2000
DOI: 10.1021/jm9904102
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Heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic Acids as Leukotriene Biosynthesis Inhibitors

Abstract: A novel series of heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids was studied as leukotriene biosynthesis inhibitors. A hypothesis of structure-activity optimization by insertion of an oxime moiety was investigated using REV-5901 as a starting point. A systematic structure-activity optimization showed that the spatial arrangement and stereochemistry of the oxime insertion unit proved to be important for inhibitory activity. The promising lead, S-(E)-11, inhibited LTB(4) biosynthesis in the intact human… Show more

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Cited by 33 publications
(32 citation statements)
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“…The 2‐substituted quinoxaline 16 was accomplished from 1,2‐diamino benzene and 1,3‐hydroxypropan‐2‐one through a one‐pot process using palladium acetate‐catalyzed aerobic oxidation, followed by in situ trapping, as reported previously, to yield 67 . Consequent conversion into the corresponding chloro derivative 68 , using trichloroisocyanuric acid, and reaction with 2,6‐difluoro‐3‐hydroxybenzamide afforded 16 .…”
Section: Resultsmentioning
confidence: 99%
“…The 2‐substituted quinoxaline 16 was accomplished from 1,2‐diamino benzene and 1,3‐hydroxypropan‐2‐one through a one‐pot process using palladium acetate‐catalyzed aerobic oxidation, followed by in situ trapping, as reported previously, to yield 67 . Consequent conversion into the corresponding chloro derivative 68 , using trichloroisocyanuric acid, and reaction with 2,6‐difluoro‐3‐hydroxybenzamide afforded 16 .…”
Section: Resultsmentioning
confidence: 99%
“…Synthetic inhibitors of 5-lipoxygenase enzyme have shown protective effect in experimental animal models of airway infl ammation and in human bronchial asthma [17][18][19][20][21][22]. Although, considerable effort has been made to design an effective inhibitor of 5-lipoxygenase, at the present time the most successful chemotype belongs to N-hydroxyurea category [16,[23][24][25][26]. This chemotype reportedly suffers from poor bioavailability; inhibitor specifi city and safety issues like hepatic and renal abnormality, myelosuppression, mild gastrointestinal abnormality etc [26][27].…”
Section: Introductionmentioning
confidence: 99%
“…Treatment of 30 with aqueous sodium hydroxide solution and subsequent DMF-DMA followed by the addition of methylhydrazine yielded amino pyrazole analogue 31, which after reductive alkylation with 4-(quinolin-2-yl)-benzaldehyde gave compound 32. 27) Further reductive alkylation with formaldehyde afforded compound 33.…”
mentioning
confidence: 99%