progesterone carboxymethyloxime

{{short description|Chemical compound}}

{{Drugbox

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| 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

| image = Progesterone carboxymethyloxime.svg

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| routes_of_administration = By mouth

| class = Progestogen; Neurosteroid

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| CAS_number = 50909-89-2

| CAS_supplemental =
118860-31-4 (potassium)

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| PubChem = 11977776

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| ChemSpiderID = 10151119

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| ChEBI = 62042

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| synonyms = 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

| C=23 | H=33 | N=1 | O=4

| 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

| StdInChI_Ref =

| StdInChI = 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

| StdInChIKey_Ref =

| StdInChIKey = PPELYUTTZHLIAZ-CDUDAXDSSA-N

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Progesterone carboxymethyloxime, or progesterone 3-(O-carboxymethyl)oxime (P4-3-CMO), is a progestin which was never marketed.{{cite journal| vauthors = Basu K, Mitra AK |title=Effects of 3-hydrazone modification on the metabolism and protein binding of progesterone|journal=International Journal of Pharmaceutics|volume=65|issue=1–2|date = November 1990 |pages=109–114|issn=0378-5173|doi=10.1016/0378-5173(90)90015-V}}{{cite journal| vauthors = Basu K, Kildsig DO, Mitra AK |title=Synthesis and kinetic stability studies of progesterone derivatives|journal=International Journal of Pharmaceutics|volume=47|issue=1–3| date = November 1988 |pages=195–203|issn=0378-5173|doi=10.1016/0378-5173(88)90231-1}}{{cite journal | vauthors = Singh H, Jindal DP, Yadav MR, Kumar M | title = Heterosteroids and drug research | volume = 28 | pages = 233–300 | date = 1991 | pmid = 1843548 | doi = 10.1016/S0079-6468(08)70366-7 | isbn = 9780444812759 | journal = Progress in Medicinal Chemistry }} It is an oral prodrug of progesterone with improved pharmacokinetic properties. 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. 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. Drugs with low aqueous solubility are not absorbed well in the intestines because their dissolution in water is limited.{{cite book| vauthors = Liu R |title=Water-Insoluble Drug Formulation, Second Edition|url=https://books.google.com/books?id=4cfzT2ZY8hUC&pg=PA105|date=18 January 2008|publisher=CRC Press|isbn=978-1-4200-0955-2|pages=105–}}

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). 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). As such, P4-3-CMO could have both improved absorption and increased metabolic stability relative to progesterone. However, the compound has not been further assessed nor studied in humans.