Quinoline-carboxylic acids are potent inhibitors that inhibit the binding of insulin-like growth factor (IGF) to IGF-binding proteins.
4-benzylquinolines 5, based on a series of isoquinolines 1, were prepared and tested as inhibitors of the IGF/IGFBP-3 complex based on their ability to displace IGF-I from its binding to IGF-binding protein-3. SAR studies on the 6,7-dihydroxy moiety of the quinoline 5a showed that the catecol moiety could be replaced with other functional groups. Computational modeling of the 5a/mini-IGFBP-5 complex revealed the possible binding site of 5a on IGFBP-5.
Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
Yun-Fei
YF
Zhu
Xiao-Chuan
XC
Wang
Patrick
P
Connors
Keith
K
Wilcoxen
Yinghong
Y
Gao
Raymond
R
Gross
Nathalie
N
Strack
Timothy
T
Gross
James R
JR
McCarthy
Qiu
Q
Xie
Nicholas
N
Ling
Chen
C
Chen
D000146:Acids, Carbocyclic / Q000737:chemistry* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000146:Acids, Carbocyclic; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D011804:Quinolines; D007334:Insulin-Like Growth Factor I