Novel second generation analogs of eribulin. Part II: Orally available and active against resistant tumors in vivo
| Autor: | Edgar Schuck, Bruce A. Littlefield, Sean Eckley, Wanjun Zheng, Hongsheng Cheng, Huiming Zhang, Melvin J. Yu, Hong Du, Yimin Jiang, Carlson Eric, Yongbo Hu, Karen TenDyke, Murray J. Towle, Bryan M. Lewis, Philip Saxton, Boris M. Seletsky, Vipul Kumar, Krista Condon, Sridhar Narayan |
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| Rok vydání: | 2010 |
| Předmět: |
Eribulin Mesylate
Clinical Biochemistry Pharmaceutical Science Administration Oral Biological Availability Antineoplastic Agents Pharmacology Biochemistry chemistry.chemical_compound Mice In vivo Oral administration Drug Discovery medicine Animals Humans Furans Molecular Biology P-glycoprotein Mice Inbred BALB C biology Organic Chemistry Ketones medicine.disease Metastatic breast cancer Xenograft Model Antitumor Assays Multiple drug resistance chemistry Drug Resistance Neoplasm biology.protein Molecular Medicine Efflux Eribulin |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(6) |
| ISSN: | 1464-3405 |
| Popis: | Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. |
| Databáze: | OpenAIRE |
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