Synthesis and biological evaluation of sulfonamidooxazoles and beta-keto sulfones: selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.
The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeutic potential for metabolic syndrome, type 2 diabetes and related metabolic dysfunctions.
Xiang
Jason
J
Chemical and Screening Sciences, Wyeth Research, MA 02140, USA. jxiang@wyeth.com
Ipek
Manus
M
Suri
Vipin
V
Massefski
Walt
W
Pan
Ning
N
Ge
Ying
Y
Tam
May
M
Xing
Yuzhe
Y
Tobin
James F
JF
Xu
Xin
X
Tam
Steve
S
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010080:Oxazoles; D013450:Sulfones; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1