(5-氯-2-甲基-1H-吲哚-3-基)乙酸甲酯 | 172595-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: (5-氯-2-甲基-1H-吲哚-3-基)乙酸甲酯
• 英文名称: methyl 2-(5-chloro-2-methyl-1H-indol-3-yl)acetate
• 英文别名: methyl (5-chloro-2-methyl-1H-indol-3-yl)acetate；1-[5-chloro-2-methyl-1H-indol-3-yl]-acetic acid methyl ester
• CAS: 172595-66-3
• 化学式: C₁₂H₁₂ClNO₂
• 分子量: 237.686
• InChiKey: HHLUVAJKICYMKX-UHFFFAOYSA-N

物化性质

• 沸点：
  385.4±37.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (5-氯-2-甲基-1H-吲哚-3-基)乙酸甲酯 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 以84%的产率得到(5-氯-2-甲基吲哚-3)-乙酸
  参考文献：
  名称：

  INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS

  摘要：

  公开的是以下化合物的结构（I）：这些化合物可用作CRTH2受体的拮抗剂。还公开了含有化合物（I）的药物组合物以及利用化合物（I）治疗对抑制内源配体与CRTH2受体结合响应的疾病或疾病的用途。进一步描述了制备和使用这些化合物的方法。

  公开号：

  US20110105509A1
• 作为产物：
  描述：

  2-氯苯肼盐酸盐 生成 (5-氯-2-甲基-1H-吲哚-3-基)乙酸甲酯
  参考文献：
  名称：

  Indole derivatives useful to treat estrogen-related neoplasms and

  摘要：

  本发明涉及一种新型吲哚衍生物，可用于下调雌激素受体表达。还包括用于治疗肿瘤或控制患有肿瘤疾病的患者中的肿瘤生长的方法，特别是与乳腺、卵巢和宫颈组织相关的雌激素依赖性肿瘤。本发明的另一实施例是一种预防性治疗患有发展肿瘤疾病风险的患者的方法。还提供了一种用于治疗自身免疫疾病的方法。还包括新型吲哚衍生物的药物组合物。

  公开号：

  US05877202A1

文献信息

• Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
  作者：Elena De Vita、Peter Schüler、Scott Lovell、Jasmin Lohbeck、Sven Kullmann、Eitan Rabinovich、Amiram Sananes、Bernd Heßling、Veronique Hamon、Niv Papo、Jochen Hess、Edward W. Tate、Nikolas Gunkel、Aubry K. Miller

  DOI：10.1021/acs.jmedchem.8b01106

  日期：2018.10.11

  Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity based probe, could be used to pull down active endogenous KLK6.
• Inhibition of Cytosolic Phospholipase A₂α: Hit to Lead Optimization
  作者：John C. McKew、Megan A. Foley、Paresh Thakker、Mark L. Behnke、Frank E. Lovering、Fuk-Wah Sum、Steve Tam、Kun Wu、Marina W. H. Shen、Wen Zhang、Mario Gonzalez、Shanghao Liu、Anu Mahadevan、Howard Sard、Soo Peang Khor、James D. Clark

  DOI：10.1021/jm0507882

  日期：2006.1.1

  Compound I was previously reported to be a potent inhibitor of cPLA,(x in both artificial monomeric substrate and cell-based assays. However, I was inactive in whole blood assays previously used to characterize cyclooxygenase and lipoxygenase inhibitors. The IC(50) of 1 increased dramatically with cell number or lipid/detergent concentration. In an attempt to insert an electrophilic ketone between the indole and benzoic acid moieties, we discovered that increasing the distance between the two moieties gave a compound with activity in the GLU (7-hydroxycoumarinyl-gamma-linolenate) micelle assay, which contains lipid and detergent. Extensive structure-activity relationship work around this lead identified a potent pharmacophore for cPLA a inhibition. The IC(50)s between the GLU micelle and rat whole blood assays correlated highly. No correlation was found for other parameters, including lipophilicity or acidity of the required acid functionality. Compounds 25, 39, and 94 emerged as potent, selective inhibitors of cPLA(2)alpha and represent well-validated starting points for further optimization.
• Diazine Indole Acetic Acids as Potent, Selective, and Orally Bioavailable Antagonists of Chemoattractant Receptor Homologous Molecule Expressed on Th2 Cells (CRTH2) for the Treatment of Allergic Inflammatory Diseases
  作者：Neelu Kaila、Adrian Huang、Alessandro Moretto、Bruce Follows、Kristin Janz、Michael Lowe、Jennifer Thomason、Tarek S. Mansour、Cedric Hubeau、Karen Page、Paul Morgan、Susan Fish、Xin Xu、Cara Williams、Eddine Saiah

  DOI：10.1021/jm300007n

  日期：2012.6.14

  New classes of CRTH2 antagonists, the pyridazine linker containing indole acetic acids, are described. The initial hit 1 had good potency but poor permeability, metabolic stability, and PK. Initial optimization led to compounds of type 2 with low oxidative metabolism but poor oral bioavailability. Poor permeability was identified as a liability for these compounds. Addition of a linker between the indole and diazine moieties afforded a series with good potency, low rates of metabolism, moderate permeability, and good oral bioavailability in rodents, 32 was identified as the development track candidate. It was potent in cell based, binding, and whole blood assays and exhibited good PK profile. It was efficacious in mouse models of contact hypersensitivity (1 mg/kg b.i.d.) and house dust (20 mg/kg q.d.) when dosed orally. In sheep asthma, administration at 1 mg/kg iv completely blocked the LAR and AHR and attenuated the EAR phase.
• NOVEL INDOLE DERIVATIVES USEFUL TO TREAT ESTROGEN-RELATED NEOPLASMS AND DISORDERS
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0746544A1

  公开（公告）日：1996-12-11
• [EN] NOVEL INDOLE DERIVATIVES USEFUL TO TREAT ESTROGEN-RELATED NEOPLASMS AND DISORDERS<br/>[FR] NOUVEAUX DERIVES D'INDOLE UTILISES POUR TRAITER DES NEOPLASMES ET DES TROUBLES ASSOCIES AUX OESTROGENES
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：WO1995022524A1

  公开（公告）日：1995-08-24

  (EN) The present invention relates to novel indole derivatives of formula (I), useful in down-regulating estrogen receptor expression. Also included are methods for the treatment of neoplasms or of controlling the growth of a neoplasm in a patient afflicted with a neoplastic disease, especially estrogen-dependent neoplasms such as those associated with breast, ovarian and cervical tissue. Another embodiment of the present invention is a method of prophylactically treating a patient at risk of developing neoplastic disease state. Also provided is a method for treating autoimmune diseases. Also included are pharmaceutical compositions of the novel indole derivatives.(FR) La présente invention se rapporte à de nouveaux dérivés d'indole de la formule (I) qui sont utilisés dans la régulation négative de l'expression des récepteurs d'÷strogènes. L'invention se rapporte également à des procédés de traitement des néoplasmes ou de régulation du développement d'un néoplasme chez un patient atteint d'une maladie néoplasique, notamment des néoplasmes dépendant des ÷strogènes, tels que ceux associés au tissu mammaire, ovarien, et cervical. Selon un autre mode de réalisation de la présente invention, on décrit un procédé de traitement prophylactique d'un patient sujet à développer un état pathologique néoplasique. L'invention se rapporte encore à un procédé de traitement des maladies auto-immunes, ainsi que des compositions pharmaceutiques des nouveaux dérivés d'indole.