Synthesis and Reactivity of Azepino[3,4-b]indol-5-yl Trifluoromethanesulfonate

Chacun‐Lefevre, Lidwine; Joseph, Benoı̂t; Mérour, Jean‐Yves

doi:10.1016/s0040-4020(00)00374-4

Cited by 22 publications

(9 citation statements)

References 20 publications

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“…Despite the description of the total synthesis of HMD by two research groups [56-58], there have been few reported modifications to the core structure [59,60]. The second part of this paper describes the synthesis and the structure-activity relationship (SAR) of new HMD analogs with altered kinase selectivity profiles.…”

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confidence: 99%

Synthesis and Target Identification of Hymenialdisine Analogs

Wan

Hur

Cho

et al. 2004

Chemistry & Biology

131

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Hymenialdisine (HMD) is a sponge-derived natural product kinase inhibitor with nanomolar activity against CDKs, Mek1, GSK3beta, and CK1 and micromolar activity against Chk1. In order to explore the broader application of the pyrrolo[2,3-c]azepine skeleton of HMD as a general kinase inhibitory scaffold, we searched for additional protein targets using affinity chromatography in conjunction with the synthesis of diverse HMD analogs and profiled HMD against a panel of 60 recombinant enzymes. This effort has led to nanomolar to micromolar inhibitors of 11 new targets including p90RSK, KDR, c-Kit, Fes, MAPK1, PAK2, PDK1, PKCtheta, PKD2, Rsk1, and SGK. The synthesis of HMD analogs has resulted in the identification of compounds with enhanced and/or dramatically altered selectivities relative to HMD (28n) and in molecules with antiproliferative activities 30-fold higher than HMD (28p).

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confidence: 99%

Synthesis and Target Identification of Hymenialdisine Analogs

Wan

Hur

Cho

et al. 2004

Chemistry & Biology

131

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“…1-Benzoyl-2-methylsulfanyl-1,5-dihydroimidazol-4-one employed in Papeo"s approach was also useful in the first total synthesis of (Z)-axinohydantoin. Different series of analogues were synthesized (He et al, 2007;Chacun-Lefevre et al, 2000;Wan et al, 2004). Those derivatives left the main features of (Z)-HMD binding site in the kinase ATP unchanged.…”

Section: Synthesis Approach: An Alternative For Continuous Supplymentioning

confidence: 99%

New Hope on Drug Leads Development From Deep Ocean: Halogenated Alkaloids of Agelas Sponges

Hertiani

2014

Indonesian J. Pharm.

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Agelas sponge is found in abundancy from Indonesia's ocean. This sponge produces an important chemotaxonomic group of compounds, derived from pyrrole-imidazole alkaloids. This group of compounds is one of those exclusively found from marine environment. Marine sponges are reported to be promising drug lead producers having unique chemical structures of which many have no terrestrial counterparts. The objective of this report is to give an overview of the reported attempts from up to down stream to develop pyrrole-imidazole alkaloids as new drug lead. Literatures up to 2013 reporting this group of compounds from Agelas sponges were studied. Discussion on the halogenated alkaloids covers the producers, description of high chemical diversity, identification, biosynthesis and ecological relevance as well as their role as a promising drug candidate. Alternatives to provide continous supplies for drug development are also discussed considering that wild harvesting of the sponge producers can lead to ecological damage in the future. Broad range of interesting pharmacological importance as well as several success in developing synthetic route for production supports its development as drug candidate.

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“…However, being potent pan -kinase inhibitors, HMD and analogues represent a potential for the treatment of neurodegenerative disorders, inflammatory pathologies, diabetes and cancer. Different series of HMD analogues were synthesized in order to establish a SAR [ 1 , 80 , 81 ]. In those derivatives, the main features that allow ( Z )-HMD to bind in the kinase ATP binding site were left unchanged, while attempts have been performed in order to improve selectivity and permeability [ 82 – 84 ].…”

Section: Cyclic Monomersmentioning

confidence: 99%

A Submarine Journey: The Pyrrole-Imidazole Alkaloids

et al. 2009

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In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity – from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products.

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Synthesis and Reactivity of Azepino[3,4-b]indol-5-yl Trifluoromethanesulfonate

Cited by 22 publications

References 20 publications

Synthesis and Target Identification of Hymenialdisine Analogs

Synthesis and Target Identification of Hymenialdisine Analogs

New Hope on Drug Leads Development From Deep Ocean: Halogenated Alkaloids of Agelas Sponges

A Submarine Journey: The Pyrrole-Imidazole Alkaloids

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