4-amino-1-((2R,5R,8R,14R)-2-(4-aminobutyl)-8-benzyl-5-isobutyl-4,7,10-trioxo-14-phenyl-3,6,9,12-tetraazapentadecan-1-oyl)piperidine-4-carboxylic acid | 2168572-99-2

• 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: 4-amino-1-((2R,5R,8R,14R)-2-(4-aminobutyl)-8-benzyl-5-isobutyl-4,7,10-trioxo-14-phenyl-3,6,9,12-tetraazapentadecan-1-oyl)piperidine-4-carboxylic acid
• 英文别名: Riminkefon；4-amino-1-[(2R)-6-amino-2-[[(2R)-4-methyl-2-[[(2R)-3-phenyl-2-[[2-[[(2R)-2-phenylpropyl]amino]acetyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid
• CAS: 2168572-99-2
• 化学式: C₃₈H₅₇N₇O₆
• 分子量: 707.914
• InChiKey: AYIXVIHRKYGICQ-LHJVHYEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  51
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  209
• 氢给体数：
  7
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-amino-1-((2R,5R,8R,14R)-2-(4-aminobutyl)-8-benzyl-5-isobutyl-4,7,10-trioxo-14-phenyl-3,6,9,12-tetraazapentadecan-1-oyl)piperidine-4-carboxylic acid 在 磷酸 作用下， 以 异丙醇 为溶剂， 反应 2.5h， 以90%的产率得到
  参考文献：
  名称：

  SALT OF A PHENYLPROPIONAMIDE DERIVATIVE AND PREPARATION METHOD THEREFOR

  摘要：

  公开号：

  EP3722286B1
• 作为产物：
  描述：

  4-benzyloxycarbonylamino-piperidine-4-carboxylic acid benzyl ester 在 哌啶 、 palladium on activated charcoal 、 氢气 、 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-) 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-amino-1-((2R,5R,8R,14R)-2-(4-aminobutyl)-8-benzyl-5-isobutyl-4,7,10-trioxo-14-phenyl-3,6,9,12-tetraazapentadecan-1-oyl)piperidine-4-carboxylic acid
  参考文献：
  名称：

  Discovery of SHR0687, a Highly Potent and Peripheral Nervous System-Restricted KOR Agonist

  摘要：

  Analgesics with no abuse liability are highly demanded in the market. KOR agonists have been proved to be strong analgesics without MOR agonist-related side effects, such as respiratory depression, tolerance, and dependence liability; however, activation of KOR in the central nervous system (CNS) may cause sedation and anxiety. It has been reported that peripheral KOR activation produces comparable bioactivity without CNS-related side effects. Herein, we designed and synthesized a novel tetrapeptide (SHR0687), which was shown to be a highly potent KOR agonist with excellent selectivity over other opioid receptors, such as MOR and DOR. In addition, SHR0687 displayed favorable PK profiles across species, as well as robust in vivo efficacy in a rat carrageenan-induced pain model. Notably, SHR0687 exhibited negligible blood-brain barrier penetration, which was meaningful in minimizing CNS-related side effects.

  DOI：

  10.1021/acsmedchemlett.0c00287

文献信息

• PHARMACEUTICAL COMPOSITION OF KOR RECEPTOR AGONIST
  申请人：JIANGSU HENGRUI MEDICINE CO., LTD.

  公开号：US20210205404A1

  公开（公告）日：2021-07-08

  Disclosed in the present invention is a pharmaceutical composition of a KOR receptor agonist, which comprises 4-amino-N—[N2-[N—[N—[N-((R)-2-phenyl propyl)glycyl]-D-phenylalanyl]-D-leucyl]-D-lysyl]piperidine-4-carboxylic acid or available salts thereof, and an acetate buffer solution.

  本发明公开了一种KOR受体激动剂的药物组合物，包括4-氨基-N-[N2-[N-[N-[N-((R)-2-苯基丙基)甘氨酰]-D-苯丙氨基]-D-亮氨酰]-D-赖氨酰]哌啶-4-羧酸或其可用盐，以及醋酸缓冲溶液。
• USE OF KOR AGONIST IN COMBINATION WITH MOR AGONIST IN PREPARING DRUG FOR TREATING PAIN
  申请人：JIANGSU HENGRUI MEDICINE CO., LTD.

