2-benzyl-2-methyl-succinic acid | 32980-47-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-benzyl-2-methyl-succinic acid
• 英文别名: 3-phenyl-2-methylcarboxymethylpropionic acid；α-Methyl-α-benzyl-bernsteinsaeure；(+/-)-2-Methyl-2-benzyl-bernsteinsaeure；2-Benzyl-3-methyl-bernsteinsaeure；2-Methyl-2-benzyl-bernsteinsaeure；2-Benzyl-2-methylbernsteinsaeure；2-benzyl-2-methylbutanedioic acid
• CAS: 32980-47-5
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: QFWZQNUAZRYHFF-UHFFFAOYSA-N

物化性质

• 熔点：
  144 °C(Solv: benzene (71-43-2))
• 沸点：
  338.4±22.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyl-2-methyl-succinic acid 在 盐酸 、 硫酸 作用下， 生成
  参考文献：
  名称：

  Tricyclic cyanoguanidines: synthesis, site of action and insecticidal activity of a novel class of reversible acetylcholinesterase inhibitors

  摘要：

  Bridged-tricyclic cyanoguanidines 1 were found to be active as insecticides. The preparation and structure-activity relationships of oxacyclic (X=O) and carbocyclic (X=CH2) analogues of 1 is described. Compounds 1 were found to inhibit acetylcholinesterase with IC50 values comparable to the organophosphate Paraoxon. Unlike organophosphates. cyanoguanidines 1 were shown to reversibly bind acetylcholinesterase. This mode of action is shared by the structurally-related natural product Huperzine A. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00326-1
• 作为产物：
  描述：

  2-苄基丙酸 在 硫酸 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 77.0h， 生成 2-benzyl-2-methyl-succinic acid
  参考文献：
  名称：

  2-Benzyl-2-methylsuccinic acid as inhibitor for carboxypeptidase A. synthesis and evaluation

  摘要：

  Recently, Asante-Appiah et al. (Asante-Appiah, E.; Seetharaman, J.; Sicheri, F.; Yang, D. S.-C.; Chan, W. W.-C. Biochemistry 1997, 36, 8710-8715) reported that 2-ethyl-2-methylsuccinic acid isa highly potent inhibitor for carboxypeptidase A (CPA), a prototypic zinc protease. The X-ray crystal structure of the complex of the enzyme formed with 2-ethyl-2-methylsuccinic acid revealed that at the active site of CPA there is present a small cavity which accommodates the methyl group of the inhibitor. These investigators postulated that incorporation of a methyl group at the alpha-position to the carboxylate of existing inhibitors of CPA would improve the inhibitory potency. We have synthesized racemic and optically active 2-benzyl-2-methylsuccinic acids and evaluated their inhibitory activities for CPA to find the K-i values to be 0.28, 0.15, and 17 mu M for racemic form, (R)-, and (S)-enantiomer, respectively. Contrary to the expectation, the effect on the binding affinity by the incorporation of the methyl group is minimal. The validity of the proposition that the small cavity may be utilized for the improvement of the inhibitory potency appears questionable. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00110-8

文献信息

• Potential Hypocholesteremic Derivatives of Styrylacetic Acid II: cis- and trans-3-Methyl-4-phenyl-3-butenoic Acid Analogs
  作者：E.S. Stratford、L.M. Smith、G.W. Tomecko

  DOI：10.1002/jps.2600670120

  日期：1978.1

  testing for in vitro cholesterol biosynthesis inhibitory activity of 2-indeneacetic acid, 2-methyl-1,2-dihydro-2-naphthoic acid, and their 5- and 7-chloro derivatives, respectively are described. These compounds were prepared as trans- and cis-analogs of the known antilipemic agent 3-methyl-4-phenyl-3-butenoic acid. Although both series of compounds showed cholesterol biosynthesis inhibitory properties

  分别描述了2-茚满乙酸，2-甲基-1,2-二氢-2-萘甲酸及其5-和7-氯衍生物的体外胆固醇生物合成抑制活性的合成和初步生物学测试。这些化合物被制备为已知的抗血脂药3-甲基-4-苯基-3-丁烯酸的反式和顺式类似物。尽管两个系列的化合物均显示出胆固醇生物合成抑制特性，但氯取代仅在顺式系统中增强了效能。根据顺式化合物与氯贝特类抗血脂药之间的可能关系讨论了这些发现。
• Carboxyalkyl tricyclic derivatives useful as inhibitors of enkephalinase
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05455242A1

