A practical large-scale synthesis of 17α-acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914)

Steroids

Volumn 65, Issue 7, 2000, Pages 395-400

  Rao, Pemmaraju N ^a   Acosta, C Kirk ^a   Bahr, Martin L ^a   Burdett, James E ^a   Cessac, James W ^a   Morrison, Paul A ^a   Kim, Hyun K ^b  

^a SW Found for Biological Research   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

Antiprogestins; Steroids; Synthesis

Indexed keywords

17ALPHA ACETOXY 11BETA (4 DIMETHYLAMINOPHENYL) 19 NORPREGNA 4,9 DIENE 3,20 DIONE; ANTIGESTAGEN; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OXIDATION; PURIFICATION; REACTION ANALYSIS;

CHROMATOGRAPHY, THIN LAYER; CONTRACEPTIVES, POSTCOITAL, SYNTHETIC; MAGNETIC RESONANCE SPECTROSCOPY; NORPREGNADIENES; SPECTROSCOPY, FOURIER TRANSFORM INFRARED;

EID: 0033935074     PISSN: 0039128X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0039-128X(00)00100-8     Document Type: Article

References (14)

1. Philibert D, Deraedt R, Teutsch G, Tournemine C, Sakez E. A new lead for steroidal antihormones. 64th Annual Meeting of the Endocrine Society: Abstract 668, 1982.
2. Teutsch G. 11β-Substituted 19-norsteroids: At the crossroads between hormone agonists and antagonists. Adrenal Steroid Antagonism. Proc. Satell. Workshop Int. Congr. Endocrinol. Berlin, Fed. Rep. Germany: de Gruyter, 1984, pp. 43-75.
3. Balieu E.E. Contragestion and other clinical applications of RU-486, an antiprogesterone at the receptor. Science. 245:1989;1351-1358.
4. Teutsch G., Philibert D. History and perspective of antiprogestins from the chemist's point of view. Human Reproduction. 9:(suppl. 1):1994;12-31.
5. Cook CE, Wani MC, Lee Y-W, Reel JR, Rector D, inventors; Research Triangle Institute, USA, assignee. 11β-Substituted Progesterone Analogs. US Patent 4,954,490, 1990.
6. Cook CE, Wani MC, Lee Y-W, Reel JR, Rector D, inventors. Research Triangle Institute, USA, assignee. 11β-Substituted Progesterone Analogs. US Patent 5,073,548, 1991.
7. Reel J.R., Hild-Petito S.H., Blye R.P. Antiovulatory and postcoital antifertility activity of the antiprogestin CDB-2914 when administered as single, multiple, or continuous doses to rats. Contraception. 58:1998;129-136.
8. CDB-2914 has been evaluated in three Phase I clinical trials by Dr. Lynnette Nieman, Clinical Director, NICHD, NIH: Phase I (safety study)-Dose response relationship for CDB-2914 in normally cycling women in mid-leuteal phase. Phase I (extended)- Evaluation of effects of CDB-2914 on ovulation and endometrial maturation when given in normally cycling women in mid-follicular phase. Phase I (extended)-Evaluation of effects of CDB-2914 given in the peri-ovulatory phase (LH surge + 2 days). Phase II: Randomized and double-masked study for comparison of the efficacies of CDB-2914 and Levonorgestrel in emergency contraception is currently in progress in the United States as a multi-center study under the direction of Drs. Diana Blithe and Trent Mackay.
9. Kim HK, Rao PN, Burdett JE, Acosta CK, inventors. NIH and SFBR, USA, assignees. Method for preparing 17α-Acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3, 20-dione, intermediates useful in the method, and methods for the preparation of such intermediates. US Patent 5,929,262, 1999.
10. Livingston D.A. Application of silicon chemistry in the corticosteroid field. Adv Med Chem. 1:1992;137-175.
11. Livingston D.A., Petre J.E., Bergh C.L. Intramolecular cyanohydrin elaboration. Construction of corticosteroids from 17-ketosteroids. J Am Chem Soc. 112:1990;6449-6450.
12. Freeman P.K., Hutchinson L.L. Alkyllithium reagents from alkyl halides and lithium radical anions. J Org Chem. 45:1980;1924-1930.
13. Fry J.L., Choi H., Pinkerton A.A. Synthesis of 2-cumyladamantan-2-ol by the catalytic use of 4,4′-di-t-butylbiphenyl as an electron-transfer agent with lithium in a Barbier-type reaction of adamantanone and cumyl chloride. J Chem Soc Chem Comm. 1987;225-226.
14. Teutsch G., Klich M., Bouchoux F., Cerede E., Philibert D. Synthesis of a fluorescent steroid derivative with high affinities for the glucocorticoid and progesterone receptors. Steroids. 59:1994;22-26.