(S)-6-((5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-6-oxohexanoic acid | 178486-36-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (S)-6-((5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-6-oxohexanoic acid
• 英文别名: (S)-N-propyl-N-[5-methoxy-1,2,3,4-tetrahydro-2-naphthyl]-5-carboxypentanamide；6-[[(2S)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]-propylamino]-6-oxohexanoic acid
• CAS: 178486-36-7
• 化学式: C₂₀H₂₉NO₄
• 分子量: 347.455
• InChiKey: HFNHREKCTIAFHC-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-6-((5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-6-oxohexanoic acid 在 lithium aluminium tetrahydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 N¹,N⁶-bis((S)-5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N¹,N⁶-dipropylhexane-1,6-diamine
  参考文献：
  名称：

  Novel Bivalent Ligands for D2/D3 Dopamine Receptors: Significant Cooperative Gain in D2 Affinity and Potency

  摘要：

  This report describes development of a series of novel bivalent molecules with a pharmacophore derived from the D2/D3 agonist 5-OH-DPAT. The spacer length in the bivalent compounds had a pronounced influence on affinity for D2 receptors. A 23-fold increase of D2 affinity was observed at a spacer length of 9 or 10 (compounds lid and 14b) as compared to monovalent 5-OH-DPAT (K-ij 2.5 and 2.0 vs 59 nM for 11d and 146 vs 5-OH-DPAT, respectively). The functional potency of 11d and 14b indicated a 24- and 94-fold increase in potency at the D2 receptor as compared to 5-OH-DPAT (EC50; 1.7 and 0.44 vs 41 nM for 11d and 14b vs 5-OH-DPAT, respectively). These are the most potent bivalent agonists for the D2 receptor known to date. This synergism is consonant with cooperative interaction at the two orthosteric binding sites in the homodimeric receptor.

  DOI：

  10.1021/ml3002117
• 作为产物：
  描述：

  己二酸单乙酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 (S)-6-((5-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)(propyl)amino)-6-oxohexanoic acid
  参考文献：
  名称：

  Novel Bivalent Ligands for D2/D3 Dopamine Receptors: Significant Cooperative Gain in D2 Affinity and Potency

  摘要：

  This report describes development of a series of novel bivalent molecules with a pharmacophore derived from the D2/D3 agonist 5-OH-DPAT. The spacer length in the bivalent compounds had a pronounced influence on affinity for D2 receptors. A 23-fold increase of D2 affinity was observed at a spacer length of 9 or 10 (compounds lid and 14b) as compared to monovalent 5-OH-DPAT (K-ij 2.5 and 2.0 vs 59 nM for 11d and 146 vs 5-OH-DPAT, respectively). The functional potency of 11d and 14b indicated a 24- and 94-fold increase in potency at the D2 receptor as compared to 5-OH-DPAT (EC50; 1.7 and 0.44 vs 41 nM for 11d and 14b vs 5-OH-DPAT, respectively). These are the most potent bivalent agonists for the D2 receptor known to date. This synergism is consonant with cooperative interaction at the two orthosteric binding sites in the homodimeric receptor.

  DOI：

  10.1021/ml3002117

文献信息

• Derivatives of 2-amino-1,2,3,4-tetrahydronaphthalene active on the
  申请人：Zambon Group

  公开号：US05674909A1

  公开（公告）日：1997-10-07

  Compounds of formula ##STR1## wherein R, R', R", R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, X, Y, m, n and p have the meanings reported in the description; and their pharmaceutically acceptable salts are described. The compounds of formula I are useful in the treatment of arterial hypertension and congestive heart failure, of renal failure, of peripheral arteriopathies, of cerebrovascular insufficiencies and of ischemic cardiopathy.

  公式为##STR1##的化合物，其中R，R'，R"，R.sub.1，R.sub.2，R.sub.3，R.sub.4，R.sub.5，R.sub.6，X，Y，m，n和p的含义如描述所述；并描述了它们的药学上可接受的盐。公式I的化合物在治疗动脉高血压和充血性心力衰竭，肾功能衰竭，外周动脉病变，脑血管不足和缺血性心脏病方面有用。
• DERIVATIVES OF 2-AMINO-1,2,3,4-TETRAHYDRO-NAPHTHALENE ACTIVE ON THE CARDIOVASCULAR SYSTEM
  申请人：ZAMBON GROUP S.p.A.

  公开号：EP0781126B1

  公开（公告）日：2001-12-12
• US5632978A
  申请人：——

  公开号：US5632978A

  公开（公告）日：1997-05-27
• Novel Bivalent Ligands for D2/D3 Dopamine Receptors: Significant Cooperative Gain in D2 Affinity and Potency
  作者：Sanjib Gogoi、Swati Biswas、Gyan Modi、Tamara Antonio、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/ml3002117

  日期：2012.12.13

  This report describes development of a series of novel bivalent molecules with a pharmacophore derived from the D2/D3 agonist 5-OH-DPAT. The spacer length in the bivalent compounds had a pronounced influence on affinity for D2 receptors. A 23-fold increase of D2 affinity was observed at a spacer length of 9 or 10 (compounds lid and 14b) as compared to monovalent 5-OH-DPAT (K-ij 2.5 and 2.0 vs 59 nM for 11d and 146 vs 5-OH-DPAT, respectively). The functional potency of 11d and 14b indicated a 24- and 94-fold increase in potency at the D2 receptor as compared to 5-OH-DPAT (EC50; 1.7 and 0.44 vs 41 nM for 11d and 14b vs 5-OH-DPAT, respectively). These are the most potent bivalent agonists for the D2 receptor known to date. This synergism is consonant with cooperative interaction at the two orthosteric binding sites in the homodimeric receptor.