Structure-activity relationship (SAR) studies of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione: development of potential substrate-specific ERK1/2 inhibitors.
A series of analogs of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione, a putative substrate-specific ERK1/2 inhibitor, were synthesized and biologically characterized in human leukemia U937 cells to define its pharmacophore. It was discovered that shift of ethoxy substitution from the 4- to the 2-position on the phenyl ring significantly improved functional activities of inhibiting cell proliferation and inducing apoptosis. This may provide access to a new lead for developing ERK1/2 substrate-specific inhibitors.
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
Qianbin
Q
Li
Adnan
A
Al-Ayoubi
Tailiang
T
Guo
Hui
H
Zheng
Aurijit
A
Sarkar
Tri
T
Nguyen
Scott T
ST
Eblen
Steven
S
Grant
Glen E
GE
Kellogg
Shijun
S
Zhang
D017209:Apoptosis; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003198:Computer Simulation; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
C546148:3-(2-aminoethyl)-5-(4-ethoxybenzylidene)thiazolidine-2,4-dione; D047428:Protein Kinase Inhibitors; D045162:Thiazolidinediones; D048052:Mitogen-Activated Protein Kinase 3