N-methyl-3,4,5-trimethoxyphenethylamine | 4838-96-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-methyl-3,4,5-trimethoxyphenethylamine
• 英文别名: N-methyl-N-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-amine；N-Methylmescaline；N-methyl-2-(3,4,5-trimethoxyphenyl)ethanamine
• CAS: 4838-96-4
• 化学式: C₁₂H₁₉NO₃
• 分子量: 225.288
• InChiKey: OTXANOLOOUNVSR-UHFFFAOYSA-N

物化性质

• 熔点：
  201-202 °C
• 沸点：
  315.5±37.0 °C(Predicted)
• 密度：
  1.025±0.06 g/cm3(Predicted)
• 保留指数：
  1700;1692.7

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-3,4,5-trimethoxyphenethylamine 在 lithium aluminium tetrahydride 、 PPA 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.33h， 生成 N-methylanhalinine
  参考文献：
  名称：

  [EN] NOVEL MONOAMINE RE-UPTAKE INHIBITOR
  [FR] NOUVEL INHIBITEUR DE RECAPTAGE DE MONOAMINE

  摘要：

  公开号：

  WO2009118765A8
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 硼烷四氢呋喃络合物 、 草酰氯 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 35.5h， 生成 N-methyl-3,4,5-trimethoxyphenethylamine
  参考文献：
  名称：

  好氧C?H活化的生物催化对映选择性氧化C?C偶联

  摘要：

  弥合差距：小檗碱桥酶 (BBE) 被用于第一个制备性氧化生物催化 C  C 偶联，导致新的分子内键。这种独特的转化需要 O 2作为唯一的化学计量氧化剂，并通过动力学拆分获得新的光学纯 ( S )-小檗碱2和 ( R )-1-苄基-1,2,3,4-四氢异喹啉1生物碱衍生物。

  DOI：

  10.1002/anie.201006268

文献信息

• Synthesis and calcium antagonistic activity of (+)-(R)- and (-)-(S)-3-acetyl-2-(5-methoxy-2-(4-(N-methyl-N-(3,4,5-trimethoxyphenethyl)amino)butoxy)phenyl)benzothiazoline hydrochloride.
  作者：Masanobu FUJITA、Atsutoshi OTA、Susumu ITO、Koji YAMAMOTO、Yoichi KAWASHIMA、Tadashi ISO、Jun-ichi IWAO

  DOI：10.1248/cpb.38.936

  日期：——

  SA2572 ((±)-1), 3-acetyl-2-[5-methoxy-2-[-[N-methyl-N-(3, 4, 5-trimethoxyphenethyl)amino]butoxy]phenyl]-benzothiazoline hydrocholoride is a newly synthesized Ca2+ antagonist having a inhibitory effect on the fast Na+ inward channel In order to clarify the absolute configurations and the pharmacological properties of both enantiomers, compounds ((+)-1 and (-)-1) were synthesized. The configurations of these compounds were assigned on the basis of an X-ray crystallographic analysis of synthetic precursor (5). The in vitro Ca2+ channel blocking activities of (+)-1 and (-)-1 were evaluated in terms of the inhibitory activities on depolarization-induced contraction of guinea pig taenia cecum and rabbit aorta. The in vivo efficacy of the enantiomers was evaluated with their hypotensive effects in spontaneously hypertensive rats. Compound (-)-1 showed more potent Ca2+ antagonistic activities on guinea pig taenia cecum and rabbit aorta and the hypotensive effect than those activities of (+)-1. In the electrophysiological study of Langendorff perfused rabbit hearts, compound (+)-1 showed more potent inhibitory effect on the fast Na+ inward channel than that of compound (-)-1, and an approximately equal potent inhibitory effect on the slow Ca2+ inward channel as compared (-)-1. Stereoselectivity of the pharmacological activity was found.

