N-{4-[5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pyridin-3-yl]-thiazol-2-yl}-guanidine | 135451-75-1

• 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: N-{4-[5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pyridin-3-yl]-thiazol-2-yl}-guanidine
• 英文别名: 2-(Diaminomethyleneamino)-4-(5-phthalimidomethylpyridin-3-yl)thiazole；2-[4-[5-[(1,3-dioxoisoindol-2-yl)methyl]pyridin-3-yl]-1,3-thiazol-2-yl]guanidine
• CAS: 135451-75-1
• 化学式: C₁₈H₁₄N₆O₂S
• 分子量: 378.414
• InChiKey: UDUOUWQYFCIFNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-{4-[5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pyridin-3-yl]-thiazol-2-yl}-guanidine 在 盐酸 、 一水合肼 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 N-[5-(2-Guanidino-thiazol-4-yl)-pyridin-3-ylmethyl]-acetamide
  参考文献：
  名称：

  Studies on antiulcer drugs. 7. 2-Guanidino-4-pyridylthiazoles as histamine H2-receptor antagonists with potent gastroprotective effects against nonsteroidal antiinflammatory drug-induced injury

  摘要：

  A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and histamine-H-2-receptor-antagonist activities. Several compounds showed superior anti-aspirin-ulcer activity to that of clinically used H-2-antagonists in the rat. Among them, 4-[6-(acetamidomethyl)pyridin-2-yl]-2-guanidinothiazole (8) demonstrated potent inhibitory activities against gastric lesions caused by two kinds of nonsteroidal antiinflammatory drugs, aspirin and indomethacin, respectively, in addition to strong antisecretory activity. Compound 8 possessed a preventable ability for the aspirin-induced reduction of the gastric mucosal blood flow at an intragastric administration of 32 mg/kg in the rat. On the other hand, famotidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.

  DOI：

  10.1021/jm00027a007
• 作为产物：
  描述：

  N-[4-(5-Hydroxymethyl-pyridin-3-yl)-thiazol-2-yl]-guanidine 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-{4-[5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pyridin-3-yl]-thiazol-2-yl}-guanidine
  参考文献：
  名称：

  Studies on antiulcer drugs. 7. 2-Guanidino-4-pyridylthiazoles as histamine H2-receptor antagonists with potent gastroprotective effects against nonsteroidal antiinflammatory drug-induced injury

  摘要：

  A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and histamine-H-2-receptor-antagonist activities. Several compounds showed superior anti-aspirin-ulcer activity to that of clinically used H-2-antagonists in the rat. Among them, 4-[6-(acetamidomethyl)pyridin-2-yl]-2-guanidinothiazole (8) demonstrated potent inhibitory activities against gastric lesions caused by two kinds of nonsteroidal antiinflammatory drugs, aspirin and indomethacin, respectively, in addition to strong antisecretory activity. Compound 8 possessed a preventable ability for the aspirin-induced reduction of the gastric mucosal blood flow at an intragastric administration of 32 mg/kg in the rat. On the other hand, famotidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.

  DOI：

  10.1021/jm00027a007

文献信息

• Thiazole derivatives, processes for the preparation thereof and
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05371097A1

  公开（公告）日：1994-12-06

  A compound of the formula: ##STR1## wherein R.sup.1 is amino, acylamino, cyclo(lower)alkenylamino having amino and oxo, imido, triazolylamino, benzoisothiazolylamino, wherein each of said heterocyclicamino groups may be substituted by one or more substituent(s) selected from the group consisting of lower alkyl, amino and oxo, 2-cyano-3-lower alkylguanidino, 2-acyl-3-lower alkylguanidino, 2-acylguanidino, (1-lower alkylamino-2-nitrovinyl)amino, hydroxy, halogen, cyano, acyl, benzimidazolylthio, triazolyl substituted with amino, or a group of the formula: ##STR2## in which R.sup.4 is hydrogen, cyano, or acyl, and R.sup.5 is amino or lower alkoxy, R.sup.2 and R.sup.3 are each hydrogen, acyl or lower alkyl which may have halogen; or R.sup.2 and R.sup.3 are linked together to form lower alkylene, Y is ##STR3## in which R.sup.6 is hydrogen or halogen, and A is lower alkylene, or pharmaceutically acceptable salt thereof.

  该化合物的化学式为：##STR1## 其中R.sup.1为氨基，酰胺基，环(较低)烯基氨基，具有氨基和氧代的亚胺基，三唑基氨基，苯并异噻唑基氨基，其中所述的每个杂环氨基基团可以被选自较低烷基，氨基和氧代的一个或多个取代基取代，2-氰基-3-较低烷基胍基，2-酰基-3-较低烷基胍基，2-酰基胍基，(1-较低烷基氨基-2-硝基乙烯基)氨基，羟基，卤素，氰基，酰基，苯并咪唑基硫醚，三唑基被氨基取代，或一个化学式为：##STR2## 其中R.sup.4为氢，氰基或酰基，R.sup.5为氨基或较低烷氧基，R.sup.2和R.sup.3为氢，酰基或较低烷基，可以具有卤素；或R.sup.2和R.sup.3连接在一起形成较低烷基，Y为##STR3## 其中R.sup.6为氢或卤素，A为较低烷基，或其药学上可接受的盐。
• New thiazole derivatives, and pharmaceutical composition comprising the
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US05364871A1

