4-(Anilino)pyrrole-2-carboxamides

Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor

Ken ichi Wakabayashi, Keisuke Imai, Hiroyuki Miyachi, Yuichi Hashimoto, Aya Tanatani

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky N-alkyl group, such as a cyclohexylmethyl or benzyl group, increased the binding affinity for wild-type AR and the potency for growth inhibition of androgen-dependent SC-3 cells. Among the compounds obtained, N-[4-[(benzyl)(4-nitrophenyl)amino]-1-methylpyrrole-2-carbonyl]pyrrolidine (22) is as potent an AR antagonist as the typical anilide-type AR antagonists hydroxyflutamide and bicalutamide. Further, compound 22 had potent binding affinity for T877A mutated AR, and dose-dependently inhibited the testosterone-induced production of prostate-specific antigen in LNCaP cells bearing T877A AR.

Original languageEnglish
Pages (from-to)6799-6812
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number14
DOIs
Publication statusPublished - Jul 15 2008
Externally publishedYes

Fingerprint

Androgen Receptor Antagonists
Androgen Antagonists
Pyrroles
Androgen Receptors
Cytoplasmic and Nuclear Receptors
Anilides
Tumors
Prostate
Bearings (structural)
Neoplasms
Prostate-Specific Antigen
Androgens
Testosterone
Growth

Keywords

  • Androgen
  • Antagonist
  • Mutated receptor
  • Pyrrole-2-carboxamide

ASJC Scopus subject areas

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

Cite this

4-(Anilino)pyrrole-2-carboxamides : Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor. / Wakabayashi, Ken ichi; Imai, Keisuke; Miyachi, Hiroyuki; Hashimoto, Yuichi; Tanatani, Aya.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 14, 15.07.2008, p. 6799-6812.

Research output: Contribution to journalArticle

Wakabayashi, Ken ichi ; Imai, Keisuke ; Miyachi, Hiroyuki ; Hashimoto, Yuichi ; Tanatani, Aya. / 4-(Anilino)pyrrole-2-carboxamides : Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 14. pp. 6799-6812.
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