4-(2-amino-ethylamino)benzoic acid | 227312-86-9

• 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: 4-(2-amino-ethylamino)benzoic acid
• 英文别名: 4-(2-azaniumylethylamino)benzoate
• CAS: 227312-86-9
• 化学式: C₉H₁₂N₂O₂
• 分子量: 180.206
• InChiKey: FCTDPDWTVUINMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-amino-ethylamino)benzoic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.25h， 生成 2(S)-{2(S)-[4-(2-guanidino-ethylamino)benzoylamino]-3-methyl-butyrylamino}-3-phenyl-propionic acid
  参考文献：
  名称：

  Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

  摘要：

  Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3 beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.004
• 作为产物：
  描述：

  4-氨基苯甲酸甲酯 在 lithium hydroxide 、 4 A molecular sieve 、 sodium cyanoborohydride 、 溶剂黄146 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 3.0h， 生成 4-(2-amino-ethylamino)benzoic acid
  参考文献：
  名称：

  Modifications of the GSK3β substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics

  摘要：

  Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3 beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.004

文献信息

• Synthesis and Structure-Activity Study of Protease Inhibitors. V. Chemical Modification of 6-Amidino-2-naphthyl 4-Guanidinobenzoate.
  作者：Toyoo NAKAYAMA、Seizo TAIRA、Masato IKEDA、Hiroshi ASHIZAWA、Minoru ODA、Katsumasa ARAKAWA、Setsuro FUJII

  DOI：10.1248/cpb.41.117

  日期：——

  By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, C1^- and C1s^- as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]-benzoate (41, FUT-187) was found to be a suitable compound for oral administration with anti-complement activity superior to that of compound I.

  通过开发6-氨基脲基-2-萘基4-胍基苯甲酸（I，FUT-175）作为基本结构，合成了其多种衍生物，并测试了它们对胰蛋白酶、纤溶酶、激肽释放酶、凝血酶、C1^-和C1s^-的抑制活性，以及对补体介导的溶血作用的影响。还对这些化合物在豚鼠中对补体介导的Forssman休克的保护作用进行了研究。研究发现，6-氨基脲基-2-萘基4-[（4, 5-二氢-1H-咪唑-2-基）氨基]-苯甲酸（41，FUT-187）是一种适合口服给药的化合物，其抗补体活性优于化合物I。
• Novel Indoline Compounds
  申请人：LEBRETON Luc

  公开号：US20080119465A1

  公开（公告）日：2008-05-22

  Sulfonylindoline compounds of formula I, wherein R1 through R4, Y and Z have defined meanings, a process for preparation of such compounds, and the use as pharmaceutically active substances, particularly for the treatment or inhibition of neurodegeneration, cardiovascular disease, inflammatory disease, hypercholesterolemia, dyslipidemia, obesity or diabetes.

  公式I的磺胺基吲哚化合物，其中R1至R4，Y和Z具有定义的含义，一种制备这种化合物的过程，以及用作药用活性物质，特别用于治疗或抑制神经退行性疾病、心血管疾病、炎症性疾病、高胆固醇血症、血脂异常、肥胖或糖尿病。
• DUAL INHIBITORS OF FARNESYLTRANSFERASE AND GERANYLGERANYLTRANSFERASE I
  申请人：H. Lee Moffitt Cancer Center and Research Institute, Inc.

  公开号：US20130190355A1

  公开（公告）日：2013-07-25

  Many GTPases such as Ras, Ral and Rho require post-translational farnestylation or geranylgeranylation for mediating malignant transformation. Dual farnesyltransferase (FT) (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) were developed as anticancer agents from based on an ethylenediamine scaffold. On the basis of a 4-fold substituted ethylenediamine scaffold, the inhibitors are structurally simple and readily derivatized, facilitating extensive structure-activity relationship studies. The most potent inhibitor is compound exhibited an in vitro hFTase IC 50 value of 25 nM and a whole cell H-Ras processing IC 50 value of 90 nM. Several of the inhibitors proved highly selective for hFTase over the related prenyltransferase enzyme geranylgeranyltransferase-I (GGTase-I). A crystal structure of an inhibitor cocrystallized with farnesyl pyrophosphate in the active site of rat FTase illustrates that the para-benzonitrile moiety is stabilized by a π-π stacking interaction with the Y361β residue, suggesting an importance of this component of the inhibitors.

