Ultrasound-promoted synthesis and immunosuppressive activity of novel quinazoline derivatives.
An environmentally friendly and mild Bischler cyclization was developed to access quinazolines with diverse substitution. Based on this method, a library of 53 quinazoline derivatives was prepared and tested in vitro for cytotoxicity and inhibition on T-cell and B-cell proliferation. Compounds 6b, 7b, 17b, 33, and 35 showed higher inhibitory activity on both T-cell and B-cell proliferations, with IC(50) values of 6.16, 6.30, 5.43, 2.54, and 9.80 μM on T-cell, respectively. All the tested compounds showed no obvious cytotoxicity at 10 μM concentration. The preliminary structure-activity relationship was concluded revealing that 4-position is the key modification site for potent quinazoline immunosuppressive agent.
State Key lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
Lei
L
Zhang
Zhe
Z
Gao
Chen
C
Peng
Zheng-Yang
ZY
Bin
Dan
D
Zhao
Jing
J
Wu
Qiang
Q
Xu
Jian-Xin
JX
Li
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D005260:Female; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014465:Ultrasonics
D007166:Immunosuppressive Agents; D011799:Quinazolines