DU-41164

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DU-41164
DU-41164.svg
Clinical data
Synonyms1,2β-Methylene-6-fluoro-17α-acetoxy-δ6-retroprogesterone; 6-Fluoro-17α-hydroxy-1,2β-methylene-9β,10α-pregna-4,6-diene-3,20-dione 17α-acetate; 6-Fluoro-1,2β-methylene-3,20-dioxo-9β,10α-pregna-4,6-dien-17α-yl acetate; (1α,​2α,​9β,​10α)​-17-​Acetoxy​-​6-​fluoro-​1,​2-​dihydro-​3'H-​cyclopropa[1,​2]​pregna-​1,​4,​6-​triene-​3,​20-​dione
Routes of
administration
By mouth
Drug classProgestin; Progestogen
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC24H29FO4
Molar mass400.49 g/mol g·mol−1
3D model (JSmol)

DU-41164, also known as 1,2β-methylene-6-fluoro-17α-acetoxy-δ6-retroprogesterone, is a progestin which was developed by Philips-Duphar in the 1970s and was never marketed.[1][2][3][4][5] It is a combined derivative of 17α-hydroxyprogesterone and retroprogesterone.[1][2][3][4] The drug shows extremely high potency as a progestogen in animals; it was reported to possess 500 times the affinity of progesterone for the progesterone receptor expressed in rabbit uterus (Ki = 0.87 pM and 0.41 nM, respectively), and showed 600 times the progestogenic potency of subcutaneous progesterone when given orally in animals.[1][2] The affinity of DU-41164 for the progesterone receptor was described in 1974 as "probably the highest reported for any steroid-receptor interaction".[2] The drug showed no androgenic, anabolic, antiandrogenic, estrogenic, or corticosteroid activity in animals.[3] Although highly potent in animals, DU-41164 produced little or no progestogenic effect at dosages of 50 and 200 µg/day in women, suggesting major species differences.[3] A closely related compound, DU-41165, has been developed as a photoaffinity label for the progesterone receptor.[3]

References[edit]

  1. ^ a b c Halkes SJ, Hartog J, Morsink L, de Wachter AM (December 1972). "Investigations on sterols. 38. Synthesis of 1,2β-methylene-17α-acetoxy-9β,10α-pregnanes, a class of potent progestational agents". J. Med. Chem. 15 (12): 1288–92. doi:10.1021/jm00282a022. PMID 4635976.
  2. ^ a b c d Terenius L (June 1974). "Affinities of progestogen and estrogen receptors in rabbit uterus for synthetic progestogens". Steroids. 23 (6): 90919. doi:10.1016/0039-128X(74)90063-4. PMID 4134774.
  3. ^ a b c d e Morsink L, de Wachter AM, Brenner P, Cekan SZ, Guerrero R, Hagenfeldt K, Diczfalusy E (May 1976). "Endocrine effects of two new retro-steroids in animal models and in women". Acta Endocrinol. 82 (1): 193–212. doi:10.1530/acta.0.0820193. PMID 57688.
  4. ^ a b Pinney KG, Carlson KE, Katzenellenbogen JA (February 1990). "[3H]DU41165: a high affinity ligand and novel photoaffinity labeling reagent for the progesterone receptor". J. Steroid Biochem. 35 (2): 179–89. doi:10.1016/0022-4731(90)90272-T. PMID 2308335.
  5. ^ AdrainD. Nunn (27 April 2018). Radiopharmaceuticals: Chemistry and Pharmacology. CRC Press. pp. 1–. ISBN 978-1-351-41989-5.