Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.
Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.
AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. cmeng@atherogenics.com
Charles Q
CQ
Meng
X Sharon
XS
Zheng
Liming
L
Ni
Zhihong
Z
Ye
Jacob E
JE
Simpson
Kimberly J
KJ
Worsencroft
Martha R
MR
Hotema
M David
MD
Weingarten
Jason W
JW
Skudlarek
Joshua M
JM
Gilmore
Lee K
LK
Hoong
Russell R
RR
Hill
Elaine M
EM
Marino
Ki-Ling
KL
Suen
Charles
C
Kunsch
Martin A
MA
Wasserman
James A
JA
Sikorski
D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D006571:Heterocyclic Compounds; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D002599:Chalcone