N¹⁰-propargyl-5,8-dideazapteroic acid | 101248-32-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N¹⁰-propargyl-5,8-dideazapteroic acid
• 英文别名: Ici M247496；4-[(2-amino-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]benzoic acid
• CAS: 101248-32-2
• 化学式: C₁₉H₁₆N₄O₃
• 分子量: 348.361
• InChiKey: UZTMEKSOOJWLIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N¹⁰-propargyl-5,8-dideazapteroic acid 在 4-二甲氨基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Folate receptor binding conjugates of antifolates

  摘要：

  本文描述了抗叶酸类化合物、可释放连接剂和药物的共轭物，以及含有它们的制药组合物。这些共轭物对于治疗源于病原细胞群的疾病是有用的。本文还描述了治疗这种疾病的方法。

  公开号：

  US09192682B2
• 作为产物：
  描述：

  4-(2-丙炔-1-氨基)苯甲酸乙酯 在 sodium hydroxide 、 calcium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 89.0h， 生成 N¹⁰-propargyl-5,8-dideazapteroic acid
  参考文献：
  名称：

  Quinazoline antifolates inhibiting thymidylate synthase. Variation of the amino acid

  摘要：

  Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.

  DOI：

  10.1021/jm00156a033

文献信息

• Folate analogs. 26. Syntheses and antifolate activity of 10-substituted derivatives of 5,8-dideazafolic acid and of the poly-.gamma.-glutamyl metabolites of N10-propargyl-5,8-dideazafolic acid (PDDF)
  作者：M. G. Nair、Nitin T. Nanavati、Indira G. Nair、Roy L. Kisliuk、Y. Gaumont、M. C. Hsiao、Thomas I. Kalman

  DOI：10.1021/jm00159a032

  日期：1986.9

  growth of L. casei, thymidylate synthesis in permeabilized L1210 cells, and L. casei thymidylate synthase. Two analogues of 5,8-dideazafolic acid (2 and 3), one with a 2-butyne and another with a cyclopropylmethyl substituent at N10, were also synthesized and evaluated for their antifolate activities using the above-mentioned test systems. They were considerably less active than PDDF or its polyglutamylated

  通过固相方法，由N10-炔丙基-5,8-二脱氮杂戊酸合成了链长不超过5个谷氨酸残基的n10-炔丙基-5,8-双脱氮草酸（PDDF）的聚γ-谷氨酰胺衍生物。 。使用需要叶酸的微生物，完整和通透的L1210细胞以及作为衍生自干酪乳杆菌的二氢叶酸还原酶和胸苷酸合酶的抑制剂，评估了这些化合物的抗叶酸活性。PDDF（1）的多谷氨酰化衍生物在抑制干酪乳杆菌的生长，透化的L1210细胞中胸苷酸合成以及干酪乳杆菌胸苷酸合酶方面比母体化合物更具活性。5,8-二氮杂二酸（2和3）的两个类似物，一个在N10处带有2-丁炔，另一个带有环丙基甲基取代基，还使用上述测试系统合成和评估了它们的抗叶酸活性。它们的活性远不如PDDF或其聚谷氨酰化衍生物。在通透的L1210细胞中，N10-炔丙基-5,8-二氮杂戊酰基三，四和五谷氨酸盐与5-氟脱氧尿酸酯等效，作为胸苷酸合成的抑制剂。已显示，PDDF的聚谷氨酰胺代谢物是最有效的
• [EN] DUAL DISULFIDE DRUG CONJUGATES<br/>[FR] CONJUGUÉS DE MÉDICAMENTS À DEUX GROUPES DISULFURE
  申请人：ENDOCYTE INC

  公开号：WO2016168471A1

  公开（公告）日：2016-10-20

  The invention described herein pertains to dual disulfide drug conjugates. In particular, the invention described herein pertains to dual disulfide drug conjugates that target the folate receptor for delivery of conjugated drugs to a mammalian recipient. Also described are methods of making and using dual disulfide drug conjugates.

  本发明涉及双二硫醚药物共轭物。具体而言，本发明涉及双二硫醚药物共轭物，其靶向叶酸受体，用于将共轭药物传递给哺乳动物接受者。还描述了制备和使用双二硫醚药物共轭物的方法。
• New enzymes and prodrugs for ADEPT
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0728018B1

  公开（公告）日：2003-08-06
• THERAPY
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0728018A1

  公开（公告）日：1996-08-28
• FOLATE RECEPTOR BINDING CONJUGATES OF ANTIFOLATES
  申请人：Leamon Christopher Paul

  公开号：US20110172254A1

  公开（公告）日：2011-07-14

  Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.