2-(piperazin-1-yl)benzo[d]thiazole hydrochloride | 35463-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(piperazin-1-yl)benzo[d]thiazole hydrochloride
• 英文别名: 2-(Piperazin-1-yl)-1,3-benzothiazole hydrochloride；2-piperazin-1-yl-1,3-benzothiazole;hydrochloride
• CAS: 35463-74-2
• 化学式: C₁₁H₁₃N₃S*ClH
• mdl: MFCD11099490
• 分子量: 255.771
• InChiKey: BDUGDVVACNJZPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.37
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  56.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(piperazin-1-yl)benzo[d]thiazole hydrochloride 、 氯甲酸丙酯 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 生成 4-benzothiazol-2-yl-piperazine-1-carboxylic acid propyl ester
  参考文献：
  名称：

  1,4-二取代哌嗪。3.哌嗪基苯并噻唑。

  摘要：

  DOI：

  10.1021/jm00276a039
• 作为产物：
  描述：

  4-(2-苯并噻唑基)-1-哌嗪羧酸叔丁酯 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-(piperazin-1-yl)benzo[d]thiazole hydrochloride
  参考文献：
  名称：

  抗隐孢子虫先导物 SLU-2633 的三唑并哒嗪替代物的构效关系

  摘要：

  隐孢子虫病是一种腹泻病，对儿童和免疫功能低下的人尤其有害。感染由寄生虫隐孢子虫引起，严重时会导致脱水、营养不良甚至死亡。硝唑尼特是 FDA 唯一批准的药物，但对儿童的疗效有限，对免疫功能低下的患者无效。为了解决这一未满足的医疗需求，我们之前鉴定出三唑并哒嗪 SLU-2633 对小隐孢子虫有效，EC 50为 0.17 µM。在本研究中，我们通过探索不同的杂芳基，开发了用于取代三唑并哒嗪头基的构效关系（SAR），目的是在保持效力的同时降低对 hERG 通道的亲和力。合成了 64 种 SLU-2633 的新类似物，并分析了其相对小隐孢子虫的效力。最有效的化合物 7,8-二氢-[1,2,4]三唑并[4,3 -b ]哒嗪17a的Cp EC 50为 1.2 µM，比 SLU-2633 低 7 倍但亲脂效率 (LipE) 得分有所提高。发现17a在 hERG 膜片钳测定中相对于 10 µM 的 SLU-2633

  DOI：

  10.1016/j.bmc.2023.117295

文献信息

• NOVEL 3-(4(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, METHOD OF PREPARING SAME AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING METABOLIC DISEASE INCLUDING SAME AS EFFECTIVE INGREDIENT
  申请人：HYUNDAI PHARM CO., LTD

  公开号：US20160024063A1

  公开（公告）日：2016-01-28

  The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.

  本发明涉及一种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物，其制备方法以及包含该衍生物作为活性成分的药物组合物，用于预防和治疗代谢性疾病。本发明的这种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物、其光学异构体或其药用可接受盐，对于激活GPR40蛋白并相应地促进胰岛素分泌具有优良活性，且在与其他药物联合使用时没有毒性。也就是说，本发明的这种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物、其光学异构体或其药用可接受盐，可以与其他药物联合使用，并且能显著促进GPR40蛋白的激活，使得包含其作为活性成分的组合物能有效地用作预防和治疗诸如肥胖、I型糖尿病、II型糖尿病、糖耐量异常、胰岛素抵抗、高血糖、高脂血症、高甘油三酯血症、高胆固醇血症、血脂异常和X综合症等代谢性疾病的药物组合物。
• NOVEL 3-(4-(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, METHOD OF PREPARING SAME AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING METABOLIC DISEASE INCLUDING SAME AS EFFECTIVE INGREDIENT
  申请人：Hyundai Pharm Co., Ltd.

  公开号：EP2987791A1

  公开（公告）日：2016-02-24

  The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.

