D-精氨酸,N2-[N-[N-[N-(N-L-酪氨酰甘氨酰)甘氨酰]-L-苯基丙氨酰]-L-亮氨酰]-(9CI) | 27782-63-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: D-精氨酸,N2-[N-[N-[N-(N-L-酪氨酰甘氨酰)甘氨酰]-L-苯基丙氨酰]-L-亮氨酰]-(9CI)
• 中文别名: 5,7-二羟基-3,6,4'-三甲氧基黄酮
• 英文名称: 5,7-Dihydroxy-3,6-dimethoxy-2-(4-methoxy-phenyl)-chromen-4-one
• 英文别名: santin；5,7-dihydroxy-3,6,4'-trimethoxyflavone；3,6,4'-trimethoxy-5,7-dihydroxyflavone；5,7-dihydroxy-3,6-dimethoxy-2-(4-methoxyphenyl)chromen-4-one
• CAS: 27782-63-4
• 化学式: C₁₈H₁₆O₇
• 分子量: 344.321
• InChiKey: DWZAJFZEYZIHPO-UHFFFAOYSA-N

物化性质

• 熔点：
  157-159 °C
• 沸点：
  597.0±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  94.4
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 海关编码：
  2914509090
• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  D-精氨酸,N2-[N-[N-[N-(N-L-酪氨酰甘氨酰)甘氨酰]-L-苯基丙氨酰]-L-亮氨酰]-(9CI) 、 乙酸酐 以 吡啶 为溶剂， 反应 12.0h， 生成 5,7-Diacetoxy-3,6,4'-trimethoxy-flavon
  参考文献：
  名称：

  Phenylbenzopyrones structure-activity studies identify betuletol derivatives as potential antitumoral agents

  摘要：

  We have analyzed the cytotoxicity of 22 compounds with a phenylbenzo-gamma-pirone core structure, most of them obtained from natural sources, in five human tumor cell lines (HL-60, A431, SK-OV-3, HeLa and HOS). Betuletot 3-methyl ether and its diacetate were the most cytotoxic compounds. The HL-60 cell line was especially sensitive to these compounds, with IC50 values of approximately I mu M. Treatment of HL-60 cells with betuletol 3-methyl ether was associated with apoptosis induction which was prevented by a non-specific caspase inhibitor (z-VAD-fmk) and also by a specific inhibitor of caspase-8 (z-IETD-fmk) indicating activation of the extrinsic apoptotic pathway. The results suggest that betuletol 3-methyl ether has potential as new anticancer agent. (c) 2006 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejphar.2006.07.020
• 作为产物：
  描述：

  5,7,3'-trihydroxy-3,6,4',5'-tetramethoxyflavone 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 硫酸二甲酯 作用下， 以 丙酮 为溶剂， 反应 1.0h， 以69%的产率得到D-精氨酸,N2-[N-[N-[N-(N-L-酪氨酰甘氨酰)甘氨酰]-L-苯基丙氨酰]-L-亮氨酰]-(9CI)
  参考文献：
  名称：

  Garden子科天然和半合成黄酮作为酪氨酸酶抑制剂的体外生物学评价和分子对接研究

  摘要：

  在不引起永久性色素沉着或刺激的情况下，难以治疗色素沉着过度症。最有效的色素减退剂是酪氨酸酶抑制剂，但是目前使用的某些已经显示出严重的副作用。如几类黄酮已经显示能力抑制酪氨酸酶，天然甲氧基黄酮的文库中分离（1 - 7从萌芽渗出物）栀子oudiepe和半合成衍生物（8，9）进行了评价。最具活性的化合物的IC 50在微摩尔范围内。最强的抑制剂1，2和3全部共享一个3'，4'-二甲氧基-5'-羟基三取代的B环。这些SAR结论已通过分子对接研究得到证实。阐明了与酶的相互作用方式，并观察到活性最高的化合物与酪氨酸酶催化残基之间的重要相互作用。所有这些数据提供了一个化合物库，这些化合物可以作为新的脱色剂和配方设计的潜在领导者。

  DOI：

  10.1016/j.bioorg.2018.10.034

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES AS ITK INHIBITORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE EN TANT QU'INHIBITEURS D'ITK
  申请人：PRINCIPIA BIOPHARMA INC

  公开号：WO2014036016A1

  公开（公告）日：2014-03-06

  The present disclosure is directed to certain inhibitors of kinases such as ITK, BLK, BMX, BTK, JAK3, TEC, TXK, HER2 (ERBB2), or HER4 (ERBB4), in particular ITK, pharmaceutical compositions comprising such compounds, and method of treating diseases mediated by such kinases.

