11-Ketoprogesterone

Chemical compound (8S,9S,10R,13S,14S,17S)-17-Acetyl-10,13-dimethyl-2,6,7,8,9,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3,11-dione 11-Ketoprogesterone.svg skin-invert-image 200px Ketogestin 516-15-4 94166 84982 9Y1Y86O4T5 284253 21 28 3 CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC(=O)[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C 1S/C21H28O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-17,19H,4-9,11H2,1-3H3/t15-,16+,17-,19+,20-,21+/m0/s1 WKAVAGKRWFGIEA-DADBAOPHSA-N Bio 66; U-1258; 11-Oxoprogesterone; Pregn-4-ene-3,11,20-trione 11-Ketoprogesterone (brand name Ketogestin; former developmental code names Bio 66, U-1258), or 11-oxoprogesterone, also known as pregn-4-ene-3,11,20-trione, is a pregnane steroid related to cortisone (11-keto-17α,21-dihydroxyprogesterone) that was formerly used in veterinary medicine in the treatment of bovine ketosis. Elks J The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1014 14 November 2014 Springer 978-1-4757-2085-3 1014– It was synthesized in 1940. The steroid has profound effects on carbohydrate metabolism and possesses activities associated with adrenal cortex hormones like cortisone.Veterinary Medicine https://books.google.com/books?id=PVQmAQAAMAAJ 1953 American Veterinary Publishing Company Experimentally, it is reported that ketogestin has a profound effect upon carbohydrate metabolism, accelerating production of glucose from protein (gluconegenesis). It possesses physiological activities associated with certain hormones of the adrenal cortex. Its effect on carbohydrate metabolism is similar to that of cortisone, as proved by deposition of glycogen, increasing glycosuria, and decreasing fat metabolism. This compound, however, does not cause certain undesirable activities in ketosis and other conditions as do other adrenocortical hormones, in that it does not cause retention of the sodium ion, nor does it produce hypertension during high sodium ion intake. Ketogestin is devoid of androgenic, estrogenic, or progestational activity and is nontoxic in amounts greatly exceeding pharmacological dosage. However, it is non-toxic even in high dosages, suggesting that it lacks conventional glucocorticoid activity, and it does not possess mineralocorticoid activity, unlike other adrenocortical hormones. 11-Ketoprogesterone may act through membrane glucocorticoid receptors. Harrison RW, Balasubramanian K, Yeakley J, Fant M, Svec F, Fairfield S Steroid Hormone Receptor Systems Heterogeneity of AtT-20 Cell Glucocorticoid Binding Sites: Evidence for a Membrane Receptor Advances in Experimental Medicine and Biology 117 423–440 1979 Springer 10.1007/978-1-4757-6589-2_23 474288 978-1-4757-6591-5 11-Ketoprogesterone is reportedly devoid of androgenic, estrogenic, and progestogenic activity. Kincl FA Copulatory Reflix Response to Steroids Dorfman RI Steroidal Activity in Experimental Animals and Man https://books.google.com/books?id=BbLfBAAAQBAJ&pg=PA482 22 October 2013 Elsevier Science 978-1-4832-7299-3 482– 11β-Hydroxyprogesterone has also been reported to be devoid of progestogenic activity, but has subsequently been reported to possess about 1% of the progestogenic activity of progesterone.Otto Hoffmann-Ostenhof Proceedings of the Fourth International Congress of Biochemistry, Vienna, 1-6 September, 1958 https://books.google.com/books?id=250hAQAAMAAJ 1959 and 269 In addition, it had been previously reported that 11β-hydroxyprogesterone was devoid of progestational action. However, we found that it does possess about 1% of the activity of progesterone. This trace activity is substantially enhanced by fluorination, since 9α-fluoro-11β-hydroxyprogesterone is eight times as active as the non-halogenated analogue.6 Concomitantly, Fried et al.7 described the relatively high progestational activity of 9α-bromo-11-ketoprogesterone as well. A halogenated derivative of 11-ketoprogesterone, 9α-bromo-11-ketoprogesterone, possesses relatively high progestogenic activity. Similarly to 11α-hydroxyprogesterone and 11β-hydroxyprogesterone, 11-ketoprogesterone is reported to act as an inhibitor of the enzyme 11β-hydroxysteroid dehydrogenase. Piwien-Pilipuk G, Galigniana MD Oxidative stress induced by L-buthionine-(S,R)-sulfoximine, a selective inhibitor of glutathione metabolism, abrogates mouse kidney mineralocorticoid receptor function Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1495 3 263–280 February 2000 10699465 10.1016/s0167-4889(99)00166-4 free It has also been found to act as a weak negative allosteric modulator of the GABAA receptor. Zhong Y, Simmonds MA Pharmacological characterisation of multiple components in the enhancement by pregnanolone and propofol of [3H]flunitrazepam binding to GABAA receptors Neuropharmacology 35 9–10 1193–1198 1996 9014134 10.1016/s0028-3908(96)00056-1 20839591 See also 11-Dehydrocorticosterone (11-keto-21-hydroxyprogesterone) 21-Deoxycortisone (11-keto-17α-hydroxyprogesterone) References 30em Category:11β-Hydroxysteroid dehydrogenase inhibitors Category:GABAA receptor negative allosteric modulators Category:Pregnanes Category:Triketones