期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 24, 期 4, 页码 1144-1147出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.12.126
关键词
Cleavable linkers; Drug targeting; Liver targeting; Carboxylesterase
资金
- Pfizer Global Research Development
- NIH [P50 GM103368-01]
A design for the selective release of drug molecules in the liver was tested, involving the attachment of a representative active agent by an ester linkage to various 2-substituted 5-aminovaleric acid carbamates. The anticipated pathway of carboxylesterase-1-mediated carbamate cleavage followed by lactamization and drug release was frustrated by unexpectedly high sensitivity of the ester linkage toward hydrolysis by carboxylesterase-2 and other microsomal components. (C) 2014 Elsevier Ltd. All rights reserved.
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