(S)-3-(4-(4-(2-(6-methoxy-3,4-dihydroisoquinoline-2(1H)-yl)ethyl)benzyloxy)phenyl)hex-4-ynoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (S)-3-(4-(4-(2-(6-methoxy-3,4-dihydroisoquinoline-2(1H)-yl)ethyl)benzyloxy)phenyl)hex-4-ynoic acid
• 英文别名: (S)-3-(4-(4-(2-(6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)benzyloxy)phenyl)hex-4-ynoic acid；(3S)-3-[4-[[4-[2-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]methoxy]phenyl]hex-4-ynoic acid
• 化学式: C₃₁H₃₃NO₄
• 分子量: 483.607
• InChiKey: UESLHWHSRBKIQU-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲氧基苯乙基氨基甲酸乙酯 在 lithium aluminium tetrahydride 、 水 、 caesium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 (S)-3-(4-(4-(2-(6-methoxy-3,4-dihydroisoquinoline-2(1H)-yl)ethyl)benzyloxy)phenyl)hex-4-ynoic acid
  参考文献：
  名称：

  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

  摘要：

  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。

  公开号：

  US20160024063A1

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。
• 3-(4-(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, SUITABLE FOR PREVENTING AND TREATING METABOLIC DISEASES
  申请人：Hyundai Pharm Co., Ltd.

  公开号：EP2987791B1

  公开（公告）日：2019-07-17
• 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：US20170296539A1

  公开（公告）日：2017-10-19

  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.