Non-glutamate Type Pyrrolo[2,3-d]pyrimidine Antifolates. I : Synthesis and Biological Properties of Pyrrolo[2,3-d]pyrimidine Antifolates Containing Tetrazole Congener of Glutamic Acid
スポンサーリンク
概要
- 論文の詳細を見る
Either the α- or γ-carboxyl group of the glutamic acid moiety of N-[4-[3-(2,4-diamino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)propyl]benzoyl]-L-glutamic acid (1b, TNP-351) and its related compound (1a) was replaced with a 1H-tetrazle ring, and the inhibitory effects of the resulting compounds on dihydrofolate reductase (DHFR) and the growth of murine fibrosarcoma Meth A cells were examined. The γ-tetrazole analogs (2) were found to be much more potent DHFR inhibitors than TNP-351,and strongly inhibited the growth of Meth A cells. On the other hand, the α-tetrazole analogs (3) were much less active against Meth A cells, even though their DHFR-inhibitory activity was comparable to that of TNP-351. These findings suggest that the α-carboxyl group plays an important role in effective uptake via the reduced folate carrier, and a novel DHFR inhibitor could be obtained by chemically modifying the γ-carboxyl moiety while leaving the α-carboxyl group intact.
- 公益社団法人日本薬学会の論文
- 1995-02-15
著者
-
秋元 浩
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd.,
-
大津 紘一郎
Pharmaceutical Research Laboratories III Pharmaceutical Research Division, Takeda Chemical Industrie
-
伊藤 文雄
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
-
秋元 浩
武田薬品工業(株)
-
秋元 浩
武田薬品工業
-
秋元 浩
武田薬品工業(株)化学研究所
-
秋元 浩
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
-
Wajima M
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
-
和島 恵
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
-
Wajima Megumi
Pharmaceutical Research Laboratories Iii. Takeda Chemical Industries Ltd.
-
大津 紘一郎
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
-
幸重 浩一
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd.,
-
幸重 浩一
Pharmaceutical Research Laboratories Iii Takeda Chemical Industries Ltd.
関連論文
- 古細菌tRNAに存在する修飾ヌクレオチド : アーケオシンの生合成機構 -tRNA-グアニントランスグリコシラーゼの基質塩基の検索-
- 古細菌tRNAに存在する修飾ヌクレオチド : アーケオシンの生合成機構 -tRNA-グアニントランスグリコシラーゼの精製及びその機能-
- Chemical Modification of Fumagillin. III. Modification of the Spiro-epoxide
- Synthesis and Antitumor Activity of 5-Fluoro-4-(furfurylidene aminooxy)hexahydro-2,6-dioxo-5-pyrimidinecarboxylates
- Chemical Modification of Fumagillin. I. 6-O-Acyl, 6-O-Sulfonyl, 6-O-Alkyl, and 6-O-(N-Substituted-carbamoyl)fumagillols
- Enhancement of the Anti-tumor Activity of Recombinant Interleukin-2 (rIL-2) by Immunocomplexing with an F (ab')_2 Fragment of Murine Monoclonal Antibody against rIL-2
- Chemical Modification of Ansamitocins. III. Synthesis and Biological Effects of 3-Acyl Esters of Maytansinol
- Chemistly of O-Silylated Ketene Acetals : Stereocontrolled Synthesis of 3-Benzoylamino-2,3-dideoxy-pentoses by a 1,3-Addition to Chiral Nitrones
- The Chemistry of O-Silylated Ketene Acetals : Synthesis of N-Benzoyl-L-daunosamine
- Chemistry of O-Silylated Ketene Acetals. Novel Chemical Transformation of Vinyl Sulfoxides and Related Sulfoxides(Organic,Chemical)
- Chemical Modification of Ansamitocins. II. Synthesis of 3-Epimaytansionoids via 3-Maytansinones
- Chemical Modification of Ansamitocins. I. Synthesis and Properties of 4,5-Deoxymaytansinoids
- Chemistry of O-Silylated Ketene Acetals : Preparation of α-Siloxy Phenyl Sulfides and Methyl 3-(Phenylthio) butyrates from Alkyl Phenyl Sulfoxides
- Semisynthetic β-Lactam Antibiotics. IX. Synthesis and Antibacterial Activity of 7-[2-(2-Aminothiazol-4-yl)-2-sulfoacetamido]-cephalosporanic Acid and Its Derivatives
- Non-glutamate Type Pyrrolo[2,3-d]pyrimidine Antifolates. II. Synthesis and Antitumor Activity of N^5-Substituted Glutamine Analogs
- Non-glutamate Type Pyrrolo[2,3-d]pyrimidine Antifolates. I : Synthesis and Biological Properties of Pyrrolo[2,3-d]pyrimidine Antifolates Containing Tetrazole Congener of Glutamic Acid
- リサーチツールのライセンス : 製薬産業を中心として
- 知的財産戦略と研究開発--研究開発,その戦略と新課題
- 企業における知的財産戦略--ライフサイエンス産業を中心として (特集:日本薬学会第124年会薬学図書館協議会企画シンポジウム 国際競争に負けない薬学研究を創造するために--情報化時代の研究支援活動のありかた)
- 議題180 特許要件としての産業上の利用可能性及び有用性の内容と妥当性 (国際会議資料 〔AIPPI〕ジュネーブ総会の議題に対する日本部会の意見(1))
- 知的財産情報の活用 : −ライフサイエンス業界を中心として−
- 議題167 新規性及び進歩性の要件を評価するに当っての先行技術開示の現行の基準 (国際会議報告) -- (AIPPIリスボン執行委員報告(1))
- 21世紀における企業の知的財産戦略--製薬企業の一例を中心として (特集 組織化する特許戦略)
- 企業内における知的財産活動の評価--評価指標に関するひとつの提案
- Synthesis and Antitumor Activity of Pyrrolo [2,3-d]pyrimidine Antifolates with a Bridge Chain Containing a Nitrogen Atom
- 葉酸拮抗剤の新しい展開
- グローバルな知的財産戦略の重要性
- 経営戦略と知財戦略の融合--ライフサイエンス産業を中心として (特集 知的財産と技術優位性の確保)