2-Quinolinone derivative

A catalytic enantioselective intramolecular hydroarylation of alkynes was conducted with a cationic palladium(II)/(5)-xyl-H8-BINAP complex (Scheme 18.33) [31], With electron-rich aryl groups such as 2-naphthyl on the nitrogen atom, the intramolecular hydroarylation proceeded efficiently to give chiral 4-aryl-2-quinolinone derivatives. This palladium-catalyzed reaction using (S )-xyl-Segphos... 

The quinolinone derivative, OPC-88117 (73), is yet another compound described as possessing both Class I and Class III electrophysiological activities. Studies in guinea-pig papillary muscle showed that OPC-88117 at 30 increased APDgo by about 15% and decreased F ,ax by only 4% however, at 100 /iM APDgo was prolonged by 23 % and was decreased by 23 % [206]. Further experiments in isolated rabbit hearts demonstrated that OPC-88117 increased atrio-His bundle (A-H) and His bundle-ventricle (H-V) conduction times and refractory periods with a profile that was similar to, but more potent than that of lidocaine [207]. 

Extrusion of sulfur dioxide from a ring-fused dihydiothiophene derivative provides an exceptionally easy method for the preparation of heterocyclic o-dimethylene compounds. These compounds are valuable intermediates in intermolecular Diels-Alder reactions. This extrusion method was used to prepare the o-dimethylene compounds 44-46 <95CC1349> as well as quinolinone derivative 47 <95TL5983>. TTie dihydrothiophene dioxide moiety also played an important role in the formation of the intramolecular Diels-Alder reaction of N-substituted pyrrole 48 <95CC807>. 

OPC 21268 is a quinolinone derivative, a selective (V1 subtype) vasopressin receptor antagonist, with antihypertensive properties,... 

The original Gould-Jacobs reaction, i.e. the reaction of an aniline or naphthylamine with diethyl (ethoxymethylene)malonate followed by cyclization of the intermediate at ca. 250 °C to give quinolinone derivatives (see Houben-Weyl, Vol. E 7a, p 345),194 has been extended to the synthesis of pyridopyrimidines. The method of first preparing the intermediate (pyrimidiny-lamino)methylene compound and its subsequent thermal cyclization has been discussed (vide supra). 

Aripiprazole is an arylpiperazine quinolinone derivative that has complex functional activity at several aminergic receptors currently thought to be important in the pathophysiology and pharmacotherapy of schizophrenia, including dopamine D2 and serotonin 5-HTia and 5-HT2A/C receptors. The affinity of aripiprazole for D2 receptors is relatively high however, it has a low propensity to cause untoward extrapyramidai symptoms and hyperprolactinemia (58). 

The constituents of the tumorigenic plant Melochia tomentosa include 6-methoxy-7,8-methylenedioxycoumarin, three cyclopeptide alkaloids, melo-chinone (a quinolinone derivative), and two novel phenylpentyl-isatins, melosatins A and B, for which the structures (3) and (4) have been deduced. The structure of melosatin A was confirmed by synthesis (Scheme 1),... 

This methodology with some variations has been utilized in the synthesis of numerous heterocyclic systems, such as heterocycle-fused quinolinone derivatives [391], l,4-benzodiazepin-2-ones [392], benzo-, naphtho- and heterocycle-fused pyrrolo[2,l-c][l,4]diazepines [393], quinolinone or pyrrolidinone derivatives [394], dibenzo[fl,c]phenanthridines [395], thiazolo-fused quinolinones [396], isoindolinone and isoquinolin-2-one derivatives [397], indoline derivatives [398], 5-aroyl-pyrrolidinones [399,400], indazolone derivatives [401,402], substituted indolizidinones [403], 1-arylpyrrolopyrazinones [404], stmcturally diverse... 

Dihydro-2(lFl)-quinolinone derivatives and related analogues with inotropic eiiects 13MRM1801. 

Notably, Torii and colleagues reported the intramolecular carbonylative Heck coupling of 3-(2-haloarylamino)prop-2-enoates to the corresponding quinolinone derivatives [21]. In the presence of a catalytic amount of Pd(OAc)2 under 20 bar of CO at 120 °C, quinolinones were synthesized in good yields (Scheme 7.4). A related carbonylative cross-coupling of aryl iodides with alkynones was reported... 