  公开（公告）日：1995-10-03

  The present invention relates to compounds of the formula ##STR1## wherein B.sub.1 and B.sub.2 are each independently hydrogen; hydroxy; --OR.sub.2 wherein R.sub.2 is a C.sub.1 -C.sub.4 alkyl or an Ar--Y group wherein Ar is aryl and Y is a hydrogen or C.sub.1 -C.sub.4 alkyl; or, where B.sub.1 and B.sub.2 are attached to adjacent carbon atoms, B.sub.1 and B.sub.2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; A is a bond, methylene or oxygen, sulfur or NR.sub.4 or NCOR.sub.5 wherein R.sub.4 is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group and R.sub.5 is --CF.sub.3, a C.sub.1 -C.sub.10 alkyl or an Ar--Y-- group; R.sub.3 is hydrogen or --CH.sub.2 OC(O)C(CH.sub.3).sub.3 ; R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkyl or --CH.sub.2 OC(O)--C(CH.sub.3).sub.3 ; and n is an integer 1 to 3, which are useful as inhibitors of enkephalinase and ACE.

  本发明涉及以下结构的化合物 ##STR1## 其中B.sub.1和B.sub.2分别独立地是氢；羟基；--OR.sub.2 其中R.sub.2是C.sub.1 -C.sub.4烷基或Ar--Y基团，其中Ar是芳基，Y是氢或C.sub.1 -C.sub.4烷基；或者，当B.sub.1和B.sub.2连接到相邻的碳原子时，B.sub.1和B.sub.2可以与所述相邻碳原子一起形成苯环或亚甲二氧基；A为键，亚甲基或氧、硫或NR.sub.4或NCOR.sub.5，其中R.sub.4为氢，C.sub.1 -C.sub.4烷基或Ar--Y--基团，R.sub.5为--CF.sub.3，C.sub.1 -C.sub.10烷基或Ar--Y--基团；R.sub.3为氢或--CH.sub.2 OC(O)C(CH.sub.3).sub.3；R.sub.1为氢，C.sub.1 -C.sub.4烷基或--CH.sub.2 OC(O)--C(CH.sub.3).sub.3；n为1到3的整数，这些化合物可用作脑啡肽酶和ACE的抑制剂。
• [EN] ANTICOAGULANT COMPOUNDS<br/>[FR] COMPOSES ANTICOAGULANTS
  申请人：MERCK & CO INC

  公开号：WO2003013526A1

  公开（公告）日：2003-02-20

  Compounds of the invention are useful in inhibiting carboxypeptidase U and associated thrombotic occlusions having the structure (I) and pharmaceutically acceptable salts thereof, wherein t is N or N(R2'), u is C(R3) or N(R2'), and v is C(R2), N or N(R2), provided that, 1) when t is N and u is C(R3), then v is N(R2); 2) when t is N and u is N(R2'), then v is C(R2), and 3) when t is N(R2') and u is C(R3), then v is N or N(R2).

  本发明的化合物在抑制羧肽酶U和相关的血栓闭塞性疾病中具有用途，其结构式为(I)及其药学上可接受的盐，其中t为N或N(R2')，u为C(R3)或N(R2')，v为C(R2)、N或N(R2)，但需满足以下条件：1）当t为N且u为C(R3)时，则v为N(R2)；2）当t为N且u为N(R2')时，则v为C(R2)；3）当t为N(R2')且u为C(R3)时，则v为N或N(R2)。
• Carboxyalkyl derivatives useful as inhibitors of enkephalinase and ace
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05472959A1

  公开（公告）日：1995-12-05

  The invention relates to compounds of the formula ##STR1## wherein B.sub.1 and B.sub.2 are each independently hydrogen; hydroxy; --OR.sub.2 wherein R.sub.2 is a C.sub.1 -C.sub.4 alkyl or an Ar--Y group wherein Ar is aryl and Y is a hydrogen or C.sub.1 -C.sub.4 alkyl; or, where B.sub.1 and B.sub.2 are attached to adjacent carbon atoms, B.sub.1 and B.sub.2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; A is a bond, methylene or oxygen, sulfur, NR.sub.4 or NCOR.sub.5 wherein R.sub.4 is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group and R.sub.5 is --CF.sub.3, a C.sub.1 -C.sub.10 alkyl or an Ar--Y-- group; R.sub.3 is hydrogen or --CH.sub.2 OC(O)C(CH.sub.3).sub.3 ; R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkyl or --CH.sub.2 OC(O)--C(CH.sub.3).sub.3 ; and n is an integer 1 to 3, that are useful as inhibitors of enkephalinase and ACE.

