New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships

  • J Med Chem. 1988 Jan;31(1):84-91. doi: 10.1021/jm00396a013.
H Nakai  1 ,  M Konno ,  S Kosuge ,  S Sakuyama ,  M Toda ,  Y Arai ,  T Obata ,  N Katsube ,  T Miyamoto ,  T Okegawa
Affiliations
  • 1. Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
PMID: 3336036 DOI: 10.1021/jm00396a013
Abstract

(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD4-induced smooth muscle contraction on guinea pig ileum and LTC4-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C4 and D4. Among both series, ONO-RS-347 (18k) and ONO-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.

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