4-氯-6,7,8,9-四氢-5H-嘧啶并[4,5-B]吲哚 | 173458-87-2

• 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: 4-氯-6,7,8,9-四氢-5H-嘧啶并[4,5-B]吲哚
• 英文名称: 4-chloro-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indole
• CAS: 173458-87-2
• 化学式: C₁₀H₁₀ClN₃
• 分子量: 207.662
• InChiKey: SFKNMBDVWLKVID-UHFFFAOYSA-N

物化性质

• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  4-氯-6,7,8,9-四氢-5H-嘧啶并[4,5-B]吲哚 、 6-amino-5-chlorobenzothiazolone 在 title compound 作用下， 生成 5-chloro-6-(6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]indol-4-ylamino)-1,3-benzothiazol-2(3H)-one
  参考文献：
  名称：

  SUBSTITUTED PYRROLOPYRIMIDINES

  摘要：

  本发明涉及替代吡咯吡嘧啶化合物通式I：其中A、X、R1、R2、m和n如本文所述和定义的那样，以及制备所述化合物的方法，用于制备所述化合物的中间体化合物，包含所述化合物的制药组合物和组合物，以及用于制造治疗或预防疾病的制药组合物的使用，特别是治疗或预防增殖过度和/或血管生成障碍的疾病，作为唯一的治疗剂或与其他活性成分组合使用。

  公开号：

  US20150133426A1
• 作为产物：
  描述：

  2-amino-1-benzyl-4,5,6,7-tetrahydro-1H-indole-3-carbonitrile 在 三氯化铝 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 9.5h， 生成 4-氯-6,7,8,9-四氢-5H-嘧啶并[4,5-B]吲哚
  参考文献：
  名称：

  4-(Phenylamino)pyrrolopyrimidines:  Potent and Selective, ATP Site Directed Inhibitors of the EGF-Receptor Protein Tyrosine Kinase

  摘要：

  Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGF-R protein tyro sine kinase (PTK), 4(phenylamino)-7H-pyrrolo[2,3-d]pyrimidines have been identified as a novel class of potent EGF-R protein tyrosine kinase inhibitors. In an interactive process, this class of compounds was then optimized. 13, 14, 28, 36, 37, and 44, the most potent compounds of this series, inhibited the EGF-R PTK with IC50 values in the low nanomolar range. High selectivity toward a panel of nonreceptor tyrosine kinases (c-Src, v-Abl) and serine/threonine kinases (PKC alpha, PKA) was observed. Kinetic analysis revealed competitive type kinetics relative to ATP. In cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by compounds 13, 36, 37, and 44 at IC50 values between 0.1 and 0.4 mu M, whereas PDGF-induced tyrosine phosphorylation was not affected by concentrations up to 10 M. In addition, these compounds were able to selectively inhibit c-fos mRNA expression in EGF-dependent cell lines with IC50 values between 0.1 and 2 mu M, but did not affect c-fos mRNA induction in response to PDGF or PMA (IC50 > 100 mu M) Proliferation of the EGF-dependent MK cell line was inhibited with similar IC50 values. From SAR studies, a binding mode for 4-(phenylamino)-7H-pyrrolo [2,3-d]pyrimidines as well as for the structurally related 4-(phenylamino)quinazolines at the ATP-binding site of the EGF-R tyrosine kinase is proposed. 4-(Phenylamino)-7H-pyrrolo [2,3-d]pyrimidines therefore represent a new class of highly potent tyrosine kinase inhibitors which preferentially inhibit the EGF-mediated signal transduction pathway and, ha ire the potential for further evaluation as anticancer agents.

  DOI：

  10.1021/jm960118j

文献信息

• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011056739A1

  公开（公告）日：2011-05-12

  Disclosed are compounds having formula (I), wherein R1, R2, R3, R4, Z1, Z2, Z3 and Z4 are as defined herein, and methods of making and using the same.

