4-chloro-5-methyl-5H-pyrimido[5,4-b]indole hydrochloride | 132994-26-4

• 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
• 英文名称: 4-chloro-5-methyl-5H-pyrimido[5,4-b]indole hydrochloride
• 英文别名: 4-chloro-5-methylpyrimido<5,4-b>indole；1-chloro-9-methyl-9H-2,4,9-triaza-fluorene；4-chloro-5,N-methylindolo[3,2-d]pyrimidine；4-chloro-5-methyl-5H-pyrimido[5,4-b]indole；4-Chloro-5-methylpyrimido[5,4-b]indole
• CAS: 132994-26-4
• 化学式: C₁₁H₈ClN₃
• 分子量: 217.658
• InChiKey: SXPRAZDMASJQLG-UHFFFAOYSA-N

物化性质

• 熔点：
  153-154 °C
• 沸点：
  314.2±35.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-5-methyl-5H-pyrimido[5,4-b]indole hydrochloride 在 氯磺酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 1-chloro-9-methyl-9H-2,4,9-triaza-fluorene-6-sulphonic acid dimethylamide
  参考文献：
  名称：

  [EN] PYRROLOPYRIMIDINE DERIVATIVES AS MODULATORS OF MULTI-DRUG RESISTANCE (MDR)
  [FR] DERIVES PYRROLOPYRIMIDINIQUES CONVENANT COMME MODULATEURS DE LA MULTIRESISTANCE AUX MEDICAMENTS

  摘要：

  化合物是一种公式为（I）的吡咯吡嘧啶，其中R1从H、未取代或取代的Cl-C6烷基、（CH2）nAr1、（CH2）pNR4R5、卤素和（CH2）pX中选择；R2为（CH2）pArl；R3从H、未取代或取代的Cl-C6烷基、（CH2）pZ和（CH2）pArl中选择；P为未取代或取代的不饱和5、6或7成员碳环或杂环；R4和R5相同或不同，从H、未取代或取代的Cl-C6烷基、（CH2）nC3-C10环烷基、（CH2）nAr1和（CH2）nOR6中选择，或者R4和R5与它们连接的氮原子一起形成饱和的含氮五元或六元杂环，可能含有一个额外的杂原子，选择自O、N和S，未取代或取代；R6从H、未取代或取代的Cl-C6烷基、C3-C10环烷基、（CH2）nOC1-C6烷基、未取代或取代的（CH2）nO（CH2）nAr1、未取代或取代的（CH2）nCO2C1-C6烷基和（CH2）nAr1中选择；X从CN、叠氮、（CH2）nNHSO2R6和（CH2）nNHCOR6中选择；Z从CN、CO2R6和CONR4R5中选择；Ar1当多个存在于给定的取代基组内时相同或不同，为未取代或取代的不饱和C6-C10成员碳环或未取代或取代的不饱和5-11成员杂环；p为1至6的整数；n当多个存在于给定的取代基组内时相同或不同，为0或1至6的整数；但是，公式（I）的吡咯吡嘧啶化合物不是1-（4-苄基哌嗪-1-基）-9H-2,4,9-三氮杂萘；其药学上可接受的盐具有作为MRP（多药耐药蛋白）抑制剂的活性，因此可用于调节多药耐药性，例如在增强化疗药物的细胞毒性方面。

  公开号：

  WO2004111052A1
• 作为产物：
  描述：

  ethyl 3-amino-1-methylindole-2-carboxylate 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 10.0h， 生成 4-chloro-5-methyl-5H-pyrimido[5,4-b]indole hydrochloride
  参考文献：
  名称：

  Synthesis and biological activity of condensed pyrrolo[3,2-d]pyrimidines

  摘要：

  DOI：

  10.1007/bf00766579

文献信息

• Tyrosine Kinase Inhibitors. 16. 6,5,6-Tricyclic Benzothieno[3,2-<i>d</i>]pyrimidines and Pyrimido[5,4-<i>b</i>]- and -[4,5-<i>b</i>]indoles as Potent Inhibitors of the Epidermal Growth Factor Receptor Tyrosine Kinase
  作者：H. D. Hollis Showalter、Alexander J. Bridges、Hairong Zhou、Anthony D. Sercel、Amy McMichael、David W. Fry

  DOI：10.1021/jm9903949

  日期：1999.12.1

  Investigation of 4-position side chains in the indolopyrimidines confirmed that m-bromoaniline was an optimal substituent for potency. Investigation of substitution within the C-(benzo)ring of benzothienopyrimidines confirmed that introduction of an extra ring can change sharply the effects of substituents when compared to similar bicyclic nuclei, and only two substituents were found which even moderately

