(S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid | 1246826-07-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid
• 英文别名: TT-OAD2 (free base)；(2S)-2-[[(3S,8S)-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-7-[(1S)-1-phenylpropyl]-3,6,8,9-tetrahydro-2H-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino]-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propanoic acid
• CAS: 1246826-07-2
• 化学式: C₅₀H₄₇Cl₂N₃O₆
• 分子量: 856.846
• InChiKey: DEDPYBWOUXWMOX-ZTAAISNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  61
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid 在 氢溴酸 作用下， 以 2-甲基四氢呋喃 为溶剂， 生成 (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid hydrobromide
  参考文献：
  名称：

  US2023/174547

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-2-{[(3S,8S)-3-[4-(3,4-dichlorobenzyloxy)phenyl]- 7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]amino}-3-[4-(2,3-dimethylpyridin-4-yl)phenyl]propionic acid hydrochloride 在 sodium hydroxide 作用下， 以 2-甲基四氢呋喃 、 水 为溶剂， 以88.4 %的产率得到(S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl) propionic acid
  参考文献：
  名称：

  US2023/174546

  摘要：

  公开号：

文献信息

• [EN] METHODS FOR PREPARING METHYL (S)-2-AMINO-3-(4-(2,3-DIMETHYLPYRIDIN-4-YL)PHENYL)PROPIONATE AND HYDROCHLORIC ACID SALTS THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION DE MÉTHYL(S)-2-AMINO-3-(4-(2,3-DIMÉTHYLPYRIDIN-4-YL)PHÉNYL)PROPIONATE ET DE SELS D'ACIDE CHLORHYDRIQUE ASSOCIÉS
  申请人：VTV THERAPEUTICS LLC

  公开号：WO2021242807A1

  公开（公告）日：2021-12-02

  The invention provides methods for preparing key intermediates for the synthesis of (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)-2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propionic acid ("OAD2") and salts thereof. The key intermediates include methyl (S)-2-amino-3-[4-(2,3-dimethylpyridin-4-yl)-phenyl]-propionate and hydrochloric acid salts thereof. Compared with the prior art, the methods may not require column chromatographic separation and purification, and may have the advantages of potentially lower cost, higher yield, and suitability for industrial scale production.

  本发明提供制备(S)-2-(3S,8S)-3-(4-(3,4-二氯苯甲氧基)苯基-7-((S)-1-苯基丙基)-2,3,6,7,8,9-六氢-[1,4]-二氧杂环[2,3-g]异喹啉-8-基甲酰氨基)-3-(4-(2,3-二甲基吡啶-4-基)苯基)丙酸（“OAD2”）及其盐的合成关键中间体的方法。该关键中间体包括(S)-2-氨基-3-[4-(2,3-二甲基吡啶-4-基)苯基]-丙酸甲酯及其盐酸盐。与现有技术相比，该方法可能不需要柱层析分离和纯化，并具有潜在的成本更低、产量更高和适合工业规模生产的优点。
• [EN] INTERMEDIATES AND METHODS FOR PREPARING A GLP-1 RECEPTOR AGONIST<br/>[FR] INTERMÉDIAIRES ET PROCÉDÉS DE PRÉPARATION D'UN AGONISTE DU RÉCEPTEUR GLP-1
  申请人：VTV THERAPEUTICS LLC

  公开号：WO2021242806A1

  公开（公告）日：2021-12-02

  The present invention relates to a methods and key intermediates useful for preparing the GLP‑1 receptor agonist (S)-2-(3S,8S)-3-(4-(3,4-dichlorobenzyloxy)phenyl-7-((S)-1-phenylpropyl)- 2,3,6,7,8,9-hexahydro-[1,4]-dioxino[2,3-g]isoquinolin-8-ylformylamino)-3-(4-(2,3-dimethylpyridin-4-yl)phenyl)propanoic acid dihydrochloride ("OAD2 dihydrochloride"). The methods may be run on industrial scale and in higher yield than previously disclosed methods.

  本发明涉及一种用于制备GLP-1受体激动剂(S)-2-(3S,8S)-3-(4-(3,4-二氯苯甲氧基)苯基-7-((S)-1-苯基丙基)-2,3,6,7,8,9-六氢-[1,4]-二噁烷[2,3-g]异喹啉-8-基甲酰胺)-3-(4-(2,3-二甲基吡啶-4-基)苯基)丙酸二盐酸盐（“OAD2二盐酸盐”）的方法和关键中间体。该方法可以在工业规模上运行，并且比先前披露的方法产量更高。
• SUBSTITUTED AZOANTHRACENE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：Mjalli Adnan M.M.

  公开号：US20110160198A1

  公开（公告）日：2011-06-30

  The present invention is directed to substituted azoanthracene derivatives or pharmaceutically acceptable salts thereof that modulate the human GLP-1 receptor and that may be useful in the treatment of diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial, such as diabetes mellitus type 2. The invention is also directed to pharmaceutical compositions comprising these compounds and to the use of these compounds and compositions in the treatment of such diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial.

  本发明涉及替代的偶氮蒽衍生物或其药学上可接受的盐，其调节人类GLP-1受体，并可用于治疗调节人类GLP-1受体有益的疾病、紊乱或病症，如2型糖尿病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在治疗调节人类GLP-1受体有益的这些疾病、紊乱或病症中的使用。
• Substituted azoanthracene derivatives, pharmaceutical compositions, and methods of use thereof
  申请人：Mjalli Adnan M. M.

  公开号：US08383644B2

  公开（公告）日：2013-02-26

  The present invention is directed to substituted azoanthracene derivatives or pharmaceutically acceptable salts thereof that modulate the human GLP-1 receptor and that may be useful in the treatment of diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial, such as diabetes mellitus type 2. The invention is also directed to pharmaceutical compositions comprising these compounds and to the use of these compounds and compositions in the treatment of such diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial.

  本发明涉及取代的偶氮蒽衍生物或其药学上可接受的盐，其调节人类GLP-1受体，并可在治疗调节人类GLP-1受体有益的疾病、疾病、或病情，如2型糖尿病。本发明还涉及包含这些化合物的制药组合物，以及在治疗这些有益的疾病、疾病或病情中使用这些化合物和组合物。
• Substituted Azoanthracene Derivatives, Pharmaceutical Compositions, and Methods of Use Thereof
  申请人：TransTech Pharma, Inc

  公开号：US20130096150A1

  公开（公告）日：2013-04-18

  The present invention is directed to substituted azoanthracene derivatives or pharmaceutically acceptable salts thereof that modulate the human GLP-1 receptor and that may be useful in the treatment of diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial, such as diabetes mellitus type 2. The invention is also directed to pharmaceutical compositions comprising these compounds and to the use of these compounds and compositions in the treatment of such diseases, disorders, or conditions in which modulation of the human GLP-1 receptor is beneficial.

  本发明涉及取代的偶氮蒽衍生物或其药学上可接受的盐，其调节人类GLP-1受体并可用于治疗调节人类GLP-1受体有益的疾病、疾病或病状，例如2型糖尿病。本发明还涉及包含这些化合物的制药组合物以及将这些化合物和组合物用于治疗这些有益的疾病、疾病或病状的用途。