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Novel 1H-benzimidazol-4-ols with potent 5-lipoxygenase inhibitory activity.

Authors
  • Buckle, D R
  • Foster, K A
  • Taylor, J F
  • Tedder, J M
  • Thody, V E
  • Webster, R A
  • Bermudez, J
  • Markwell, R E
  • Smith, S A
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Dec 01, 1987
Volume
30
Issue
12
Pages
2216–2221
Identifiers
PMID: 3681891
Source
Medline
License
Unknown

Abstract

The synthesis and structure--activity profile of 2-substituted benzimidazol-4-ols as inhibitors of cell-free RBL-1 5-lipoxygenase are discussed, and their potency is compared with that of the standard inhibitors phenidone, AA 861, BW 755C, and nordihydroguaiaretic acid. In contrast to the standard compounds, most did not inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vivo when administered at 200 microM ip to rats subjected to peritoneal anaphylaxis, although five compounds containing a methoxylated benzyl group (compounds 36, 39, 42, and 43) or hydroxylated benzyl group (41) showed similar activity to that of phenidone, nordihydroguaiaretic acid, and AA 861. Of the many compounds tested, two, 5-tert-butyl-7-methyl-2-(trifluoromethyl)-1H-benzimidazol-4-ol (57) and 2-(4-methoxybenzyl)-7-methyl-1H-benzimidazol-4-ol (36), like dexamethasone, inhibited monocyte accumulation in a pleural exudate model of inflammation. Standard lipoxygenase inhibitors such as phenidone, BW 755C, and AA 861 were inactive in this system.

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