities when compared to standard ascorbic acid. Furthermore, anticancer studies revealed that the meta- A nd para-chloro-substituted molecule 7a exerted the best activity against all the pancreatic cancer cells tested. Also, appreciable binding affinity (-8.10 kcal mol-1) was observed during molecular docking between B-cell lymphoma 2 and 7a. The structural diversifications of the potent chemical entities besides further exploration in connection with the biological profiles of the same are underway.
- Sivaramakarthikeyan, Ramar,Iniyaval, Shunmugam,Padmavathy, Krishnaraj,Liew, Hui-Shan,Looi, Chin-King,Mai, Chun-Wai,Ramalingan, Chennan
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p. 17046 - 17057
(2019/11/14)
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- On the Knorr synthesis of 6-bromo-4-methylquinolin-2(1H)-one
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In the course of our work on infectious diseases, we were led to prepare 6-bromo-2-chloro-4-methylquinoline as a starting material. Since surprisingly little has been reported in the literature, the two synthetic steps to this compound were investigated. The synthesis involves a condensation between -keto esters and 4-bromoaniline and the cyclization of the resulting anilides into 6-bromoquinolin-2(1H)-one, otherwise known as the Knorr reaction. The 1H NMR monitoring of the first step allowed us to optimize the conditions leading specifically to the anilide without the occurrence of the alternative crotonate. To illustrate the scope of our finding, few additional anilides featuring electron-attracting groups were prepared. The study of their cyclization revealed some unsuspected steric effect governing this second step. Aside from rectifying a few claims in this chemistry, this study led to a three-step preparation of 6-bromo-2-chloro-4-methylquinoline in 48% overall yield from 4-bromoaniline. Georg Thieme Verlag Stuttgart - New York.
- Wlodarczyk, Nicolas,Simenel, Catherine,Delepierre, Muriel,Barale, Jean-Christophe,Janin, Yves L.
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experimental part
p. 934 - 942
(2011/05/05)
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- IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS
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Compounds of Formula (I) in which A, B, R1, R1a, R2, R3, R4, R5, R6, R7 and R8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1
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Page/Page column 46
(2008/12/04)
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