2-(4-phthalimidobutyl)-8H-indeno[1,2-d]thiazole | 172259-75-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(4-phthalimidobutyl)-8H-indeno[1,2-d]thiazole
• 英文别名: 2-[4-(4H-indeno[1,2-d][1,3]thiazol-2-yl)butyl]isoindole-1,3-dione
• CAS: 172259-75-5
• 化学式: C₂₂H₁₈N₂O₂S
• 分子量: 374.463
• InChiKey: HELVTYGLGQPISJ-UHFFFAOYSA-N

物化性质

• 沸点：
  573.3±38.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  78.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  富马酸 、 2-(4-phthalimidobutyl)-8H-indeno[1,2-d]thiazole 在 甲胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以32%的产率得到2-(4-aminobutyl)-8H-indeno[1,2-d]thiazole fumarate
  参考文献：
  名称：

  New thiazole derivatives as potent and selective 5-hydroxytriptamine 3 (5-HT 3 ) receptor agonists for the treatment of constipation

  摘要：

  The syntheses and biological evaluation of a series of novel indeno[1,2-d]thiazole derivatives are described. Several groups reported 5-HT3 receptor agonists which were mainly evaluated for their activities on the von Bezold-Jarisch reflex (B-J reflex). We discovered that tetrahydrothiazolopyridine derivative 1b had a contractile effect on the isolated guinea pig colon with weak B-J reflex. Our efforts to find a new type of 5-HT3 receptor agonists on the isolated guinea pig colon focused on the synthesis of a fused thiazole derivative 1d modified from 1b and reverse-fused thiazole derivatives (7-10). In this series, 10f (YM-31636) showed high affinity and selectivity for the cloned human 5-HT3 receptor; furthermore, it showed potent and selective 5-HT3 receptor agonistic activity. YM-31636 was examined for its effects on defecation in animals, thus evaluating the compound as an agent against constipation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00557-6
• 作为产物：
  描述：

  5-(1,3-二氧代异吲哚-2-基)戊腈 在 盐酸 、 二硫代磷酸二乙酯 作用下， 以 乙酸乙酯 、 异丙醇 为溶剂， 反应 12.0h， 生成 2-(4-phthalimidobutyl)-8H-indeno[1,2-d]thiazole
  参考文献：
  名称：

  New thiazole derivatives as potent and selective 5-hydroxytriptamine 3 (5-HT 3 ) receptor agonists for the treatment of constipation

  摘要：

  The syntheses and biological evaluation of a series of novel indeno[1,2-d]thiazole derivatives are described. Several groups reported 5-HT3 receptor agonists which were mainly evaluated for their activities on the von Bezold-Jarisch reflex (B-J reflex). We discovered that tetrahydrothiazolopyridine derivative 1b had a contractile effect on the isolated guinea pig colon with weak B-J reflex. Our efforts to find a new type of 5-HT3 receptor agonists on the isolated guinea pig colon focused on the synthesis of a fused thiazole derivative 1d modified from 1b and reverse-fused thiazole derivatives (7-10). In this series, 10f (YM-31636) showed high affinity and selectivity for the cloned human 5-HT3 receptor; furthermore, it showed potent and selective 5-HT3 receptor agonistic activity. YM-31636 was examined for its effects on defecation in animals, thus evaluating the compound as an agent against constipation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00557-6

文献信息

• 5-HT.sub.3 receptor agonist, novel thiazole derivative and intermediate
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05834499A1

  公开（公告）日：1998-11-10

  A 5-HT.sub.3 receptor against containing a thiazole derivative as the effective ingredient is provided and is represented by the Formula (I): ##STR1## wherein the A ring is substituted or unsubstituted and represents a benzene or a heterocyclic ring with one or two heteroatoms; one of L.sub.1 or L.sub.2 represents a single bond and the other is non-existent or represents an alkylene or alkenylene group; R represents: ##STR2##

  提供了一种含有噻唑衍生物作为有效成分的5-HT.sub.3受体，其化学式如下（I）所示：##STR1##其中A环是取代或未取代的，代表苯环或含有一或两个杂原子的杂环；L.sub.1或L.sub.2中的一个代表单键，另一个不存在或代表烷基或烯基基团；R代表：##STR2##
• 5-HT 3 RECEPTOR AGONIST, NOVEL THIAZOLE DERIVATIVE, AND INTERMEDIATE THEREFOR
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0749966A1

