7-methoxy-1-(trimethylsilyloxy)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile | 182621-29-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 7-methoxy-1-(trimethylsilyloxy)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile
• 英文别名: 7-methoxy-1-cyano-1-(trimethylsilyloxy)-1,2,3,4-tetrahydro-naphthalene；1-cyano-1-trimethylsilyloxy-7-methoxytetralin；7-methoxy-1-trimethylsilyloxy-3,4-dihydro-2H-naphthalene-1-carbonitrile
• CAS: 182621-29-0
• 化学式: C₁₅H₂₁NO₂Si
• 分子量: 275.423
• InChiKey: VICIPVWRNCBHAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-methoxy-1-(trimethylsilyloxy)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile 在 盐酸 、 tin(II) chloride dihdyrate 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 72.0h， 以60 mg的产率得到1,2,3,4-四氢-7-甲氧基-1-萘甲酸
  参考文献：
  名称：

  [EN] AMINOTRIAZOLE IMMUNOMODULATORS FOR TREATING AUTOIMMUNE DISEASES
  [FR] IMMUNOMODULATEURS D'AMINOTRIAZOLE POUR TRAITER DES MALADIES AUTO-IMMUNES

  摘要：

  1-酰基-3-(杂芳基)-1H-1,2,4-三唑-5-胺的公式(I)化合物被公开。这些化合物在存在凝血酶和其他凝血因子时抑制凝血因子XIIa。它们可用于治疗自身免疫疾病。

  公开号：

  WO2017123518A1
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 生成 7-methoxy-1-(trimethylsilyloxy)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile
  参考文献：
  名称：

  J. Med. Chem. 2005, 48, 3953-3979

  摘要：

  DOI：

文献信息

• A Direct and Efficient Synthetic Method for Nitriles from Ketones
  作者：Stéphane Kloubert、Monique Mathé-Allainmat、Jean Andrieux、Michel Langlois

  DOI：10.1080/00397910008087438

  日期：2000.8

  Cyclic cyano derivatives 3 were obtained by the reaction of Me3SiCN/ZnI2 with the cyclic ketones 2 which gave the trimethylsilyloxy nitriles 4. They were directly transformed to cyano derivatives 3 (70-80% yield) by the reductive reagent Me3SiCl-NaI in acetonitrile in the presence of H2O.
• Novel Potent Antagonists of Human Neuropeptide Y Y5 Receptors. Part 3: 7-Methoxy-1-hydroxy-1-substituted Tetraline Derivatives
  作者：Hiromichi Itani、Harunobu Ito、Yoshihiko Sakata、Yoshifumi Hatakeyama、Hiroko Oohashi、Yoshinari Satoh

  DOI：10.1016/s0960-894x(02)00018-5

  日期：2002.3

  As a part of our continuing research on NPY-Y5 receptor antagonists in the series of novel 6-methoxybenzo[a]cycloheptene derivatives, we discovered a novel skeleton, 7-methoxy-1-hydroxytetraline 7 which had been used as an intermediate, to be more suitable for increasing potencies leading to compound 3 (FR230481). Additionally. we discovered that the naphthalenesulfonamide moiety which was thought to be an essential pharmacophore could be replaced by the 5-chlorobenzothiazolin-3-acetic acid moiety to lead to potent compound 4 (FR233118). The structure-activity relationships on compounds 3, 4 and their related derivatives are described. Unfortunately. although compounds 3 and 4 had very high affinities for Y5 receptors, their poor permeabilities to brain were shown by exo-vivo binding assays when orally administered. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Novel potent antagonists of human neuropeptide Y Y5 receptors. Part 2: substituted benzo[a]cycloheptene derivatives
  作者：Hiromichi Itani、Harunobu Ito、Yoshihiko Sakata、Yoshifumi Hatakeyama、Hiroko Oohashi、Yoshinari Satoh

  DOI：10.1016/s0960-894x(02)00002-1

  日期：2002.3

  Novel berizo[a]cycloheptene derivatives were prepared for the purpose of searching new neuropeptide Y-Y5 (NPY-Y5) receptor antagonists, The structure activity relationships Lire described and compound 2o (FR226928) showed the most potent affinity for Y5 receptor of all we prepared and was found to have higher potency and better selectivity for Y5 over Y1 receptor affinities when compared with the known lead compound 1. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis and pharmacological evaluation of 4a-phenanthrenamine derivatives acting at the phencyclidine binding site of the N-methyl-D-aspartate receptor complex
  作者：Christopher F. Bigge、Thomas C. Malone、Sheryl J. Hays、Graham Johnson、Perry M. Novak、Leonard J. Lescosky、Daniel M. Retz、Daniel F. Ortwine、Albert W. Probert

  DOI：10.1021/jm00066a007

  日期：1993.7

  A novel series of octahydrophenanthrenamines and their heterocyclic analogues have been synthesized as potential noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor complex. The compounds were evaluated for their affinity at the phencyclidine (PCP) binding site by determining their ability to displace [H-3]TCP from crude rat brain synaptic membranes. A wide range of affinities were observed, with the most potent analogs possessing IC50's equivalent to that of the reference agent MK-801 (3,dizocilpine). NMDA antagonist activity was demonstrated by prevention of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Selected compounds were also studied in vivo to determine their ability to prevent the lethal effects of systemically injected NMDA in the mouse. In general, the SAR of the phenanthrenamine series may be summarized as follows: (a) for the amino group at C4a, NHMe > NH2 > NHEt much-greater-than NC5H10; (b) for the B-ring substitution, X = CH2 > S > 0; (c) unsaturation of the C ring decreases receptor affinity; (d) cis-ring fusion between the B and C rings is desirable; (e) 6-hydroxy or 6-methoxy substitution of the phenanthrenamine system identified an additional hydrogen bonding interaction that substantially increased receptor affinity; (f) spiro analogues (such as 55, IC50 = 3400 nM), which altered the point of attachment of the C ring, caused a substantial reduction in PCP-site affinity. Molecules from this series were useful for refining a pharmacophore model consistent with previous models of the PCP site. In this model, the (R)-(+)-phenanthrenamine 13 superimposes closely onto MK-801 (3), and the angular 4a-amino group is believed to hydrogen bond with a putative receptor site atom. In the phenanthrenamine and thiaphenanthrenamine series, the (R)-(+)-enantiomers (9, 13, and 44) are more potent by approximately 5-10-fold than their corresponding (S)-(-)-enantiomers with respect to their affinity for the PCP site, their ability to prevent accumulation of [Ca-45(2+)] in cultured neuronal cells, and their protection against the lethal effects of NMDA in mice. In general, there was no separation between the dose that prevented NMDA lethality and the dose that produced ataxia in mice, except in the case of the thiaphenanthrenamines 41 and 43. We have not yet obtained evidence that this small separation in activity offers a therapeutic advantage in the treatment of cerebral ischemia or other neurodegenerative disorders.
• EP1403256
  申请人：——

  公开号：——

  公开（公告）日：——