6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol | 5200-96-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol
• 英文别名: 6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-ol；Benzocyclohepten-3-ol；1.2-benzo-cyclohepten-(1)-ol-(5)；4,5-Benzo-cycloheptanol
• CAS: 5200-96-4
• 化学式: C₁₁H₁₄O
• 分子量: 162.232
• InChiKey: RQZVYMMATMNWHG-UHFFFAOYSA-N

物化性质

• 熔点：
  96-97 °C
• 沸点：
  289.4±29.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 30.0h， 生成 4-phenyl-1-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)piperidine
  参考文献：
  名称：

  Synthesis, GluN2B affinity and selectivity of benzo[7]annulen-7-amines

  摘要：

  Due to their beneficial side effect profile, NMDA receptor antagonists interacting selectively with the allosteric ifenprodil binding site of the GluN2B subunit are of major interest for the treatment of neurological and neurodegenerative disorders. A series of benzo[7]annulen-7-amines 6 was designed by conformational restriction of ifenprodil (1). At first the benzo[7]annulen-7-one 11 was prepared in a three-step synthesis comprising of a double Knoevenagel condensation of phthalaldehyde (7) with dimethyl 3-oxoglutarate (8), hydrogenation of 9 and saponification/decarboxylation of 10. Reductive amination of the ketone 11 with primary amines and NaBH(OAc)(3) led to the secondary amines 6a-d, cis-6h and trans-6i. The tertiary amines 6e-g were obtained by S(N)2-substitution of the nosylate 13. Although H-bond forming substituents in 2- and 5-position are missing, the amines 6 exhibit high affinity towards GluN2B containing NMDA receptors. A distance of four to five bond lengths between the basic amino moiety and the phenyl ring in the side chain appears to be optimal for high GluN2B affinity. The phenylcyclohexylamine cis-6h and the 4-benzylpiperidine 6g show the highest GluN2B affinities (K-i = 2.3 nM and 2.9 nM, respectively). With respect to selectivity against the PCP binding site, sigma(1) and sigma(2) receptors the phenylpiperazine 6f is the most promising GluN2B antagonist. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.004
• 作为产物：
  描述：

  7-oxo-7H-benzocycloheptene-6-carboxylic acid 在 盐酸 、 乙醇 、 sodium 作用下， 生成 6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol
  参考文献：
  名称：

  Thiele; Weitz, Justus Liebigs Annalen der Chemie, 1910, vol. 377, p. 20

  摘要：

  DOI：

文献信息

• Structure–Activity Relationship in the Domain of Odorants Having Marine Notes
  作者：Jean-Marc Gaudin、Olga Nikolaenko、Jean-Yves de Saint Laumer、Beat Winter、Pierre-Alain Blanc

  DOI：10.1002/hlca.200790126

  日期：2007.7

  9-tetrahydro-7H-benzocyclohepten-7-ones 11 (Schemes 5 and 6), since the lead compound for the olfactory note of perfumes based on marine accords is a well-known benzodioxepinone named Calone 1951® (9b). We meticulously described the odor profile of each synthesized compound and discussed relevant structure–odor relationships (Tables 1–3). In particular, we revealed a correlation between the conformation of the seven-membered

  我们合成或重新合成了大量2 H -1,5-benzodioxepin-3（4 H）-ones 9（方案1），4,5-dihydro-1-benzoxepin-3（2 H）-ones 10（方案3和4）和5,6,8,9-四氢-7 H-苯并环庚烯-7-酮11（方案5和6），因为基于海洋协议的香水嗅觉的先导化合物很好命名-known benzodioxepinone使Calone 1951年®（9B）。我们精心描述的每个合成的化合物的气味特征和讨论有关结构气味的关系（表1 - 3）。特别地，我们揭示了七元环的构象与这些化合物的活性之间的相关性（表4和图3）。我们还阐明了芳环上烷基取代基的位置和大小的影响。
• Benzocycloarene hydroxylation by P450 biocatalysis
  作者：Martin P. Mayhew、Adrian E. Roitberg、Yadu Tewari、Marcia J. Holden、David J. Vanderah、Vincent L. Vilker

  DOI：10.1039/b107584p

  日期：2002.1.24

  Experimental and theoretical studies of the hydroxylation of a family of benzocycloarene compounds [benzocyclobutene, benzocyclopentene (indan), benzocyclohexene (tetralin), and benzocycloheptene] by wild type and Y96F mutant P450cam were performed in order to understand the factors affecting product distribution, catalytic rate and cofactor utilization. The products of all reactions except that of benzocycloheptene were regiospecifically hydroxylated in the 1-position. Reaction energetics predominated over active site steric constraints in this case so that quantum mechanical calculations (B3LYP/6-31G*) comparing the energetics of all possible radical intermediates successfully predicted hydroxylation at the 1- and 3-positions of benzocycloheptene, and at the 1-position for the other three compounds. However, the fact that the ratio of 1-alcohol to 3-alcohol changes significantly between wild type and Y96F mutant P450cam indicates that active site geometry and composition also play a significant role in determining BCA7 product regiospecificity. The indan and tetralin reaction products were stereoselective for the R enantiomer (88 and 94%, respectively). Steric constraints of the active site were confirmed by molecular dynamics calculations (locally enhanced sampling dynamics) to control enantiomer distribution for tetralin hydroxylation. NADH coupling, binding affinity, and product turnover rates were dramatically higher for Y96F P450cam, showing that the removal of the active site hydroxyl group on tyrosine makes the enzyme better suited for oxidation of these hydrophobic compounds. NADH coupling, binding affinity and product turnover rate for each enzyme generally increased with arene ring size. For both enzymes, NADH coupling and product turnover rates were correlated with the extent of high-spin shift upon substrate binding as determined by the shift in Soret absorption bands at 417 and 391 nm.

