Amnesia-reversal activity of a series of cyclic imides

Butler, Donald E.; Leonard, Jim; Caprathe, Bradley W.; L'Italien, Yvon J.; Pavia, Michael R.; Hershenson, Fred M.; Poschel, Paul H.; Marriott, John G.

doi:10.1021/jm00386a010

Cited by 62 publications

(15 citation statements)

References 3 publications

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“…This has been exploited in the pharmaceutical industry in search of biphasic dose responses that may lead to new drugs to reduce anxiety [50–52]. Many examples exist of agents that will differentially induce a U‐shaped dose response to optimize a memory response using structure‐activity relationship methods [53,54]. It therefore is necessary to place the above statement of Stebbing–namely, that all chemicals can induce hormesis–within a broader context.…”

Section: Are There Chemical Structural Determinants Of Hormesis?mentioning

confidence: 99%

Hormesis: Why it is important to toxicology and toxicologists

Calabrese

2008

Enviro Toxic and Chemistry

619

233

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Abstract-This article provides a comprehensive review of hormesis, a dose-response concept that is characterized by a low-dose stimulation and a high-dose inhibition. The article traces the historical foundations of hormesis, its quantitative features and mechanistic foundations, and its risk assessment implications. The article indicates that the hormetic dose response is the most fundamental dose response, significantly outcompeting other leading dose-response models in large-scale, head-to-head evaluations. The hormetic dose response is highly generalizable, being independent of biological model, endpoint measured, chemical class, and interindividual variability. Hormesis also provides a framework for the study and assessment of chemical mixtures, incorporating the concept of additivity and synergism. Because the hormetic biphasic dose response represents a general pattern of biological responsiveness, it is expected that it will become progressively more significant within toxicological evaluation and risk assessment practices as well as have numerous biomedical applications.

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Section: Are There Chemical Structural Determinants Of Hormesis?mentioning

confidence: 99%

Hormesis: Why it is important to toxicology and toxicologists

Calabrese

2008

Enviro Toxic and Chemistry

619

233

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“…39,40) But it failed in our case largely due to the poor solubility of both substrates and products in refluxing acetic anhydride. Fortunately, the intramolecular N-acylation of 8a was achieved successfully in almost quantitative yield by refluxing it in xylene for 8 h with a Dean-Stark trap.…”

mentioning

confidence: 75%

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Wang

Cao

Shi

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Recently, A-ring alkoxyl subsitituted b-carbolin-1-ones (1, Chart 1) were reported to inhibit colon and lung tumors in a patent literature.1) Subsequently, we found that 3-aryl b-carbolin-1-ones (2) inhibit the proliferation of HeLa cells with IC 50 values in the low micromolar range and that the aromatic substitution on C3 in 2 proved to be essential for their biological activity.2,3) To broaden the scope of previous studies, aryl-substituted 2-pyridone-containing derivatives, such as pyrido[2,1-a]isoindole-4-one (3) and 1H-indeno[1,2-b]pyridine-2-one (4), were designed as our synthetic targets to make it possible to probe their structure-activity relationships.Some alkaloids having frameworks of 3 and 4 occur in nature, 4-7) whose analogues were synthesized more often in laboratories for their potent bioactivities as receptor ligands, [8][9][10] enzyme inhibitors 11) or anti-tumor agents.12,13)Since 3 and 4 are a pair of structural isomers, it is reasonable to expect that they could be prepared from a common precursor, which should have a structure of 6-substituted 2-pyridone allowing a disconnection between methylene and Cring in 3 and 4 (Chart 1). However, neither such precursor nor procedure has been employed for this purpose so far. [14][15][16][17][18][19][20][21][22][23][24][25][26] Since the methods for preparation of 3-unsubstituted 2-pyridone have been well established in recent years, 27-37) herein we report a novel synthetic route to 3 and 4 as shown in Chart 2. The route starts from an aldol condensation between 2-acetylbenzoic acid (5) and aryl aldehyde (6) to yield chalcone (7), which subsequently undergoes a [3ϩ3] annulation to give 2-(2-pyridon-6-yl)benzoic acid (8). Serving as a common precursor, 8 goes through an intramolecular N-acylation to produce 2-aryl pyrido[2,1-a]isoindole-4,6-diones (9), or carries out an intramolecular C-acylation to yield 4-aryl 1-methyl-1H-indeno[1,2-b]pyridine-2,5-diones (11) regioselectively. Results and DiscussionPreparation of 2-Aryl Pyrido[2,1-a]isoindole-4,6-diones (9a-j) Following the known procedure, 38) the mixtures of 2-acetylbenzoic acid (5) and aryl aldehydes 6a-j were treated respectively with NaOH in aqueous EtOH at room temperature for 20 h. As shown in Table 1, the corresponding products 2-(3-aryl acryloyl)benzoic acids (7a-j) were yielded conveniently in high yields. However, the aryl aldehydes bearing an electron-withdrawing group, such as o-, m-, A novel and practical preparation of 2-pyridone-containing tricyclic alkaloid derivatives was developed. By regioselective intramolecular N-and C-acylation of 2-(4-aryl-2-pyridon-6-yl)benzoic acid, a pair of structural isomers 2-aryl pyrido[2,1-a]isoindole-4,6-diones and 4-aryl 1-methyl-1H-indeno[1,2-b]-pyridine-2,5-diones, as potential inhibitors of tumor cell proliferation, were prepared respectively.

