Tryptamine and homotryptamine-based sulfonamides as potent and selective inhibitors of 15-lipoxygenase.
A series of inhibitors of mammalian 15-lipoxygenase based on tryptamine and homotryptamine scaffolds is described. Compounds with aryl substituents at C-2 of the indole core of tryptamine and homotryptamine sulfonamides (e.g., 37a-p) proved to be potent inhibitors of the isolated enzyme. Selected compounds also demonstrated desirable inhibition selectivities over isozymes 5- and P-12-LO.
Weinstein
David S
DS
Bristol-Myers Squibb Pharmaceutical Research Institute, Bristol-Myers Squibb, PO Box 4000, Princeton, NJ 08543, USA. david.weinstein@bms.com
Liu
Wen
W
Gu
Zhengxiang
Z
Langevine
Charles
C
Ngu
Khehyong
K
Fadnis
Leena
L
Combs
Donald W
DW
Sitkoff
Doree
D
Ahmad
Saleem
S
Zhuang
Shaobin
S
Chen
Xing
X
Wang
Feng-Lai
FL
Loughney
Deborah A
DA
Atwal
Karnail S
KS
Zahler
Robert
R
Macor
John E
JE
Madsen
Cort S
CS
Murugesan
Natesan
N
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D014363:Tryptamines / Q000737:chemistry*
D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D013449:Sulfonamides; D014363:Tryptamines