Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer

Tomohiro Kaku, Takenori Hitaka, Akio Ojida, Nobuyuki Matsunaga, Mari Adachi, Toshimasa Tanaka, Takahito Hara, Masuo Yamaoka, Masami Kusaka, Teruaki Okuda, Satoru Asahi, Shuichi Furuya, Akihiro Tasaka

研究成果: ジャーナルへの寄稿記事

101 引用 (Scopus)

抄録

A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17, 20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of la in the homology model of 17, 20-1yase, the 6, 7-dihydro-5H-pyrrolo[l, 2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1 mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.

元の言語英語
ページ(範囲)6383-6399
ページ数17
ジャーナルBioorganic and Medicinal Chemistry
19
発行部数21
DOI
出版物ステータス出版済み - 11 1 2011

Fingerprint

Steroid 17-alpha-Hydroxylase
Prostatic Neoplasms
Derivatives
Phase III Clinical Trials
Dehydroepiandrosterone
Castration
Structure-Activity Relationship
Scaffolds
Haplorhini
Testosterone
Serum
orteronel
imidazole
naphthalene

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. / Kaku, Tomohiro; Hitaka, Takenori; Ojida, Akio; Matsunaga, Nobuyuki; Adachi, Mari; Tanaka, Toshimasa; Hara, Takahito; Yamaoka, Masuo; Kusaka, Masami; Okuda, Teruaki; Asahi, Satoru; Furuya, Shuichi; Tasaka, Akihiro.

:: Bioorganic and Medicinal Chemistry, 巻 19, 番号 21, 01.11.2011, p. 6383-6399.

研究成果: ジャーナルへの寄稿記事

Kaku, T, Hitaka, T, Ojida, A, Matsunaga, N, Adachi, M, Tanaka, T, Hara, T, Yamaoka, M, Kusaka, M, Okuda, T, Asahi, S, Furuya, S & Tasaka, A 2011, 'Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer', Bioorganic and Medicinal Chemistry, 巻. 19, 番号 21, pp. 6383-6399. https://doi.org/10.1016/j.bmc.2011.08.066
Kaku, Tomohiro ; Hitaka, Takenori ; Ojida, Akio ; Matsunaga, Nobuyuki ; Adachi, Mari ; Tanaka, Toshimasa ; Hara, Takahito ; Yamaoka, Masuo ; Kusaka, Masami ; Okuda, Teruaki ; Asahi, Satoru ; Furuya, Shuichi ; Tasaka, Akihiro. / Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. :: Bioorganic and Medicinal Chemistry. 2011 ; 巻 19, 番号 21. pp. 6383-6399.
@article{13074e7fda24428788b5f6f7cbc936b5,
title = "Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer",
abstract = "A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17, 20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of la in the homology model of 17, 20-1yase, the 6, 7-dihydro-5H-pyrrolo[l, 2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1 mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.",
author = "Tomohiro Kaku and Takenori Hitaka and Akio Ojida and Nobuyuki Matsunaga and Mari Adachi and Toshimasa Tanaka and Takahito Hara and Masuo Yamaoka and Masami Kusaka and Teruaki Okuda and Satoru Asahi and Shuichi Furuya and Akihiro Tasaka",
year = "2011",
month = "11",
day = "1",
doi = "10.1016/j.bmc.2011.08.066",
language = "English",
volume = "19",
pages = "6383--6399",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "21",

}

TY - JOUR

T1 - Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer

AU - Kaku, Tomohiro

AU - Hitaka, Takenori

AU - Ojida, Akio

AU - Matsunaga, Nobuyuki

AU - Adachi, Mari

AU - Tanaka, Toshimasa

AU - Hara, Takahito

AU - Yamaoka, Masuo

AU - Kusaka, Masami

AU - Okuda, Teruaki

AU - Asahi, Satoru

AU - Furuya, Shuichi

AU - Tasaka, Akihiro

PY - 2011/11/1

Y1 - 2011/11/1

N2 - A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17, 20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of la in the homology model of 17, 20-1yase, the 6, 7-dihydro-5H-pyrrolo[l, 2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1 mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.

AB - A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17, 20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of la in the homology model of 17, 20-1yase, the 6, 7-dihydro-5H-pyrrolo[l, 2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1 mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=84856780403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856780403&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2011.08.066

DO - 10.1016/j.bmc.2011.08.066

M3 - Article

C2 - 21978946

AN - SCOPUS:84856780403

VL - 19

SP - 6383

EP - 6399

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 21

ER -