(+/-)-1,2,3,4-tetrahydro-8-methoxy-2-oxo-3-(2-propenyl)-1-naphthalenecarboxylic acid methyl ester | 134465-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (+/-)-1,2,3,4-tetrahydro-8-methoxy-2-oxo-3-(2-propenyl)-1-naphthalenecarboxylic acid methyl ester
• 英文别名: 1,2,3,4Tetrahydro-8-methoxy-2-oxo-3-(2-propenyl)-1-naphthalene-carboxylic Acid Methyl Ester；methyl 8-methoxy-2-oxo-3-prop-2-enyl-3,4-dihydro-1H-naphthalene-1-carboxylate
• CAS: 134465-81-9
• 化学式: C₁₆H₁₈O₄
• 分子量: 274.317
• InChiKey: HJZBMBGOPMDDES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-1,2,3,4-tetrahydro-8-methoxy-2-oxo-3-(2-propenyl)-1-naphthalenecarboxylic acid methyl ester 在 lithium chloride 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 5.0h， 以94%的产率得到(+/-)-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
• 作为产物：
  描述：

  8-甲氧基-3,4-二氢-1H-2-萘酮 在 lithium diisopropyl amide 作用下， 反应 25.5h， 生成 (+/-)-1,2,3,4-tetrahydro-8-methoxy-2-oxo-3-(2-propenyl)-1-naphthalenecarboxylic acid methyl ester
  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

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

  公开号：EP0476016A1

  公开（公告）日：1992-03-25
• US5545755A
  申请人：——

  公开号：US5545755A

  公开（公告）日：1996-08-13
• US6331636B1
  申请人：——

  公开号：US6331636B1

  公开（公告）日：2001-12-18
• [EN] THERAPEUTICALLY USEFUL 2-AMINOTETRALIN DERIVATIVES
  申请人：THE UPJOHN COMPANY

  公开号：WO1990015047A1

  公开（公告）日：1990-12-13

  (EN) This invention is therapeutically useful 2-aminotetralins and pharmaceutically acceptable acid addition salts thereof of formula (I). These compounds are useful to treat central nervous system disorders, hypertension, diabetes, sexual impotency and to control appetite.(FR) La présente invention concerne des 2-aminotétraline thérapeutiquement utiles et leurs sels d'addition d'acide pharmaceutiquement acceptables, de formule (I). Ces composés sont utiles pour traiter des troubles du système nerveux central, l'hypertension, le diabète, l'impuissance sexuelle et pour réguler l'appétit.