Synthesis of new sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors.
A series of new sulfonyl pyrrolidine derivatives was designed, synthesized, and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The compounds 4c, 4j, 5a, and 5b were equally or more potent MMP-2 inhibitors than the positive control LY52. The FlexX docking was done to explain the reason for the different potency between MMP-2 and AP-N. Structure-activity relationships were also briefly discussed.
Cheng
Xian-Chao
XC
Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No.44 Wenhuaxi Road, Jinan 250012, China. chengxianchao2000@yahoo.com.cn
Wang
Qiang
Q
Fang
Hao
H
Tang
Wei
W
Xu
Wen-Fang
WF
D001665:Binding Sites / Q000187:drug effects; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D061965:Matrix Metalloproteinase Inhibitors; D008956:Models, Chemical; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011759:Pyrrolidines; D013450:Sulfones; D018826:CD13 Antigens