Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).
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.
Murata
Natsuko
N
Pharmaceuticals Development Department, Meiji Dairies Corporation, Tokyo, Japan. natsuko_murata@meiji-milk.com
Fujimori
Shiho
S
Ichihara
Yoshitatsu
Y
Sato
Yoshio
Y
Yamaji
Taketo
T
Tsuboi
Hiroshi
H
Uchida
Masayuki
M
Suzuki
Hiroto
H
Yamada
Masashi
M
Oikawa
Tsutomu
T
Nemoto
Hideo
H
Nobuhiro
Junko
J
Choshi
Tominari
T
Hibino
Satoshi
S
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D002277:Carcinoma / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005461:Fluorine / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
C516643:9alpha-fluoromedroxyprogesterone acetate; D000970:Antineoplastic Agents; D005461:Fluorine; D017258:Medroxyprogesterone Acetate