5-Lipoxygenase inhibitors with histamine H 1 receptor antagonist activity

Lewis, Timothy A.; Bayless, Lynn; Eckman, Joseph; Ellis, James L.; Grewal, Gurmit; Libertine, Lyn; Nicolas, Jean Marie; Scannell, Ralph T.; Wels, Bruce F.; Wenberg, Karen; Wypij, Donna M.

doi:10.1016/j.bmcl.2004.02.005

Cited by 35 publications

(11 citation statements)

References 16 publications

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“…One of the most recent compounds to enter this clinically and commercially important market is rupatadine (16) (Picado, 2006;Fantin et al, 2008), which blocks both peripheral H 1 receptors and the platelet activation pathway, as a platelet-activating factor antagonist (Merlos et al, 1997). Efletirizine, however, was developed as a topical agent to fit the pharmacophores for H 1 receptor antagonists and inhibitors of lipoxygenase (an enzyme involved in the production of leukotrienes) (Salmun, 2002;Lewis et al, 2004b) but was discontinued in the late phases of development. Regarding the H 1 receptor antagonists already in the pharmacopoeia, few studies have been conducted on teratogenicity or embryotoxicity with high doses of antihistamines in animal testing, and it is recommended that antihistamines should not be used in pregnancy (Gilboa et al, 2014).…”

Section: F Clinical Pharmacologymentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

et al. 2015

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Section: F Clinical Pharmacologymentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

et al. 2015

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“…Incorporation of an N-hydroxyurea functionality onto well-characterized PAF receptor antagonists consisting of 2,5-diaryltetrahydrofurans (CMI-392) resulted in a potent dual function compound (5-LO and PAF) [79] which may provide therapeutic advantages over agents with only single activity [77]. Similarly, hybrid molecules containing N-hydroxyureas or N-hydroxycarbamates (5-LO pharmacophore) connected to benzhydryl piperazines (H 1 receptor antagonistic moiety) are currently developed for the treatment of asthma [80], [81].…”

Section: Molecular Pharmacology Of 5-lipoxygenase Inhibitorsmentioning

confidence: 99%

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Werz¹

2007

Planta Med

155

135

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4 , D 4 and E 4 . LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structureactivity relationships are discussed.

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“…Oxygenation of arachidonic acid by lipoxygenase (LOX) to form leukotriens proceeds through radical intermediates, and thus, LOX participates in the production of free radicals. Superoxide dismutase-like activity, radio-protective, and good antiphlogistic activities were found in copper complexes of Schiff' bases [8]. In search of novel anti-inflammatory drugs and continuation of our research [9,10], we have planned to report in this paper the synthesis of a series of 7-(substituted benzylideneamino)-4-methyl-2H-chromen-2-one derivatives III a -l and their anti-inflammatory and analgesic activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Substituted 7‐(Benzylideneamino)‐4‐Methyl‐2H‐Chromen‐2‐one Derivatives as Anti‐inflammatory and Analgesic Agents

Ronad

Dharbamalla

Hunshal

et al. 2008

Archiv der Pharmazie

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A series of novel Schiff' base-containing a 7-amino-4-methylcoumarin moiety have been synthesized III a-l, characterized by spectroscopic data and studied for their anti-inflammatory and analgesic activity. The results of the anti-inflammatory and analgesic activity evaluation of 7-(substituted benzylideneamino)-4-methyl-2H-chromen-2-one derivatives III a-l proved to be comparable or more potent with respect to the reference drugs. In particular, compounds 7-(4-chlorobenzylideneamino)-4-methyl-2H-chromen-2-one III f, 7-(2,4-dichlorobenzylideneamino)-4-methyl-2H-chromen-2-one III g and 7-(4-bromobenzylideneamino)-4-methyl-2H-chromen-2-one III h exhibited potent anti-inflammatory and analgesic activity.

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5-Lipoxygenase inhibitors with histamine H 1 receptor antagonist activity

Cited by 35 publications

References 16 publications

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Synthesis of Novel Substituted 7‐(Benzylideneamino)‐4‐Methyl‐2H‐Chromen‐2‐one Derivatives as Anti‐inflammatory and Analgesic Agents

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