[(S)-1-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester | 372523-99-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(S)-1-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 372523-99-4
• 化学式: C₂₂H₃₄N₂O₅
• 分子量: 406.522
• InChiKey: SFPMCSLBTXHRCX-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(S)-1-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 乙酸乙酯 为溶剂， 生成 (S)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3,3-dimethyl-2-(thiophen-2-ylmethylamino)butan-1-one
  参考文献：
  名称：

  N- Acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: The first orexin-2 receptor selective non-peptidic antagonist

  摘要：

  The identification of potent and selective orexin-2 receptor (OX2R) antagonists is described based on the modification of N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogue 1, recently discovered during high throughput screening (HTS). Substitution of an acyl group in 1 with tert-Leucine (tert-Leu), and introduction of a 4-pyridylmethyl substituent onto the amino function of tert-Leu improved compound potency, selectivity, and water solubility. Thus, compound 29 is a promising tool to investigate the role of orexin-2 receptors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.038
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 、 6,7-二甲氧基-1,2,3,4-四氢异喹啉盐酸盐 在 吡啶 、 4-二甲氨基吡啶 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 生成 [(S)-1-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  N- Acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: The first orexin-2 receptor selective non-peptidic antagonist

  摘要：

  The identification of potent and selective orexin-2 receptor (OX2R) antagonists is described based on the modification of N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogue 1, recently discovered during high throughput screening (HTS). Substitution of an acyl group in 1 with tert-Leucine (tert-Leu), and introduction of a 4-pyridylmethyl substituent onto the amino function of tert-Leu improved compound potency, selectivity, and water solubility. Thus, compound 29 is a promising tool to investigate the role of orexin-2 receptors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.038

文献信息

• N-acyltetrahydroisoquinoline derivatives
  申请人：——

  公开号：US20040044031A1

  公开（公告）日：2004-03-04

  This invention relates to novel compounds represented by the general formula [I] 1 (wherein, R 1 and R 4 are the same or different, and represent hydrogen atoms, lower alkyl groups or the like; R 2 and R 3 are the same or different, and represent lower alkoxy groups or lower alkyl groups; R 5 represents a lower alkyl group or aralkyl group optionally having substituent(s); R 6 represents a hydrogen atom or a lower alkyl group; X represents O, S or NH; m represents an integer of 0 to 3; n represents an integer of 0 or 1; and Ar represents a phenyl group or heteroaryl group optionally having substituent(s)). The compounds of the invention have an antagonistic action on orexin receptors, and are useful for treatment of appetite abnormality, obesity, sleeping disorder or the like.

  本发明涉及由一般式[I]1表示的新化合物（其中，R1和R4相同或不同，表示氢原子、低烷基或类似物；R2和R3相同或不同，表示低烷氧基或低烷基；R5表示一个低烷基或具有取代基的芳基烷基；R6表示氢原子或低烷基；X表示O、S或NH；m表示0到3的整数；n表示0或1的整数；Ar表示苯基或杂环芳基，可选地具有取代基）。本发明的化合物具有对促食素受体的拮抗作用，可用于治疗食欲异常、肥胖症、睡眠障碍或类似疾病。
• N-ACYLTETRAHYDROISOQUINOLINE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1288202A1

  公开（公告）日：2003-03-05

  This invention relates to novel compounds represented by the general formula [I] (wherein, R' and R4 are the same or different, and represent hydrogen atoms, lower alkyl groups or the like; R2 and R3 are the same or different, and represent lower alkoxy groups or lower alkyl groups; R5 represents a lower alkyl group or aralkyl group optionally having substituent(s); R6 represents a hydrogen atom or a lower alkyl group; X represents O, S or NH; m represents an integer of 0 to 3; n represents an integer of 0 or 1; and Ar represents a phenyl group or heteroaryl group optionally having substituent(s)). The compounds of the invention have an antagonistic action on orexin receptors, and are useful for treatment of appetite abnormality, obesity, sleeping disorder or the like.

  本发明涉及通式[I]所代表的新型化合物。 (其中，R'和R4相同或不同，代表氢原子、低级烷基或类似物；R2和R3相同或不同，代表低级烷氧基或低级烷基；R5代表低级烷基或可选具有取代基的芳烷基；R6代表氢原子或低级烷基；X代表O、S或NH；m代表0至3的整数；n代表0或1的整数；Ar代表可选具有取代基的苯基或杂芳基）。 本发明的化合物对奥曲肽受体具有拮抗作用，可用于治疗食欲异常、肥胖、睡眠障碍或类似疾病。
• US6838465B2
  申请人：——

  公开号：US6838465B2

  公开（公告）日：2005-01-04
• N- Acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline: The first orexin-2 receptor selective non-peptidic antagonist
  作者：Masaaki Hirose、Shin-ichiro Egashira、Yasuhiro Goto、Takashi Hashihayata、Norikazu Ohtake、Hisashi Iwaasa、Mikiko Hata、Takehiro Fukami、Akio Kanatani、Koji Yamada

  DOI：10.1016/j.bmcl.2003.08.038

  日期：2003.12

  The identification of potent and selective orexin-2 receptor (OX2R) antagonists is described based on the modification of N-acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline analogue 1, recently discovered during high throughput screening (HTS). Substitution of an acyl group in 1 with tert-Leucine (tert-Leu), and introduction of a 4-pyridylmethyl substituent onto the amino function of tert-Leu improved compound potency, selectivity, and water solubility. Thus, compound 29 is a promising tool to investigate the role of orexin-2 receptors. (C) 2003 Elsevier Ltd. All rights reserved.