AI Article Synopsis
- Several prodrug strategies were employed to modify amino groups in nNOS inhibitors to enhance their ability to cross the blood-brain barrier (BBB).
- The primary amine was converted to an azide, while the secondary amine was transformed into either an amide or carbamate to reduce their charge.
- Despite these modifications, the expected improvement in BBB penetration was not achieved, indicating that these prodrug techniques may not be effective for central nervous system applications.
Article Abstract
Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood-brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775413 | PMC |
| http://dx.doi.org/10.1016/j.bmc.2009.08.065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!