Rogletimide

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]

Pharmacodynamics of aromatase inhibitors

Generation	Medication	Dosage	% inhibition^a	Class^b	IC50^c
First	Testolactone	250 mg 4x/day p.o.	?	Type I	?
		100 mg 3x/week i.m.	?
	Rogletimide	200 mg 2x/day p.o. 400 mg 2x/day p.o. 800 mg 2x/day p.o.	50.6% 63.5% 73.8%	Type II	?
	Aminoglutethimide	250 mg mg 4x/day p.o.	90.6%	Type II	4,500 nM
Second	Formestane	125 mg 1x/day p.o. 125 mg 2x/day p.o. 250 mg 1x/day p.o.	72.3% 70.0% 57.3%	Type I	30 nM
		250 mg 1x/2 weeks i.m. 500 mg 1x/2 weeks i.m. 500 mg 1x/1 week i.m.	84.8% 91.9% 92.5%
	Fadrozole	1 mg 1x/day p.o. 2 mg 2x/day p.o.	82.4% 92.6%	Type II	?
Third	Exemestane	25 mg 1x/day p.o.	97.9%	Type I	15 nM
	Anastrozole	1 mg 1x/day p.o. 10 mg 1x/day p.o.	96.7–97.3% 98.1%	Type II	10 nM
	Letrozole	0.5 mg 1x/day p.o. 2.5 mg 1x/day p.o.	98.4% 98.9%–>99.1%	Type II	2.5 nM
Footnotes: ^a = In postmenopausal women. ^b = Type I: Steroidal, irreversible (substrate-binding site). Type II: Nonsteroidal, reversible (binding to and interference with the cytochrome P450 heme moiety). ^c = In breast cancer homogenates. Sources: See template.

Rogletimide

Clinical data
Other names	Roglethimide; Pyridoglutethimide
Routes of administration	By mouth
Drug class	Aromatase inhibitor
Identifiers
IUPAC name 3-ethyl-3-(pyridin-4-yl)piperidine-2,6-dione
CAS Number	92788-10-8
PubChem CID	56487
ChemSpider	50963
UNII	14P4QR28QF
Chemical and physical data
Formula	C12H14N2O2
Molar mass	218.256 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C1NC(=O)CCC1(c2ccncc2)CC

References

1. 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.
2. 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.
3. 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.