A novel class of sodium/calcium exchanger inhibitor: design, synthesis, and structure–activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives

Hasegawa, Hirohiko; Muraoka, Masami; Ohmori, Mikiko; Matsui, Kazuki; Kojima, Atsuyuki

doi:10.1016/j.bmc.2005.03.019

Cited by 11 publications

(10 citation statements)

References 24 publications

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“…In this system, Val-Met-Arg-Phe-NH 2 (1) and dimethylamiloride (3), which are known inhibitors of the Na (21) showed strongest activity. Since we have investigated the effects of substituents at the 3-position of the 3,4-dihydro-2(1H)-quinazolinone on the activities, 19,20) we introduced a 1-benzylpiperidin-4-yl at the 3-position of 4-phenyl-3,4-dihydropyrido [4,3-d]pyrimidin-2(1H)-one. As we anticipated, compound 26 increased the activity dramatically, showing the strong activity with an IC 30 value of 0.02 mM.…”

Section: Pharmacological Results and Discussionmentioning

confidence: 99%

“…Synthesis of 4-phenyl-3,4-dihydropyrido [2,3- (20), and 4-phenyl-3,4-dihydropyrido [4,3-d]pyrimidin-2(1H)-one (21) having a N,N-diethylaminoethyl as a chain aminoalkyl group at the 3-position is illustrated in Chart 1. Trichloroacetylation of aminobenzoylpyridine 10, 21) 11, 21) and 12 21) with trichloroacetyl chloride, followed by …”

Section: Chemistrymentioning

confidence: 99%

“…We have already reported design, synthesis and structureactivity relationships for 3,4-dihydro-2(1H)-quinazolinone derivatives with the inhibitory activities of the Na ϩ /Ca 2ϩ exchanger. 19,20) In the previous article, we disclosed that these studies based on lead compound 8 with a moderate potent inhibitory activity led to the identification of a structurally novel and highly potent inhibitor against the Na ϩ /Ca 2ϩ exchanger 9 (SM-15811), which directly inhibited the Na ϩ -dependent Ca 2ϩ influx via the Na ϩ /Ca 2ϩ exchanger in cardiomyocytes with high potency and exerted the protective effect against myocardial ischemic reperfusion injury (Fig. 2).…”

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confidence: 99%

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Design, Synthesis, and Structure-Activity Relationships of 3,4-Dihydropyridopyrimidin-2(1H)-one Derivatives as a Novel Class of Sodium/Calcium Exchanger Inhibitor

Hasegawa¹,

Muraoka²,

Ohmori³

et al. 2005

Chem. Pharm. Bull.

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Section: Pharmacological Results and Discussionmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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confidence: 99%

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Design, Synthesis, and Structure-Activity Relationships of 3,4-Dihydropyridopyrimidin-2(1H)-one Derivatives as a Novel Class of Sodium/Calcium Exchanger Inhibitor

Hasegawa¹,

Muraoka²,

Ohmori³

et al. 2005

Chem. Pharm. Bull.

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“…Benzothiazines and 3,4-dihydroquinazoline-2-thiones are an important class of heterocyclest hat are prevalent in ag reat number of natural products and biologically activem olecules. [33][34][35][36] In this context, the Xu and Shen group developed catalyst-controlled solvent-free chemoselective syntheses of 2amino-3,1-benzothiazines 15 and 3,4-dihydroquinazoline-2-thiones 16 by using ortho-aminocinnamates 13 and isothiocyanates 14 (Scheme 11). They tested aw ide range of Lewis acids, including Yb(OTf) 3 ,S m(OTf) 3 3 ], and LiN(SiMe 3 ) 2 ,t oa ttemptt oa ttain exclusive chemoselectivity.…”