  公开（公告）日：1994-11-15

  A compound of the formula: ##STR1## wherein R.sup.1 is amino, ureido, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylsulfonylamino, lower alkoxy(lower)alkanoylamino, mono or di or trihalo(lower)alkanoylamino, hydroxy(lower)alkanoylamino, protected hydroxy(lower)alkanoylamino, or a group of the formula: ##STR2## in which R.sup.4 is hydrogen or sulfamoyl, R.sup.5 is amino or lower alkoxy, R.sup.2 is hydrogen, lower alkyl, lower alkoxy(lower)alkyl, di(lower)alkylamino(lower)alkyl, (C.sub.3 -C.sub.7)-cycloalkyl, lower alkenyl or mono or di or trihalo(lower)alkyl; R.sup.3 is hydrogen or lower alkyl; or R.sup.2 and R.sup.3 are linked together to form lower alkylene, Y is ##STR3## in which R.sup.6 is hydrogen, A is lower alkylene, and W is NH; or R.sup.2 -W is piperidino or morpholino, or pharmaceutically acceptable salt thereof.

  该化合物的公式为：##STR1##其中R.sup.1为氨基，尿素基，较低的酰胺基，较低的烷氧羰基胺基，较低的烷基磺酰胺基，较低的烷氧（较低）酰胺基，单烷基或二或三卤代（较低）烷酰胺基，羟基（较低）烷酰胺基，保护羟基（较低）烷酰胺基，或公式：##STR2##其中R.sup.4为氢或磺酰基，R.sup.5为氨基或较低的烷氧基，R.sup.2为氢，较低的烷基，较低的烷氧（较低）烷基，二（较低）烷基氨基（较低）烷基，（C.sub.3-C.sub.7）-环烷基，较低的烯基或单烷基或二或三卤代（较低）烷基；R.sup.3为氢或较低的烷基；或者R.sup.2和R.sup.3相连形成较低的烷基，Y为##STR3##其中R.sup.6为氢，A为较低的烷基，W为NH；或R.sup.2-W为哌啶基或吗啉基，或其药学上可接受的盐。
• 2,6,7-Trisubstituted-3-methylenebicyclo [3.3.0]octanes and process for production thereof
  申请人：TEIJIN LIMITED

  公开号：EP0216585A2

  公开（公告）日：1987-04-01

  A 2,6,7-trisubstituted-3-methylenebicyclo[3.3.0]octane of formula (I) or an enantiomer thereof, or a mixture of these in an arbitrary ratio. The compound is a key intermediate for preparation of isocarbacyclins which are useful as medicines for the circulatory system such as an antithrombotic agent, an antilipidemic agent, a hypotensive agent or an antiarterosclerotic agent.

  式 (I) 的 2,6,7-三取代-3-亚甲基双环[3.3.0]辛烷或其对映体，或其任意比例的混合物。该化合物是制备异碳双环化合物的关键中间体，异碳双环化合物可用作循环系统药物，如抗血栓药、降血脂药、降血压药或抗动脉硬化药。
• New thiazole derivatives, processes for the preparation thereof and pharmaceutical compositon comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0417751A2

  公开（公告）日：1991-03-20

  A compound of the formula : wherein R' is amino which may have suitable substituent ( s). hydroxy. halogen, cyano, acyl, heterocyclic thio, heterocyclic group or a group of the formula : in which R4 is hydrogen, cyano or acyl. and R5 is amino or lower alkoxy. R2 and R3 are each hydrogen, acyl or lower alkyl which may have halogen: or R2 and R3 are linked together to form lower alkylene. in which R6 is hydrogen or halogen, and A is bond or lower alkylene, provided that when R1 is amino which may have suitable substituent(s) and A is bond; or R1 is lower alkylthioureido and A is lower alkylene, then and pharmaceutically acceptable salt thereof, processes for their preparation and pharmaceutical compositions comprising them as an active. ingredient.

  式中的化合物 其中 R'为氨基，可具有合适的取代基（s）、羟基、卤素、氰基、酰基、杂环硫基、杂环基团或式......的基团： 其中 R4 是氢、氰基或酰基。 R5 是氨基或低级烷氧基。 R2 和 R3 各为氢、酰基或低级烷基，其中可含卤素：或 R2 和 R3 连接在一起形成低级亚烷基。 其中 R6 是氢或卤素，以及 A 是键或低级亚烷基、 条件是 当 R1 是氨基，可有适当的取代基，且 A 为键；或 R1 为低级烷基硫脲基，且 A 为低级亚烷基时 且 A 为低级亚烷基，则 以及它们的药学上可接受的盐、它们的制备方法和含有它们作为活性成分的药物组合物。
• Isocarbacyclin derivatives
  申请人：TEIJIN LIMITED

  公开号：EP0427708A1

  公开（公告）日：1991-05-15

  The invention relates to compounds of the following formula (A): wherein R⁷² is a carboxyl group or a salt or ester thereof; R² is H; R³ is H; R⁴ is H, a methyl group or a vinyl group; R⁵ is an unsubstituted linear or branched C₃-C₈ alkyl group or a C₃-C₁₀ cycloalkyl group; n is 1 and m is an integer of 1 to 6. Pharmaceutically acceptable salts thereof are also disclosed.

  本发明涉及下式（A）的化合物： 其中 R⁷² 是羧基或其盐或酯；R² 是 H；R³ 是 H；R⁴ 是 H、甲基或乙烯基；R⁵ 是未取代的直链或支链 C₃-C₈ 烷基或 C₃-C₁₀ 环烷基；n 是 1，m 是 1-6 的整数。还公开了其药学上可接受的盐类。