  公开（公告）日：1996-12-27

  A 5-HT3 receptor agonist containing a thiazole derivative represented by general formula (I) as the effective ingredient; a specified compound useful as a 5-HT3 receptor agonist; and a specified thioamide derivative useful as an intermediate therefor. wherein each symbol represents the following meaning: Ring A: the following ring which may be substituted by one or more substituents selected from the group consisting of a halogen atom, a lower alkyl group and a lower alkoxyl group: 1) a benzene ring, or 2) a 5-membered or 6-membered unsaturated heterocyclic ring having one or two hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, L1 and L2: one of them represents a single bond, and the other one represents non-existence, or an alkylene group having 1 to 4 carbon atoms or an alkenylene group having 2 to 5 carbon atoms, R: a group represented by one of the following formulae: L3: a lower alkylene group, L4: a single bond or a lower alkylene group, R1 and R2: the same or different and individually a hydrogen atom, a lower alkyl group or an amino-protecting group, R3: a hydrogen atom, a lower alkyl group, an oxo group or a protected or unprotected amino group, R4: non-existence or a hydrogen atom, a lower alkyl group, an aralkyl group or an amino-protecting group, Ring B: the following monocyclic or bicyclic ring which may contain an oxygen atom: 1) a nitrogen-containing saturated heterocyclic ring having 4 to 16 ring-forming atoms, or 2) a nitrogen-containing heterocyclic ring having one unsaturated bond and 4 to 16 ring-forming atoms, and Ring D: a saturated carbon ring having 4 to 8 ring-forming atoms,

  一种 5-HT3 受体激动剂，含有作为有效成分的通式(I)代表的噻唑衍生物；一种用作 5-HT3 受体激动剂的特定化合物；以及一种用作其中间体的特定硫酰胺衍生物。 其中各符号代表以下含义： 环 A：可被选自卤素原子、低级烷基和低级烷氧基的一个或多个取代基取代的下环： 1) 苯环，或 2) 5 元或 6 元不饱和杂环，其中有一个或两个杂原子，选自由氮原子、氧原子和硫原子组成的组、 L1 和 L2：其中一个代表单键，另一个代表不存在的键，或代表具有 1 至 4 个碳原子的亚烷基或具有 2 至 5 个碳原子的烯基、 R：由下式之一代表的基团： L3：低级亚烷基、 L4：单键或低级亚烷基、 R1和R2：相同或不同，各自为氢原子、低级烷基或氨基保护基团、 R3：一个氢原子、一个低级烷基、一个氧代基团或一个受保护或不受保护的氨基、 R4：不存在或为氢原子、低级烷基、芳烷基或氨基保护基团、 环 B：可含有一个氧原子的单环或双环： 1) 具有 4 至 16 个成环原子的含氮饱和杂环，或 2) 具有一个不饱和键和 4 至 16 个成环原子的含氮杂环，以及 环 D：具有 4 至 8 个成环原子的饱和碳环、
• New thiazole derivatives as potent and selective 5-hydroxytriptamine 3 (5-HT 3 ) receptor agonists for the treatment of constipation
  作者：Naoki Imanishi、Kiyoshi Iwaoka、Hiroyuki Koshio、Shin-ya Nagashima、Ken-ichi Kazuta、Mitsuaki Ohta、Shuichi Sakamoto、Hiroyuki Ito、Shinobu Akuzawa、Tetsuo Kiso、Shin-ichi Tsukamoto、Toshiyasu Mase

  DOI：10.1016/s0968-0896(02)00557-6

  日期：2003.4

  The syntheses and biological evaluation of a series of novel indeno[1,2-d]thiazole derivatives are described. Several groups reported 5-HT3 receptor agonists which were mainly evaluated for their activities on the von Bezold-Jarisch reflex (B-J reflex). We discovered that tetrahydrothiazolopyridine derivative 1b had a contractile effect on the isolated guinea pig colon with weak B-J reflex. Our efforts to find a new type of 5-HT3 receptor agonists on the isolated guinea pig colon focused on the synthesis of a fused thiazole derivative 1d modified from 1b and reverse-fused thiazole derivatives (7-10). In this series, 10f (YM-31636) showed high affinity and selectivity for the cloned human 5-HT3 receptor; furthermore, it showed potent and selective 5-HT3 receptor agonistic activity. YM-31636 was examined for its effects on defecation in animals, thus evaluating the compound as an agent against constipation. (C) 2003 Elsevier Science Ltd. All rights reserved.