α-(4-bromomethylphenyl)acetic acid tert-butyl ester | 77292-91-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: α-(4-bromomethylphenyl)acetic acid tert-butyl ester
• 英文别名: 4-(bromomethyl)benzeneacetic acid 1,1-dimethylethyl ester；tert-butyl 4-(brmomethyl)phenylacetate；tert-butyl 2-(4-(bromomethyl)phenyl)acetate；tert-butyl 4-bromomethylphenylacetate；(4-bromomethyl-phenyl)-acetic acid tert-butyl ester；1,1-dimethylethyl 2-(4-bromomethylphenyl)acetate；tert-butyl 2-[4-(bromomethyl)phenyl]acetate
• CAS: 77292-91-2
• 化学式: C₁₃H₁₇BrO₂
• 分子量: 285.181
• InChiKey: RSSSPVYGYNGCSG-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P501,P260,P270,P234,P271,P264,P280,P390,P362+P364,P303+P361+P353,P301+P330+P331,P301+P312+P330,P304+P340+P310,P305+P351+P338+P310,P406,P405
• 危险品运输编号：
  3261
• 危险性描述：
  H302+H312+H332,H314,H290
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  α-(4-bromomethylphenyl)acetic acid tert-butyl ester 在 吡啶 、 盐酸 、 氢氧化钾 、 sodium hydroxide 、 sodium tetrahydroborate 、 碘 、 苄基三甲基氢氧化铵 、 potassium iodide 作用下， 以 1,4-二氧六环 、 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 (4-{2-tert-Butoxycarbonylamino-3-[2-tert-butoxycarbonylamino-3-(4-tert-butoxycarbonylmethyl-phenyl)-propyldisulfanyl]-propyl}-phenyl)-acetic acid tert-butyl ester
  参考文献：
  名称：

  Investigation of the Active Site of Aminopeptidase A Using a Series of New Thiol-Containing Inhibitors

  摘要：

  Aminopeptidase A (APA) and aminopeptidase N (APN) are two metallopeptidases which have been suggested to be involved in the enzymatic cascade of the renin-angiotensin system. APA liberates angotensin III from angiotensin II by releasing the N-terminal aspartate, and APN participates in the inactivation of angiotensin III. As the role of angiotensin III in the regulation of blood pressure in the central nervous system and at the periphery is controversial, it was of interest to develop selective and efficient inhibitors of APA. Starting from Glu-thiol,(1) which was the first efficient APA inhibitor described, but however is equipotent on APA (K-i = 0.14 mu M) and APN (K-i = 0.12 mu M), beta-amino thiols bearing various carboxyalkyl chains have been synthesized and their inhibitory potencies measured on both purified enzymes. Compounds containing a carboxylated aromatic ring inhibited APA and APN with K-i values in the micromolar range but were slightly more active on APA. Conversely, inhibitors containing a cyclohexyl ring were more efficient on APN. Various modifications of the structure of Glu-thiol decreased inhibitory activity on both enzymes but increased the selectivity for APA, and compound 9d ((S)-4-amino-6-mercaptohexanoic acid) was 23 times more potent on APA (K-i = 2.0 mu M) than on APN (K-i = 45 mu M).

  DOI：

  10.1021/jm00035a014
• 作为产物：
  描述：

  对叔丁基苯乙酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 作用下， 以 四氯化碳 为溶剂， 以32%的产率得到α-(4-bromomethylphenyl)acetic acid tert-butyl ester
  参考文献：
  名称：

