5-Ureidobenzofuranone indoles as potent and efficacious inhibitors of PI3 kinase-[alpha] and mTOR for the treatment of breast cancer
Journal Article
·
· Bioorg. Med. Chem. Lett.
- Wyeth
A series of 5-ureidobenzofuran-3-one indoles as potent inhibitors of PI3K{alpha} and mTOR has been developed. The best potency in cells was obtained when the urea group was extended to a 4-[2-(dimethylamino)ethyl]methylamino amidophenyl group. A 7-fluoro group on the indole ring also enhanced cellular potency. Compound 18i, incorporating the optimal functional groups, showed high potency in cellular lines and was further studied in vivo. It was able to inhibit the biomarker phosphorylation for 8 h when dosed at 25 mg/kg iv. In the MDA-MB-361 breast cancer model, it shrank the tumor size remarkably when dosed at 25 mg/kg iv on days 1, 5, and 9.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1002829
- Journal Information:
- Bioorg. Med. Chem. Lett., Vol. 20, Issue (12) ; 06, 2010; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
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