2-{o-fluoro-p-[N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzamido}-4-(tetrazol-5-yl)butyric acid | 153538-08-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{o-fluoro-p-[N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzamido}-4-(tetrazol-5-yl)butyric acid
• 英文别名: Plevitrexed, (+/-)-；2-[[4-[(2,7-dimethyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-2-fluorobenzoyl]amino]-4-(2H-tetrazol-5-yl)butanoic acid
• CAS: 153538-08-0
• 化学式: C₂₆H₂₅FN₈O₄
• 分子量: 532.534
• InChiKey: IEJSCSAMMLUINT-UHFFFAOYSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  9

制备方法与用途

生物活性方面，(Rac)-Plevitrexed ((Rac)-ZD 9331; (Rac)-BGC9331) 是 Plevitrexed 的外消旋体。Plevitrexed 则是一种口服有效的胸苷酸合酶（TS）抑制剂。

文献信息

• Polymer Conjugate Of Folic Acid Or Folic Acid Derivative
  申请人：Nakanishi Takeshi

  公开号：US20110294980A1

  公开（公告）日：2011-12-01

  Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein a substituent represented by formula (I) is bonded to a carboxy group of a block copolymer which is composed of a polyethylene glycol and a polymer having a carboxy group in a side chain, or a pharmacologically acceptable salt thereof. [In the formula, A represents a monocyclic or fused aromatic group; G represents an optionally substituted (C1-C6) alkylene group; Y represents a hydrogen atom or a substituent; and E represents a residue of folic acid or a folic acid derivative.]

  揭示了一种叶酸或叶酸衍生物的聚合物共轭物，其中未使用酰胺键。该化合物在活体内具有化学稳定性和适当的药物释放速率。具体揭示了一种叶酸或叶酸衍生物的聚合物共轭物，其中配体由式(I)所表示的取代基与由聚乙二醇和具有侧链上羧基的聚合物组成的嵌段共聚物的羧基结合，或其药理学上可接受的盐。[在该式中，A代表单环或融合芳香基团；G代表可选取代的(C1-C6)烷基基团；Y代表氢原子或取代基；E代表叶酸或叶酸衍生物的残基。]
• POLYMER CONJUGATE OF FOLIC ACID OR FOLIC ACID DERIVATIVE
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：EP2284209A1

  公开（公告）日：2011-02-16

  Disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein an amide bond is not used. The compound has chemical stability and adequate drug release rate in the living organism. Specifically disclosed is a polymer conjugate of folic acid or a folic acid derivative, wherein a substituent represented by formula (I) is bonded to a carboxy group of a block copolymer which is composed of a polyethylene glycol and a polymer having a carboxy group in a side chain, or a pharmacologically acceptable salt thereof. [In the formula, A represents a monocyclic or fused aromatic group; G represents an optionally substituted (C1-C6) alkylene group; Y represents a hydrogen atom or a substituent; and E represents a residue of folic acid or a folic acid derivative.]

  本发明公开了一种叶酸或叶酸衍生物的聚合物共轭物，其中未使用酰胺键。该化合物在生物体内具有化学稳定性和足够的药物释放率。具体公开了一种叶酸或叶酸衍生物的聚合物共轭物，其中由式（I）代表的取代基键合到嵌段共聚物的羧基上，嵌段共聚物由聚乙二醇和侧链中含有羧基的聚合物组成，或其药理学上可接受的盐。 [式中，A 代表单环或融合芳香基团；G 代表任选取代的（C1-C6）亚烷基；Y 代表氢原子或取代基；E 代表叶酸残基或叶酸衍生物。］
• Compositions and methods for the detection and treatment of methylthioadenosine phosphorylase deficient cancers
  申请人：——

  公开号：US20040247600A1

  公开（公告）日：2004-12-09

  Compositions and methods involving agents that specifically bind to methylthioadenosine phosphorylase (MTAP) protein are disclosed. Illustrative compositions comprise binding agents that bind to human MTAP protein in biological samples, including embedded samples. The binding agents are useful, for example, in the detection, prognosis, and/or treatment of MTAP deficient cancers. Also disclosed are kits containing the reagents necessary for the detection of human MTAP protein in an embedded sample.

  本发明公开了涉及与甲硫腺苷磷酸化酶（MTAP）蛋白特异性结合的制剂的组合物和方法。说明性组合物包括与生物样本（包括嵌入样本）中的人类 MTAP 蛋白结合的结合剂。这些结合剂可用于例如 MTAP 缺乏性癌症的检测、预后和/或治疗。还公开了含有检测包埋样本中人 MTAP 蛋白所需的试剂的试剂盒。
• Antisense oligonucleotides against thymidylate synthase
  申请人：Koropatnick J. Donald

  公开号：US20050272683A1

  公开（公告）日：2005-12-08

  Antisene oligonucleotides targeted to sequences in thymidylate synthase (TS) mRNA. In particular the invention relates to antisense oligonucleotides targeted to sequences in the 3′ end of TS mRNA, which are both cytostatic on their own when administered to human tumour cell lines, and which also enhance the toxicity of anticancer drugs such as Tomudex. The invention also relates to antisense oligonucleotides targeted to sequences at or near the translation start site at the 5′ end of TS mRNA which induce TS gene transcription and enhance cell growth. The invention further relates to a combination product comprising an antisense oligonucleotide in combination with an anticancer agent such as Tomudex (N-(5[N-3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl)-L-glutamic acid) or the Zeneca development compound ZD 9331 ((S)-2-(2-fluoro-4-[N-(4-hydroxy-2,7-dimethylquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino] benzamido-4-(1H-1,2,3,4-tetrazol-5-yl) butyric acid), and to the use of such a combination product in the treatment of cancer.

  针对胸腺嘧啶酸合成酶（TS）mRNA 序列的反义寡核苷酸。特别是本发明涉及以 TS mRNA 3′末端序列为靶向的反义寡核苷酸，这种寡核苷酸在给人类肿瘤细胞系用药时本身具有细胞抑制作用，而且还能增强 Tomudex 等抗癌药物的毒性。本发明还涉及以 TS mRNA 5′端翻译起始位点或其附近序列为靶向的反义寡核苷酸，它能诱导 TS 基因转录并促进细胞生长。本发明进一步涉及一种组合产品，该产品包括反义寡核苷酸与抗癌剂如 Tomudex（N-(5-[N-3,4-二氢-2-甲基-4-氧代喹唑啉-6-基甲基)-N-甲基氨基]-2-苯甲酰基)-L-谷氨酸）或 Zeneca 开发的化合物 ZD 9331（(S)-2-(2-氟-4-[N-(4-羟基-2、(S)-2-(2-氟-4-[N-(4-羟基-2,7-二甲基喹唑啉-6-基甲基)-N-(丙-2-炔基)氨基]苯甲酰胺基-4-(1H-1,2,3,4-四唑-5-基)丁酸)，以及这种组合产品在癌症治疗中的应用。
• ANTISENSE OLIGONUCLEOTIDES AGAINST THYMIDYLATE SYNTHASE
  申请人：ZENECA LIMITED

  公开号：EP1017800A1

  公开（公告）日：2000-07-12