(+/-)-1,2,3,4-tetrahydro-8-methoxy-3-(2-propenyl)-2-oxonaphthalene | 134465-82-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+/-)-1,2,3,4-tetrahydro-8-methoxy-3-(2-propenyl)-2-oxonaphthalene
• 英文别名: 1,2,3,4Tetrahydro-8-methoxy-3-(2-propenyl)2-oxo-naphthalene；8-methoxy-3-prop-2-enyl-3,4-dihydro-1H-naphthalen-2-one
• CAS: 134465-82-0
• 化学式: C₁₄H₁₆O₂
• 分子量: 216.28
• InChiKey: IYDBENHUBBUCPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-1,2,3,4-tetrahydro-8-methoxy-3-(2-propenyl)-2-oxonaphthalene 、 乙二醇 以88%的产率得到
  参考文献：
  名称：

  Lin Chiu-Hong, Haadsma-Svensson Susanne R., Phillips Gillian, Lahti Rober+, J. Med. Chem., 36 (1993) N 8, S 1069-1083

  摘要：

  DOI：
• 作为产物：
  描述：

  8-甲氧基-3,4-二氢-1H-2-萘酮 在 lithium chloride 、 lithium diisopropyl amide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 30.5h， 生成 (+/-)-1,2,3,4-tetrahydro-8-methoxy-3-(2-propenyl)-2-oxonaphthalene
  参考文献：
  名称：

  Centrally acting serotonergic agents. Synthesis and structure-activity relationships of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin

  摘要：

  The synthesis and structure-activity relationships (SAR) of C-1- or C-3-substituted derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) are described. These analogs were synthesized via alkylation of the tetralone derivatives followed by reductive amination. All of the analogs were inactive at the dopamine D2 receptor. Among the 8-OMe or 8-OH C-1,N-disubstituted analogs synthesized, the cis analogs were more potent in the 5-HT1A binding assay than the corresponding trans analogs. However, in the case of 1-(cyclopropylmethyl)-N-n-propyl analogs, the trans isomer has a slightly higher 5-HT1A affinity than its cis counterpart. The order of binding potency for C-1 substitution was found to be allyl > hydroxymethyl> n-propyl > cyclopropylmethyl much greater than carbomethoxy. Interestingly, the 5-OMe analogs were found to be inactive in both the 5-HT1A and dopamine D2 binding assays. In the C-3 allyl-substituted analogs, 5-HT1A agonist activity was found to be considerably lower. In these examples, the trans analogs showed weak 5-HT1A binding activity whereas the cis analogs were inactive. Analogs with C-1,N,N-trisubstitution also showed a marked decrease in 5-HT1A binding affinity. Overall, the SAR study showed that cis C-1 substitution maintains the 5-HT1A agonist activity of 8-OH-DPAT whereas trans C-1 substitution displays somewhat diminished activity. On the other hand, the trans C-3 substitution shows modest agonist activity whereas cis C-3 substitution removes the activity completely.

  DOI：

  10.1021/jm00058a003

文献信息

• Centrally acting serotonergic and dopaminergic agents. 2. Synthesis and structure-activity relationships of 2,3,3a,4,9,9a-hexahydro-1H-benz[f]indole derivatives
  作者：Chiu Hong Lin、Susanne R. Haadsma-Svensson、Gillian Phillips、Robert A. Lahti、Robert B. McCall、Montford F. Piercey、Peggy J. K. D. Schreur、Phillip F. Von Voigtlander、Martin W. Smith、Connie G. Chidester

  DOI：10.1021/jm00060a015

  日期：1993.4

  trans-5-methoxy analogs showed selective 5-HT1A receptor activity in vitro but displayed mixed 5-HT1A and D2 agonist properties in vivo. The corresponding trans-5-hydroxy analogs were found to be potent D2 agonists with full intrinsic activity. An examination of nitrogen substitution (R2 in 3) revealed that analogs with either an allyl or an n-propyl group displayed equipotent activities. Substitution

  研究了5-和8-羟基-2-（二-正丙基氨基）-四氢萘的构象受限的线性三环类似物的血清素能和多巴胺能特性。这些2,3,3a，4,9,9a-六氢-1H-苯并[f]吲哚（3）的顺式和反式类似物，其中五元环稠合在2-的氮和C-3碳之间氨基四氢萘是由5-甲氧基四氢萘酮和8-甲氧基四氢萘酮合成的。反式-5-甲氧基-Nn-丙基和-N-烯丙基类似物的对映异构体是通过对其二对甲苯甲酰基-L（或D）酒石酸盐的分步重结晶而获得的。在体外5-HT1A和D2结合试验中评估了所有类似物，并在生化和行为测试中进一步研究了所选类似物。在5取代的系列中（3中的R1），发现反式异构体比相应的顺式异构体具有更高水平的药理活性。反式-5-甲氧基类似物在体外显示选择性的5-HT1A受体活性，但在体内显示混合的5-HT1A和D2激动剂特性。发现相应的反式5-羟基类似物是具有完全内在活性的有效D2激动剂。氮取代的研究（3中的R2）表明
• Therapeutically useful 2-aminotetralin derivatives
  申请人：The Upjohn Company

  公开号：US05545755A1

  公开（公告）日：1996-08-13

  This invention is therapeutically useful 2-aminotetralins and pharmaceutically acceptable acid addition salts thereof of the formula ##STR1## R, R.sub.1 to R.sub.5 and p are as defined in the specification, these compounds are useful to treat central nervous system disorders, hypertension, diabetes, sexual impotency and to control appetite.

  这项发明涉及治疗作用的2-氨基四氢萘及其药学上可接受的酸盐，其化学式为##STR1##其中R，R.sub.1至R.sub.5和p在说明书中有定义，这些化合物可用于治疗中枢神经系统疾病、高血压、糖尿病、性功能障碍和控制食欲。
• Lin Chiu-Hong, Haadsma-Svensson Susanne R., Phillips Gillian, Lahti Rober+, J. Med. Chem., 36 (1993) N 8, S 1069-1083
  作者：Lin Chiu-Hong, Haadsma-Svensson Susanne R., Phillips Gillian, Lahti Rober+

  DOI：——

  日期：——
• THERAPEUTICALLY USEFUL 2-AMINOTETRALIN DERIVATIVES
  申请人：THE UPJOHN COMPANY

  公开号：EP0476016A1

  公开（公告）日：1992-03-25
• (1,2N) AND (3,2N)-CARBOCYCLIC-2-AMINO TETRALIN DERIVATIVES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0482084B1

  公开（公告）日：1997-05-07