  本发明涉及一种新型 3-(4-(苄氧基)苯基)己-4-氨基酸衍生物、其制备方法以及以其为活性成分的药物组合物，用于预防和治疗代谢性疾病。本发明的新型 3-(4-(苄氧基)苯基)己-4-氨基酸衍生物、其光学异构体或其药学上可接受的盐具有很好的激活 GPR40 蛋白和促进胰岛素分泌的活性，但与其他药物合用时无毒性。也就是说，本发明的新型 3-(4-(苄氧基)苯基)己-4-氨基酸衍生物、其光学异构体或其药学上可接受的盐可以与其他药物联合使用，并能显著促进 GPR40 蛋白的活化、因此，以其为有效成分的组合物可作为药物组合物有效地用于预防和治疗代谢性疾病，如肥胖、I 型糖尿病、II 型糖尿病、糖耐量异常、胰岛素抵抗、高血糖、高脂血症、高甘油三酯血症、高胆固醇血症、血脂异常和 X 综合征等。
• Composite preparation, containing novel 3-(4--(benzyloxy)phenyl)hex-4-inoic acid derivative and another active ingredient, for preventing or treating metabolic diseases
  申请人：HYUNDAI PHARM CO., LTD.

  公开号：US10821110B2

  公开（公告）日：2020-11-03

  The present invention relates to a pharmaceutical composition for preventing or treating metabolic diseases, in which a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative and at least another active ingredient, which is selected from the group consisting of dipeptidyl peptidase-4 (DPPIV) inhibitor-based, sulfonylurea-based, thiazolidinedione (TZD)-based, biguanide-based, and sodium/glucose cotransporter 2 (SGLT2) inhibitor-based drugs, may be administered in combination or in the form of a composite preparation. The use of the composition of the present invention can provide a remarkably excellent blood sugar reducing effect in various animal diabetic disease models, and the composition of the present invention can be favorably used as a pharmaceutical composition for preventing or treating metabolic diseases, such as obesity, diabetes type I, diabetes type II, glucose intolerance symptoms, insulin resistance symptoms, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X.

  本发明涉及一种用于预防或治疗代谢性疾病的药物组合物，其中含有一种新型 3-(4-(苄氧基)苯基)己-4-氨基酸衍生物和至少另一种活性成分、其中，一种新型 3-(4-(苄氧基)苯基)己-4-嗪酸衍生物和至少另一种活性成分可以联合给药或以复合制剂的形式给药，这些活性成分选自由二肽基肽酶-4 (DPPIV) 抑制剂、磺酰脲类、噻唑烷二酮 (TZD)、双胍类和钠/葡萄糖共转运体 2 (SGLT2) 抑制剂组成的组。使用本发明的组合物可在各种动物糖尿病疾病模型中提供显著优异的降血糖效果，本发明的组合物可作为药物组合物用于预防或治疗代谢性疾病，如肥胖、I 型糖尿病、II 型糖尿病、葡萄糖不耐受症状、胰岛素抵抗症状、高血糖症、高脂血症、高甘油三酯血症、高胆固醇血症、血脂异常和 X 综合征。
• The discovery of potent antagonists of NPBWR1 (GPR7)
  作者：F. Anthony Romero、Nicholas B. Hastings、Remond Moningka、Zhiqiang Guo、Ming Wang、Jerry Di Salvo、Ying Lei、Dorina Trusca、Qiaolin Deng、Vincent Tong、Jenna L. Terebetski、Richard G. Ball、Feroze Ujjainwalla

  DOI：10.1016/j.bmcl.2011.11.126

  日期：2012.1

  The synthesis and evaluation of small molecule antagonists of the G protein-coupled receptor NPBWR1 (GPR7) are reported for the first time. [4-(5-Chloropyridin-2-yl)piperazin-1-yl][(1S,2S,4R)-4-[(1R)-1-(4-methoxyphenyl)ethyl]amino}-2-(thiophen-3-yl)cyclohexyl]methanone (1) emerged as a hit from a high-throughput screen. Examination of substituents that focused on replacing the 5-chloropyridine and 4-methoxybenzylamino groups of 1 led to the identification of compounds that exhibited subnanomolar potencies as low as 660 pM (9k) in the functional assay and 200 pM in the binding assay (91). (C) 2011 Elsevier Ltd. All rights reserved.
• COMPOSITE PREPARATION, CONTAINING NOVEL 3-(4-(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE AND ANOTHER ACTIVE INGREDIENT, FOR PREVENTING OR TREATING METABOLIC DISEASES
  申请人：Hyundai Pharm Co., Ltd.

  公开号：EP3207928B1

  公开（公告）日：2021-03-10