7-氯-3,4-二氢-2,4-二氧代-1(2H)-喹唑啉乙酸乙基酯 | 112733-45-6

• 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
• 中文名称: 7-氯-3,4-二氢-2,4-二氧代-1(2H)-喹唑啉乙酸乙基酯
• 英文名称: ethyl 2-(7-chloro-3,4-dihydro-2,4-dioxo-1(2H)-quinazolinyl)acetate
• 英文别名: ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazoline-1-yl)acetate；ethyl 1,2,3,4-tetrahydro-7-chloro-2,4-dioxoquinazolin-1-ylacetate；7-chloro-1-ethoxycarbonylmethyl-2,4(1H,3H)-quinazolinedione；ethyl 2-(7-chloro-2,4-dioxo-1,2,3,4-tetrhydroquinazolin-1-yl)acetate；ethyl 2-(7-chloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl)acetate；Ethyl 2-(7-chloro-2,4-dioxo-3,4-dihydroquinazolin-1(2H)-yl)acetate；ethyl 2-(7-chloro-2,4-dioxoquinazolin-1-yl)acetate
• CAS: 112733-45-6
• 化学式: C₁₂H₁₁ClN₂O₄
• 分子量: 282.683
• InChiKey: ZISJSCWSNPRDTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-氯-3,4-二氢-2,4-二氧代-1(2H)-喹唑啉乙酸乙基酯 、 4-溴-2-氟苄溴 在 potassium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 50.0h， 生成 折那司他
  参考文献：
  名称：

  The Process Development of a Novel Aldose Reductase Inhibitor, FK366. Part 1. Improvement of Discovery Process and New Syntheses of 1-Substituted Quinazolinediones

  摘要：

  This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 (1). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxicological and pharmacological evaluations. A new process, including regioselective alkylation of silylated quinazolinedione, provided a practical and cost-effective synthesis of FK366 in a dramatically increased yield.

  DOI：

  10.1021/op0340661
• 作为产物：
  描述：

  N-(2-氨基甲酰基-5-氯苯基)氨基乙酸乙酯 在 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 为溶剂， 生成 7-氯-3,4-二氢-2,4-二氧代-1(2H)-喹唑啉乙酸乙基酯
  参考文献：
  名称：

  Quinazoline derivatives, compositions thereof and their use in treating

  摘要：

  本发明涉及具有以下通式的化合物：##STR1## 其中R.sup.1和R.sup.2各自为氢、卤素、低级烷氧基或卤代（低级）烷基，R.sup.3为二卤代苯基、萘基（低级）烷基、苯基（低级）烷基（其上有一个或两个由卤素、低级烷氧基、卤代（低级）烷基和低级烷基组成的基团取代）或噻吩基（低级）烷基，R.sup.4为羧基或保护的羧基，Y为羰基、硫羰基或磺酰基，Z为低级亚烷基，以及其药学上可接受的盐，用于治疗糖尿病并发症。

  公开号：

  US04734419A1

文献信息

• Process for producing dioxoquinazolines
  申请人：Sumitomo Chemical Company, Limited

  公开号：US05780628A1

  公开（公告）日：1998-07-14

  A process for producing an dioxoquinazoline of following formula (II): ##STR1## wherein R.sub.1 and R.sub.2 independently represent a hydrogen atom, a halogen atom, a nitro group, a lower alkyl group, an aralkyl group, an alkoxy group, an alkoxylcarbonyl group or a group represented by YNR.sub.3 R.sub.4, wherein Y represents a direct bond, a lower alkylene group or a carbonyl group, and R.sub.3 and R.sub.4 independently represent a lower alkyl group or N, R.sub.3 and R.sub.4 may bond together to form a five- or six-membered heterocycle which comprises reacting an anthranylamide of formula (I): ##STR2## wherein X, R.sub.1 and R.sub.2 are as defined above.

  生产二氧喹啉的方法如下所示（II）的化学式：##STR1## 其中R.sub.1和R.sub.2独立地代表氢原子、卤素原子、硝基、低烷基、芳基烷基、烷氧基、烷氧羰基或由YNR.sub.3 R.sub.4表示的基团，其中Y代表直链键、低烷基烯基或羰基，而R.sub.3和R.sub.4独立地代表低烷基或N，R.sub.3和R.sub.4可以结合形成一个五元或六元杂环，其包括反应式（I）的蒽酰胺：##STR2## 其中X、R.sub.1和R.sub.2如上定义。
• Process for producing quinazoline derivatives
  申请人：Clariant GmbH

  公开号：US06001831A1

  公开（公告）日：1999-12-14

  A process for producing 1,2,3,4-tetrahydro-2,4-dioxo-quinazoline-1-yl acetic acid derivatives of the formula (I) in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are mutually independently hydrogen, halogen, OH, NO.sub.2, (C.sub.1 -C.sub.6) alkoxy, (C.sub.1 -C.sub.6) alkyl, halogen-substituted (C.sub.1 -C.sub.6) alkyl, R.sup.5 is hydrogen, (C.sub.1 -C.sub.6) alkyl, phenyl where the alkyl or phenyl radical may also be substituted by halogen atoms; in which an anthranilic acid derivative of formula (II), in which R.sup.1 to R.sup.5 have the above meaning and R.sup.6 is hydrogen, (C.sub.1 -C.sub.6) alkyl or phenyl, where the alkyl or phenyl radical may also be substituted by halogen atoms, is reacted with a metal cyanate and hydrogen chloride in the presence of an inert solvent. ##STR1##

