[(6-氨基-1,2,3,4-四氢-2-萘)甲基]二甲基胺 | 331754-31-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: [(6-氨基-1,2,3,4-四氢-2-萘)甲基]二甲基胺
• 英文名称: [(6-amino-1,2,3,4-tetrahydro-2-naphthalenyl)methyl]dimethylamine
• 英文别名: 6-[(dimethylamino)methyl]-5,6,7,8-tetrahydro-2-naphthalenamine；6-amino-2-(N,N-dimethylamino)methyltetralin；6-dimethylaminomethyl-5,6,7,8-tetrahydro-naphthalen-2-ylamine；(6R*)-6-[(dimethylamino)methyl]-5,6,7,8-tetrahydronaphthalen-2-amine；6-[(dimethylamino)methyl]-5,6,7,8-tetrahydronaphthalen-2-amine
• CAS: 331754-31-5
• 化学式: C₁₃H₂₀N₂
• 分子量: 204.315
• InChiKey: LQRIWUQSMUFWPO-UHFFFAOYSA-N

物化性质

• 沸点：
  336℃
• 密度：
  1.022
• 闪点：
  141℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [(6-氨基-1,2,3,4-四氢-2-萘)甲基]二甲基胺 在 4-二甲氨基吡啶 、 氯甲酸乙酯 、 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 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.5h， 生成 4'-chloro-N-[6-[(methylanilino)methyl]-7,8-dihydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide
  参考文献：
  名称：

  Discovery, synthesis, and structure–activity relationship of 6-aminomethyl-7,8-dihydronaphthalenes as human melanin-concentrating hormone receptor 1 antagonists

  摘要：

  Human melanin-concentrating hormone receptor 1 (hMCHR1) antagonists are promising targets for obesity treatment. We identified the tetrahydronaphthalene derivative 1a with modest binding affinity for hMCHR1 by screening an in-house G protein-coupled receptor (GPCR) ligand library. We synthesized a series of 6-aminomethyl-5,6,7,8-tetrahydronaphthalenes and evaluated their activity as hMCHR1 antagonists. Modification of the biphenylcarbonylamino group revealed that the biphenyl moiety played a crucial role in the interaction of the antagonist with the receptor. The stereoselective effect of the chiral center on binding affinity generated the novel 6-aminomethyl-7,8-dihydronaphthalene scaffold without a chiral center. Optimization of the amino group led to the identification of a potent antagonist 2s (4'-fluoro-N[6-(1-pyrrolidinylmethyl)-7,8-dihydro-2-naphthalenyl][1,1'-biphenyl]-4-carboxamide), which significantly inhibited the nocturnal food intake in rats after oral administration. Pharmacokinetic analysis confirmed that 2s had good oral bioavailability and brain penetrance. This antagonist appears to be a viable lead compound that can be used to develop a promising therapy for obesity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.038
• 作为产物：
  描述：

  N-(6-dimethylaminomethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-acetamide hydrochloride 在 盐酸 、 sodium hydroxide 作用下， 生成 [(6-氨基-1,2,3,4-四氢-2-萘)甲基]二甲基胺
  参考文献：
  名称：

  Amine compounds, their production and use as amyloid-&bgr; production inhibitors

  摘要：

  该化合物的化学式如下：其中Ar是一种芳香环组合基团，可以是取代的或者是取代的融合芳香基团；X是（i）一个键，（ii）—S—，—SO—或—SO2—，（iii）C1-6烷基，C2-6烯基或C2-6炔基等，（iv）—CO—O—或（v）—（CH2）p-X1—，—（CH2）p-X1—（CH2）q-，—（CH2）r-CO—X1—，—SO2—NR8—或—（CH2）r-SO2—NR8—其中X1是O或NR8，R8是H，一个可以被取代的碳氢基团或酰基，p是0到5，q是1到5，p+q是1到5，r是1到4；Y是一个二价的C1-6脂肪烃基，可选含有O或S，可以是取代的；R1和R2分别是H或一个可以被取代的较低烷基，或者R1和R2形成一个可以被取代的含氮杂环；环A是一个苯环，可以进一步被取代；环B是一个4至8元环，可以进一步被取代，或其盐具有抑制淀粉样蛋白β蛋白的产生和/或分泌的作用，并且可作为预防和/或治疗神经退行性疾病等的药物组成部分。

  公开号：

  US06310107B1

文献信息

• [EN] NOVEL AMINOTETRALINE COMPOUNDS FOR USE IN MCH RECEPTOR RELATED DISORDERS<br/>[FR] NOUVEAUX COMPOSES AMINOTETRALINE UTILES POUR SOIGNER LES TROUBLES ASSOCIES AU RECEPTEUR MCH
  申请人：7TM PHARMA AS