Section: Acid-catalyzed Thia-michaela Ddition Reactionsmentioning

confidence: 99%

Thia‐Michael Addition: An Emerging Strategy in Organic Synthesis

2018

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The thia-Michael addition reactionh as been demonstrated to be ah ighly powerful tool in organic synthesis. Indeed, the influential natureo ft his reactionh as been wellestablished in the fields of medicinal chemistry,c atalysis, drug discovery,a nd materials science. The emergence of numerous synthetic strategies that take advantage of thia-Michael addition reactions of electron-deficienta lkenes has unleashed countless opportunities for the design and synthesis of diverse biologically relevant organosulfurc ompounds. However,d espite myriad potential synthetic applications, there has not been anye xclusive reviewso ft he thia-Michael addition reaction. Therefore, this Focus Review plots the journeyo ft he thia-Michael addition reaction in organic synthesis, and is categorized according to catalyzed and catalyst-free thia-Michael addition reactions. Figure 1. Summary of the applicationsoft hia-Michael adducts.[a] Dr.Scheme1.Catalyzed pathways for the thia-Michael addition reaction.EW-G = electron-withdrawing group.Scheme2.Acetic-acid-catalyzed thia-Michael additionr eaction proposed by Allen et al. [24] AsianJ.O rg.Scheme3.Indium-bromide-catalyzed thia-Michael addition reaction.Scheme4.Thia-Michael addition reaction followed by a1 ,2-addition of TMSCN in one pot. TMSCN = trimethylsilyl cyanide.Scheme5.Bi III -catalyzedt hia-Michael additionreactiono fa,b-unsaturated carbonyl compounds. Tf = trifluoromethanesulfonyl.Scheme6.Bismuth-triflate-catalyzed synthesis of bis-thioether compounds. Bn = benzyl.Scheme7.Iron-/copper-catalyzed thia-Michael additionr eaction.Scheme8.VO(OTf) 2 -mediated synthesis of b-mercapto ketones. Np = naphthyl.Scheme9.Substrate scope for the synthesis of 3-sulfanyl-substituted 1-(arylamino)-pyrrolidine-2,5-diones.Scheme10. Regio-and enantioselective addition at the d position of conjugated systems.Scheme11. Mechanistic modelf or the enantioselective d addition of at hiol to an a,b,g,d-unsaturated dienone,catalyzed by achiral Fe III Àsalenc omplex.Scheme12. Chemoselectivesynthesis of 2-amino-3,1-benzothiazines (15) and 3,4-dihydroquinazoline-2-thiones (16)byu sing ortho-aminocinnamate (13)a nd isothiocyanates 14.Scheme13. Reactionmechanism for the chemoselective synthesis of 2amino-3,1-benzothiazines (15)and 3,4-dihydroquinazoline-2-thiones (16).Scheme14. ZrCl 4 -assisted three-component reactionf or the synthesiso fbaryl-b-mercapto ketones.Scheme15. LiF-nanocube-mediated thia-Michael addition reaction.Scheme57. Ni II -catalyzed enantioselective synthesiso f2-aryl-3-nitrothiochroman-4-ols.Scheme58. Te ntative reaction mechanism for the Ni II -catalyzed asymmetric synthesis of 2-aryl-3-nitrothiochroman-4-ols.Scheme59. Pepsin-catalyzed synthesis of functionalized chiral dihydrothiophenes.Scheme69. Mechanistic aspects of the stereoselectives ynthesis of tetrahydrothioxanthenones.Scheme70. Enantioselectivesynthesis of methyl 2-((R)-2-nitro-1-(aryl/heteroaryl)ethylthio)acetatesa nd thiomorpholin-3-ones.Scheme71. Water-accelerated thia-Michael additionr eaction proposedb y Chakraborti and co-work...

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“…8−11 The C4-substituted quinazolinone framework is known to exhibit a wide range of biological properties. For example, SM-15811 is a potent Na + /Ca 2+ exchanger inhibitor, 12−14 proquazone is an anti-inflammatory drug, 15,16 and 4-disubstituted 3,4-dihydroquinazolinones are T-type channel selective calcium blockers with in vivo central nervous system efficacy in epilepsy and tremor models 17,18 (Figure 1). Finally, the 3,4-dihydroquinazolinones DPC 961 and DPC 083 and related analogs are potent human immunodeficiency virus non-nucleoside reverse transcriptase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted aza-Friedel–Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4-Aryl 3,4-Dihydroquinazolinones

2018

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A one-pot microwave-assisted aza -Friedel–Crafts arylation of N -acyliminium ions, generated in situ from o -formyl carbamates and different amines, is reported. This metal-free protocol provides rapid access to diverse 4-aryl 3,4-dihydroquinazolinones in excellent yield without any aqueous workup. A solvent-directed process for the selective aza -Friedel–Crafts arylation of electron-rich aryl/heteroaryl/butenyl-tethered N -acyliminium ions is also described.

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A novel class of sodium/calcium exchanger inhibitor: design, synthesis, and structure–activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives

Cited by 11 publications

References 24 publications

Design, Synthesis, and Structure-Activity Relationships of 3,4-Dihydropyridopyrimidin-2(1H)-one Derivatives as a Novel Class of Sodium/Calcium Exchanger Inhibitor

Design, Synthesis, and Structure-Activity Relationships of 3,4-Dihydropyridopyrimidin-2(1H)-one Derivatives as a Novel Class of Sodium/Calcium Exchanger Inhibitor

Thia‐Michael Addition: An Emerging Strategy in Organic Synthesis

Microwave-Assisted aza-Friedel–Crafts Arylation of N-Acyliminium Ions: Expedient Access to 4-Aryl 3,4-Dihydroquinazolinones

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