(R)-5-(sec-butylamino)-4-carbamoyl-2-methylbenzoic acid | 1149386-14-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-5-(sec-butylamino)-4-carbamoyl-2-methylbenzoic acid
• 英文别名: (R)-5-(sec-butylamino)-4-(aminocarbonyl)-2-methylbenzoic acid；5-[[(2R)-butan-2-yl]amino]-4-carbamoyl-2-methylbenzoic acid
• CAS: 1149386-14-0
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: HGFIWHHGOLVVHN-MRVPVSSYSA-N

物化性质

• 沸点：
  400.5±45.0 °C(Predicted)
• 密度：
  1.213±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-5-(sec-butylamino)-4-carbamoyl-2-methylbenzoic acid 、 [6-(3-Amino-8-azabicyclo[3.2.1]octan-8-yl)pyridin-3-yl]-cyclopropylmethanone 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 XL888
  参考文献：
  名称：

  Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90

  摘要：

  With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.052
• 作为产物：
  描述：

  Methyl 4-cyano-2-methyl-5-nitrobenzoate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 copper(l) iodide 、 二碘甲烷 、 双氧水 、 铁粉 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium hydroxide 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 二甲基亚砜 为溶剂， 生成 (R)-5-(sec-butylamino)-4-carbamoyl-2-methylbenzoic acid
  参考文献：
  名称：

  Discovery of XL888: A novel tropane-derived small molecule inhibitor of HSP90

  摘要：

  With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.052

文献信息

• [EN] TROPANE COMPOUNDS<br/>[FR] COMPOSÉS DE TROPANE
  申请人：EXELIXIS INC

  公开号：WO2009055077A1

  公开（公告）日：2009-04-30

  A compound according to Formula I or II: (I) or (II) wherein R1, R1b, R2, L1, and L2 and L2b are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

  根据公式I或II的化合物：（I）或（II），其中R1、R1b、R2、L1和L2以及L2b的定义如规范中所述，以及其药物组合物和使用方法。
• [EN] METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR UNE DÉGRADATION DE PROTÉINE CIBLÉE
  申请人：RANOK THERAPEUTICS HANGZHOU CO LTD

  公开号：WO2020207396A1

  公开（公告）日：2020-10-15

  Provided herein are methods and compositions for targeted protein degradation. In one aspect, a protein degradation chimera is provided, comprising: a first moiety that is capable of binding to a chaperone complex component; a second moiety that is capable of binding to a target protein or proteins, wherein the target protein (s) is targeted for degradation; and a tether configured to covalently couple the first moiety and the second moiety.

  本文提供了用于靶向蛋白质降解的方法和组合物。在一个方面，提供了一种蛋白质降解嵌合体，包括：能够结合到辅助蛋白复合物成分的第一部分；能够结合到目标蛋白质的第二部分，其中目标蛋白质被靶向降解；以及用于共价耦合第一部分和第二部分的连接物。
• Tropane compounds
  申请人：Exelixis, Inc.

  公开号：US08012956B2

  公开（公告）日：2011-09-06

  A compound according to Formula I or II: wherein R1, R1b, R2, L1, and L2 and L2b are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

  一种根据公式I或II的化合物：其中R1、R1b、R2、L1和L2和L2b如规范中所定义，其药物组成物和使用方法。
• TROPANE COMPOUNDS
  申请人：Exelixis, Inc.

  公开号：EP2074120A1

  公开（公告）日：2009-07-01
• METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION
  申请人：Ranok Therapeutics (Hangzhou) Co. Ltd.

  公开号：US20220168427A1

  公开（公告）日：2022-06-02

  Provided herein are methods and compositions for targeted protein degradation. In one aspect, a protein degradation chimera is provided, comprising: a first moiety that is capable of binding to a chaperone complex component; a second moiety that is capable of binding to a target protein or proteins, wherein the target protein (s) is targeted for degradation; and a tether configured to covalently couple the first moiety and the second moiety.