N-[(2S)-7-甲氧基-1,2,3,4-四氢萘-2-基]苯甲酰胺 | 231623-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: N-[(2S)-7-甲氧基-1,2,3,4-四氢萘-2-基]苯甲酰胺
• 英文名称: N-[(2S)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]benzamide
• CAS: 231623-76-0
• 化学式: C₁₈H₁₉NO₂
• 分子量: 281.354
• InChiKey: PFYJVMSKADSJPP-INIZCTEOSA-N

物化性质

• 熔点：
  164.6 °C
• 沸点：
  509.6±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-[(2S)-7-甲氧基-1,2,3,4-四氢萘-2-基]苯甲酰胺 在 dimethyl sulfide borane 、 palladium 10% on activated carbon 、 氢气 、 copper diacetate 、 三溴化硼 、 铁粉 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 methyl 3-amino-5-[((7S)-7-{(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-5,6,7,8-tetrahydro-2-naphthalenyl)oxy]benzoate
  参考文献：
  名称：

  Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety

  摘要：

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.

  DOI：

  10.1021/jm800222k
• 作为产物：
  描述：

  N-(7-methoxy-3,4-dihydronaphthalen-2-yl)benzamide 在 RuBr₂((R)-(6,6'-(MeO)2-biphenyl-2,2'-diyl)bis(Ph₂-phosphane) 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、5.0 MPa 条件下， 反应 64.0h， 以100%的产率得到N-[(2S)-7-甲氧基-1,2,3,4-四氢萘-2-基]苯甲酰胺
  参考文献：
  名称：

  使用对映选择性加氢选择性合成手性非典型β-肾上腺素苯基乙醇氨基四氢呋喃激动剂SR58611A

  摘要：

  我们已经开发出非典型的β-肾上腺素苯基乙醇氨基四氢呋喃激动剂SR58611A的另一种合成方法。已合成了两种关键中间体，涉及对氨基酮和烯酰胺的对映选择性氢化，分别提供了> 96％ee和> 98％ee的相应氨基醇和酰胺。

  DOI：

  10.1016/s0040-4039(99)00807-2

文献信息

• Alternative synthesis of the chiral atypical β-adrenergicphenylethanolaminotetraline agonist SR58611A using enantioselective hydrogenation
  作者：Marc Devocelle、André Mortreux、Francine Agbossou、Jean-Robert Dormoy

  DOI：10.1016/s0040-4039(99)00807-2

  日期：1999.6

  We have developed an alternative synthesis of the atypical β-adrenergic phenylethanolaminotetraline agonist SR58611A. Two key intermediates have been synthesised involving enantioselective hydrogenation of an aminoketone and an enamide providing the corresponding amino alcohol and amide in >96 and >98 % ee respectively.

  我们已经开发出非典型的β-肾上腺素苯基乙醇氨基四氢呋喃激动剂SR58611A的另一种合成方法。已合成了两种关键中间体，涉及对氨基酮和烯酰胺的对映选择性氢化，分别提供了> 96％ee和> 98％ee的相应氨基醇和酰胺。
• Tetrahedron Lett. 1999, 40, 4551-4554
  作者：

  DOI：——

  日期：——
• Eur. J. Med. Chem. 1994, 29, 259-267
  作者：

  DOI：——

  日期：——
• Discovery of a Novel Series of Benzoic Acid Derivatives as Potent and Selective Human β₃ Adrenergic Receptor Agonists with Good Oral Bioavailability. 3. Phenylethanolaminotetraline (PEAT) Skeleton Containing Biphenyl or Biphenyl Ether Moiety
  作者：Masashi Imanishi、Yutaka Nakajima、Yasuyo Tomishima、Hitoshi Hamashima、Kenichi Washizuka、Minoru Sakurai、Shigeo Matsui、Emiko Imamura、Koji Ueshima、Takao Yamamoto、Nobuhiro Yamamoto、Hirofumi Ishikawa、Keiko Nakano、Naoko Unami、Kaori Hamada、Yasuhiro Matsumura、Fujiko Takamura、Kouji Hattori

  DOI：10.1021/jm800222k

  日期：2008.8.1

  We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds (10c, 10m) with a good balance of potency, selectivity, and pharmacokinetic profile. Further optimization of the two lead compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of high potency (EC(50) = 0.38 nM) for beta(3), high selectivity over beta(1) and beta(2), and good pharmacokinetic properties in rats, dogs, and monkeys.