1,2-Diaryl-1-ethanone and pyrazolo [4,3-c] quinoline-4-one as novel selective cyclooxygenase-2 inhibitors

Baruah, Biswajita; Dasu, Kavitha; Vaitilingam, Balasubramanian; Vanguri, Akhila; Casturi, Seshagiri Rao; Yeleswarapu, Koteswar Rao

doi:10.1016/j.bmcl.2003.10.052

Cited by 34 publications

(4 citation statements)

References 12 publications

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“…Thus, we have identified a class of vicinal substituted diarylheterocycles with a tricyclic core that act as potent COX-2 inhibitors. This is much more surprising because, to the best of our knowledge, this type of compound has not been described yet as a COX inhibitor in prominent reports and reviews regarding COX. − ,− As far as we know, there exist a few reports for COX-2 inhibitors with a tricyclic core but only having none or one phenyl substituent; some of them were designed as conformationally restricted derivatives of monocyclic COXIBs. − Because the elegant scheme presented by Singh and Mittal to classify COX-2 inhibitors lacks this class of inhibitors, herewith we present an updated scheme (Figure ) with the aim to stimulate synthetic approaches for the synthesis of novel COX-2 inhibitors with a tricyclic core.…”

Section: Resultsmentioning

confidence: 99%

Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-hi]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure

et al. 2015

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A new compound class of diaryl-substituted heterocycles with tricyclic dihydropyrrolo[3,2,1-hi]indole and pyrrolo[3,2,1-hi]indole core structures has been designed and was synthesized by a modular sequence of Friedel-Crafts acylation, amide formation, and McMurry cyclization. This synthesis route represents a novel and versatile access toward dihydropyrrolo[3,2,1-hi]indoles and is characterized by good chemical yields and high modularity. From a set of 19 derivatives, 11 candidates were selected for determination of their COX inhibition potency and were found to be selective inhibitors with high affinity to COX-2 (IC50 ranging from 20-2500 nM and negligible inhibition of COX-1). The binding mode of the novel inhibitors in the active side of COX-2 was calculated in silico using the protein-ligand docking program GOLD by application of the molecular structures of two compounds derived from X-ray crystallography. Two novel compounds with high affinity to COX-2 (6k = 70 nM, 8e = 60 nM) have a fluoro substituent, making them promising candidates for the development of (18)F-radiolabeled COX-2 inhibitors for imaging purposes with positron emission tomography (PET).

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Section: Resultsmentioning

confidence: 99%

Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-hi]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure

et al. 2015

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“…Their activity can shift from agonist (anxiolytic, hypnotic, anticonvulsant), through antagonist (without pharmacological response) to inverse agonist (pro-convulsant and anxiogenic) 1–4 . The pyrazolo[4,3- c ]-quinolone have also been identified as cyclooxygenase-2 (COX-2) inhibitors which can reduce pain and inflammation 5 , as phosphodiesterase-4 inhibitors with antiasthmatic properties 6 , as well as Topoisomerase II inhibitors, which results in a high level of cytotoxicity and antitumour activity 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors

Malvacio

Cuzzolin

Sturlese

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e2 and 4h2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.

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“…A perusal of literature reveals that the synthesis of fused pyrazole derivatives containing the well-established pharmacophore, (4-aminosulfonyl)phenyl group, for evaluation as anti-inflammatory drug is still in its infancy. The limited studies performed indicate that fusion of pyrazole ring to other heterocycles such as in compounds 1 (Bertenshaw et al, 1996;Seibert et al, 1994) and 2 (Baruah et al, 2004) (Chart 1) is well tolerated in terms of both in vitro and in vivo activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4-b]pyridines

et al. 2010

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Novel series of pyrazolo [3,4-b]pyridines with basic skeleton different from the known COX inhibitors were synthesized from 5-amino-1-[4-(aminosulfonyl)phenyl]-3-phenyl-1H-pyrazole, which in turn was prepared by the condensation of (4-sulfamoylphenyl)hydrazine with a-cyanoacetophenone. All the newly synthesized compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema assay. Some of the most potent compounds were evaluated in different COX and LOX assays. Some of the new compounds were found to possess moderate anti-inflammatory activity.

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1,2-Diaryl-1-ethanone and pyrazolo [4,3-c] quinoline-4-one as novel selective cyclooxygenase-2 inhibitors

Cited by 34 publications

References 12 publications

Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-hi]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure

Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-hi]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure

Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors

Synthesis and anti-inflammatory evaluation of some pyrazolo[3,4-b]pyridines

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