  对野生型和 Y96F 突变体 P450cam 对一系列苯并环烯烃化合物[苯并环丁烯、苯并环戊烯（茚）、苯并环己烯（四萘）和苯并环庚烯]的羟化反应进行了实验和理论研究，以了解影响产物分布、催化速率和辅助因子利用率的因素。除苯并环庚烯反应外，所有反应的产物都在 1 位发生了特异性羟基化。在这种情况下，反应能量优先于活性位点立体约束，因此量子力学计算（B3LYP/6-31G*）比较了所有可能的自由基中间体的能量，成功预测了苯并环庚烯在 1 位和 3 位发生羟基化，而其他三种化合物则在 1 位发生羟基化。然而，1-醇与 3-醇的比例在野生型和 Y96F 突变体 P450cam 之间发生显著变化这一事实表明，活性位点的几何形状和组成在决定 BCA7 产物的区域特异性方面也起着重要作用。茚和四氢萘反应产物对 R 对映体具有立体选择性（分别为 88% 和 94%）。分子动力学计算（局部增强采样动力学）证实了活性位点的立体限制控制了四氢萘酚羟化的对映体分布。Y96F P450cam 的 NADH 偶联度、结合亲和力和产物周转率都显著提高，这表明去除活性位点酪氨酸上的羟基后，该酶更适合氧化这些疏水性化合物。每种酶的 NADH 偶联度、结合亲和力和产物周转率通常随着炔环大小的增加而增加。对于这两种酶来说，NADH 偶联和产物周转率与底物结合时的高自旋偏移程度相关，高自旋偏移是由 417 和 391 纳米波长处的索雷特吸收带偏移确定的。
• Structure–Affinity Relationships of 2,3,4,5-Tetrahydro-1<i>H</i>-3-benzazepine and 6,7,8,9-Tetrahydro-5<i>H</i>-benzo[7]annulen-7-amine Analogues and the Discovery of a Radiofluorinated 2,3,4,5-Tetrahydro-1<i>H</i>-3-benzazepine Congener for Imaging GluN2B Subunit-Containing <i>N</i>-Methyl-<scp>d</scp>-aspartate Receptors
  作者：Hazem Ahmed、Ahmed Haider、Jasmine Varisco、Maja Stanković、Rahel Wallimann、Stefan Gruber、Irina Iten、Surya Häne、Adrienne Müller Herde、Claudia Keller、Roger Schibli、Dirk Schepmann、Linjing Mu、Bernhard Wünsch、Simon M. Ametamey

  DOI：10.1021/acs.jmedchem.9b00812

  日期：2019.11.14

  Aspiring to develop a positron emission tomography (PET) imaging agent for the GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), a key therapeutic target for drug development toward several neurological disorders, we synthesized a series of 2,3,4,5-tetrahydro-1H-3-benzazepine and 6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine analogues. After in vitro testing via competition binding assay

  渴望开发一种正电子发射断层摄影（PET）成像剂用于的GluN2B亚基Ñ甲基d天冬氨酸受体（NMDAR），用于药物开发的朝向几个神经病症的关键的治疗靶，我们合成了一系列的2,3 ，4，5-四氢-1 H -3-苯并ze庚因和6,7,8,9-四氢-5 H-苯并[7] Annulen-7-胺类似物。通过竞争结合测定和放射自显影进行体外测试后，[ 18就对σ1和σ2受体的特异性和选择性而言，F] PF-NB1成为表现最佳的示踪剂，因此被选择用于进一步的体内评估。铜介导的放射性氟化以良好的放射化学收率和较高的摩尔活度完成。在Wistar大鼠中进行了广泛的体内表征，包括PET成像，生物分布，受体占有率和代谢产物研究。[ 18 F] PF-NB1结合对富含GluN2B的前脑区域具有选择性，并且被GluN2B拮抗剂CP-101606特异性阻断，没有剂量依赖性，且没有脑放射性代谢物。[ 18 F] PF-NB1是一种很有前途的氟18
• Process for producing optically active chroman derivative and intermediate
  申请人：Mitsuda Masaru

  公开号：US20050014818A1

  公开（公告）日：2005-01-20

  A process for easily producing various optically active chroman derivatives that are useful as pharmaceutical intermediates from inexpensive starting materials is provided. Cyclic hemiacetal (1) obtained from dihydrocoumarin through one step is asymmetrically reduced to produce an optically active halohydrin derivative (3), and the optically active halohydrin derivative (3) is cyclized to produce an optically active chroman derivative (13):

  提供一种从廉价起始材料中轻松制备各种光学活性的色基衍生物作为药物中间体的方法。通过一步反应从二氢香豆素得到的环糖半缩醛（1）经不对称还原制备出光学活性卤代醇衍生物（3），然后将光学活性卤代醇衍生物（3）环化得到光学活性色基衍生物（13）。
• [EN] TRICYCLIC HPK1 INHIBITOR AND USE THEREOF<br/>[FR] INHIBITEUR DE HPK1 TRICYCLIQUE ET SON UTILISATION<br/>[ZH] 三并环类HPK1抑制剂及其用途
  申请人：SHANDONG XUANZHU PHARMA CO LTD

  公开号：WO2022188823A1

  公开（公告）日：2022-09-15

  本发明属于医药技术领域，具体涉及一类三并环类HPK1抑制剂化合物、其药学上可接受的盐或其立体异构体，含有所述化合物、其药学上可接受的盐或其异构体的药物组合物及制剂，制备所述化合物、其药学上可接受的盐或其立体异构体的方法，以及所述化合物、其药学上可接受的盐或其立体异构体的用途。