DU-41164

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]

DU-41164
Clinical data
Other names1,2β-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
IUPAC name
  • (2aS,3aR,3bR,3cR,5aS,6R,8aS,8bR)-6-Acetyl-10-fluoro-3b,5a-dimethyl-2-oxo-2,2a,3,3a,3b,3c,4,5,5a,6,7,8,8a,8b-tetradecahydrocyclopenta[a]cyclopropa[g]phenanthren-6-yl acetate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H29FO4
Molar mass400.490 g·mol−1
3D model (JSmol)
SMILES
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@@H]3[C@H]2C=C(C4=CC(=O)[C@H]5C[C@H]5[C@@]34C)F)C)OC(=O)C
InChI
  • InChI=1S/C24H29FO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)15-9-18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15-,16-,17+,18+,22-,23+,24-/m0/s1
  • Key:WJSHHKQEKQVLOP-QHAUNDHQSA-N

References
  1. 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. Terenius L (June 1974). "Affinities of progestogen and estrogen receptors in rabbit uterus for synthetic progestogens". Steroids. 23 (6): 909–919. doi:10.1016/0039-128X(74)90063-4. PMID 4134774.
  3. 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. 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.


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