  羧酸和四唑作为胆囊收缩素类似物中硫酸盐的等排替代物。

  摘要：

  制备了一系列诱导饱腹感的肽胆囊收缩素（CCK-8）的类似物，其中活化外围受体所需的硫酸化酪氨酸被羧基（烷基）-或四唑基（烷基）-苯丙氨酸替代，以研究是否有机酸可以充当受体上的硫酸根基团。必要的中间体是通过以前报道的方法或通过将羧基（烷基）或四唑基（烷基）苯基甲基溴与甘氨酸衍生的阴离子烷基化，然后进行保护基操作而制备的，并将这些中间体掺入乙酰基CCK-7衍生物中采用固相合成。在CCK结合试验中，使用均质的大鼠胰膜作为受体源，评估肽类似物对外周（CCK-A）受体的亲和力，或使用牛纹状体作为受体源，评估对中枢（CCK-B）受体的亲和力。进一步评估了它们在腹膜内注射后对大鼠食物摄入的影响。报道的许多化合物在CCK-A受体结合测定中均具有活性，尽管其效力不如乙酰基-CCK-7，并且可以减少食物摄入量，且效力可与乙酰基-CCK-7媲美。在旨在评估食欲抑制活性的膳食喂养模型中，乙酰基-CCK-7的ED50为7

  DOI：

  10.1021/jm00107a037

文献信息

• Fused pyrimidinone matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20030004172A1

  公开（公告）日：2003-01-02

  Selective MMP-13 inhibitors are fused pyrimidinones of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: W, together with the carbon atoms to which it is attached, form a 5-membered ring diradical 2 X is O, S, SO, SO 2 , NR 5 , or CH 2 ; 3 B is O or NR 5 ; or A and B are taken together to form —C≡C—; R 1 , R 4 , and R 5 are hydrogen, alkyl, alkenyl, alkynyl, (CH 2 ) n aryl, (CH 2 ) n cycloalkyl, C 1 -C 6 alkanoyl, or (CH 2 ) n heteroaryl; R 2 and R 3 are hydrogen, alkyl, alkenyl, alkynyl CN, NO 2 , NR 4 R 5 , (CH 2 ) n cycloalkyl, (CH 2 ) n aryl, or (CH 2 ) n heteroaryl; R 2 may further be halo; n is an integer of from 0 to 5; and R 4 and R 5 when taken together with a nitrogen to which they are both attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing O, S, or N, and substituted or unsubstituted; with the proviso that R 1 and R 3 are not both selected from hydrogen and C 1 -C 6 alkyl.

  选择性MMP-13抑制剂是具有以下结构的嘧啶酮类化合物或其药用盐： 其中： W与其连接的碳原子一起形成一个5元环二自由基； X为O、S、SO、SO2、NR5或CH2； B为O或NR5； 或A和B结合形成—C≡C—； R1、R4和R5为氢、烷基、烯基、炔基、( )n芳基、( )n环烷基、C1-C6烷酰基或( )n杂环芳基； R2和R3为氢、烷基、烯基、炔基、CN、NO2、NR4R5、( )n环烷基、( )n芳基或( )n杂环芳基；R2还可以是卤素； n为0到5的整数； R4和R5与它们都连接的氮一起形成含碳原子且可选择含有O、S或N的3-8元环，可以是取代或未取代的； 但要注意R1和R3不同时选择自氢和C1-C6烷基。
• Arylmethoxy Isoindoline Derivatives and Compositions Comprising and Methods of Using the Same
  申请人：Man Hon-Wah

  公开号：US20110196150A1

  公开（公告）日：2011-08-11

  Provided are 4′-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

  提供了4'-芳基甲氧基异吲哚啉化合物，以及其药用盐、溶剂合物、包合物、立体异构体和前药。公开了这些化合物的使用方法和药物组合物。
• Analogs of tyrosine sulfate or tyrosine phosphate containing peptides
  申请人：Hoffmann-La Roche Inc.

  公开号：US05182263A1

  公开（公告）日：1993-01-26

  Analogs of Tyrosine Sulfate or Tyrosine Phosphate containing peptides, the novel intermediate compounds used in the preparation of these analogs, as well as a method for suppressing appetite in subjects by administering to the subject an effective amount of CCK analog wherein one or more of any Tyrosine Sulfate present is substituted with a radical of the invention.

