4-甲氧基-7-甲基苯并噻唑-2-胺 | 88686-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 4-甲氧基-7-甲基苯并噻唑-2-胺
• 中文别名: 4-甲氧基-7-甲基-1,3-苯并噻唑-2-胺
• 英文名称: 2-amino-4-methoxy-7-methylbenzothiazole
• 英文别名: 2-Amino-7-methyl-4-methoxybenzothiazole；4-methoxy-7-methyl-1,3-benzothiazol-2-amine；2-Amino-4-methoxy-7-methyl-benzthiazol；4-methoxy-7-methylbenzo[d]thiazol-2-amine；4-methoxy-7-methyl-benzothiazol-2-ylamine
• CAS: 88686-30-0
• 化学式: C₉H₁₀N₂OS
• 分子量: 194.257
• InChiKey: BPFSLCTUFLBWNK-UHFFFAOYSA-N

物化性质

• 熔点：
  165-166 °C
• 沸点：
  362.1±34.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934200090

反应信息

• 作为反应物：
  描述：

  4-甲氧基-7-甲基苯并噻唑-2-胺 在 氢溴酸 作用下， 生成 2-氨基-7-甲基-4-苯并噻唑醇
  参考文献：
  名称：

  某些 Oxine 型化合物的螯合稳定性。二、4-羟基苯并噻唑1

  摘要：

  4-羟基苯并噻唑、2-氨基-4-羟基苯并噻唑、2-甲氨基-4-羟基苯并噻唑和 2-氨基-4-羟基-7-甲基苯并噻唑的酸解离常数在 50% v/v 对二恶烷中于 25 和通过 Calvin-Bjerrum 电位滴定技术获得配体与 Cu(II)、Pb(II)、Ni(H)、Co(II)、Zn(II) 和 Cd(II) 的螯合稳定性常数。将结果与先前报道的 8-羟基喹啉、4-羟基苯并咪唑和 4-羟基苯并恶唑的结果进行比较。4-羟基苯并噻唑螯合物的稳定性常数低于相应的8-羟基喹啉的稳定性常数。这是由较大的氮氧距离和供体氮原子上不利的电子取向来解释的。稳定性值高于 4-羟基苯并咪唑和 4-羟基苯并恶唑，这归因于 1-位较大硫原子的影响。（授权）

  DOI：

  10.1021/ja01471a002
• 作为产物：
  描述：

  2-甲氧基-5-甲基苯胺 在 盐酸 、 溴 作用下， 以 氯仿 、 水 为溶剂， 反应 12.33h， 生成 4-甲氧基-7-甲基苯并噻唑-2-胺
  参考文献：
  名称：

  Synthesis and analysis of pheomelanin degradation products. 2

  摘要：

  DOI：

  10.1021/jo00180a009

文献信息

• Structure‐Guided Design of G‐Protein‐Coupled Receptor Polypharmacology
  作者：Stefanie Kampen、Duc Duy Vo、Xiaoqun Zhang、Nicolas Panel、Yunting Yang、Mariama Jaiteh、Pierre Matricon、Per Svenningsson、Jose Brea、Maria Isabel Loza、Jan Kihlberg、Jens Carlsson

  DOI：10.1002/anie.202101478

  日期：2021.8.9

  AbstractMany diseases are polygenic and can only be treated efficiently with drugs that modulate multiple targets. However, rational design of compounds with multi‐target profiles is rarely pursued because it is considered too difficult, in particular if the drug must enter the central nervous system. Here, a structure‐based strategy to identify dual‐target ligands of G‐protein‐coupled receptors is presented. We use this approach to design compounds that both antagonize the A2A adenosine receptor and activate the D2 dopamine receptor, which have excellent potential as antiparkinson drugs. Atomic resolution models of the receptors guided generation of a chemical library with compounds designed to occupy orthosteric and secondary binding pockets in both targets. Structure‐based virtual screens identified ten compounds, of which three had affinity for both targets. One of these scaffolds was optimized to nanomolar dual‐target activity and showed the predicted pharmacodynamic effect in a rat model of Parkinsonism.
• Synthesis and evaluation of non-catechol D-1 and D-2 dopamine receptor agonists: benzimidazol-2-one, benzoxazol-2-one, and the highly potent: benzothiazol-2-one 7-ethylamines
  作者：Joseph Weinstock、Dimitri E. Gaitanopoulos、Orum D. Stringer、Robert G. Franz、J. Paul Hieble、Lewis B. Kinter、William A. Mann、Kathryn E. Flaim、George Gessner