  公开号：WO2003087046A1

  公开（公告）日：2003-10-23

  Novel compounds of formula (I) which modulate MCH activity are disclosed in which A is a linker; Ar1 is an aryl or heteroaryl group; R1 and R2 are hydrogen, straight or branched alkyl, alkenyl or alkynyl groups, cycloalkyl groups, alkylcycloalkyl groups, alkylaryl groups, alkylheterocyclyl groups, alkylheteroaryl groups and may be linked to each other; R3 is a hydrogen atom, Alk-, Alk-O-, hydroxy or keto group; R4 and R5 are hydrogen, halogen atoms, alkoxy groups, hydroxy, alkylamino groups, dialkylamino groups, hydroxylalkyl groups, carboxamido groups, acylamido groups, acyl groups, -CHO, nitrile, alkyl, alkenyl or alkynyl groups, -CF3, -OCF3, -SCF3; -SCH3, -SO2NH2, -SO2NHAlk, -SO2Nalk2, -SO2Alk; n is 1 or 2; R8 is halogen atoms, alkyl, alkenyl or alkynyl groups, cycloalkyl groups with 3-7 carbons, alkylcycloalkyl groups, alkylaryl groups, alkylheterocyclyl groups, heteroaryloxyl groups, alkylheteroaryl groups, arylalkoxy groups, aryloxy groups, alkoxy groups, dialkylamino groups, -CONHAlk, -CONHAr, -CONAlk2, -NHCO-Alk, -NHCO-Ar, -CO-Alk, -CO-Ar, -SCH3, -CF3, -OCF3, -SCF3; or R8 is R6-Ar2-B-; in which B is a connecting moiety; Ar2 is an aryl or heteroaryl group; R6 is an R5 group; and which are useful in the treatment or prevention of e.g. obesity, depression, diabetes, bulimia etc.

  化合物的新结构式（I），其调节MCH活性的方法已被披露，其中A是一个连接物；Ar1是芳基或杂环芳基；R1和R2是氢、直链或支链烷基、烯基或炔基、环烷基、烷基环烷基、烷基芳基、烷基杂环烷基、烷基杂芳基，它们之间可能相互连接；R3是氢原子、烷基、烷氧基、羟基或酮基；R4和R5是氢、卤素原子、烷氧基、羟基、烷基氨基、二烷基氨基、羟基烷基、羧酰胺基、酰胺基、酰基、-CHO、腈基、烷基、烯基或炔基、-CF3、-OCF3、-SCF3、-SCH3、-SO2NH2、-SO2NHAlk、-SO2Nalk2、-SO2Alk；n为1或2；R8是卤素原子、烷基、烯基或炔基、含有3-7个碳的环烷基、烷基环烷基、烷基芳基、烷基杂环烷基、杂芳氧基、烷基杂芳基、芳基烷氧基、芳氧基、烷氧基、二烷基氨基、-CONHAlk、-CONHAr、-CONAlk2、-NHCO-Alk、-NHCO-Ar、-CO-Alk、-CO-Ar、-SCH3、-CF3、-OCF3、-SCF3；或R8是R6-Ar2-B-；其中B是连接基；Ar2是芳基或杂环芳基；R6是一个R5基团；这些化合物在治疗或预防肥胖、抑郁症、糖尿病、暴食症等方面是有用的。
• Melanin concentrating hormone antagonist
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US07115750B1

  公开（公告）日：2006-10-03

  A melanin-concentrating hormone antagonist which comprises a compound of the formula: wherein Ar1 is a cyclic group which may have substituents; X is a spacer having a main chain of 1 to 6 atoms; Y is a bond or a spacer having a main chain of 1 to 6 atoms; Ar is a monocyclic aromatic ring which may be condensed with a 4 to 8 membered non-aromatic ring, and may have further substituents; R1 and R2 are independently hydrogen atom or a hydrocarbon group which may have substituents; R1 and R2, together with the adjacent nitrogen atom, may form a nitrogen-containing hetero ring which may have substituents; R2 may form a spiro ring together with Ar; or R2, together with the adjacent nitrogen atom and Y, may form a nitrogen-containing hetero ring which may have substituents; or a salt thereof; which is useful as an agent for preventing or treating obesity, etc.

