Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)-benzothiazolone derivatives

Guenadil, Faouzi; Aichaoui, Hocine; Kapanda, Coco N.; Lambert, Didier M.; McCurdy, Christopher R.; Poupaert, Jacques H.

doi:10.1007/s00706-010-0419-9

Cited by 5 publications

(7 citation statements)

References 26 publications

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“…Therefore, an aromatic bromination reaction of commercially available benzoxazol2(3H)‐one ( 25 ) with bromine was conducted (Scheme ) . As previously reported, the reaction took place with high regioselectivity resulting exclusively in the desired 6‐bromobenzoxazolone 26 . The formation of 26 was proved unequivocally by 15 N‐GHMBC NMR experiments.…”

Section: Resultssupporting

confidence: 65%

“…Coupling reaction of acids 33 a and 33 b with aminobenzoxazolone 35 using 1,1′‐carbonyldiimidazole (CDI) or EDC⋅HCl and HOBT hydrate resulted in oxalamides 8 a and 8 b . Aromatic amine 35 was prepared by regioselective nitration of benzoxazolone 25 in 6‐position (proven by 15 N‐GHMBC experiments) and subsequent reduction with ammonium formate and Pd/C according to Yahia et al …”

Section: Resultsmentioning

confidence: 99%

“…[19] The bromofluoro intermediates 23 a [25,26] www.chemmedchem.org ic bromination reactiono fc ommerciallya vailableb enzoxa-zol2(3H)-one (25)w ithb romine was conducted (Scheme 3). [27] As previously reported, [28] the reaction took place with high regioselectivity resulting exclusively in the desired 6-bromobenzoxazolone 26.T he formation of 26 was proved unequivocally by 15 N-GHMBC NMR experiments.B ecauseP d-assisted coupling of aryl bromide 26 with propargyl alcohol did not take place, the benzoxazolone NH moiety was protected by am ethyl or methoxymethyl moiety (MOM). After Sonogashira couplingr eaction of aryl bromide 27 a, [29] propargyl alcohol 28 was oxidized with PhI(OAc) 2 /TEMPO or Dess-Martin periodinanet o give aldehyde 29 in 27 %a nd 51 %y ield, respectively.R eductive amination of aldehyde 29 with primary amine 7c and NaBH(OAc) 3 did not provide the desired secondary amine 9a, but tertiary amine 9b.…”

Section: Synthesismentioning

confidence: 99%

“…Coupling reactiono fa cids 33 a and 33 b with aminobenzoxazolone 35 using 1,1'-carbonyldiimidazole (CDI) or EDC·HCl and HOBT hydrate resulted in oxalamides 8a and 8b.Aromatic amine 35 was prepared by regioselective nitration of benzoxazolone 25 [28] in 6-position (provenb y 15 N-GHMBC experiments) [28] ands ubsequent reduction with ammonium formate and Pd/C according to Yahia et al [31] Indoles were chosen as second scaffold to investigate the effect of benzylpiperidine substitution by fluorinated phenylalkylamine building blocks (Scheme 5). Ta miz et al have shown that ab asic amino moiety in the side chain is not essential to achieve high GluN2B affinity as well as selectivity.…”

Section: Synthesismentioning

confidence: 99%

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Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands

et al. 2018

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The 4‐benzylpiperidine moiety is a central structural element of potent N‐methyl‐d‐aspartate (NMDA) receptor antagonists containing the GluN2B subunit. To obtain novel GluN2B ligands suitable for positron emission tomography, the benzylpiperidine moiety was replaced with fluorinated ω‐phenylalkylamino groups. For this purpose three primary propyl‐ and butylamines 7 a–c and one butyraldehyde 7 d bearing a fluorine atom and an ω‐phenyl moiety were prepared in 3‐ to 7‐step syntheses. Compounds 7 a–d were attached to various scaffolds of potent GluN2B antagonists (scaffold hopping) instead of the original 4‐benzylpiperidine moiety. Although benzoxazol‐2‐ones and indoles with a benzylpiperidine moiety show high GluN2B affinity, the corresponding fluorophenylalkylamine derivatives did not result in high Glu2B affinity. Moderate GluN2B affinity was observed for a 3‐(fluoroalkyl)‐substituted tetrahydro‐1H‐3‐benzazepine (Ki=239 nm). However, high GluN2B affinity was obtained for the tetrahydro‐5H‐benzo[7]annulen‐7‐amines 12 a–c (Ki=17–30 nm). Docking studies resulted in the same binding pose for 12 a as for the lead compound Ro 25‐6981. It can be concluded that some GluN2B ligands (benzoxazolones, indoles) do not tolerate replacement of the 4‐benzylpiperidine moiety with flexible fluorinated phenylalkyl side chains, but other scaffolds such as tetrahydro‐3‐benzazepines and ‐benzo[7]annulenes retain interaction with NMDA receptors containing the GluN2B subunit.

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Section: Resultssupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

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Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands

et al. 2018

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“…The 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones derivatives, in particular are interesting, with anti-inflammatory, analgesic, antiepiliptic and antiviral properties. They are important building block in organic synthesis and in the design of new pharmacophores [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Due to their wide range of application, the syntheses of these derivatives by Friedel-Crafts acylation reaction have received great deal of attention [16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

FeCl3-DMF complex as efficient catalyst for the synthesis of 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones

Guenadil¹

2019

Bull. Chem. Soc. Eth.

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Synthesis and biological profile of benzoxazolone derivatives

Prasher

Mall

Sharma

2023

Archiv der Pharmazie

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The benzoxazolone nucleus is an ideal scaffold for drug design, owing to its discrete physicochemical profile, bioisosteric preference over pharmacokinetically weaker moieties, weakly acidic behavior, presence of both lipophilic and hydrophilic fragments on a single framework, and a wider choice of chemical modification on the benzene and oxazolone rings. These properties apparently influence the interactions of benzoxazolone‐based derivatives with their respective biological targets. Hence, the benzoxazolone ring is implicated in the synthesis and development of pharmaceuticals with a diverse biological profile ranging from anticancer, analgesics, insecticides, anti‐inflammatory, and neuroprotective agents. This has further led to the commercialization of several benzoxazolone‐based molecules and a few others under clinical trials. Nevertheless, the SAR exploration of benzoxazolone derivatives for the identification of potential “hits” followed by the screening of “leads” provides a plethora of opportunities for further exploration of the pharmacological profile of the benzoxazolone nucleus. In this review, we aim to present the biological profile of different derivatives based on the benzoxazolone framework.

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Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)-benzothiazolone derivatives

Cited by 5 publications

References 26 publications

Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands

Replacement of the Benzylpiperidine Moiety with Fluorinated Phenylalkyl Side Chains for the Development of GluN2B Receptor Ligands

FeCl3-DMF complex as efficient catalyst for the synthesis of 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones

Synthesis and biological profile of benzoxazolone derivatives

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