An Efficient Approach to the Total Synthesis of Ammosamide B

Yang, Sheng-Wei; Wang, Chunmeng; Tang, Kai-Xiang; Sun, Leilei

doi:10.1002/ejoc.201501560

Cited by 8 publications

(4 citation statements)

References 61 publications

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“…These compounds were originally found to possess activity against HCT-116 cells by targeting the cellular cytokinetic protein myosin, each with IC 50 = 320 nM. 57 , 58 Throughout the next few years 25 would be synthesized several times by notable groups 59 , 60 , 61 , 62 , however, in 2012 Reddy et al . synthesized several analogs and tested for their quinone reductase 2 (QR2) activity.…”

Section: Natural Products Which Have Benefited From Analog Developmenmentioning

confidence: 99%

A look around the West Indies: The spices of life are secondary metabolites

Demeritte

Wuest

2020

Bioorganic & Medicinal Chemistry

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Section: Natural Products Which Have Benefited From Analog Developmenmentioning

confidence: 99%

A look around the West Indies: The spices of life are secondary metabolites

Demeritte

Wuest

2020

Bioorganic & Medicinal Chemistry

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“…In Scheme , benzo[ cd ]indol-2(1 H )-one derivatives were prepared (Tables and ). The synthesis of intermediate 39 is no longer described in the same way as reported by Yang et al Starting from inexpensively available 4-chloroindoline-2,3-dione, the intermediate was nitrated with nitric acid sulfuric acid system from −25 to −10 °C to afford compound 40 . Intermediates 43 and 44 were synthesized from 39 by hydrogenation and dechlorination.…”

Section: Chemistrymentioning

confidence: 99%

Discovery of Benzo[cd]indol-2(1H)-ones and Pyrrolo[4,3,2-de]quinolin-2(1H)-ones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain with Potential High Efficiency against Acute Gouty Arthritis

Jiang

Zhang

et al. 2019

J. Med. Chem.

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The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.

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“…make their further derivatization become meaningful and attractive. In our preliminary work on the total synthesis of ammosamide B, 2 we found that the compound has poor hydrophilic and lipophilic solubility when the amino groups were exposed. Fortunately, the lipophilic solubility was improved when the amino groups were acylated.…”

mentioning

confidence: 99%