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Two series of phenylephrine derivatives were prepared and tested as inhibitors of leukotriene D4 (LTD4) induced and ovalbumin-induced bronchospasm in the guinea pig. The most potent compound of the urea series, (R)-N,N-diethyl-N-[2-hydroxy-2-[3-(2-quinolinylmethoxy)phenyl]ethyl]-N- methylurea (3, Wy-47,120), was orally active with ED50's of 56 mg/kg vs. LTD4 and 55 mg/kg vs. ovalbumin. When tested as an antagonist of LTD4-induced contraction of isolated guinea pig tracheal strips, 3 was a competitive inhibitor with a p kappa B value of 5.22. In the second series, (R)-3-methyl-5-[3-(2-quinolinylmethoxy)phenyl]-2-oxazolidinone (26, Wy-47,674) had oral ED50's of 36 mg/kg against LTD4 and 95 mg/kg against ovalbumin. Compound 26 selectively antagonized contractile responses of guinea pig trachea evoked by LTD4 (p kappa B = 6.09). In the cat coronary artery, 3 dilated the preparation and blocked the coronary constrictor effect of LTD4. Compound 3 (0.13 mg/kg, iv) also preserved myocardial integrity in rats 48 h after coronary artery ligation. When tested in the rat alcohol-induced gastric lesion model, 3 and 26 manifested a dose-dependent mucosal protection against ethanol.
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
April 2000,
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
July 1986,
Journal of medicinal chemistry,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
January 1990,
Methods in enzymology,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
January 1988,
Journal of medicinal chemistry,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
July 1998,
Bioorganic & medicinal chemistry letters,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
January 1989,
Advances in prostaglandin, thromboxane, and leukotriene research,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
April 1992,
Journal of medicinal chemistry,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
April 1987,
The Journal of pharmacology and experimental therapeutics,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
September 1991,
Journal of medicinal chemistry,
J H Musser, and
D M Kubrak, and
R H Bender, and
A F Kreft, and
S T Nielsen, and
A M Lefer, and
J Chang, and
A J Lewis, and
J M Hand
June 2002,
Bioorganic & medicinal chemistry letters,
