N-<4-(prop-2-ynylamino)benzoyl>-L-glutamic acid | 100020-46-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-<4-(prop-2-ynylamino)benzoyl>-L-glutamic acid
• 英文别名: L-Glutamic acid, N-[4-(2-propyn-1-ylamino)benzoyl]-；(2S)-2-[[4-(prop-2-ynylamino)benzoyl]amino]pentanedioic acid
• CAS: 100020-46-0
• 化学式: C₁₅H₁₆N₂O₅
• 分子量: 304.302
• InChiKey: XGHKIOZAWXBXBP-LBPRGKRZSA-N

物化性质

• 沸点：
  621.4±55.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  diethyl N-(4-(prop-2-ynylamino)benzoyl)-L-glutamate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以58%的产率得到N-<4-(prop-2-ynylamino)benzoyl>-L-glutamic acid
  参考文献：
  名称：

  Quinazoline antifolates inhibiting thymidylate synthase: benzoyl ring modifications

  摘要：

  Four new analogues of the antifolate N10-propargyl-5,8-dideazafolic acid were prepared that were substituted in the benzoyl ring. The 2'-chloro and 2'-methyl analogues were prepared from the appropriately substituted p-nitrobenzoic acids. The route to the 3'-chloro and 3',5'-dichloro analogues was by chlorination of diethyl N10-propargyl-5,8-dideazafolate and diethyl N-[4-(prop-2-ynylamino)benzoyl]-L-glutamate, respectively, using sulfuryl chloride. The compounds were tested for their inhibition of purified L1210 thymidylate synthase (TS), for their inhibition of purified L1210 dihydrofolate reductase (DHFR), and for their inhibition of the growth of L1210 cells in culture. The 2'-chloro substituent reduced the TS inhibition by twofold and the 2'-methyl substituent reduced it by 20-fold; the 3'-chloro and 3',5'-dichloro derivatives were very poor inhibitors. The substituents only slightly affected the DHFR inhibition. None of the compounds improved upon N10-propargyl-5,8-dideazafolic acid in inhibiting the growth of L1210 cells in culture.

  DOI：

  10.1021/jm00154a007

文献信息

• Anti-cancer quinazoline derivatives
  申请人：BRITISH TECHNOLOGY GROUP LIMITED

  公开号：EP0204529A2

  公开（公告）日：1986-12-10

  Quinazoline derivatives of the formula wherein R is 1) hydrogen or 2) a straight or branched chain saturated or unsaturated hydrocarbon group, or 3) a straight or branched chain saturated or unsaturated hydrocarbon group which is substituted by at least one heteroatom, the or each heteroatom being halogeno when R is a C, hydrocarbon group, by a saturated carbocyclic group or by a group containing at least one heteroatom, the or each heteroatom being 0, N or S when R contains a cyclic group; n is 0,1 or 2; Z represents -CH=CH- or-O-or-S-; X or, when n is an integer of at least 2, each X independently, represents a halogeno, C1-C4 alkyl, aryl or aralkyl group or a group including at least one heteroatom and Y represents a group of formula: or where m ≥1 (poly-L-glutamic acid residues) or or or a pharmaceutically acceptable salt or ester thereof are good inhibitors of thymidylate synthase but have reduced hepatic toxicity compared to their 2-amino quinazolinyl analogues. This renders compounds of formula I of value as anti-tumour agents. Compounds of formula I can be prepared by condensing appropriately substituted 6-halomethyl or sul- phonylmethyl quinazolines with appropriating substituted p-amino benzoyl-, furoyl- or thienylcarbonyl aspartates, glutamates, alanines or amino butyric acids and removing the protecting groups.

  式中的喹唑啉衍生物 其中 R 是 1) 氢 或 2) 直链或支链饱和或不饱和烃基，或 3) 被至少一个杂原子取代的直链或支链饱和或不饱和烃基，当 R 为 C、烃基时，该杂原子或每个杂原子为卤代；当 R 含有环状基团时，该杂原子或每个杂原子为 0、N 或 S；n 为 0、1 或 2；Z 代表-CH=CH- 或-O-或-S-；X 或，当 n 为至少 2 的整数时，每个 X 独立地代表卤素、C1-C4 烷基、芳基或芳烷基或包含至少一个杂原子的基团，Y 代表式中的一个基团： 或 其中 m ≥1（多 L-谷氨酸残基）或 或 或其药学上可接受的盐或酯是胸腺嘧啶酸合成酶的良好抑制剂，但与 2-氨基喹唑啉类似物相比，肝毒性较低。这使得式 I 化合物具有抗肿瘤剂的价值。通过将适当取代的 6-卤甲基或砜甲基喹唑啉与适当取代的对氨基苯甲酰、呋喃基或噻吩基羰基天冬氨酸、谷氨酸、丙氨酸或氨基丁酸缩合并除去保护基团，可制备式 I 化合物。
• 6-Aryl aminomethyl quinoline derivatives and their use as anti-tumour agents
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0318225A2

  公开（公告）日：1989-05-31

  The invention relates to a quinoline of the formula:- wherein each of R¹ and R², which may be the same or different, is hydrogen, halogeno, hydroxy, cyano, carbamoyl, nitro or amino, alkyl, alkoxy, alkylthio, alkylamino, dialkylamino or alkanoylamino each of up to 4 carbon atoms, or substituted alkyl or alkoxy each of up to 3 carbon atoms, provided that both R¹ and R² are not hydrogen; the quinoline ring may bear further substituents; R³ is hydrogen or alkyl of up to 4 carbon atoms; R⁴ is hydrogen, alkyl, alkenyl or alkynyl each of up to 4 carbon atoms or substituted alkyl of up to 3 carbon atoms; Ar is phenylene, naphthylene or heterocyclene which is unsubstituted or which bears one or more substituents; R⁵ is such that R⁵-NH₂ is an amino acid; or a pharmaceutically-acceptable salt or ester thereof. The compounds possess anti-tumour activity.

  本发明涉及一种式如下的喹啉 其中R¹和R²可以相同或不同，各自为氢、卤素、羟基、氰基、氨基甲酰基、硝基或氨基、烷基、烷氧基、烷硫基、烷基氨基、二烷基氨基或烷酰氨基，各自最多为4个碳原子，或取代的烷基或烷氧基，各自最多为3个碳原子，条件是R¹和R²都不是氢； 喹啉环可带有其他取代基； R³ 是氢或最多 4 个碳原子的烷基； R⁴ 是氢、各含最多 4 个碳原子的烷基、烯基或炔基或含最多 3 个碳原子的取代烷基； Ar 是未取代的苯基、萘基或杂环基，或带有一个或多个取代基； R⁵ 是 R⁵-NH₂ 是氨基酸； 或其药学上可接受的盐或酯。 这些化合物具有抗肿瘤活性。
• Anti-tumor agents
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0239362B1

  公开（公告）日：1991-12-04
• Anti-tumour agents
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0284338B1

  公开（公告）日：1993-12-22
• US7528141B2
  申请人：——

  公开号：US7528141B2

  公开（公告）日：2009-05-05