Studies on Aromatase Inhibitors IV. Synthesis and Biological Evaluation of N, N-Disubstituted-5-aminopyrimidine Derivatives

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概要

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• In order to study the potency of the 5-aminopyrimidine skeleton as an aromatase inhibitor, we synthesized various N, N-disubstituted-5-aminopyrimidine derivatives and evaluated their aromatase-inhibitory activity (in vitro) and their inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). Compounds with the fluoro-substituted benzyl group showed potent aromatase inhibition. Among them, 5-[(4-cyanophenyl)(3,5-difluorobenzyl)amino]pyrimidine (5w, YM553) was a highly potent compound with an IC_<50> value of 0.038nM for aromatase from human placenta. Its inhibitory effect was approximately four times greater than that of YM511. In addition, YM553 was a weak inhibitor of other enzymes involved in steroid hormone synthesis. These results indicate that YM553,as well as YM511 (a 4-amino-4H-1,2,4-triazole derivative), is a promising agent for the treatment of estrogen-dependent diseases.

• 公益社団法人日本薬学会の論文
• 1997-08-15

著者

• Okada M

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Isomura Y

  Yamanouchi Pharmaceutical Co. Ltd. Ibaraki Jpn

• OKADA Minoru

  Medical Chemistry Research II, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• YODEN Toru

  Medical Chemistry Research II, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• KAWAMINAMI Eiji

  Medical Chemistry Research II, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• SHIMADA Yosiaki

  Medicinal Chemistry Research III, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical C

• KUDOU Masafumi

  Metabolic Diseases Research, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., L

• ISOMURA Yasuo

  Medical Chemistry Research II, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co.,

• SHIMADA Yasuo

  Mitsuboshi Pharmacutical Co.

• Yoden T

  Institute For Technology Development Yamanouchi Pharmaceutical Co. Ltd.

• Okada M

  Biofrontier Institute Inc

• Shimada Y

  Mitsuboshi Pharmaceutical Co

• Kudoh Masafumi

  Drug Discovery Research Astellas Pharma Inc.

• Kawaminami Eiji

  Medicinal Chemistry Research Ii Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.

• Kawaminami Eiji

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co.ltd.

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