Coumarin, chromone, and 4(3H)-pyrimidinone novel bicyclic and tricyclic derivatives as antiplatelet agents: synthesis, biological evaluation, and comparative molecular field analysis

Roma, G.; Braccio, Mario Di; Carrieri, Antonio; Grossi, Giancarlo; Leoncini, Giuliana; Signorello, Maria Grazia; Carotti, Angelo

doi:10.1016/s0968-0896(02)00307-3

Cited by 69 publications

(30 citation statements)

References 21 publications

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“…The anti-platelet activity study of coumarins identified the 4-piperazinyl-substituted coumarin 162 as a lead structure [177]. A recent in vitro study on the collagen and ADP-induced aggregation of human platelet has shown that the similar pyridyloxy coumarin 163 is among the most potent anti-platelet agents with IC 50 values in the range of 0.5-0.98 µM [178].…”

Section: Miscellaneousmentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

221

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Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also in depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models. Photobiological studies on pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.

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Section: Miscellaneousmentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

221

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“…С введением сложноэфирных или карбамидных группировок появляется спо-собность активно ингибировать рост вирусов им-мунодефицита человека [7], простого герпеса [8] и возбудителя лихорадки Западного Нила [9]. Пи-ридо[1,2-а]пиримидины перспективны также как противомикробные средства [10,11], кардиопро-текторы [12] и антикоагулянты [13]. Принимая во внимание эти факты, становится понятным стремление химиков не только предложить эф-фективные методы синтеза пиридо[1,2-а]пири-мидинов [10,14,15], но и в деталях изучить их строение [16][17][18][19][20][21][22].…”

Section: Issn 2308-8303unclassified

“…В частности, сиг-нал протона гидроксильной группы в протонном спектре сильно уширен, что препятствует про-ведению корреляционных экспериментов, а зна-чит и точному установлению его локализации. В спектре ЯМР 13 С уширены сигналы атомов С(2) и С(9), расположенных вблизи атома азота N(1), что очевидно связано с наличием быстрых об-менных процессов в данном фрагменте молеку-лы. На этом основании можно предположить, что атом водорода не фиксирован на 2-ОН-группе, а этиловый эфир 2-гидрокси-8-метил-4-оксо-4Н-пиридо[1,2-а]пиримидин-3-карбоновой кислоты и в растворе существует в виде равновесной сме-си двух таутомерных форм: 1 ↔ 1а.…”

Section: Issn 2308-8303unclassified

Improved synthesis, spectral characteristics and spatial structure of ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate

Украинец¹,

Bereznyakova²,

Taran³

et al. 2014

J. org. pharm. chem.

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by-product -2-hydroxy-8-methyl-N-(4-methypyridin-2-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide. It has been found by X-ray diffraction analysis that in the crystal the ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a] 2-амінопіридини; естери; 2-гідрокси-4-оксо-4Н-піридо[1,2-а]піримідин-3-карбонові кислоти Запропоновано покращений спосіб одержання етилового естеру 2-гідрокси-8-метил-4-оксо-4Н-піридо [1,2-а] побіч-ного 2-гідрокси-8-метил-4-оксо-N-(4-метилпіридин-2-іл)-4Н-піридо[1,2-а]піримідин-3-карбоксаміду. За до-помогою рентгеноструктурного аналізу встановлено, що в кристалі синтезований етиловий естер 2-гідрокси-8-метил-4-оксо-4Н-піридо[1,2-а]

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“…12–14 These tricyclic derivatives were also reported to exhibit anticancer activity. 15,16 In the last few years, we have developed synthetic methodologies to access a large library of novel diversified tricyclic derivatives.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach

Xiang

Zhang

et al. 2016

ACS Comb. Sci.

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An efficient discovery strategy by combining diversity-oriented synthesis and converging cellular screening is described. By a three-round screening process, we identified novel tricyclic pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR (EC50 < 1.0 µM), which exhibits much less toxicity toward normal cells (EC50 > 100 µM against normal human fibroblasts). The most active hits also exhibited drug-like properties suitable for further preclinical research. This redeployment of antidepressing compounds for anticancer applications provides promising future prospects for treating drug-resistant tumors with fewer side effects.

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Coumarin, chromone, and 4(3H)-pyrimidinone novel bicyclic and tricyclic derivatives as antiplatelet agents: synthesis, biological evaluation, and comparative molecular field analysis

Cited by 69 publications

References 21 publications

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Improved synthesis, spectral characteristics and spatial structure of ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate

Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach

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