  揭示了具有化学式（I）的化合物，其中R1、R2、R3、R4、Z1、Z2、Z3和Z4如本文所定义，并且揭示了制备和使用这些化合物的方法。
• [EN] LIM KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA LIM KINASE
  申请人：AMAKEM NV

  公开号：WO2015150337A1

  公开（公告）日：2015-10-08

  The present invention relates to new kinase inhibitors, more specifically LIM Kinase inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and Prophylaxis of disease. In particular, the present invention relates to new LIMK inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and Prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said Compounds in the manufacture of a medicament for the application to a number of therapeutic indications including Ophthalmic and intestinal diseases.

  本发明涉及新的激酶抑制剂，更具体地是LIM激酶抑制剂，包括这种抑制剂的组合物，特别是制药品，以及这种抑制剂在治疗和预防疾病中的用途。具体来说，本发明涉及新的LIMK抑制剂，包括这种抑制剂的组合物，特别是制药品，以及这种抑制剂在治疗和预防疾病中的用途。此外，本发明涉及治疗方法和使用所述化合物制造药物的用途，适用于多种治疗适应症，包括眼科和肠道疾病。
• [EN] SUBSTITUTED PYRROLOPYRIMIDINES<br/>[FR] PYRROLOPYRIMIDINES SUBSTITUÉES
  申请人：BAYER PHARMA AG

  公开号：WO2013174743A1

  公开（公告）日：2013-11-28

  The present invention relates to substituted pyrrolopyrimidine compounds general formula I : in which A, X, R1, R2, m and n are as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式I的取代吡咯吡嘧啶化合物，其中A、X、R1、R2、m和n如本文所述和定义，以制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和配方，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是治疗或预防高增殖和/或血管生成障碍的疾病，作为唯一药剂或与其他活性成分组合使用。
• 4-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)-3,6-DIHYDROPYRIDINE-1-(2H)-CARBOXAMIDE DERIVATIVES AS LIMK AND/OR ROCK KINASES INHIBITORS FOR USE IN THE TREATMENT OF CANCER
  申请人：Centre National de la Recherche Scientifique

  公开号：EP3915990A1

  公开（公告）日：2021-12-01

  The present invention concerns a compound of formula (I), in particular as LIMK and/or ROCK kinases inhibitors. The present invention also concerns these new inhibitors for use for the treatment of a condition selected in the group consisting of: cancers, virion infections, ocular hypertension and glaucoma formation, Neurofibromatosis type 1 and 2, psoriatic lesions, inflammatory diseases and hyperalgesia, central sensitization and chronic pain, reproduction erectile dysfunction, and neuronal diseases. The present description discloses the syntheses and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 32 to 127; examples 1 to 96; families 1 to 8; compounds; biological studies; tables). An exemplary compound is e.g. 4-(5-m ethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-N-phenyl-3,6-dihydropyridine-1-(2H)-carboxamide (example 1; compound 5).

  本发明涉及一种化合物，特别是作为LIMK和/或ROCK激酶抑制剂的化合物（I）的公式。本发明还涉及这些新抑制剂的用途，用于治疗所选组中的疾病，包括：癌症、病毒感染、眼压增高和青光眼形成、神经纤维瘤病1和2型、银屑病损、炎症性疾病和过敏症、中枢敏化和慢性疼痛、生殖勃起功能障碍和神经疾病。本说明披露了示例化合物的合成和表征，以及其药理学数据（例如第32至127页；示例1至96；家族1至8；化合物；生物学研究；表格）。一个示例化合物是4-(5-甲基-7H-吡咯并[2,3-d]嘧啶-4-基)-N-苯基-3,6-二氢吡啶-1-(2H)-甲酰胺（示例1；化合物5）。
• AKT protein kinase inhibitors
  申请人：Mitchell S. Ian

  公开号：US20050130954A1

  公开（公告）日：2005-06-16

  The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.

  本发明提供化合物，包括已解决的对映体、二对映异构体、溶剂化物和药学上可接受的盐，其包括公式：A-L-CR，其中CR是一个环核心基团，L是一个连接基团，A如此处所定义。同时提供了使用本发明化合物作为AKT蛋白激酶抑制剂和用于治疗增殖性疾病如癌症的方法。