methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate | 1261086-08-1

• 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: methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate
• 英文别名: Methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate
• CAS: 1261086-08-1
• 化学式: C₁₂H₁₅NO₄
• 分子量: 237.255
• InChiKey: RIOMEJMBANVCDA-UHFFFAOYSA-N

物化性质

• 沸点：
  349.1±32.0 °C(Predicted)
• 密度：
  1.182±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate 在 吡啶 、 硫酸 作用下， 以 二氯甲烷 、 三氟乙酸 为溶剂， 反应 5.0h， 生成 2-ethyl 3,7-dimethyl 3,4-dihydroisoquinoline-2,3,7(1H)-tricarboxylate
  参考文献：
  名称：

  Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists

  摘要：

  Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients. (c) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112196
• 作为产物：
  描述：

  甲醇 、 4-羧基苯丙氨酸盐酸盐 在 硫酸 、 potassium carbonate 作用下， 以83%的产率得到methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate
  参考文献：
  名称：

  用于肽合成的生物正交和交联氨基酸的合成

  摘要：

  通过遗传或化学方法将非规范氨基酸掺入蛋白质的能力使人们可以在确定的残基处将新的化学性质引入蛋白质。然后可以使用常见的有机转化来修饰这种残基。这样，可以在不干扰肽链中任何其他相邻氨基酸的情况下改变肽的结构或功能。在这里，我们描述的合成和多种潜在的应用对-取代的苯丙氨酸衍生物，其包含异硫氰酸酯，α-二氮酮或硝酮官能团。总之，以良好的总产率合成了三种新型氨基酸。这些非规范性氨基酸允许进一步发展其他试剂无法实现的体外和体内化学选择性和区域选择性生物共轭反应。

  DOI：

  10.1007/s00726-010-0594-3

文献信息

• [EN] GLP-1 RECEPTOR MODULATORS<br/>[FR] NOUVEAUX MODULATEURS DU RÉCEPTEUR DU GLP-1
  申请人：CELGENE INTERNAT II SARL

  公开号：WO2016094729A1

  公开（公告）日：2016-06-16

  Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "^^^^" represents either or both the R and S form of the compound) (I) where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

  提供了一些化合物，这些化合物可以调节胰高血糖素样肽1（GLP-1）受体，以及它们的合成方法，以及它们的治疗和/或预防使用方法。这类化合物可以单独作为GLP-1受体的调节剂或增强剂，或者与肠促胰岛素肽（如GLP-1(7-36)和GLP-1(9-36)）一起使用，或者与基于肽的治疗方法（如艾塞那肽和利拉鲁肽）一起使用，并具有以下一般结构（其中"^^^^"代表化合物的R和S形式中的一个或两个）(I) 其中A、B、C、Y1、Y2、Z、R1、R2、R3、R4、R5、W1、n、p和q的定义如下。
• [EN] NOVEL GLP-1 RECEPTOR MODULATORS<br/>[FR] NOUVEAUX MODULATEURS DU RÉCEPTEUR GLP-1
  申请人：RECEPTOS INC

  公开号：WO2014201172A1

  公开（公告）日：2014-12-18

  Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "(Ⅰ)" represents either or both the R and S form of the compound): where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

  提供了一些化合物，这些化合物可以调节胰高血糖素样肽1（GLP-1）受体，以及它们的合成方法和治疗性及/或预防性使用方法。这些化合物可以单独作为GLP-1受体的调节剂或增强剂，或者与肠促胰岛素肽（如GLP-1(7-36)和GLP-1(9-36)）一起使用，或者与基于肽的治疗方法（如艾塞那肽和利拉鲁肽）一起使用，并具有以下一般结构（其中"(Ⅰ)"代表化合物的R和S形式中的一个或两个）：其中A、B、C、Y1、Y2、Z、R1、R2、R3、R4、R5、W1、n、p和q如本文所述定义。
• NOVEL GLP-1 RECEPTOR MODULATORS
  申请人：RECEPTOS, INC.

  公开号：US20130178420A1

  公开（公告）日：2013-07-11

  The invention relates to compounds that modulate the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds are act as modulators or potentiators of GLP-1 receptor on their own, or with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

  本发明涉及调节胰高血糖素样肽-1（GLP-1）受体的化合物、它们的合成方法以及它们的治疗和/或预防使用方法。这些化合物可以作为GLP-1受体的调节剂或增强剂，可以单独使用，也可以与受体配体（包括GLP-1肽GLP-1（7-36）和GLP-1（9-36））或肽基治疗（例如exenatide和liraglutide）一起使用，并具有以下一般结构（其中“”表示化合物的R和S形式中的任意一个或两个）：其中A、B、C、Y1、Y2、Z、R1、R2、R3、R4、R5、W1、n、p和q如本文所定义。
• GLP-1 receptor modulators
  申请人：Celgene International II SÀRL

  公开号：US10034886B2

  公开（公告）日：2018-07-31

  Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

  本研究提供了调节胰高血糖素样肽 1（GLP-1）受体的化合物及其合成方法，以及治疗和/或预防使用方法。此类化合物可单独作为 GLP-1 受体的调节剂或增效剂，或与 GLP-1(7-36) 和 GLP-1(9-36)等增量肽一起使用，或与艾塞那肽和利拉鲁肽等肽类疗法一起使用，并具有以下一般结构（其中""代表化合物的 R 和 S 形式中的一种或两种）： 其中 A、B、C、Y1、Y2、Z、R1、R2、R3、R4、R5、W1、n、p 和 q 如本文所定义。
• CARBOXYLIC ACID DERIVATIVES COMPRISING FOUR CYCLES ACTING AS GLP-1 RECEPTOR MODULATORS FOR THERAPY OF DISEASES SUCH AS DIABETES
  申请人：Receptos, Inc.

  公开号：EP2791112A2

  公开（公告）日：2014-10-22