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Isosteric analogs of lenalidomide and pomalidomide: synthesis and biological activity.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Jan 01; Vol. 23 (1), pp. 360-5. Date of Electronic Publication: 2012 Oct 27. - Publication Year :
- 2013
-
Abstract
- A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Cell Line, Tumor
Cell Proliferation drug effects
Half-Life
Humans
Interleukin-2 metabolism
Lenalidomide
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Rats
Structure-Activity Relationship
T-Lymphocytes drug effects
T-Lymphocytes metabolism
Thalidomide chemistry
Thalidomide pharmacokinetics
Thalidomide toxicity
Tumor Necrosis Factor-alpha metabolism
Thalidomide analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23168019
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.10.071