Synthesis and in Vivo Antitumor Evaluation of 2-Methoxyestradiol 3-Phosphate, 17-Phosphate, and 3,17-Diphosphate

Edsall, Allison B.; Agoston, Gregory E.; Treston, Anthony M.; Plum, Stacy M.; McClanahan, Robert H.; Tong, L.; Song, Wei; Cushman, Mary

doi:10.1021/jm070639e

Cited by 18 publications

(19 citation statements)

References 25 publications

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“…In particular, CA-4 has recently benefited from a phosphate prodrug administration (3P). Similarly, Cushman’s group also addressed the issue of low water solubility by producing water soluble 2-ME derivatives by coupling phosphate to the hydroxyl groups in positions 3 and 17 (150). The 3-phosphate ( 184 , Fig.…”

Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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Tubulin dynamics is a promising target for new chemotherapeutic agents. The colchicine binding site is one of the most important pockets for potential tubulin polymerization destabilizers. Colchicine binding site inhibitors (CBSI) exert their biological effects by inhibiting tubulin assembly and suppressing microtubule formation. A large number of molecules interacting with the colchicine binding site have been designed and synthesized with significant structural diversity. CBSIs have been modified as to chemical structure as well as pharmacokinetic properties, and tested in order to find a highly potent, low toxicity agent for treatment of cancers. CBSIs are believed to act by a common mechanism via binding to the colchicine site on tubulin. The present review is a synopsis of compounds that have been reported in the past decade that have provided an increase in our understanding of the actions of CBSIs.

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Section: Reported Cbsi In Preclinical Studiesmentioning

confidence: 99%

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

et al. 2012

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“…Because the AT reaction is not efficient to produce alkylphosphate from alkylalcohol, an alternative is the usage of chlorophosphate in the presence of a Lewis acid catalyst. For this purpose, Ti( t -BuO) 4 was identified as an effective catalyst [52–53]. The use of phenol as a nucleophilic species resulted in better yields.…”

Section: Reviewmentioning

confidence: 99%

Atherton–Todd reaction: mechanism, scope and applications

Corre¹,

Berchel²,

Couthon‐Gourvès³

et al. 2014

Beilstein J. Org. Chem.

145

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SummaryInitially, the Atherton–Todd (AT) reaction was applied for the synthesis of phosphoramidates by reacting dialkyl phosphite with a primary amine in the presence of carbon tetrachloride. These reaction conditions were subsequently modified with the aim to optimize them and the reaction was extended to different nucleophiles. The mechanism of this reaction led to controversial reports over the past years and is adequately discussed. We also present the scope of the AT reaction. Finally, we investigate the AT reaction by means of exemplary applications, which mainly concern three topics. First, we discuss the activation of a phenol group as a phosphate which allows for subsequent transformations such as cross coupling and reduction. Next, we examine the AT reaction applied to produce fire retardant compounds. In the last section, we investigate the use of the AT reaction for the production of compounds employed for biological applications. The selected examples to illustrate the applications of the Atherton–Todd reaction mainly cover the past 15 years.

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“…Furthermore, it was indicated that the electronic effects of 2-and 17-position substituents significantly affect microtubule polymerization inhibition of analogues of 2ME2 [151]. Additionally, transformation of these compounds to a phosphate prodrug at position 3 would be a successful strategy to address the problem of limited aqueous solubility and the resulting limited bioavailability [152].…”

Section: -Methoxyestradiol and Analoguesmentioning

confidence: 99%

Cancer Therapeutic Agents Targeting Hypoxia-Inducible Factor-1

Wang¹,

Zhou

2011

CMC

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The discovery of hypoxia-inducible factor-1 has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past two decades. Today it is generally accepted that HIF-1 plays a pivotal role in the cellular response to tumor hypoxia which represents a major obstacle to the success of radiotherapy and chemotherapy. Meanwhile, many details involved in the expression, accumulation and transactivation of HIF-1 have been well elucidated. Targeting HIF-1 has become a novel and efficient strategy for cancer therapy and a number of agents have been developed aiming to suppress HIF-1. This review will concisely introduce the general knowledge on the molecular biology of HIF-1 and possible targets along the HIF-1 pathway. Moreover, a number of compounds reported with anti-HIF-1 activity are included and mainly classified as direct and indirect inhibitors based on their different modes of action. While direct HIF-1 inhibitors prevent HIF-1 from transactivation, DNA binding and subsequently initiating transcriptional activity, indirect HIF-1 inhibitors generally block the transcription or translation of HIF-1α or promote the degradation of HIF-1α protein. According to different structural features, direct HIF-1 inhibitors are divided into several groups: polyamides, quinols and naphthoquinone spiroketal analogues, shikonin derivatives, epidithiodiketopiperazines, and two representative drugs: echinomycin and bortezomib. In the same way, indirect inhibitors comprise the following classes: polyphenols, benzoazaheterocycles, rapamycins, camptothecins, geldanamycins, (aryloxyacetylamino)benzoic acid analogues, 2-methoxyestradiol and analogues, hydroxamic acid compounds and others. The rest with mechanism still not so clear would also be listed and introduced, with an emphasis on the marinederived natural products. The in vitro and/or in vivo activities of these compounds and their mechanisms of HIF-1 inhibition would be discussed and the SARs of unique structural types of HIF-1 inhibitors will be briefly concluded.

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Synthesis and in Vivo Antitumor Evaluation of 2-Methoxyestradiol 3-Phosphate, 17-Phosphate, and 3,17-Diphosphate

Cited by 18 publications

References 25 publications

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site

Atherton–Todd reaction: mechanism, scope and applications

Cancer Therapeutic Agents Targeting Hypoxia-Inducible Factor-1

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