Diversity-oriented synthesis of α-aminophosphonates: A new class of potential anticancer agents

Bhattacharya, Asish K.; Raut, Dnyaneshwar S.; Rana, Kalpeshkumar C.; Polanki, Innaiah K.; Khan, Mohd Sajid; Iram, Sana

doi:10.1016/j.ejmech.2013.05.036

Cited by 59 publications

(10 citation statements)

References 37 publications

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“…The lack of knowledge of the molecular target often precludes further work on such compounds, but it is nonetheless a first step in demonstrating bio-compatibility for scaffold types not previously or widely explored, and the utility of the DOS transformations that make them. Three-component reactions (3-CR) have proved popular in preparing DOS libraries, such as the one-pot acid-catalysed 3-CR between a range of aldehydes, amines and alkyl/aryl phosphites leading to cytotoxic α-aminophosphonates [57], or novel cytotoxic 1,4-thiazepan-3-ones also made using a 3-CR [58]. The click-chemistry cycloaddition of azides and alkynes is a synthetic transformation that produces triazole scaffolds with physicochemical properties consistent with cellular activity, as shown by antiproliferative carbohydrate-cyclopamine conjugates [59] and cytotoxic 14, 15 and 16-membered macrocylic glyco-conjugates [60].…”

Section: Dos Applied To Cancer Drug Discovery Screening Strategiesmentioning

confidence: 99%

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Collins

Jones

2014

Molecules

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How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the present) considers the applications of diversity-oriented synthesis (DOS), biology-oriented synthesis (BIOS) and associated strategies to cancer biology and drug discovery, summarising the syntheses of novel and often highly complex scaffolds from pluripotent or synthetically versatile building blocks. We highlight the role of diversity-oriented synthetic strategies in producing new chemical tools to interrogate cancer biology pathways through the assembly of relevant libraries and their application to phenotypic and biochemical screens. The use of diversity-oriented strategies to explore structure-activity relationships in more advanced drug discovery projects is discussed. We show how considering appropriate and variable focus in library design has provided a spectrum of DOS approaches relevant at all stages in anti-cancer drug discovery.

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Section: Dos Applied To Cancer Drug Discovery Screening Strategiesmentioning

confidence: 99%

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Collins

Jones

2014

Molecules

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“…Due to their similarities to α-amino acids and a wide range of applications, α-aminophosphonic acids are continuously gaining importance in organic synthesis. So far, a number of applications such as antiviral [3,4] or cytotoxic agents [5,6], enzyme inhibitors [7,8] immune system activators [9] or antibacterial activities [10] have attracted considerable attention. The importance of these acids and their derivatives in the search for new pharmaceutical uses has been extensively discussed in numerous review articles [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells

et al. 2020

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In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.

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“…In this context, α-aminophosphonates have particularly attracted considerable attention owing to their biological activities [27–33] since they are considered as important surrogates for α-amino carboxylic acids, peptide mimics as well as versatile intermediates for the design of potential anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

Ayadi¹,

Elleuch²,

Vrancken³

et al. 2016

Beilstein J. Org. Chem.

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An efficient synthesis of a series of γ-ketoallylphosphonates through a direct conversion of both primary and secondary Morita–Baylis–Hillman (MBH) alcohols by trialkyl phosphites with or without DMAP, used as additive, and under solvent-free conditions, is described herein for the first time. Subsequently, a highly regioselective Luche reduction of the primary phosphonate 2a (R = H) gave the corresponding γ-hydroxyallylphosphonate 5 that further reacted with tosylamines in the presence of diiodine (15 mol %) as a catalyst, affording the corresponding SN2-type products 6a–d in 63 to 70% isolated yields. Alternatively, the alcohol 5 produced the corresponding acetate 7 which, mediated by Ce(III), was successfully converted into the corresponding γ-aminoallylphosphonates 8a–d.

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Diversity-oriented synthesis of α-aminophosphonates: A new class of potential anticancer agents

Cited by 59 publications

References 37 publications

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

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