  本发明涉及式子##STR1##的化合物，其中B.sub.1和B.sub.2分别独立地为氢; 羟基; --OR.sub.2，其中R.sub.2是C.sub.1-C.sub.4烷基或Ar--Y基团，其中Ar是芳基，Y是氢或C.sub.1-C.sub.4烷基; 或者，当B.sub.1和B.sub.2附加在相邻的碳原子上时，B.sub.1和B.sub.2可以与所述相邻碳原子一起取代成苯环或亚甲二氧基; A是键，亚甲基或氧，硫，NR.sub.4或NCOR.sub.5，其中R.sub.4是氢，C.sub.1-C.sub.4烷基或Ar--Y--基团，R.sub.5是--CF.sub.3，C.sub.1-C.sub.10烷基或Ar--Y--基团; R.sub.3是氢或--CH.sub.2OC（O）C（CH.sub.3）.sub.3; R.sub.1是氢，C.sub.1-C.sub.4烷基或--CH.sub.2OC（O）--C（CH.sub.3）.sub.3; n是1到3的整数，这些化合物对于脑啡肽酶和ACE的抑制剂是有用的。
• Carboxyalkyl tricylic derivatives useful as inhibitors of enkephalinase
  申请人：Merrell Dow Pharmaceuticals Inc.

  公开号：US05488047A1

  公开（公告）日：1996-01-30

  The present invention relates to compounds of the formula ##STR1## wherein B.sub.1 and B.sub.2 are each independently hydrogen; hydroxy; --OR.sub.2 wherein R.sub.2 is a C.sub.1 -C.sub.4 alkyl or an Ar-Y group wherein Ar is aryl and Y is a hydrogen or C.sub.1 -C.sub.4 alkyl; or, where B.sub.1 and B.sub.2 are attached to adjacent carbon atoms, B.sub.1 and B.sub.2 can be taken together with said adjacent carbons to form a benzene ring or methylenedioxy; A is a bond, methylene or oxygen, sulfur or NR.sub.4 or NCOR.sub.5 wherein R.sub.4 is hydrogen, a C.sub.1 -C.sub.4 alkyl or an Ar--Y-- group and R.sub.5 is --CF.sub.3, a C.sub.1 -C.sub.10 alkyl or an Ar--Y-- group; R.sub.3 is hydrogen or --CH.sub.2 OC(O)C(CH.sub.3).sub.3 ; R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkyl or --CH.sub.2 OC(O)--C(CH.sub.3).sub.3 ; and n is an integer 1 to 3, which are useful as inhibitors of enkephalinase and ACE.

  本发明涉及公式##STR1##的化合物，其中B.sub.1和B.sub.2各自独立地为氢；羟基；--OR.sub.2，其中R.sub.2为C.sub.1-C.sub.4烷基或Ar-Y基，其中Ar为芳基，Y为氢或C.sub.1-C.sub.4烷基；或者，当B.sub.1和B.sub.2附着在相邻的碳原子上时，B.sub.1和B.sub.2可以与所述相邻的碳原子一起形成苯环或亚甲二氧基；A是键，亚甲基或氧、硫或NR.sub.4或NCOR.sub.5，其中R.sub.4为氢、C.sub.1-C.sub.4烷基或Ar-Y基，R.sub.5为--CF.sub.3，C.sub.1-C.sub.10烷基或Ar-Y基；R.sub.3为氢或--CH.sub.2OC(O)C(CH.sub.3).sub.3；R.sub.1为氢、C.sub.1-C.sub.4烷基或--CH.sub.2OC(O)--C(CH.sub.3).sub.3；n为整数1至3，这些化合物可用作脑啡肽酶和ACE的抑制剂。