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 names	P4-3-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 class	Progestogen; 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	50909-89-2 118860-31-4 (potassium)
PubChem CID	11977776
ChemSpider	10151119
ChEBI	CHEBI:62042
CompTox Dashboard (EPA)	DTXSID501287492
ECHA InfoCard	100.164.875
Chemical and physical data
Formula	C23H33NO4
Molar mass	387.520 g·mol−1
3D model (JSmol)	Interactive image
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

• List of neurosteroids § Inhibitory > Synthetic > Pregnanes
• List of progestogen esters § Oximes of progesterone derivatives