  公开号：US20200368309A1

  公开（公告）日：2020-11-26

  Disclosed is the use of a KOR agonist in combination with a MOR agonist in preparing a drug for treating pain. The KOR agonist is selected from a compound as shown in the general formula (I), and the MOR agonist is selected from a compound as shown in the general formula (II), wherein the definitions of each substituent in the general formula (I) and (II) are the same as defined in the description.

  本发明揭示了在制备用于治疗疼痛的药物时，使用KOR激动剂与MOR激动剂的组合。其中，KOR激动剂选自通用式（I）所示的化合物，MOR激动剂选自通用式（II）所示的化合物，其中通用式（I）和（II）中每个取代基的定义与描述中定义的相同。
• PHENYL PROPANAMIDE DERIVATIVE, AND MANUFACTURING METHOD AND PHARMACEUTICAL APPLICATION THEREOF
  申请人：Jiangsu Hengrui Medicine Co., Ltd.

  公开号：EP3466962A1

  公开（公告）日：2019-04-10

  The present invention provides a phenyl propanamide derivative as represented by formula (I), a manufacturing method of the derivative, application of the derivative as a κ-opioid receptor (KOR) agonist, and application of the derivative for manufacturing a pharmaceutical product for treating and/or preventing pain or a pain-related disease.

  本发明提供了一种由式（I）表示的苯基丙酰胺衍生物、该衍生物的制造方法、该衍生物作为κ-阿片受体（KOR）激动剂的应用，以及该衍生物在制造治疗和/或预防疼痛或疼痛相关疾病的药物产品中的应用。
• SALT OF PHENYLPROPIONAMIDE DERIVATIVE AND PREPARATION METHOD THEREFOR
  申请人：Jiangsu Hengrui Medicine Co., Ltd.

  公开号：EP3722286A1

  公开（公告）日：2020-10-14

  The present invention provides a salt of a phenylpropionamide derivative and a preparation method therefor. The present invention specifically provides an acetate, hydrochloride, phosphate, citrate, benzoate, or fumarate of 4-amino-1-((2R,5R,8R,14R)-2-(4-aminobutyl)-8-benzyl-5-isobutyl-4,7,10-trioxo-14-phenyl-3,6,9,12-tetraazapentadecan-1-acyl)piperidine-4-carboxylic acid, and a preparation method therefor. The salt of the compound of formula (I) of the present invention has good stability, and the simple process thereof facilitates easy operation. The invention is better suited for clinical treatment.

  本发明提供了一种苯丙酰胺衍生物的盐及其制备方法。本发明具体提供了4-氨基-1-((2R,5R,8R,14R)-2-(4-氨基丁基)-8-苄基-5-异丁基-4,7,10-三氧代-14-苯基-3,6,9,12-四氮杂十五烷-1-酰基)哌啶-4-羧酸的醋酸盐、盐酸盐、磷酸盐、柠檬酸盐、苯甲酸盐或富马酸盐及其制备方法。本发明的式(I)化合物盐稳定性好，工艺简单，便于操作。本发明更适合临床治疗。
• Salt of phenylpropionamide derivative and preparation method therefor
  申请人：Jiangsu Hengrui Medicine CO., LTD.

  公开号：US11180530B2

  公开（公告）日：2021-11-23

  A salt of a phenylpropionamide derivative and a preparation method therefor is described. Specifically, the salt of the compound of formula (I) has good stability, and can be better used in clinical treatment. The process for preparing the salt of the compound of formula (I) of the present invention is simple and easy to operate.

  本研究描述了一种苯丙酰胺衍生物的盐及其制备方法。具体来说，式（I）化合物的盐具有良好的稳定性，可以更好地用于临床治疗。本发明式（I）化合物盐的制备工艺简单，易于操作。