Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

Aya Nakagawa; Shigeyuki Uno; Makoto Makishima; Hiroyuki Miyachi; Yuichi Hashimoto

doi:10.1016/j.bmc.2008.05.016

Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

Aya Nakagawa, Shigeyuki Uno, Makoto Makishima, Hiroyuki Miyachi, Yuichi Hashimoto

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,4-dihydro-1,3-dioxoquinolin-2(1H)-yl)benzonitrile (DEPIQ-4CN) showed the most potent activity, with IC₅₀ values of 74-78 nM in alkaline phosphatase activity and reporter gene assays.

Original language	English
Pages (from-to)	7046-7054
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2008.05.016
Publication status	Published - Jul 15 2008
Externally published	Yes

Keywords

Antagonist
Isoquinoline
Nuclear receptor ligand
Progesterone
Structural development

ASJC Scopus subject areas

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

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10.1016/j.bmc.2008.05.016

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title = "Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton",

abstract = "Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,4-dihydro-1,3-dioxoquinolin-2(1H)-yl)benzonitrile (DEPIQ-4CN) showed the most potent activity, with IC50 values of 74-78 nM in alkaline phosphatase activity and reporter gene assays.",

keywords = "Antagonist, Isoquinoline, Nuclear receptor ligand, Progesterone, Structural development",

author = "Aya Nakagawa and Shigeyuki Uno and Makoto Makishima and Hiroyuki Miyachi and Yuichi Hashimoto",

note = "Funding Information: The authors are grateful to Dr. Hiroshi Fukasawa (Institute of Medicinal Molecular Design) for his helpful discussions and technical assistance in biological assays. The work described in this paper was partially supported by Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science.",

year = "2008",

month = jul,

day = "15",

doi = "10.1016/j.bmc.2008.05.016",

language = "English",

volume = "16",

pages = "7046--7054",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

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T1 - Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

AU - Nakagawa, Aya

AU - Uno, Shigeyuki

AU - Makishima, Makoto

AU - Miyachi, Hiroyuki

AU - Hashimoto, Yuichi

N1 - Funding Information: The authors are grateful to Dr. Hiroshi Fukasawa (Institute of Medicinal Molecular Design) for his helpful discussions and technical assistance in biological assays. The work described in this paper was partially supported by Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science.

PY - 2008/7/15

Y1 - 2008/7/15

N2 - Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,4-dihydro-1,3-dioxoquinolin-2(1H)-yl)benzonitrile (DEPIQ-4CN) showed the most potent activity, with IC50 values of 74-78 nM in alkaline phosphatase activity and reporter gene assays.

AB - Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,4-dihydro-1,3-dioxoquinolin-2(1H)-yl)benzonitrile (DEPIQ-4CN) showed the most potent activity, with IC50 values of 74-78 nM in alkaline phosphatase activity and reporter gene assays.

KW - Antagonist

KW - Isoquinoline

KW - Nuclear receptor ligand

KW - Progesterone

KW - Structural development

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U2 - 10.1016/j.bmc.2008.05.016

DO - 10.1016/j.bmc.2008.05.016

M3 - Article

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AN - SCOPUS:47349119904

SN - 0968-0896

VL - 16

SP - 7046

EP - 7054

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton

Abstract

Keywords

ASJC Scopus subject areas

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