7-<2-(trifluoroacetamido)ethyl>-1,3-benzothiazol-2(3H)-one | 108773-08-6

• 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: 7-<2-(trifluoroacetamido)ethyl>-1,3-benzothiazol-2(3H)-one
• 英文别名: 2,2,2-trifluoro-N-[2-(2-oxo-3H-1,3-benzothiazol-7-yl)ethyl]acetamide
• CAS: 108773-08-6
• 化学式: C₁₁H₉F₃N₂O₂S
• 分子量: 290.266
• InChiKey: BVDNPOBCAUQLBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-<2-(trifluoroacetamido)ethyl>-1,3-benzothiazol-2(3H)-one 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以1.23 g的产率得到7-(2-aminoethyl)-1,3-benzothiazol-2(3H)-one hydrochloride
  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-(2-hydroxyphenyl)ethylamine hydrobromide 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 sodium nitrate 、 氢气 、 lanthanum(III) nitrate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 为溶剂， 反应 28.5h， 生成 7-<2-(trifluoroacetamido)ethyl>-1,3-benzothiazol-2(3H)-one
  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)-1,3-Benzthia- or oxa- zol-2(3H) -ones
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0174811A2

  公开（公告）日：1986-03-19

  Compounds of formula (I): O-C2-8-alkanoyl derivatives thereof and pharmaceutically acceptable salts are described in which X is -S- or -0-, R1 and R2 are, each, hydrogen, C1-6-alkyl, allyl, benzyl, phenethyl, methoxyphenethyl or hydroxyphenethyl; and R3 and R4 are, each, hydroxy, hydrogen, halo, C1-3-alkyl or C1-3alkoxy. The compounds are dopamine agonists and have antihypertensive activity. Pharmaceutical compositions and methods of use are described, as are processes for their preparation.

  式(I)化合物： 其中 X 为-S-或-0-，R1 和 R2 分别为氢、C1-6-烷基、烯丙基、苄基、苯乙基、甲氧基苯乙基或羟基苯乙基；R3 和 R4 分别为羟基、氢、卤代、C1-3-烷基或 C1-3 烷氧基。这些化合物是多巴胺激动剂，具有抗高血压活性。本文描述了药物组合物和使用方法，以及其制备工艺。
• Nouveaux amides alkyl hétérocycliques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0506539A1

  公开（公告）日：1992-09-30

  Composés de formule générale (I) : dans laquelle: A représente un atome d'oxygène ou de soufre, X représente un groupement CH2 ou une liaison simple, R représente : * ou bien un atome d'hydrogène ou un groupement alkyle inférieur et dans ce cas p = 1 et B représente un chaînon -CH2-CH2-NR1-CO-R2 où R1 représente un atome d'hydrogène ou un groupement alkyle inférieur linéaire ou ramifié,    et R2 représente : . un atome d'hydrogène, . un groupement cycloalkyle ou alkyle inférieur linéaire ou ramifié, éventuellement substitué par un atome d'halogène, . un groupement cycloalkyle substitué par un groupement alkyle inférieur linéaire ou ramifié, . un groupement aryle ou hétéroaryle ou arylalkyle inférieur ou aryle substitué ou hétéroaryle substitué ou arylakyle substitué, étant entendu que par groupement hétéroaryle on entend un groupement insaturé mono ou bicyclique comprenant de 1 à 3 hétéroatomes choisis parmi azote, oxygène, ou soufre chaque cycle comprenant 4 ou 5 sommets, . un groupement de formule :    G représentant un groupement alkyle inférieur linéaire ou ramifié,    R3 et R4 identiques ou différents représentent chacun un groupement alkyle inférieur ou un atome d'hydrogène ou un groupement phényle ou phénylalkyle inférieur, ou R3 et R4 forment avec l'atome d'azote auquel ils sont attachés un système hétérocyclique, aromatique ou non, mono ou bicyclique comprenant éventuellement un autre hétéroatome choisis parmi azote, oxygène ou soufre et éventuellement substitué par un ou plusieurs groupements alkyle inférieur ou oxo, aryle ou arylalkyle inférieur, ou aryle substitué ou arylalkyle inférieur substitué, étant entendu que dans les définitions de R2, R3 et R4, le terme substitué affectant les groupements aryle et arylalkyle et hétéroaryle signifie que ces groupements sont substitués par un ou plusieurs radicaux choisis parmi alkyle inférieur, alkoxy inférieur, trifluorométhyle ou atome d'halogène, ou bien R1 forme avec R2 et le groupement N-CO un système hétérocyclique de formule : avec J étant un radical alkyle linéaire ou ramifié comprenant de 2 à 8 atomes de carbone, * ou bien un chaînon (CH2)2-NR1-CO-R2 avec R1 et R2 ayant la même définition que précédemment et dans ce cas p vaut 0 ou 1 et B représente un groupement alkoxy inférieur, Médicaments.

  通式(I)化合物： 其中 A 代表氧原子或硫原子、 X 代表 CH2 基团或单键 R 代表： * 或氢原子或低级烷基，在这种情况下 p = 1，B 代表-CH2-CH2-NR1-CO-R2 链成员，其中 R1 代表氢原子或直链或支链低级烷基、 而 R2 代表......： 氢原子 环烷基或直链或支链低级烷基，可选择被卤原子取代，或 被直链或支链低级烷基取代的环烷基，、 芳基或杂芳基或芳基-低级烷基或取代芳基或取代杂芳基或取代芳烷基，不言而喻，杂芳基是指包含 1 至 3 个选自氮、氧和硫的杂原子的单环或双环不饱和基团，每个环包含 4 或 5 个环成员、 式......的基团 代表直链或支链低级烷基的 G、 R3 和 R4（可以相同或不同）各自代表一个低级烷基或一个氢原子或一个苯基或苯基-低级烷基，或 R3 和 R4 与它们所连接的氮原子一起形成一个单环或双环、芳香族或非芳香族杂环系统，该系统可选择包括另一个选自氮、氧和硫的杂原子，并可选择被一个或多个低级烷基或氧代取代、芳基或芳基（低级）烷基，或取代的芳基或取代的芳基（低级）烷基，不言而喻，在 R2、R3 和 R4 的定义中，适用于芳基、芳基（低级）烷基和杂芳基的术语 "取代 "是指这些基团被一个或多个选自低级烷基、低级烷氧基、三氟甲基或卤素的基团取代、 或 R1 与 R2 和 N-CO 基团形成式 ： J为由 2 至 8 个碳原子组成的直链或支链烷基、 * 或 (CH2)2-NR1-CO-R2 链成员，其中 R1 和 R2 的定义同上，在这种情况下 p 为 0 或 1，B 代表低级烷氧基、 药用产品。
• 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：——
• Amides alkyl hétérocycliques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0506539B1

  公开（公告）日：1997-05-02
• 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.