| Iupac name | 3-ethyl-3-(pyridin-4-yl)piperidine-2,6-dione |
|---|---|
| Width | 175px |
| Routes of administration | By mouth |
| Class | Aromatase inhibitor |
| Cas number | 92788-10-8 |
| Pubchem | 56487 |
| Chemspiderid | 50963 |
| Unii | 14P4QR28QF |
| Synonyms | Roglethimide; Pyridoglutethimide |
| C | 12 |
| H | 14 |
| N | 2 |
| O | 2 |
| Smiles | O=C1NC(=O)CCC1(c2ccncc2)CC |
Rogletimide, also known as pyridoglutethimide, is a medication which was never marketed.[1] It is related in chemical structure to the sedative/hypnotic drug glutethimide, but instead has pharmacological activity as a selective aromatase inhibitor similar to the related drug aminoglutethimide and has no significant sedative-hypnotic effect.[2] This makes it potentially useful in the treatment of breast cancer, and with fewer side effects than aminoglutethimide, but its lower potency caused it to be unsuccessful in clinical trials.[1][3]
Synthesis
Base catalyzed alkylation of ethyl 4-pyridylacetate [54401-85-3] (1) with iodoethane gives ethyl 2-(4-pyridyl)butyrate [76766-56-8] (2). Base catalyzed conjugate addition of the carbanion to acrylamide (3) gives (4). The last step is an intramolecular cyclization to rogletimide (5).
References
- ^ Frederick A. Luzzio (17 May 2019). Imides: Medicinal, Agricultural, Synthetic Applications and Natural Products Chemistry. Elsevier Science. pp. 361–. ISBN 978-0-12-815676-6.
- ^ Vanden Bossche HV, Moereels H, Koymans LM (1994). "Aromatase inhibitors--mechanisms for non-steroidal inhibitors". Breast Cancer Research and Treatment. 30 (1): 43–55. doi:10.1007/bf00682740. PMID 7949204. S2CID 24414161
- ^ MacNeill FA, Jones AL, Jacobs S, Lønning PE, Powles TJ, Dowsett M (October 1992). "The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer". British Journal of Cancer. 66 (4): 692–7. doi:10.1038/bjc.1992.339. PMC 1977412. PMID 1419608