4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

Tsou, Hwei‐Ru; MacEwan, Gloria; Birnberg, Gary H.; Zhang, Nan; Brooijmans, Natasja; Toral‐Barza, Lourdes; Hollander, Irwin; Ayral‐Kaloustian, Semiramis; Yu, Ker

doi:10.1016/j.bmcl.2010.02.012

Cited by 19 publications

(11 citation statements)

References 28 publications

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“…Azadienes 1 could be synthesized from enones and sulfonamides according to the known literature procedures. ,, Among them, azadienes 1a – d , 1e , 1f – j , 1k , 1l , 1m , and 1n are the known compound. Starting materials benzofuran-3(2 H )-ones and intermediate enones , are the known compounds.…”

Section: Methodsmentioning

confidence: 99%

Copper-Catalyzed Alkynylation/Cyclization/Isomerization Cascade for Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines and Benzofuro[3,2-b]pyridines

Xie

Sun

et al. 2019

J. Org. Chem.

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An efficient copper-catalyzed cascade alkynylation/cyclization/isomerization reaction of aurone-derived azadienes with terminal alkynes has been developed, giving a series of 1,2-dihydrobenzofuro[3,2-b]pyridines with excellent yields. The obtained 1,2-dihydrobenzofuro[3,2-b]pyridines can be conveniently transformed into the corresponding benzofuro[3,2-b]pyridines under basic conditions. Additionally, benzofuro[3,2-b]pyridines can also be prepared from azadienes and terminal alkynes in a one-pot reaction. The synthetic utility was demonstrated by the synthesis of three bioactive molecules with potent topoisomerase inhibition in high yields. This strategy provides a facile approach to 1,2-dihydrobenzofuro[3,2-b]pyridines and benzofuro[3,2-b]pyridines.

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Section: Methodsmentioning

confidence: 99%

Copper-Catalyzed Alkynylation/Cyclization/Isomerization Cascade for Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines and Benzofuro[3,2-b]pyridines

Xie

Sun

et al. 2019

J. Org. Chem.

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“…In the search for new structures which were both potent and selective as ATP-competitive inhibitors of mTOR, the synthesis of a two new families of 4-substituted-7-azaindoles were described (Scheme 28) [117]. Initial high throughput screening lead to the identification of an indole-bearing 4,6-dihydroxybenzofuranone 155 whose activity was increased by substituting a 7-azaindole core.…”

Section: M-tor Kinase Inhibitorsmentioning

confidence: 99%

The Azaindole Framework in the Design of Kinase Inhibitors

et al. 2014

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This review article illustrates the growing use of azaindole derivatives as kinase inhibitors and their contribution to drug discovery and innovation. The different protein kinases which have served as targets and the known molecules which have emerged from medicinal chemistry and Fragment-Based Drug Discovery (FBDD) programs are presented. The various synthetic routes used to access these compounds and the chemical pathways leading to their synthesis are also discussed. An analysis of their mode of binding based on X-ray crystallography data gives structural insights for the design of more potent and selective inhibitors.

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“…Compound 7 was further subjected to deprotection with AlCl 3 25 to give 2-bromo-1-(2-hydroxy-5nitrophenyl)hexan-1-one (8), confirmed the compound by 1 H NMR and observed that the absence of O−CH 3 protons at δ 4.03. Cyclization 26,27 of 8 (scheme 8) in the presence of TEA gave an 2-butyl-5-nitrobenzofuran-3(2H)-one (8a), further reduction with sodium borohydride 28 afforded an in situ intermediate of 2-butyl-5nitro-2,3-dihydrobenzofuran-3-ol (8b) and dehydration of in situ substrate by 15% aqueous HCl 28 furnished 2-butyl-5-nitrobenzofuran (9) with 70-75% of yield. The obtained 9 was confirmed using 1 H NMR, single proton signal at δ 6.49 attributed to third position 28 for preparation of 10 was involved Friedel-Crafts acylation of 9 with 4methoxybenzoyl chloride in the presence of SnCl 4 which is one of the expensive reagents and replaced the reagent by AlCl 3 with significant yield and purity.…”

Section: Reagents and Conditionmentioning

confidence: 99%

An alternative approach to synthesis of 2-n-butyl-5-nitrobenzofuran derivative: A key starting material for dronedarone hydrochloride

et al. 2012

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4-Substituted-7-azaindoles bearing a ureidobenzofuranone moiety as potent and selective, ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)

Cited by 19 publications

References 28 publications

Copper-Catalyzed Alkynylation/Cyclization/Isomerization Cascade for Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines and Benzofuro[3,2-b]pyridines

Copper-Catalyzed Alkynylation/Cyclization/Isomerization Cascade for Synthesis of 1,2-Dihydrobenzofuro[3,2-b]pyridines and Benzofuro[3,2-b]pyridines

The Azaindole Framework in the Design of Kinase Inhibitors

An alternative approach to synthesis of 2-n-butyl-5-nitrobenzofuran derivative: A key starting material for dronedarone hydrochloride

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