  SA2572 ((±)-1)，即3-乙酰基-2-[5-甲氧基-2-[N-甲基-N-(3，4，5-三甲氧基苯乙基)氨基]丁氧基]苯基]-苯并噻唑啉盐酸盐，是一种新合成的Ca2+拮抗剂，具有抑制快速Na+内向通道的作用。为了阐明两种对映体((+)-1和(-)-1)的绝对构型和药理学特性，进行了合成。通过合成前体(5)的X射线晶体学分析，确定了这些化合物的构型。在体外，评估了(+)-1和(-)-1对豚鼠结肠带和兔主动脉去极化诱导收缩的抑制活性，从而评价了它们对Ca2+通道的阻断活性。在体内，通过评估对映体对自发性高血压大鼠的降压效果来评价其疗效。化合物(-)-1在豚鼠结肠带和兔主动脉上表现出比(+)-1更强的Ca2+拮抗活性及降压效果。在Langendorff灌流兔心电生理学研究中，化合物(+)-1对快速Na+内向通道的抑制作用比化合物(-)-1更强，而对慢速Ca2+内向通道的抑制作用与(-)-1相当。发现了药理活性的立体选择性。
• Novel calcium antagonists. Synthesis and structure-activity relationship studies of benzothiazoline derivatives
  作者：Koji Yamamoto、Masanobu Fujita、Keizo Tabashi、Yoichi Kawashima、Eishin Kato、Masayuki Oya、Tadashi Iso、Junichi Iwao

  DOI：10.1021/jm00400a006

  日期：1988.5

  A series of novel compounds having a benzothiazoline skeleton was studied for their structure-activity relationship (SAR) with respect to Ca2+ antagonistic activity. As test compounds, analogues of 3-acyl-2-arylbenzothiazolines (3) were synthesized. Benzothiazoline derivatives (3) exerted higher Ca2+ antagonistic activity than the corresponding thiazolidine derivatives (2). Effects of substituents

  研究了一系列具有苯并噻唑啉骨架的新型化合物的相对于Ca2 +拮抗活性的结构活性关系（SAR）。作为测试化合物，合成了3-酰基-2-芳基苯并噻唑啉的类似物（3）。苯并噻唑啉衍生物（3）比相应的噻唑烷衍生物（2）具有更高的Ca2 +拮抗活性。研究了取代基R1-R4，氨基烷氧基和R2的取代位置以及亚甲基链的长度对生物活性的影响。化合物4 [3-乙酰基-2- [5-甲氧基-2- [4- [N-甲基-N-（3,4,5-三甲氧基苯乙基）氨基]丁氧基]苯基]苯并噻唑啉盐酸盐]显示出有效的Ca2 +拮抗活性体外对Langendorff灌注兔心脏中Na +向内快速通道和Ca2 +向内缓慢通道的双重抑制。
• Compositions and methods for treating nephritis and inhibiting TGF -&bgr; related conditions using pyridylacrylamide derivatives
  申请人：Tsumura & Co.

  公开号：US06313153B1

  公开（公告）日：2001-11-06

  The present invention relates to an agent for treating nephritis and a TGF-&bgr; inhibiting agent comprising as an effective ingredient a pyridylacrylamide derivative represented by the following formula (I): wherein Ar1 is a substituted or unsubstituted pyridyl group, Ar2 is a substituted or unsubstituted phenyl group, R1 is a hydrogen atom, an alkyl group or an aryl group, R2 is a hydrogen atom, an alkyl group, a cyano group or an alkoxycarbonyl group, R3 is a hydrogen atom or an optionally substituted alkyl group, X is an oxygen or sulfur atom, A and B are same or different and each represent a hydrogen atom, a hydroxyl group, an alkoxy group or an alkylthio group, or A and B together form an oxo or thioxo group, or a group represented by the formula: ═N—Y in which Y is a dialkylamino, hydroxyl, aralkyloxy or alkoxy group, or a group represented by the formula: —Z1—M—Z2— which Z1 and Z2 are same or different and each represent an oxygen or sulfur atom or an imino group optionally substituted by an alkyl group, and M is an alkylene group or a 1,2-phenylene group, or A is a hydroxyl group and B is a 1-alkylimidazol-2-yl group, and n is an integer of 1 to 3, or a pharmaceutically acceptable salt thereof; as well as the pyridylacrylamide derivatives.

