N-[2-(4-chlorophenyl)ethyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: N-[2-(4-chlorophenyl)ethyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamide
• 英文别名: N-[2-(4-chlorophenyl)ethyl]-6,7-dihydroxy-3,4-dihydroisoquinoline-2(1H)-carboxamide；N-[2-(4-chlorophenyl)ethyl]-6,7-dihydroxy-3,4-dihydro-1H-isoquinoline-2-carboxamide
• 化学式: C₁₈H₁₉ClN₂O₃
• 分子量: 346.813
• InChiKey: BEVKMBYRCPSWIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  72.8
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-氯苯乙胺 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 4.0h， 生成 N-[2-(4-chlorophenyl)ethyl]-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamide
  参考文献：
  名称：

  新型卡塞平类似物的合成和SAR在多种癌症类型中均具有显着的抗癌作用

  摘要：

  我们先前证明，辣椒素（CPZ）是一种合成的瞬时受体潜在香草酸亚型1（TRPV1）拮抗剂，在体内具有显着的抗癌作用。这项研究的目的是基于CPZ药效团和类似物之间的结构-活性关系（SAR），开发出更有效的类似物。我们生成了30种新型化合物，并筛选了它们在培养的HeLa宫颈癌细胞中的抗增殖作用。细胞活力分析鉴定出多种IC 50s  <15μM的化合物和一种化合物29 IC 50  <5μM的化合物；比CPZ强六倍。我们验证两个引线化合物的抗增殖功效17和29，在体内在无胸腺裸鼠中使用HeLa衍生的异种移植物。与对照处理的动物相比，两种类似物到第8天都显着减少了肿瘤体积（p <0.001），没有明显的不良反应。钙成像确定化合物17激活TRPV1，而化合物29既不激活也不抑制TRPV1。表示不涉及TRPV1信号的唯一作用机制。使用一组其他肿瘤类型的细胞生存力分析，包括口腔鳞状细胞癌，非小细胞肺癌（N

  DOI：

  10.1016/j.bmc.2018.11.040

文献信息

• NOVEL CAPSAZEPINE ANALOGS FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES
  申请人：The Board of Regents of The University of Texas System

  公开号：EP3549582A2

  公开（公告）日：2019-10-09

  The present disclosure relates generally to derivatives of capsazepine and methods of use thereof. In some aspects, the present disclosure relates to using capsazepine derivatives to treat cancer or other hyperproliferative diseases.

  本公开一般涉及卡扎西平的衍生物及其使用方法。在某些方面，本公开涉及使用卡扎西平衍生物治疗癌症或其他过度增殖性疾病。
• Capsazepine analogs for the treatment of cancer and other proliferative diseases
  申请人：THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM

  公开号：US10457676B2

  公开（公告）日：2019-10-29

  The present disclosure relates generally to derivatives of capsazepine and methods of use thereof In some aspects, the present disclosure relates to using capsazepine derivatives to treat cancer or other hyperproliferative diseases. In some aspects of the present disclosure, the disclosure provides capsazepine derivatives which may be useful in the treatment of cancer. Such cancers that the compounds may be used to treating include but are not limited to breast, cervical, oral, head, neck, or prostate cancer. In some aspects, the compounds may be useful in treating a tumor by direct injection of the compound into the tumor, particularly an oral tumor. In other aspects, the compounds are administered systemically. The compounds of the present disclosure may also be used to treat the pain associated with a tumor for which it is being administered.

  本公开总体上涉及卡扎西平的衍生物及其使用方法 在某些方面，本公开涉及使用卡扎西平衍生物治疗癌症或其他增殖过度疾病。在本公开的某些方面，本公开提供了可用于治疗癌症的卡氮平类衍生物。这些化合物可用于治疗的癌症包括但不限于乳腺癌、宫颈癌、口腔癌、头颈癌或前列腺癌。在某些方面，通过将化合物直接注射到肿瘤，特别是口腔肿瘤中，化合物可用于治疗肿瘤。在其他方面，化合物可全身给药。本公开的化合物还可用于治疗与所给药的肿瘤相关的疼痛。
• WO2007/11290
  申请人：——

  公开号：——

  公开（公告）日：——
• SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region)
  作者：Magnus Berglund、María F. Dalence-Guzmán、Staffan Skogvall、Olov Sterner

  DOI：10.1016/j.bmc.2007.11.056

  日期：2008.3

  Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (Gregion), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the Gregion in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the Gregion. (C) 2007 Elsevier Ltd. All rights reserved.
• [EN] Bronchorelaxing agents based on indol- and isoquinoline derivatives<br/>[FR] AGENTS BROCHORELAXANTS BASÉS SUR DES DÉRIVÉS ET D'ISOQUINOLÉINE
  申请人：RESPIRATORIUS AB

  公开号：WO2007011290A1

  公开（公告）日：2007-01-25

  [EN] A compound of formula (I) and its acid addition salts, wherein R1-FIj are H, lower (CrC6) alkyl; halogen; NR5R6, wherein R5, R6 are H, lower alkyl, C2-C6 acyl, SO2R7, wherein R7 is lower alkyl, CF3, aryl, substituted aryl; CN; COR8, wherein R8 is H, OH, lower alkyl, lower alkoxy; SO2R9, wherein R9 is OR10, wherein R10 is H, lower alkyl or NRnR12, wherein R11 and R12 is H or lower alkyl; ORi3, wherein R13 is H, lower alkyl, C2-C6 acyl, C1-C8 carboxy, C1-C8 carbamoyl; X is O or S; A is H, lower alkyl; B is C1-C18 alkyl optionally substituted; M is zero or 1; with the proviso that no more than three of R1-R4 are H, for treating and preventing bronchoconstructive pulmonary disease.
  [FR] Cette invention concerne un composé de formule (I) et ses sels additifs acides, formule selon laquelle R₁-R₄ sont H, alkyle inférieur (C₁-C₆) ; halogène ; NR₅R₆, lesquels R₅, R₆ sont H, alkyle inférieur, C₂-C₆ acyle, SO₂R₇, lequel R₇ est alkyle inférieur, CF₃, aryle, aryle substitué ; CN; COR₈, lequel R₈ est H, OH, alkyle inférieur, alkoxy inférieur ; SO₂R9, lequel R₉ est OR₁₀, lequel R₁₀ est H, alkyle inférieur ou NR_nR₁₂, lequel R₁₁ et R₁₂ est H ou alkyle inférieur ; ORi₃, lequel R₁₃ est H, alkyle inférieur, C₂-C₆ acyle, C₁-C₈ carboxy, C₁-C₈ carbamoyl ; X est O ou S ; A est H, alkyle inférieur ; B est C₁-C₁₈ alkyle substitué par option ; M est zéro ou ₁ ; à condition que trois R₁-R₄ au maximum soient H, pour le traitement et la prévention de la maladie pulmonaire bronchoconstructive.