Retinoidal Pyrimidinecarboxylic Acids.Unexpected Diaza-Substituent Effects in Retinobenzoic Acid

• OHTA Kiminori

• KAWACHI Emiko

• INOUE Noriko

• FUKASAWA Hiroshi

• HASHIMOTO Yuichi

• ITAI Akiko

• KAGECHIKA Hiroyuki

書誌事項

タイトル別名

• Retinoidal Pyrimidinecarboxylic Acids. Unexpected Diaza-Substituent Effects in Retinobenzoic Acids.

抄録

Several pyridine-and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carbamoyl]pyridine-3-carboxylic acid (2b) and 6-[(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)carboxamido]pyridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)amino]pyrimidene-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 48 (10), 1504-1513, 2000

  公益社団法人 日本薬学会

キーワード

• retinoid
• reinoic acid receptor
• reinoid X receptor
• pyrimidine

詳細情報

• CRID: 1390001204162707456
• NII論文ID: 130003773969
• NII論文ID: 110003635317
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.48.1504
• COI: 1:CAS:528:DC%2BD3cXntlCgur4%3D
• ISSN: 13475223
• ISSN: 00092363
• ISSN: http://id.crossref.org/issn/00092363
• NDL書誌ID: 5513351
• PubMed: 11045459
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5513351
• Web Site: http://www.jstage.jst.go.jp/article/cpb1958/48/10/48_10_1504/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可