- IRE-1α INHIBITORS
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PROBLEM TO BE SOLVED: To provide compounds which directly inhibit inositol requiring enzyme 1 (IRE-1α activity) in vitro, prodrugs, and pharmaceutically acceptable salts thereof. SOLUTION: The present invention provides a compound represented by formula (A) [R3 and R4 are H or the like; Q5-Q8, together with the benzene ring to which they are attached, form a benzofused ring, where at least one of Q5-Q8 is a heteroatom selected from N, O, and S. COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 1226; 1227
(2016/10/07)
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- (Phenylmethoxy)phenyl Derivatives of Ω-Oxo- and Ω-Tetrazolylalkanoic Acids and Related Tetrazoles. Synthesis and Evaluation as Leukotriene D4 Receptor Antagonists
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Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists.In the Ω--Ω-oxoalkanoic acid series, 5-phenyl>-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv).Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds.Inthe Ω-alkyl>tetrazolyl>alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat.The pKB value in the guinea pig ileum for 1--2H-tetrazol-5-yl>methyl>phenoxy>methyl>phenyl>ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv.The sodium salts of 8 (9) and 25(26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner.Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.
- Dillard, Robert D.,Hahn, Richard A.,McCullough, Doris,Carr, F. Patrick,Rinkema, Lynn E.,et al.
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p. 2768 - 2778
(2007/10/02)
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- Studies on Cannabinoids: Part IV - Synthesis of 9,10,11,11a-Tetrahydro-3-methoxy-6H,8H-pyridobenzoxazine Involving an Unusual Case of Demethylation by Lithium Aluminium Hydride
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The synthesis of title compound is described by condensation of 2-(2'-hydroxy-4'-methoxyphenyl)piperidine (10) with methylene bromide.The former in turn is obtained by selective demethylation of on of the methoxy groups during the LAH reduction of 6-(2',4
- Malik, O. P.,Kapil, R. S.,Anand, Nitya
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p. 912 - 914
(2007/10/02)
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