  本公开涉及特定激酶抑制剂，如ITK、BLK、BMX、BTK、JAK3、TEC、TXK、HER2（ERBB2）或HER4（ERBB4），特别是ITK，包括这些化合物的药物组合物，以及治疗由这些激酶介导的疾病的方法。
• Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
  申请人：YOSHIDA Kenji

  公开号：US20100111852A1

  公开（公告）日：2010-05-06

  Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.

  提供了特异性结合于细胞表面表达的Claudin 3的单克隆抗体。本发明的抗体对于具有增强Claudin 3表达的癌症的诊断是有用的，如卵巢癌、前列腺癌、乳腺癌、子宫癌、肝癌、肺癌、胰腺癌、胃癌、膀胱癌和结肠癌。本发明提供了对这些癌症细胞具有细胞毒作用的单克隆抗体。公开了诱导Claudin 3表达细胞受损的方法以及通过与Claudin 3结合抗体接触Claudin 3表达细胞来抑制Claudin 3表达细胞增殖的方法。本申请还公开了癌症的诊断或治疗方法。
• Antivascular and anti-parasite activities of natural and hemisynthetic flavonoids from New Caledonian Gardenia species (Rubiaceae)
  作者：Linh H. Mai、Guy G. Chabot、Philippe Grellier、Lionel Quentin、Vincent Dumontet、Cyril Poulain、Laila S. Espindola、Sylvie Michel、Hue T.B. Vo、Brigitte Deguin、Raphaël Grougnet

  DOI：10.1016/j.ejmech.2015.01.012

  日期：2015.3

  A series of 16 flavonoids were isolated and prepared from bud exudate of Gardenia urvillei and Gardenia oudiepe, endemic to New Caledonia. Most of them are rare polymethoxylated flavones. Some of these compounds showed noticeable activity against Leishmania (Leishmania) amazonensis, Plasmodium falciparum and Trypanosoma brucei gambiense, in addition to tubulin polymerization inhibition at low micromolar

  一系列的16类黄酮的分离和从芽渗出物制备栀子urvillei和栀子oudiepe，特有的新喀里多尼亚。它们大多数是稀有的聚甲氧基黄酮。这些化合物中的一些在低微摩尔浓度下，除了抑制微管蛋白聚合外，还显示出对亚马逊利什曼原虫（Leishmania），恶性疟原虫和布氏锥虫的显着活性。我们还提供了完整的NMR数据集，因为其中的黄酮含量不完整。
• [EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF INFLAMMATORY DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES LES COMPRENANT POUR LE TRAITEMENT DE TROUBLES INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2014202458A1

  公开（公告）日：2014-12-24

  The present invention discloses compounds according to Formula I: Wherein R 1a, R 1b, R 2, R 4, R5, R 6, R 7, R 8, W, X, Y, Z, Cy, and the subscript a are as defined herein. The present invention relates to compounds inhibiting autotaxin (NPP2 or ENPP2), methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving fibrotic diseases,proliferative diseases, inflammatory diseases, autoimmune diseases, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, dermatological disorders, and/or abnormal angiogenesis associated diseases by administering the compound of the invention.

  本发明公开了根据式I的化合物：其中R 1a、R 1b、R 2、R 4、R5、R 6、R 7、R 8、W、X、Y、Z、Cy和下标a如本文所定义。本发明涉及抑制自体脂肪酶（NPP2或ENPP2）的化合物，其制备方法，包含其的药物组合物，以及使用该化合物进行预防和/或治疗涉及纤维化疾病、增殖性疾病、炎症性疾病、自身免疫疾病、呼吸系统疾病、心血管疾病、神经退行性疾病、皮肤病和/或与异常血管生成相关疾病的方法。
• [EN] ARYL SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS<br/>[FR] COMPOSÉS D'HÉTÉROARYLE BICYCLIQUES SUBSTITUÉS PAR UN ARYLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2017019828A1

  公开（公告）日：2017-02-02

  Disclosed is a compound of Formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein one R3 is H and the other R3 is an aryl group substituted with zero to 3 R3a; and R1, R2, and R3a are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors for the inhibition or prevention of platelet aggregation, and the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder. Also disclosed are methods of using such compounds for the treatment of human papillomavirus. Additionally, pharmaceutical compositions comprising at least one compound of Formula (I) are disclosed.

  揭示的是Formula（I）的化合物或其立体异构体、互变异构体、药学上可接受的盐、溶剂合物或前药，其中一个R3是H，另一个R3是芳基，其上取代有零至3个R3a；R1、R2和R3a在此处有定义。还揭示了将这些化合物用作PAR4抑制剂以抑制或预防血小板聚集，并用于治疗血栓栓塞性疾病或血栓栓塞性疾病的初级预防的方法。还揭示了将这些化合物用于治疗人类乳头瘤病毒的方法。此外，还揭示了包含至少一种Formula（I）化合物的药物组合物。