  据报道，基本的苯胺基嘧啶药效基团的几种精制方法是表皮生长因子受体（EGFr）酪氨酸激酶的有效和选择性抑制剂。本文报道了一系列抑制剂，其中一些6,5-双环杂芳族系统通过其C-2和C-3位置与该苯胺嘧啶药效团融合。尽管产生的三轮车并未产生某些（5/6），6,6-双环系统的巨大效能，但最好的三轮车的EGFr TK的IC（50）约为1 nM。对吲哚并嘧啶中4-位侧链的研究证实，间溴苯胺是效力的最佳取代基。
• Tricyclic compounds capable of inhibiting tyrosine kinases of the
  申请人：Warner-Lambert Company

  公开号：US05679683A1

  公开（公告）日：1997-10-21

  Novel 4-substituted amino benzothieno\x9b3,2-d!pyrimidine and 4-substituted amino\x9b2,3-d!pyrimidine inhibitors of epidermal growth factor receptor family of tyrosine kinases are described, as well as pharmaceutical compositions of the same, which are useful in treating proliferative diseases such as cancer, synovial pannus invasion in arthritis, psoriasis, vascular restenosis and angiogenesis and additionally useful in the treatment of pancreatitis and kidney disease as well as a contraceptive agent.

  描述了一种新型的4-取代氨基苯并噻吩\9b3,2-d!嘧啶和4-取代氨基\9b2,3-d!嘧啶表皮生长因子受体家族的酪氨酸激酶抑制剂，以及相应的药物组合物，用于治疗增殖性疾病，如癌症、关节炎中的滑膜潘纳斯侵袭、牛皮癣、血管再狭窄和血管生成，此外还可用于胰腺炎和肾病的治疗，以及避孕剂。
• [EN] PYRIDO [3',2' :4,5] THIENO [3, 2-D] PYRIMIDIN- 4 - YLAMINE DERIVATIVES AND THEIR THERAPEUTICAL USE<br/>[FR] DÉRIVÉS DE PYRIDO[3',2':4,5]THIÉNO[3,2-D]PYRIMIDIN-4-YLAMINE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：BAELL JONATHAN BAYLDON

  公开号：WO2012131297A1

  公开（公告）日：2012-10-04

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain fused triaryl amine compounds of the following formula (for convenience, collectively referred to herein as "FTA compounds"), which, inter alia, inhibit LIM kinase (LIMK) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit LIMK activity, and in the treatment of diseases and conditions that are mediated by LIMK, that are ameliorated by the inhibition of LIMK activity, etc., including proliferative conditions such as cancer (e.g., breast cancer, prostate cancer, melanoma, glioma, etc.), as well as vasodilation (including, e.g., hypertension, angina, cerebral vasospasm, and ischemia following subarachnoid hemorrhage), neurodegenerative disorders, atherosclerosis, fibrosis, and inflammatory diseases (including, e.g., Crohn's disease and chronic obstructive pulmonary disease (COPD)), and glaucoma (also known as ocular hypertension).

  本发明一般涉及治疗化合物领域，更具体地涉及以下公式的某些融合三芳基胺化合物（为方便起见，统称为“FTA化合物”），该化合物等等可以抑制LIM激酶（LIMK）活性。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体内和体外抑制LIMK活性，以及治疗由LIMK介导，通过抑制LIMK活性得到改善等疾病和症状的用途，包括增生性疾病，如癌症（如乳腺癌、前列腺癌、黑色素瘤、胶质瘤等），以及血管扩张（包括高血压、心绞痛、脑血管痉挛和蛛网膜下腔出血后缺血等）、神经退行性疾病、动脉硬化、纤维化和炎症性疾病（如克罗恩病和慢性阻塞性肺病（COPD）），以及青光眼（又称眼高压）等。
• Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance
  作者：Shouming Wang、Nan Chi Wan、John Harrison、Warren Miller、Irina Chuckowree、Sukhjit Sohal、Timothy C. Hancox、Stewart Baker、Adrian Folkes、Francis Wilson、Deanne Thompson、Simon Cocks、Hayley Farmer、Anthony Boyce、Caroline Freathy、Jan Broadbridge、John Scott、Paul Depledge、Richard Faint、Prakash Mistry、Peter Charlton

  DOI：10.1021/jm0310129

  日期：2004.3.1

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.
• TRICYCLIC COMPOUNDS CAPABLE OF INHIBITING TYROSINE KINASES OF THE EPIDERMAL GROWTH FACTOR RECEPTOR FAMILY
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0741711A1

  公开（公告）日：1996-11-13