2,4-dimethoxy-7-(2-aminoethyl)benzothiazole | 108773-15-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2,4-dimethoxy-7-(2-aminoethyl)benzothiazole
• 英文别名: 2-(2,4-dimethoxy-1,3-benzothiazol-7-yl)-ethylamine；2-(2,4-Dimethoxy-1,3-benzothiazol-7-yl)ethanamine
• CAS: 108773-15-5
• 化学式: C₁₁H₁₄N₂O₂S
• 分子量: 238.31
• InChiKey: WPHMWTJMYYSSOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  85.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-dimethoxy-7-(2-aminoethyl)benzothiazole 在 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 反应 9.5h， 生成 2,4-dimethoxy-7-<2-(N-methylamino)ethyl>benzothiazole
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00390a009
• 作为产物：
  描述：

  2-chloro-4-methoxy-7-<2-(trifluoroacetamido)ethyl>benzothiazole 、 sodium methylate 在 水 作用下， 生成 2,4-dimethoxy-7-(2-aminoethyl)benzothiazole
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00390a009

文献信息

• 7-(2-aminoethyl) benzothiazolones
  申请人：Astra Pharmaceuticals Limited

  公开号：US05648370A1

  公开（公告）日：1997-07-15

  There are disclosed compounds of formula I, Ar--CH.sub.2 CH.sub.2 --NH--CR.sup.1 R.sup.2 --X--Y I in which Ar represents a group, ##STR1## X represents a C.sub.1-12 alkylene chain optionally interrupted or terminated by one or more groups selected from --S(O).sub.n --, --O--, --C(Z)--, CR.sup.6 R.sup.7, phenylmethyne, --NR.sup.8 --, --CONH--, --NHCO-- and --NHCONH--, Y represents an optionally substituted aryl or cycloalkyl group, Z represents O or S, R.sup.1, R.sup.2, R.sup.5 and R.sup.9 each independently represent hydrogen or alkyl C.sub.1-6, R.sup.3 and R.sup.4 represent hydrogen, or R.sup.3 and R.sup.4 together form a group --S--, --NR.sup.9 -- or --CH.sub.2 --, R.sup.6 and R.sup.7 independently represent hydrogen, alkyl C.sub.1-6, fluoro, cyano, or CF.sub.3, provided that at least one of R.sup.6 and R.sup.7 is other than hydrogen, R.sup.8 represents hydrogen or alkyl C.sub.1-6, or when X is interrupted or terminated by more than one --NR.sup.8 -- group may together with another R.sup.8 group form the chain --CH.sub.2 --CH.sub.2 --, and n represents 0, 1 or 2, and pharmaceutically acceptable derivatives thereof. Processes for their production and pharmaceutical compositions and methods of treatment involving their use are also described.

  公式I的化合物已被披露，其中Ar代表一个基团，X代表一个C.sub.1-12烷基链，该链可以被--S(O).sub.n --，--O--，--C(Z)--，CR.sup.6 R.sup.7，苯基甲炔，--NR.sup.8 --，--CONH--，--NHCO--和--NHCONH--等一个或多个基团中断或终止，Y代表一个可选择取代的芳基或环烷基基团，Z代表O或S，R.sup.1，R.sup.2，R.sup.5和R.sup.9各自独立地代表氢或烷基C.sub.1-6，R.sup.3和R.sup.4代表氢，或R.sup.3和R.sup.4一起形成一个基团--S--，--NR.sup.9 --或--CH.sub.2--，R.sup.6和R.sup.7独立地代表氢，烷基C.sub.1-6，氟，氰基或CF.sub.3，只要R.sup.6和R.sup.7中至少有一个不是氢，R.sup.8代表氢或烷基C.sub.1-6，或者当X被多个--NR.sup.8 --基团中断或终止时，它们可以与另一个R.sup.8基团一起形成链--CH.sub.2--CH.sub.2--，n代表0，1或2，以及其药学上可接受的衍生物。还描述了它们的生产过程和包含它们使用的治疗方法的药物组合物。
• 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：——
• Steroidal glycolipids as host resistance stimulators
  申请人：Merck & Co., Inc.

  公开号：EP0224173B1

  公开（公告）日：1993-04-28
• BIOLOGICALLY ACTIVE AMINES
  申请人：FISONS plc

  公开号：EP0558677A1

  公开（公告）日：1993-09-08
• US5648370A
  申请人：——

  公开号：US5648370A

  公开（公告）日：1997-07-15