Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

Abstract

We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%). We examined the anti-tumor effect of FMPA, complexed with dimethyl-beta-cyclodextrin (DM-beta-CyD), on rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA). FMPA showed great anti-tumor effect on DMBA-induced rat mammary carcinomas.

• Authors: Natsuko Murata, Shiho Fujimori, Yoshitatsu Ichihara, Yoshio Sato, Taketo Yamaji, Hiroshi Tsuboi, Masayuki Uchida, Hiroto Suzuki, Masashi Yamada, Tsutomu Oikawa, Hideo Nemoto, Junko Nobuhiro, Tominari Choshi, Satoshi Hibino
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 54 Issue 11 Pg. 1567-70 (Nov 2006) ISSN: 0009-2363 [Print] Japan
• PMID: 17077554 (Publication Type: Journal Article)

Chemical References

• 9alpha-fluoromedroxyprogesterone acetate
• Antineoplastic Agents
• Fluorine
• Medroxyprogesterone Acetate

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, chemical synthesis, chemistry)
• Carcinoma (drug therapy)
• Drug Screening Assays, Antitumor
• Female
• Fluorine (chemistry)
• Mammary Neoplasms, Experimental (drug therapy)
• Medroxyprogesterone Acetate (administration & dosage, analogs & derivatives, chemical synthesis, chemistry)
• Molecular Conformation
• Rats
• Rats, Sprague-Dawley
• Stereoisomerism