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Scaffold-Hopping Strategy: Synthesis and Biological Evaluation of 5,6-Fused Bicyclic Heteroaromatics To Identify Orally Bioavailable Anticancer Agents
- Source :
- Journal of Medicinal Chemistry. 54:3076-3080
- Publication Year :
- 2011
- Publisher :
- American Chemical Society (ACS), 2011.
-
Abstract
- Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F < 10%).
- Subjects :
- Indole test
Bicyclic molecule
Stereochemistry
Drug candidate
Chemistry
Strategy synthesis
Administration, Oral
Biological Availability
Antineoplastic Agents
Scaffold hopping
Combinatorial chemistry
In vitro
Bioavailability
Bridged Bicyclo Compounds
Cell Line, Tumor
Drug Discovery
Humans
Molecular Medicine
Biological evaluation
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....0a3eefd1e0f719d648b04b95b716d0ff