diethyl N-(2-chloro-4-nitrobenzoyl)-L-glutamate | 80014-91-1

• 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: diethyl N-(2-chloro-4-nitrobenzoyl)-L-glutamate
• 英文别名: N-(2-chloro-4-nitro-benzoyl)-L-glutamic acid diethyl ester；N-(2-Chlor-4-nitro-benzoyl)-L-glutaminsaeure-diaethylester；Diethyl N-(4-nitro-2-chlorobenzoyl)-(L)-glutamate；diethyl (2S)-2-[(2-chloro-4-nitrobenzoyl)amino]pentanedioate
• CAS: 80014-91-1
• 化学式: C₁₆H₁₉ClN₂O₇
• 分子量: 386.789
• InChiKey: MYTYIWXXDGYRCB-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl N-(2-chloro-4-nitrobenzoyl)-L-glutamate 在 sodium dithionite 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 以44%的产率得到diethyl N-(4-amino-2-chlorobenzoyl)-L-glutamate
  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
• 作为产物：
  描述：

  2-氯-4-硝基苯甲酸 在 吡啶 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 diethyl N-(2-chloro-4-nitrobenzoyl)-L-glutamate
  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

• Novel compounds and use
  申请人：Burroughs Welcome Co.

  公开号：US05019577A1

  公开（公告）日：1991-05-28

  The present invention provides a compound selected from: N-[4-(3 -(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino)-2-flurobenzoyl] -(L)-glutamic acid, N-[4-( 3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino)-3-flurobenzoyl ]-(L)-glutamic acid, N-[4 -(3 -(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino)-3-methylbenzoyl ]-(L)-glutamic acid, N-[4-( 2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino)-3-(methoxy)benzoy l](L)-glutamic acid and N-[4-(3 -(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propylamino)-2-chlorobenzoyl ](L)-glutamic acid, or a salt thereof, methods for the preparation of the compounds, intermediates in their preparations, pharmaceutical formulations containing them, and their use in the treatment of tumors.

  本发明提供了以下化合物之一：N-[4-(3-(2,4-二氨基-1,6-二氢-6-氧-5-嘧啶基)丙基氨基)-2-氟苯甲酰基]-(L)-谷氨酸，N-[4-(3-(2,4-二氨基-1,6-二氢-6-氧-5-嘧啶基)丙基氨基)-3-氟苯甲酰基]-(L)-谷氨酸，N-[4-(3-(2,4-二氨基-1,6-二氢-6-氧-5-嘧啶基)丙基氨基)-3-甲基苯甲酰基]-(L)-谷氨酸，N-[4-(2,4-二氨基-1,6-二氢-6-氧-5-嘧啶基)丙基氨基)-3-(甲氧基)苯甲酰基]-(L)-谷氨酸和N-[4-(3-(2,4-二氨基-1,6-二氢-6-氧-5-嘧啶基)丙基氨基)-2-氯苯甲酰基]-(L)-谷氨酸，或其盐，以及制备这些化合物的方法，制备中间体，包含它们的制药配方以及它们在肿瘤治疗中的应用。
• Quinazoline derivatives, processes for their preparation, compositions containing them and their use as anti-cancer agents
  申请人：NATIONAL RESEARCH DEVELOPMENT CORPORATION

  公开号：EP0031237A1

  公开（公告）日：1981-07-01

  Quinazoline derivatives of formula: wherein r represents: 1) a straight or branched chain unsaturated hydrocarbon group, or 2) 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 C1 hydrocarbon group; or saturated carbocyclic group; or group containing at least one heteroatom, the or each heteroatom being 0, N or S when R contains a cyclic group; and n is 0 or an integer of 1-4; 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:- wherein m . 1 (poly-L-glutamates); and the pharmaceutically acceptable salts and esters thereof, which are suitable as anti-cancer agents.

  式中的喹唑啉衍生物： 其中 r 代表1) 直链或支链不饱和烃基，或 2) 被至少一个杂原子取代的直链或支链饱和或不饱和烃基：杂原子，当 R 为 C1 烃基时，或每个杂原子为卤素；或饱和碳环基团；或含有至少一个杂原子的基团，当 R 含有环状基团时，或每个杂原子为 0、N 或 S；且 n 为 0 或 1-4 的整数；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；且 Y 代表式中的一个基团：- 1. 其中 m .1（聚-L-谷氨酸盐）；及其药学上可接受的盐和酯，可用作抗癌剂。
• Glutamic acid derivatives
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0341837A2

  公开（公告）日：1989-11-15

  The present invention relates to Compounds of formula (I): wherein R¹ is hydrogen; R² and R³ are the same or different and are each hydrogen or C₁₋₄ alkyl; R⁴ is NR¹¹R¹²; R⁵, R⁶, R¹¹ and R¹² are each hydrogen; m is zero; n is 3 and one of R⁷, R⁸, R⁹ and R¹⁰ is chloro, fluoro, methyl or methoxy and the rest are hydrogen; or n is 4 and each of R⁷, R⁸, R⁹ and R¹⁰ is hydrogen; and pharmaceutically acceptable salts thereof, methods for their preparation, pharmaceutical formulations containing them and their use in the treatment of tumours.

  本发明涉及式（I）化合物： 其中 R¹ 为氢； R² 和 R³ 相同或不同，各自为氢或 C₁₋₄ 烷基； R⁴ 是 NR¹¹R¹²； R⁵、R⁶、R¹¹ 和 R¹² 各为氢； m 为零 n 为 3，且 R⁷、R⁸、R⁹ 和 R¹⁰ 中的一个为氯、氟、甲基或甲氧基，其余为氢； 或 n 为 4，且 R⁷、R⁸、R⁹ 和 R¹⁰ 均为氢； 以及它们的药学上可接受的盐、它们的制备方法、含有它们的药物制剂和它们在治疗肿瘤中的用途。
• Analogs of Pteroylglutamic Acid. IX. Derivatives with Substituents on the Benzene Ring¹
  作者：Donna B. Cosulich、Doris R. Seeger、Marvin J. Fahrenbach、Kenneth H. Collins、Barbara Roth、Martin E. Hultquist、James M. Smith

  DOI：10.1021/ja01115a017

  日期：1953.10
• US4447608A
  申请人：——

  公开号：US4447608A

  公开（公告）日：1984-05-08