  含有酪氨酸硫酸盐或酪氨酸磷酸盐的肽类类似物，用于制备这些类似物的新型中间化合物，以及通过向受试者投与有效量的CCK类似物来抑制食欲的方法，其中任何存在的酪氨酸硫酸盐被本发明的基团所取代。
• Design and Synthesis of Non-Peptide Mimetics Mapping the Immunodominant Myelin Basic Protein (MBP83–96) Epitope to Function as T-Cell Receptor Antagonists
  作者：Mary-Patricia Yannakakis、Carmen Simal、Haralambos Tzoupis、Maria Rodi、Narges Dargahi、Monica Prakash、Athanasia Mouzaki、James Platts、Vasso Apostolopoulos、Theodore Tselios

  DOI：10.3390/ijms18061215

  日期：——

  inhibition of proliferation of activated T cells. A structure-based pharmacophore model was generated, in view of the interactions between the TCR and the HLA-MBP83-96 complex. As a result, new candidate molecules were designed based on lead compounds obtained through the ZINC database. Moreover, semi-empirical and density functional theory methods were applied for the prediction of the binding energy between

  致脑炎的T细胞与多发性硬化症（MS）的发病机理密切相关，多发性硬化症是中枢神经系统的一种自身免疫性脱髓鞘疾病。它们的刺激是由人白细胞抗原（HLA），免疫显性髓鞘碱性蛋白（MBP）表位和T细胞受体（TCR）之间的三分子复合物的形成触发的。我们在此详细介绍基于基于TCR与HLA结合识别的免疫优势MBP83-96表位的合理设计和合成非肽模拟分子的研究。我们将注意力集中在抑制三分子复合物的形成，从而抑制活化的T细胞的增殖。考虑到TCR和HLA-MBP83-96复合物之间的相互作用，产生了基于结构的药效团模型。结果，基于通过ZINC数据库获得的先导化合物设计了新的候选分子。此外，半经验和密度泛函理论方法被用于预测所提出的非肽模拟物和TCR之间的结合能。我们合成了六种分子，这些分子将在体外进一步评估为TCR拮抗剂。类似物15和16能够在一定程度上抑制来自免疫小鼠的免疫显性MBP83-99肽对T细胞的刺
• Small Peptides Containing Phosphotyrosine and Adjacent αMe-Phosphotyrosine or Its Mimetics as Highly Potent Inhibitors of Grb2 SH2 Domain
  作者：Wang-Qing Liu、Michel Vidal、Nohad Gresh、Bernard P. Roques、Christiane Garbay

  DOI：10.1021/jm9911074

  日期：1999.9.1

  small peptides with the sequence mAZ-pTyr-Xaa-Asn-NH(2), where Xaa denotes alpha-methylphosphotyrosine or its carboxylic mimetics, were synthesized as inhibitors of the Grb2 SH2 domain. Peptide 3 with (alpha-Me)pTyr as Xaa has the highest affinity for Grb2 (K(d) = 3 +/- 1 nM) and exhibits to date the best inhibitory activity (IC(50) = 11 +/- 1 nM) to displace PSpYVNVQN-Grb2 interaction in an ELISA test

  合成了一系列序列为mAZ-pTyr-Xaa-Asn-NH（2）的小肽，其中Xaa表示α-甲基磷酸酪氨酸或其羧基模拟物，作为Grb2 SH2域的抑制剂。具有（aa-Me）pTyr作为Xaa的肽3对Grb2的亲和力最高（K（d）= 3 +/- 1 nM），迄今为止显示出最佳的抑制活性（IC（50）= 11 +/- 1 nM ）以取代ELISA测试中的PSpYVNVQN-Grb2相互作用。具有（alpha-Me）Tyr，（alpha-Me）Phe（4-CO（2）H）或（alpha-Me）Phe（4-CH（2）CO（2）H）的肽的较低亲和力Xaa证明了在pY + 1位置带有双电荷的磷酸基团的重要性。分子建模显示了由（alpha-Me）pTyr残基与Grb2 SH2域提供的其他氢键相互作用。因此，这些结果表明，疏水性pY + 1残基的作用