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Abandoned drugs
Rogletimide
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    Rogletimide

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    Rogletimide
    Rogletimide.svg
    Clinical data
    Other names Roglethimide; Pyridoglutethimide
    Routes of
    administration    		 By mouth
    Drug class Aromatase inhibitor
    Identifiers
    • 3-ethyl-3-(pyridin-4-yl)piperidine-2,6-dione
    CAS Number
    PubChem CID
    ChemSpider
    UNII
    Chemical and physical data
    Formula C12H14N2O2
    Molar mass 218.256 g·mol−1
    3D model (JSmol)
    • O=C1NC(=O)CCC1(c2ccncc2)CC

    Rogletimide, also known as pyridoglutethimide, is a medication which was never marketed. 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. 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.

    Pharmacodynamics of aromatase inhibitors
    Generation Medication Dosage % inhibitiona Classb IC50c
    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.

    Synthesis

    Synthesis: Patent:

    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).



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