  一种黑色素浓缩激素拮抗剂，包括以下式的化合物： 其中Ar1是可能具有取代基团的环状基团； X是具有1到6个原子的主链的间隔物； Y是键或具有1到6个原子的主链的间隔物； Ar是可能与4到8个成员的非芳香环融合的单环芳香环，并且可能具有进一步的取代基团； R1和R2分别是氢原子或可能具有取代基团的碳氢基团；R1和R2，连同相邻的氮原子，可能形成可能具有取代基团的含氮杂环；R2可能与Ar一起形成螺环；或者R2，连同相邻的氮原子和Y，可能形成可能具有取代基团的含氮杂环；或其盐； 该化合物可用作预防或治疗肥胖等疾病的药剂。
• Amine compounds, their production and use
  申请人：——

  公开号：US20040077867A1

  公开（公告）日：2004-04-22

  A compound of the formula: 1 wherein Ar is an aromatic ring assembly group which may be substituted or a fused aromatic group which may be substituted; X is (i) a bond, (ii) —S—, —SO— or —SO 2 —, (iii) C 1-6 alkylene, C 2-6 alkenylene or C 2-6 alkynylene, etc., (iv) —CO—O— or (v) —(CH 2 )p-X 1 —, —(CH 2 )p-X 1 —CH 2 )q-, —(CH 2 )r-CO—X 1 —, —SO 2 —NR 8 — or —(CH 2 )r-SO 2 —NR 8 — wherein X 1 is O or NR 8 , R 8 is H, a hydrocarbon group which may be substituted or an acyl, p is 0 to 5, q is 1 to 5, p+q is 1 to 5, and r is 1 to 4; Y is a divalent C 1-6 aliphatic hydrocarbon group optionally containing O or S, which may be substituted; R 1 and R 2 each is H or a lower alkyl which may be substituted, or R 1 and R 2 form a N-containing heterocyclic ring which may be substituted; Ring A is a benzene ring which may be further substituted; and Ring B is a 4- to 8-membered ring which may be further substituted, or a salt thereof has the effect of inhibiting amyloid-&bgr; protein production and/or secretion and is useful as a pharmaceutical composition for preventing and/or treating the neurodegenerative disease, etc.

  化合物的公式为1，其中Ar是芳香环组装基团，可以是取代的或融合的芳香族基团，X是(i)键，(ii) -S-, -SO-或-SO2-, (iii) C1-6烷基，C2-6烯基或C2-6炔基等，(iv) -CO-O-或(v) -(CH2)p-X1-，-(CH2)p-X1-CH2)q-，-(CH2)r-CO-X1-，-SO2-NR8-或-(CH2)r-SO2-NR8-其中X1是O或NR8，R8是H，可以是取代的碳氢基团或酰基，p为0至5，q为1至5，p+q为1至5，r为1至4；Y是二价的C1-6脂肪烃基团，可以包含O或S，可以是取代的；R1和R2分别是H或可以取代的低碳烷基，或R1和R2形成一个可以取代的含氮杂环；环A是苯环，可以进一步取代；环B是4-至8成员环，可以进一步取代，或其盐具有抑制淀粉样-β蛋白产生和/或分泌的作用，并且作为预防和/或治疗神经退行性疾病的药物组成物有用。
• MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS
  申请人：Zhao Guohua

  公开号：US20090221548A1

  公开（公告）日：2009-09-03

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein R 1a , R 1b , R 1c , Q, A, R 3 , W, D and R 2 are defined herein. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了符合公式I的化合物，包括所有立体异构体、溶剂化物、前药和药物可接受的形式，其中在此定义了R1a、R1b、R1c、Q、A、R3、W、D和R2。此外，本申请提供了含有至少一种符合公式I的化合物的药物组合物，以及可选地含有至少一种额外治疗剂的组合物。最后，本申请提供了使用符合公式I的化合物的治疗方法，用于治疗患有MCHR-1调节的疾病或障碍，例如肥胖症、糖尿病、抑郁症或焦虑症的患者，通过给予符合公式I的化合物的治疗有效剂量。
• Melanin concentrating hormone receptor-1 antagonists
  申请人：Bristol-Myers Squibb Company

  公开号：US07956049B2

  公开（公告）日：2011-06-07

  The present application provides compounds, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein R1a, R1b, R1c, Q, A, R3, W, D and R2 are defined herein. Additionally, the present application provides pharmaceutical compositions containing at least one compound according to Formula I and optionally at least one additional therapeutic agent. Finally, the present application provides methods for treating a patient suffering from an MCHR-1 modulated disease or disorder such as, for example, obesity, diabetes, depression or anxiety by administration of a therapeutically effective dose of a compound according to Formula I.

  本申请提供了化合物，包括所有立体异构体、溶剂化物、前药和药学上可接受的形式，其符合式I中定义的R1a、R1b、R1c、Q、A、R3、W、D和R2。此外，本申请还提供了含有至少一种符合式I的化合物的药物组合物，以及可选地含有至少一种其他治疗剂的药物组合物。最后，本申请提供了使用符合式I的化合物的治疗方法，用于治疗患有MCHR-1调节性疾病或疾患的患者，例如肥胖症、糖尿病、抑郁症或焦虑症，通过给予符合式I的化合物的治疗有效剂量进行治疗。