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“…Серед них, зок-рема, доцільно відзначити 2-піролідиніл-5-тіооц-тові [1] та ізоіндоліл-3-тіооцтові [2][3][4] кислоти, які знайшли використання в ролі ключових бло-ків для конструювання конденсованих тіоазоци-нових структур -аналогів ізоіндолобензазоцино-вих алкалоїдів. У ряду похідних дигідробензо [f] ізохінолілтіооцтових кислот виявлені фунгіци-ди [5], 2,3-дигідроізоіндоліл-3-тіопропанових кис-лот -бактерицидні [6] та противірусні [7] аген-ти, а піролідиніл-2-тіокарбонових кислот -ам-незієвідновлюючі сполуки [8]. В контексті зазна-ченого вище не втрачає своєї актуальності про-блема спрямованої модифікації інших гетероци-клічних систем тіоалканкарбоксильними заміс-никами.…”

Section: Issn 2308-8303unclassified

Synthesis of 7-carboxyalkylthio-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-e]diazepin-4-ones

Kemskiy

Bol’but

Вовк

2014

J. org. pharm. chem.

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which is based on the intramolecular cyclization of 5-amino-N-(2,2-dialkyloxyethyl)pyrazole-4-carboxamides in the solution of formic acid with thioalkan carboxylic acids. The synthesis of the starting 5-aminopyrazolo-4-carboxamides has been performed by condensation of 2-cyano-N-(2,2-dimethoxy)-3-dimetylaminoacryl(croton) amides with alkyl hydrazines or hydrolytic cleavage of 5-(2,2-dietoxyethyl)-1,5-dihydropyrazolo-4Н-[3,4-d]pirimidin-4-ones. The scheme of this reaction proposed involves the intramolecular cyclocondensation with the initial formation of the corresponding 7-hydroxy-5,6,7,8-tetrahydropyrazolo[3,4-e] -гидрокси-5,6,7,8-тетрагидропиразоло[3,4-e]

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Amnesia-reversal activity of a series of cyclic imides

Cited by 62 publications

References 3 publications

Hormesis: Why it is important to toxicology and toxicologists

Hormesis: Why it is important to toxicology and toxicologists

Preparation of 2-Pyridone-Containing Tricyclic Alkaloid Derivatives as Potential Inhibitors of Tumor Cell Proliferation by Regioselective Intramolecular N- and C-Acylation of 2-Pyridone

Synthesis of 7-carboxyalkylthio-5,6,7,8-tetrahydro-1H-pyrazolo[3,4-e]diazepin-4-ones

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