2-(N-piperidinyl)methyl benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-(N-piperidinyl)methyl benzoic acid
• 英文别名: 2-(Piperidin-1-ium-1-ylmethyl)benzoate
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: SETGNIQLYMGVGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(N-piperidinyl)methyl benzoic acid 、 对氯苄胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到N-[(4-chlorophenyl)methyl]-2-(piperidin-1-ylmethyl)benzamide
  参考文献：
  名称：

  Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress

  摘要：

  Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing beta-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of beta-cell protective agents against ER stress-induced dysfunction and death. Through structure activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects beta-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 of 0.032 mu M. Compound 13d alleviates ER stress in beta-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant beta-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of beta-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes.

  DOI：

  10.1021/acs.jmedchem.7b00435
• 作为产物：
  描述：

  2-(1-哌啶甲基)-苯甲酸甲酯 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 2-(N-piperidinyl)methyl benzoic acid
  参考文献：
  名称：

  Discovery of a Benzamide Derivative That Protects Pancreatic β-Cells against Endoplasmic Reticulum Stress

  摘要：

  Endoplasmic reticulum (ER) stress-mediated pancreatic insulin-producing beta-cell dysfunction and death are critical elements in the onset and progression of both type 1 and type 2 diabetes. Here, through cell-based high throughput screening we identified benzamide derivatives as a novel class of beta-cell protective agents against ER stress-induced dysfunction and death. Through structure activity relationship optimization, a 3-(N-piperidinyl)methylbenzamide derivative 13d markedly protects beta-cells against ER stress-induced dysfunction and death with near 100% maximum rescue activity and an EC50 of 0.032 mu M. Compound 13d alleviates ER stress in beta-cells by suppressing ER stress-mediated activation of all three branches of unfolded protein response (UPR) and apoptotic genes. Finally, we show that 13d significantly lowers blood glucose levels and increases concomitant beta-cell survival and number in a streptozotocin-induced diabetic mouse model. Identification of beta-cell-protective small molecules against ER stress provides a new promising modality for the treatment of diabetes.

  DOI：

  10.1021/acs.jmedchem.7b00435

文献信息

• [EN] BENZAMIDE DERIVATIVES FOR INHIBITING ENDOPLASMIC RETICULUM (ER) STRESS<br/>[FR] DÉRIVÉS DE BENZAMIDE PERMETTANT D'INHIBER LE STRESS DU RÉTICULUM ENDOPLASMIQUE (ER)
  申请人：UNIV OKLAHOMA

  公开号：WO2018232264A1

  公开（公告）日：2018-12-20

  Novel 3-(N-piperidinyl)methyl benzamide derivatives are disclosed. The compounds can be used in treating diseases and conditions which are associated with abnormal cell function related to endoplasmic reticulum (ER) stress. For example, the compounds can be used as suppressors of ER stress-induced pancreatic β-cell dysfunction and death, for example in the treatment of diabetes.

  披露了新型3-(N-哌啶基)甲基苯甲酰胺衍生物。这些化合物可用于治疗与内质网（ER）应激相关的异常细胞功能引起的疾病和症状。例如，这些化合物可用作抑制ER应激诱导的胰岛素β细胞功能障碍和死亡的药物，例如用于治疗糖尿病。
• Discovery of a Novel Benzodiazepine Series of Cbl-b Inhibitors for the Enhancement of Antitumor Immunity
  作者：Jeffrey A. Boerth、Alex J. Chinn、Marianne Schimpl、Gayathri Bommakanti、Christina Chan、Erin L. Code、Kathryn A. Giblin、Andrea Gohlke、Catherine S. Hansel、Meizhong Jin、Stefan L. Kavanagh、Michelle L. Lamb、Jordan S. Lane、Carrie J. B. Larner、Adelphe M. Mfuh、Rachel K. Moore、Taranee Puri、Taylor R. Quinn、Minwei Ye、Kevin J. Robbins、Miguel Gancedo-Rodrigo、Haoran Tang、Jarrod Walsh、Jamie Ware、Gail L. Wrigley、Iswarya Karapa Reddy、Yun Zhang、Neil P. Grimster

  DOI：10.1021/acsmedchemlett.3c00439

  日期：2023.12.14

  our discovery effort toward Cbl-b inhibitors that might show therapeutic promise in immuno-oncology, where activation of the immune system can drive the recognition and killing of cancer cells. We undertook a high-throughput screening campaign followed by structure-enabled optimization to develop a novel benzodiazepine series of potent Cbl-b inhibitors. This series displayed nanomolar levels of biochemical

  Casitas B 系淋巴瘤原癌基因 b （Cbl-b） 是一种无名指 E3 连接酶，负责抑制 T 细胞、自然杀伤 （NK） 细胞和 B 细胞活化。在 Cbl-b 缺陷小鼠中观察到的由 T 细胞和 NK 细胞活性升高引起的强大抗肿瘤活性证明了我们对 Cbl-b 抑制剂的发现工作是合理的，这些抑制剂可能在免疫肿瘤学中显示出治疗前景，其中免疫系统的激活可以驱动癌细胞的识别和杀死。我们进行了高通量筛选活动，然后进行结构优化，以开发新型苯二氮卓类药物系列强效 Cbl-b 抑制剂。该系列显示出纳摩尔水平的生化效力，以及有效的 T 细胞活化。这类 Cbl-b 抑制剂的功能活性通过基于泛素的细胞测定得到进一步证实。
• Benzamide derivatives for inhibiting endoplasmic reticulum (ER) stress
  申请人：The Board of Regents of the University of Oklahoma

  公开号：US11203582B2

  公开（公告）日：2021-12-21

  Novel 3-(N-piperidinyl)methyl benzamide derivatives are disclosed. The compounds can be used in treating diseases and conditions which are associated with abnormal cell function related to endoplasmic reticulum (ER) stress. For example, the compounds can be used as suppressors of ER stress-induced pancreatic β-cell dysfunction and death, for example in the treatment of diabetes.

  新型3-(N-哌啶基)甲基苯甲酰胺衍生物被披露。这些化合物可用于治疗与内质网(ER)应激相关的异常细胞功能相关的疾病和病症。例如，这些化合物可作为ER应激诱导的胰腺β细胞功能障碍和死亡的抑制剂，例如在治疗糖尿病中使用。
• BENZAMIDE DERIVATIVES FOR INHIBITING ENDOPLASMIC RETICULUM (ER) STRESS
  申请人：The Board of Regents of the University of Oklahoma

  公开号：US20200199094A1

  公开（公告）日：2020-06-25

  Novel 3-(N-piperidinyl)methyl benzamide derivatives are disclosed. The compounds can be used in treating diseases and conditions which are associated with abnormal cell function related to endoplasmic reticulum (ER) stress. For example, the compounds can be used as suppressors of ER stress-induced pancreatic β-cell dysfunction and death, for example in the treatment of diabetes.
• US4305940A
  申请人：——

  公开号：US4305940A

  公开（公告）日：1981-12-15