  一种制备式(I)的1,2,3,4-四氢-2,4-二氧喹嗪-1-乙酸衍生物的方法，其中R.sup.1、R.sup.2、R.sup.3和R.sup.4相互独立地为氢、卤素、OH、NO.sub.2、(C.sub.1-C.sub.6)烷氧基、(C.sub.1-C.sub.6)烷基、卤素取代的(C.sub.1-C.sub.6)烷基，R.sup.5为氢、(C.sub.1-C.sub.6)烷基、苯基，其中烷基或苯基基团也可以被卤素原子取代；其中式(II)的蒽酰氨衍生物，其中R.sup.1到R.sup.5具有上述含义，R.sup.6为氢、(C.sub.1-C.sub.6)烷基或苯基，其中烷基或苯基基团也可以被卤素原子取代，在惰性溶剂的存在下与金属氰酸盐和氯化氢反应。 ##STR1##
• Quinazoline derivatives and process for their production
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04883800A1

  公开（公告）日：1989-11-28

  The invention relates to compounds having aldose reductase-inhibitory activity of the formula: ##STR1## in which R.sup.1 and R.sup.2 are each hydrogen, halogen, lower alkoxy or halo(lower)alkyl, R.sup.3 is phenyl(lower)alkyl which may have one or more substituent(s) selected from the group consisting of halogen, lower alkoxy, halo(lower)alkyl and lower alkyl, R.sup.4 is carboxy or protected carboxy, A is sulfur atom, Y is carbonyl, thiocarbonyl or sulfonyl and Z is lower alkylene, and pharmaceutically acceptable salts thereof, useful in treating diabetic complications.

  该发明涉及具有醛糖还原酶抑制活性的化合物的公式：##STR1## 其中R.sup.1和R.sup.2分别为氢，卤素，较低的烷氧基或卤代（较低）烷基，R.sup.3为苯（较低）烷基，可具有来自卤素，较低的烷氧基，卤代（较低）烷基和较低的烷基的一个或多个取代基，R.sup.4为羧基或保护羧基，A为硫原子，Y为羰基，硫代羰基或磺酰基，Z为较低的烷基，以及其药学上可接受的盐，用于治疗糖尿病并发症。
• Process for the preparation of 3-dihalobenzyl-2,4-quinazolinedione derivatives
  申请人：Fuji Chemical Industry Co., Ltd.

  公开号：US06201121B1

  公开（公告）日：2001-03-13

  A process for preparing a 3-dihalobenzyl-2,4-quinazolinedione derivative represented by the formula (V): (wherein X1, X2, X3 are independently a halogen atom, and A is an alkylene group), which comprises: reacting a dihalobenzyl derivative represented by the formula (III): (wherein X2 and X3 are each as defined above, and L is an acid residue) with a 2,4-quinazolinedione derivative having a carboxyalkyl group represented by the formula (I): (wherein X1 and A are each as defined above) to selectively substitute a hydrogen atom of an imino group at the 3-position of the derivative (1). The above process enables the efficient preparation of the compounds of the above formula (V) useful as inhibitors against aldose reductases, makes it possible to secure the safety and hygiene of workers, and can facilitate waste disposal to reduce the expenses, thus being industrially extremely advantageous.

  一种制备式(V)的3-二卤苄基-2,4-喹唑啉二酮衍生物的方法：（其中X1，X2，X3分别独立为卤素原子，A为烷基），包括：将式(III)的二卤苄基衍生物（其中X2和X3如上所定义，L为酸残基）与具有羧基烷基的2,4-喹唑啉二酮衍生物反应（其中X1和A如上所定义），以选择性取代衍生物(1)的3位亚胺基的氢原子。以上方法能够有效制备上述式(V)的化合物，用于抑制醛糖还原酶，可以确保工人的安全和卫生，并可以促进废物处理以减少费用，因此在工业上极具优势。
• New quinazoline derivatives, process for their production and pharmaceutical compositions comprising them
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0218999A2

  公开（公告）日：1987-04-22

  compound of the formula: in which R1 and R2 are each hydrogen, halogen, lower alkoxy or halo(lower)alkyl, R3 is aryl or ar(lower)alkyl, both of which may have one or more suitable substituent(s), or heterocyclic(lower)alkyl, R4 is carboxy or protected carboxy, A is oxygen or sulfur atom, Y is carbonyl, thiocarbonyl or sulfonyl and Z is lower alkylene, and pharmaceutically acceptable salts thereof, processes for their preparation and pharmaceutical compositions comprising them in admixture with pharmaceutically acceptable carriers.

  式的化合物： 其中 R1 和 R2 分别为氢、卤素、低级烷氧基或卤代（低级）烷基、 R3 是芳基或芳基（低级）烷基，两者均可带有一个或多个合适的取代基，或杂环（低级）烷基、 R4 是羧基或受保护的羧基、 A 是氧原子或硫原子 Y 是羰基、硫代羰基或磺酰基，以及 Z 是低级亚烷基、 及其药学上可接受的盐、制备方法以及由它们与药学上可接受的载体混合而成的药物组合物。