Progesterone carboxymethyloxime

Progesterone carboxymethyloxime, or progesterone 3-(O-carboxymethyl)oxime (P4-3-CMO), is a progestin which was never marketed.[1][2][3] It is an oral prodrug of progesterone with improved pharmacokinetic properties.[1] The compound was developed in an attempt to address the poor oral pharmacokinetics of progesterone, including its very low bioavailability and short biological half-life.[1][2] These properties of progesterone are thought to be caused by its low water solubility and high metabolic clearance rate due to rapid degradation in the intestines and liver.[1][2] Drugs with low aqueous solubility are not absorbed well in the intestines because their dissolution in water is limited.[4]

Progesterone carboxymethyloxime
Clinical data
Other namesP4-3-CMO; Progesterone 3-carboxymethyloxime; Progesterone 3-(O-carboxymethyl)oxime; 3-(O-Carboxymethyl-oximino)progesterone; [[(20-Oxopregn-4-en-3-ylidene)amino]oxy]acetic acid
Routes of
administration		By mouth[1]
Drug classProgestogen; Neurosteroid
Identifiers
IUPAC name
  • 2-[(E)-[(8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]amino]oxyacetic acid
CAS Number
PubChem CID
ChemSpider
ChEBI
ECHA InfoCard100.164.875
Chemical and physical data
FormulaC23H33NO4
Molar mass387.520 g·mol−1
3D model (JSmol)
SMILES
  • CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C/C(=N/OCC(=O)O)/CC[C@]34C)C
InChI
  • InChI=1S/C23H33NO4/c1-14(25)18-6-7-19-17-5-4-15-12-16(24-28-13-21(26)27)8-10-22(15,2)20(17)9-11-23(18,19)3/h12,17-20H,4-11,13H2,1-3H3,(H,26,27)/b24-16+/t17-,18+,19-,20-,22-,23+/m0/s1
  • Key:PPELYUTTZHLIAZ-CDUDAXDSSA-N

P4-3-CMO (as the potassium salt) showed water solubility that was increased by more than four orders of magnitude relative to progesterone (solubility = 9.44 mol/L and 0.0006 mol/L, respectively).[2] In addition, it showed an in vitro terminal half-life in rat liver microsomes that was 363-fold longer than that of progesterone (half-life = 795.5 minutes and 2.2 minutes, respectively).[1] As such, P4-3-CMO could have both improved absorption and increased metabolic stability relative to progesterone.[1][2] However, the compound has not been further assessed nor studied in humans.[1][2]

See also

References
  1. Basu, Krishnakali; Mitra, Ashim K. (1990). "Effects of 3-hydrazone modification on the metabolism and protein binding of progesterone". International Journal of Pharmaceutics. 65 (1–2): 109–114. doi:10.1016/0378-5173(90)90015-V. ISSN 0378-5173.
  2. Basu, Krishnakali; Kildsig, Dane O.; Mitra, Ashim K. (1988). "Synthesis and kinetic stability studies of progesterone derivatives". International Journal of Pharmaceutics. 47 (1–3): 195–203. doi:10.1016/0378-5173(88)90231-1. ISSN 0378-5173.
  3. Singh H, Jindal DP, Yadav MR, Kumar M (1991). "Heterosteroids and drug research". Prog Med Chem. Progress in Medicinal Chemistry. 28: 233–300. doi:10.1016/S0079-6468(08)70366-7. ISBN 9780444812759. PMID 1843548.
  4. Ron Liu (18 January 2008). Water-Insoluble Drug Formulation, Second Edition. CRC Press. pp. 105–. ISBN 978-1-4200-0955-2.



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