Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

Carpio, Humberto; Cooper, Gary F.; Edwards, John A.; Fried, J. H.; Garay, Gabriel L.; Guzmán, A.; Méndez, José; Muchowski, Joseph M.; Roszkowski, Adolph P.; Horn, A. R. Van; Wren, D. L.

doi:10.1016/0090-6980(87)90004-9

Cited by 24 publications

(10 citation statements)

References 19 publications

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“…As shown in Fig. 2A, l l-deoxy PGEt, EP2 and EP4 agonist [14], and 16,16-dimethyl PGE 2, a non-selective EP agonist [15], concentration-dependently inhibited the [3H]PGE2 binding, their halfmaximal concentrations for the inhibition being one-order higher than that of PGE2. In contrast, butaprost and 19(H)OH-PGE2, specific EP2 agonists, showed very weak inhibition, but Recently, a human PGE receptor subtype has been cloned, which has characteristics of the pharmacologically defined EP2 subtype [16].…”

Section: Resultsmentioning

confidence: 98%

Identification of prostaglandin E receptor ‘EP2’ cloned from mastocytoma cells as EP4 subtype

et al. 1995

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Section: Resultsmentioning

confidence: 98%

Identification of prostaglandin E receptor ‘EP2’ cloned from mastocytoma cells as EP4 subtype

et al. 1995

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“…Interestingly, the effect of either modification alone is rather modest, whereas enprostil is over 600 times as potent as PGE 2 in inhibiting gastric acid secretion. [118] Enprostil is usually administered as a racemic mixture of diastereomers with regard to the allenic axis of chirality. In the first synthesis of this isomeric mixture (Scheme 38), [119] the allenic moiety was installed by an S N 2'-reduction of the propargylic acetate 110 with lithium dimethylcuprate.…”

Section: Prostaglandins and Carbacyclinsmentioning

confidence: 99%

Synthesis and Properties of Allenic Natural Products and Pharmaceuticals

2004

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Nowadays, about 150 natural products comprising an allenic or cumulenic structure are known. The chemistry of these compounds has turned out to be a very attractive and prolific area of interest: advances in the isolation and characterization of new allenic natural products have led to the establishment of efficient synthetic procedures which in many cases also open up an access to enantiomerically pure target molecules. Inspired by the intriguing biological activities of many allenic natural products, allene moieties are now systematically introduced in pharmacologically active classes of compounds (steroids, prostaglandins, amino acids, nucleosides). The functionalized allenes thus obtained often exhibit impressive activities as mechanism-based enzyme inhibitors, cytotoxic, or antiviral agents. A prerequisite for further developments in this field is the efficient stereoselective synthesis of allene derivatives.

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“…This can be considered as activation of the lipophilic carbon chain in fatty acids to facilitate β-oxidation at either end of the molecule. Replacement of the terminal ω-alkyl chain with aromatic (Carpio et al, 1987;Serhan et al, 1995) and cycloalkyl (Serhan et al, 1995) groups is a straightforward strategy to prevent ω-oxidation while retaining biological activity (Collins & Djuric, 1993). These substituents also inhibit C15-hydroxyl group oxidation, which effectively prevents two metabolic pathways simultaneously.…”

Section: ω-Oxidationmentioning

confidence: 99%

Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs

Murray

Hraiki

Bebawy

et al. 2015

Pharmacology & Therapeutics

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Lipids have the potential for development as anticancer agents. Endogenous membrane lipids, such as ceramides and certain saturated fatty acids, have been found to modulate the viability of tumor cells. In addition, many tumors over-express cyclooxygenase, lipoxygenase or cytochrome P450 enzymes that mediate the biotransformation of ω-6 polyunsaturated fatty acids (PUFAs) to potent eicosanoid regulators of tumor cell proliferation and cell death. In contrast, several analogous products from the biotransformation of ω-3 PUFAs impair particular tumorigenic pathways. For example, the ω-3 17,18-epoxide of eicosapentaenoic acid activates anti-proliferative and proapoptotic signaling cascades in tumor cells and the lipoxygenase-derived resolvins are effective inhibitors of inflammatory pathways that may drive tumor expansion. However, the development of potential anti-cancer drugs based on these molecules is complex, with in vivo stability a major issue. Nevertheless, recent successes with the antitumor alkyl phospholipids, which are synthetic analogues of naturally-occurring membrane phospholipid esters, have provided the impetus for development of further molecules. The alkyl phospholipids have been tested against a range of cancers and show considerable activity against skin cancers and certain leukemias. Very recently, it has been shown that combination strategies, in which alkyl phospholipids are used in conjunction with established anticancer agents, are promising new therapeutic approaches. In future, the evaluation of new lipid-based molecules in single-agent and combination treatments may also be assessed. This could provide a range of important treatment options in the management of advanced and metastatic cancer.

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Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

Cited by 24 publications

References 19 publications

Identification of prostaglandin E receptor ‘EP2’ cloned from mastocytoma cells as EP4 subtype

Identification of prostaglandin E receptor ‘EP2’ cloned from mastocytoma cells as EP4 subtype

Synthesis and Properties of Allenic Natural Products and Pharmaceuticals

Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs

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