  许多GTP酶如Ras、Ral和Rho需要经过翻酰基化或戊二烯基化的后翻译修饰，以介导恶性转化。双重翻酰基转移酶(FT)(FTI)和戊二烯基转移酶-I(GGT-1)抑制剂(GGTI)是基于乙二胺支架开发的抗癌剂。基于四倍取代乙二胺支架，这些抑制剂结构简单，易于衍生，便于进行广泛的构效关系研究。其中最有效的抑制剂表现出25 nM的体外hFTase IC50值和90 nM的整个细胞H-Ras处理IC50值。其中几种抑制剂对相关的戊二烯基转移酶酶(GGTase-I)高度选择性。一种抑制剂与磷酸戊二烯基共结晶于大鼠FTase的活性位点中的晶体结构表明，对苯二腈基团通过与Y361β残基的π-π堆积相互作用稳定，表明这些抑制剂的这个组分的重要性。
• GLYCOSYLATED LINKER, COMPOUND CONTAINING GLYCOSYLATED LINKER MOIETY AND PHYSIOLOGICALLY ACTIVE SUBSTANCE MOIETY OR SALT THEREOF, AND METHODS FOR PRODUCING SAID COMPOUND OR SALT THEREOF
  申请人：Glytech, Inc.

  公开号：EP2924053A1

  公开（公告）日：2015-09-30

  [Problem] The purpose is to provide a compound containing a carrier linker moiety and a physiologically active substance moiety or a salt of the compound, wherein a carrier in the carrier linker moiety is biodegradable and is soluble in water. [Solution] The purpose can be achieved by employing a sugar chain as a carrier and focusing on the structure of a carrier-linker having a specified structure. A compound containing a carrier linker moiety and a physiologically active substance moiety or a salt of the compound is discovered.

  [问题]目的是提供一种含有载体连接体分子和生理活性物质分子或化合物盐的化合物，其中载体连接体分子中的载体可生物降解并可溶于水。 [解]采用糖链作为载体，并注重具有特定结构的载体连接体的结构，可以达到上述目的。发现了一种含有载体连接体分子和生理活性物质分子或化合物盐的化合物。
• Non-peptidic substrate-mimetic inhibitors of Akt as potential anti-cancer agents
  作者：Katherine J. Kayser-Bricker、Matthew P. Glenn、Sang Hoon Lee、Said M. Sebti、Jin Q. Cheng、Andrew D. Hamilton

  DOI：10.1016/j.bmc.2008.09.058

  日期：2009.2

  Akt has emerged as a critical target for the development of anti-cancer therapies. It has been found to be amplified, overexpressed, or constitutively activated in numerous human malignancies with oncogenesis derived from the simultaneous promotion of cell survival and suppression of apoptosis. A valuable alternative to the more common ATP-mimetic based chemotherapies is a substrate-mimetic approach, which has the potential advantage of inherent specificity of the substrate-binding pocket. In this paper we present the development of high affinity non-peptidic, substrate-mimetic inhibitors based on the minimum GSK3 beta substrate sequence. Optimization of initial peptidic leads resulted in the development of several classes of small molecule inhibitors, which have comparable potency to the initial peptidomimetics, while eliminating the remaining amino acid residues. We have identified the first non-peptidic substrate-mimetic lead inhibitors of Akt 29a-b, which have affinities of 17 and 12 mu M, respectively. This strategy has potential to provide a useful set of molecular probes to assist in the validation of Akt as a potential target for anti-cancer drug design. (C) 2009 Published by Elsevier Ltd.