Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase.
The synthesis and biological evaluation of a series of N-alkyl glycine amide analogs as LTA(4)-h inhibitors and the importance of the introduction of a benzoic acid group to the potency and pharmacokinetic parameters of our analogs are described. The lead compound in the series, 4q, has excellent potency and oral bioavailability.
Ye
Bin
B
Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA.
Bauman
John
J
Chen
Ming
M
Davey
David
D
Khim
Seock-Kyu
SK
King
Beverly
B
Kirkland
Thomas
T
Kochanny
Monica
M
Liang
Amy
A
Lentz
Dao
D
May
Karen
K
Mendoza
Lisa
L
Phillips
Gary
G
Selchau
Victor
V
Schlyer
Sabine
S
Tseng
Jih-Lie
JL
Wei
Robert G
RG
Ye
Hong
H
Parkinson
John
J
Guilford
William J
WJ
D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019817:Benzoic Acid / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D004987:Ethers; D005998:Glycine / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical
D000577:Amides; D000588:Amines; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D004987:Ethers; D019817:Benzoic Acid; D004851:Epoxide Hydrolases; D005998:Glycine; C043134:leukotriene A4 hydrolase