  DOI：10.1021/jm00390a009

  日期：1987.7

  Our interest in identifying D-1 and D-2 dopamine receptor agonists that are not catechols led us to extend previous studies with oxindoles by investigating analogues of dopamine, N,N-dipropyldopamine, m-tyramine, N,N-dipropyl-m-tyramine, and epinine in which the m-hydroxyl is replaced by the NH portion of a thiazol-2-one, oxazol-2-one, or imidazol-2-one group fused to the 2,3-position. These compounds were evaluated for their affinity and agonist activity at D-1 and D-2 receptors by using in vitro assays. Replacement of the m-hydroxy in N,N-dipropyldopamine with the thiazol-2-one group resulted in a dramatic increase in D-2 receptor affinity and activity compared to that of N,N-dipropyldopamine itself or that of the corresponding oxindole, 1. The resulting compound, 7-hydroxy-4-[2-(di-n-propylamino)ethyl]benzothiazol-2(3H)-one (4), is the most potent D-2 receptor agonist reported to date in the field-stimulated rabbit ear artery (ED50 = 0.028 nM). The benzoxazol-2-one (6), benzimidazol-2-one (5), and isatin (51) analogues showed D-2 receptor agonist potency similar to that of 1. The des-7-hydroxyl analogue of 4 (21) also has enhanced D-2 receptor activity compared to that of the corresponding oxindole, 8. 7-Hydroxy-4-(2-aminoethyl)benzothiazol-2(3H)-one, 27, a non-catechol, has enhanced D-1 and D-2 receptor activity in vitro compared to that of the corresponding oxindole, 7. In vivo, 27 increased renal blood flow and decreased blood pressure in the dog. However, these effects were mediated primarily by D-2 receptor agonist activity. This may be a result of the D-1 partial agonist activity of 27 coupled with its potent D-2 receptor activity.
• Preparation of benzoheterocyclic carbaldeydes
  作者：Frederick A. Luzzio、Marek T. Wlodarczyk

  DOI：10.1016/j.tetlet.2008.11.066

  日期：2009.2

  The preparation of benzoheterocyclic carbaldehydes in the 2-amino-substituted benzothiazole, benzoxazole and benzimidazole series is described. Starting with the methyl-substituted 2-aminobenzoheterocycle, the nitrogen is protected as an N,N-diBoc derivative. Next, free radical halogenation of the methyl group with NBS/AIBN affords the N(Boc)(2)-Protected benzylic dibromide which is directly used in the final step. A mild silver nitrite/dimethylsulfoxide-mediated conversion of the dibromide to the aldehyde functionality completes the process. (c) 2008 Elsevier Ltd. All rights reserved.
• Discovery of N-(4-methoxy-7-methylbenzo[d]thiazol-2-yl)isonicatinamide, ML293, as a novel, selective and brain penetrant positive allosteric modulator of the muscarinic 4 (M4) receptor
  作者：James M. Salovich、Paige N. Vinson、Douglas J. Sheffler、Atin Lamsal、Thomas J. Utley、Anna L. Blobaum、Thomas M. Bridges、Uyen Le、Carrie K. Jones、Michael R. Wood、J. Scott Daniels、P. Jeffrey Conn、Colleen M. Niswender、Craig W. Lindsley、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2012.05.109

  日期：2012.8

  Herein we describe the discovery and development of a novel class of M-4 positive allosteric modulators, culminating in the discovery of ML293. ML293 exhibited modest potency at the human M4 receptor (EC50 = 1.3 mu M) and excellent efficacy as noted by the 14.6-fold leftward shift of the agonist concentration-response curve. ML293 was also selective versus the other muscarinic subtypes and displayed excellent in vivo PK properties in rat with low IV clearance (11.6 mL/min/kg) and excellent brain exposure (PO PBL, 10 mg/kg at 1 h, [Brain] = 10.3 mu M, B: P = 0.85). (C) 2012 Elsevier Ltd. All rights reserved.
• WEINSTOCK J.;GAITONOPOULOS D. E.;STRINGER O. D.;WILLIAM A., J. MED. CHEM., 1987, 30, N 7, 1166-1176
  作者：WEINSTOCK J.、GAITONOPOULOS D. E.、STRINGER O. D.、WILLIAM A.

  DOI：——

  日期：——