  本发明涉及一种用于治疗肾炎的药剂和一种TGF-β抑制剂，其有效成分为以下式(I)所表示的吡啶丙烯酰胺衍生物，其中Ar1是取代或未取代的吡啶基团，Ar2是取代或未取代的苯基团，R1是氢原子、烷基或芳基，R2是氢原子、烷基、氰基或烷氧羰基，R3是氢原子或可选择取代的烷基，X是氧原子或硫原子，A和B相同或不同，每个代表氢原子、羟基、烷氧基或烷基硫基，或A和B一起形成氧代或硫代基，或由式表示的基团：═N—Y，其中Y是二烷基氨基、羟基、芳基氧基或烷氧基，或由式表示的基团：—Z1—M—Z2—，其中Z1和Z2相同或不同，每个代表氧原子或硫原子或可选择由烷基取代的亚胺基，M是烷基或1,2-苯基，或A是羟基且B是1-烷基咪唑-2-基，n为1至3的整数，或其药学上可接受的盐；以及吡啶丙烯酰胺衍生物。
• PHOSPHODIESTERASE IV INHIBITOR CONTAINING PYRIDYLACRYLAMIDE DERIVATIVE
  申请人：TSUMURA & CO.

  公开号：EP1495757A1

  公开（公告）日：2005-01-12

  This invention relates to a phosphodiesterase IV inhibitor containing as an active ingredient a pyridylacrylamide derivative represented by the following formula (I): (wherein Ar1 represents substituted or unsubstituted pyridyl; Ar2 represents phenyl substituted by alkoxy, etc.; R1 represents hydrogen, alkyl, or aryl; R2 represents hydrogen, alkyl, cyano, or alkoxycarbonyl; R3 represents hydrogen or optionally substituted alkyl; X represents oxygen or sulfur; A and B are the same or different and each independently represents hydrogen, hydroxyl, alkoxy, or alkylthio, or A and B together represent oxo, thioxo, etc., or A may be hydroxyl and B may be 1-alkylimidazol-2-yl; and n is an integer from 1 to 3) or a pharmaceutically acceptable salt thereof.

  这项发明涉及一种磷酸二酯酶IV抑制剂，其活性成分为以下式(I)所代表的吡啶丙烯酰胺衍生物：（其中Ar1代表取代或未取代的吡啶；Ar2代表被烷氧基等取代的苯基；R1代表氢、烷基或芳基；R2代表氢、烷基、氰基或烷氧羰基；R3代表氢或可选择取代的烷基；X代表氧或硫；A和B相同或不同，每个独立代表氢、羟基、烷氧基或烷基硫基，或A和B一起代表氧代、硫代等，或A可能是羟基，B可能是1-烷基咪唑-2-基；n为1至3的整数）或其药学上可接受的盐。
• A novel class of calcium-entry blockers: the 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines
  作者：Jean Gubin、Jean Lucchetti、Jean Mahaux、Dino Nisato、Gilbert Rosseels、Martine Clinet、Peter Polster、Pierre Chatelain

  DOI：10.1021/jm00084a002

  日期：1992.3

  an isopropyl or cyclopropyl group at the 2 position of the indolizine are among the most potent calcium antagonists known outside the 1,4-dihydropyridine series. The IC50 values for the inhibition of [3H]nitrendipine binding vary between 0.19 and 4.5 nM whereas the IC50 value for nifedipine is 2.5 nM. One of the compounds in this group (9ab) has now been selected for clinical development.

  描述了一系列1-磺酰林多嗪的合成和初步生物学评估。这些化合物已被证明是一类新型的有效的慢通道钙拮抗剂。发现所有化合物的活性至少与参考钙拮抗剂维拉帕米和顺-（+）-地尔硫卓相同。结构-活性关系研究表明，所有在胺部分具有芳烷基基团和在吲哚嗪的2位上具有异丙基或环丙基基团的化合物都是1,4-二氢吡啶系列以外已知最有效的钙拮抗剂。抑制[3H]硝苯地平结合的IC50值在0.19至4.5 nM之间变化，而硝苯地平的IC50值为2.5 nM。现在已选择该组中的一种化合物（9ab）用于临床开发。

表征谱图