Amano Y, Inoue K, Nishiyama S (2008) Oxidative access to quinolinone derivatives with simultaneous rearrangement of functional groups. Synlett 19 134-136... 

In 2010, Jackson and co-workers studied the Negishi cross-coupling of iodoalanine-derived zinc reagents with aryl iodides and aryl bromides/ In that work, they showed that a 3,4-dihydro-2( H)-quinolinone derivative can be produced by using 2-iodoaniline as a substrate. An interesting study on... 

In 2012, T2ik2ihashi et al. [30] reported the catalytic enantioselective synthesis of atropisomeric 2-aryl-4-quinolinone derivatives using the Buchwald-Hartwig reaction with a (i )-MOP-Pd2(dba)3 catalyst. This reaction involved the 1,4-addition of aniline to an ynone, followed by an intramolecular Buchw2ild-Hartwig amination. An enantioselectivity as high as 72% ee could be achieved (Scheme 2.4). 

Shaharyar M, Ah M, Abdullah M (2007) Synthesis and antiproliferative activity of l-[(sub)]-6-fluoro-3-[(sub)]-l, 3,4-oxadiazol-2-yl-7-piperazino-l, 4-dihydro-4-quinolinone derivatives. Med Chem Res 16 292—299... 

Motohashi, X, Maekawa, K., Kubo, K., Igarashi, X, and Sakurai, X, An efficient transformation of substituted N-acyl-a-dehydro(l-naphthyl)alanines into l,2-dihydrobenzo[f]quinolinone derivatives via photoinduced intramolecular electron transfer. Heterocycles, 57, 269-292, 2002. 

Isomeric 4,5-dihydro[4,5-/]derivative 76 has been prepared from 7,8-dihydro-5(6//)-quinolinone via a semicarbazone and its subsequent reaction with thionyl chloride (95JHC177). 

Selenium dioxide oxidation of 7,8-dihydro-5(6//)-quinolinone semicarbazone gave, in addition to the expected 4,5-dihydro selenadiazoloquinoline 95 (analogous to sulfur derivative 76), the oxidized l,2,3-selenadiazolo[4,5-/]quinoline 96, which, when heated to 210°C for 30 min, gave the dimeric [l,4]diselenino [2,3-/ 5,6-/ ]diquinoline (95JHC177). 

Treatment of the pyrrolidine derivative 130 with sodium hydride followed by A-methyl piperazine afforded pyrrolidino[l,2-a]quinolinone 4-carboxy-late 131 (93JPR397) (Scheme 25). 

As can be seen, in both the 5,6- and the 7,8-dihydroxy-2(lH)quinolinone pathways, after initial hydroxylation adjacent to the N-heteroatom, the benzene moiety of the quinoline ring is transformed to a dihydroxy derivative 5,6- or 7,8-, respectively, which subsequently undergoes ring cleavage. However, neither of them involves C—N bond cleavage and consequently do not lead to denitrogenated products. 

The first step in any of the degradation pathways is the formation of 2-quinolinone/2-hydroxyquinoline/2-oxo-l, 2-dihydroquinoline and quinoline2-oxidoreductase has been shown to be responsible for this initial metabolic reaction [318], When the oxidation is carried out by a dioxygenase, it resulted in the formation of ds-hydrodiol derivatives and when oxidation is carried out by a monooxygenase monohydroxilated derivatives are formed, via the arene oxide intermediates [323],... 

Another antenna group that is particularly effective for lanthanide luminescence is carbosty-ril derivatives (7-amino-4-methyl-2(lH)-quinolinone), which can be attached to many chelating... 

Chiral butyrolactones of type 27 and 28 have substantial value in asymmetric synthesis because they contain readily differentiable difunctional group relationships e.g. 1,5-di-carboxylic acid, 1,4-hydroxy carboxylic acid, 1,6-hydroxy-carboxylic acid, 1,6-diol etc.) that would be difficult to assemble by existing asymmetric condensation and pericyclic processes. Applications of these chiral derivatives of glutaric acid to syntheses of indole, indoline and quinolinone alkaloids are illustrated in Schemes 16-18. 

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