7-异喹啉甲酸 | 220247-71-2

• 物质功能分类: 医药中间体 - 异喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 7-异喹啉甲酸
• 中文别名: 四氢异喹啉7-甲酸盐酸盐
• 英文名称: 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid hydrochloride
• 英文别名: 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid;hydrochloride
• CAS: 220247-71-2
• 化学式: C₁₀H₁₁NO₂*ClH
• mdl: MFCD09056810
• 分子量: 213.664
• InChiKey: AAOPPOUJUYGRIN-UHFFFAOYSA-N

物化性质

• 熔点：
  339-341 °C(Solv: water (7732-18-5))

计算性质

• 辛醇/水分配系数(LogP)：
  -1.24
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  53.9
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

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

反应信息

• 作为反应物：
  描述：

  3-(2,5-dimethyl-1H-pyrrol-1-yl)-4-(methoxycarbonyl)benzoic acid 、 7-异喹啉甲酸 在 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 水 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 甲醇 为溶剂， 反应 7.0h， 生成 2-[4-carboxy-3-(2,5-dimethylpyrrol-1-yl)benzoyl]-3,4-dihydro-1H-isoquinoline-7-carboxylic acid
  参考文献：
  名称：

  [EN] PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS
  [FR] DÉRIVÉS D'ACIDE PYRROL-1-YL-BENZOÏQUE UTILES EN TANT QU'INHIBITEURS DE MYC

  摘要：

  本发明提供了式(I-A)、(I-B)和(I-C)的化合物、药用可接受的盐及其药用组合物。本发明的化合物可用于抑制Myc（例如，c-Myc）活性。本发明进一步提供了使用所述化合物治疗Myc介导的疾病（例如，癌症和其他增殖性疾病）的方法。本发明还提供了用于识别Myc抑制剂的检测方法。

  公开号：

  WO2014071247A1
• 作为产物：
  描述：

  1,2,3,4-四氢异喹啉-7-甲腈 在 盐酸 作用下， 反应 9.0h， 以93%的产率得到7-异喹啉甲酸
  参考文献：
  名称：

  Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

  摘要：

  7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the aa-adrenoceptor. To design a selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha(2)-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pK(i) = 0.599 pi - 0.0725MR + 1.55 sigma(m) + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha(2)-adrenoceptor (alpha(2) pK(i) = 0.599 pi - 0.0542MR - 0.951 sigma(m) + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha(2)-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position, These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitors of PNMT.

  DOI：

  10.1021/jm980429p

文献信息

• PYRROL-1-YL BENZOIC ACID DERIVATIVES USEFUL AS MYC INHIBITORS
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20150291521A1

  公开（公告）日：2015-10-15

  The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

  本发明提供了公式(I-A)、(I-B)和(I-C)的化合物，其药学上可接受的盐以及其制药组合物。本发明的化合物可用于抑制Myc（例如c-Myc）的活性。本发明还提供了使用本文所描述的化合物治疗Myc介导的疾病（例如癌症和其他增殖性疾病）的方法。本发明还提供了用于鉴定Myc抑制剂的检测方法。
• Identification of a Novel Aminotetralin Class of HDAC6 and HDAC8 Selective Inhibitors
  作者：Guozhi Tang、Jason C. Wong、Weixing Zhang、Zhanguo Wang、Nan Zhang、Zhenghong Peng、Zhenshan Zhang、Yiping Rong、Shijie Li、Meifang Zhang、Lingjie Yu、Teng Feng、Xiongwen Zhang、Xihan Wu、Jim Z. Wu、Li Chen

  DOI：10.1021/jm5008962

  日期：2014.10.9

  Herein we report the identification of a novel class of HDAC6 and HDAC8 selective inhibitors through a unique chemistry and phenotypic screening startegy. Tetrahy droisoquinoline 12 was identified as a potent HDAC6 and HDAC8 dual inhibitor from a focussed library through cellular tubulin acetylation and p21 induction screening assays. Scaffold hopping from 12 led to the discovery of an aminotetralin class of HDAC inhibitors. In particular, the 3-R stereoisomeer 32 showed highly potent inhibiton agains HDAC6 and HDAC6 and HDAC8 with IC50 values of 50 and 80 nM, respectively. Treatment of neuroblastoma BE(2) C cells with 32 resulted in elevated levels of acetylated tubulin, TrKA, and neurite outgrowth with only marginal effects on p21 induction and histone H3 acetylation Consistent withits weak enzymatic indhibition of HDAC, showed significantly less cytotoxicity than SAHA and moderately inhibited the growth of myeloma NCI-H929 and OPM-2 cells.
• PYRROL-1 -YL BENZOIC ACID DERIVATIVES USEFUL AS MYC INHIBITORS
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP2917203A1

  公开（公告）日：2015-09-16
• METHOD FOR IDENTIFYING MYC INHIBITORS
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP2917203B1

  公开（公告）日：2019-04-03
• US9567301B2
  申请人：——

  公开号：US9567301B2

  公开（公告）日：2017-02-14