对映体R | 1038915-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 对映体R
• 英文名称: 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide
• 英文别名: 2-{4-[(3R)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide；(R)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide；2-[4-[(3R)-piperidin-3-yl]phenyl]indazole-7-carboxamide
• CAS: 1038915-58-0
• 化学式: C₁₉H₂₀N₄O
• 分子量: 320.394
• InChiKey: PCHKPVIQAHNQLW-AWEZNQCLSA-N

物化性质

• 沸点：
  463.6±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥32mg/mL（99.88mM）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C，密闭保存，并保持干燥。

制备方法与用途

MK-4827 R-enantiomer 是一种高效抑制剂，其IC50值为2.4 nM。

反应信息

• 作为反应物：
  描述：

  对映体R 在 盐酸 作用下， 以 水 为溶剂， 反应 0.25h， 生成 (3R)-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl]piperidinium chloride
  参考文献：
  名称：

  Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors

  摘要：

  We disclose the development of a novel series of 2-phenyl-2H-indazole-7-carboxamides as poly(ADPribose)polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2-{4-[(3S)-piperidin-3yl]phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.

  DOI：

  10.1021/jm901188v
• 作为产物：
  描述：

  tert-butyl 3-phenylpiperidine-1-carboxylate 在 十羰基二铼 、 硫酸 、 sodium methylate 、 sodium acetate 、 formamide 、 三氟乙酸 、 sodium hydroxide 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 108.0h， 生成 对映体R
  参考文献：
  名称：

  一种制备PARP抑制剂Niraparib的合成方法

  摘要：

  一种新型制备PARP抑制剂Niraparib的合成方法，该方法包括以起始原料邻氨基苯甲酸甲酯经重氮偶合，环合，酰胺化、脱BOC、手性拆分得到纯度达到99.5%的Niraparib。本发明方法简便，易于操作，是一种适合工业化生产的方法。

  公开号：

  CN106496187A

文献信息

• [EN] PHARMACEUTICALLY ACCEPTABLE SALTS OF 2-{4-[(3S)-PIPERIDIN-3- YL]PHENYL} -2H-INDAZOLE-7-CARBOXAMIDE<br/>[FR] SELS PHARMACEUTIQUEMENT ACCEPTABLES DE 2-{4-[(35)-PIPÉRIDIN-3-YL]PHÉNYL)-2H-INDAZOLE-7-CARBOXAMIDE
  申请人：MERCK SHARP & DOHME

  公开号：WO2009087381A1

  公开（公告）日：2009-07-16

  The present invention relates to pharmaceutically acceptable salts of an amide substituted indazole which are inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), previously known as poly(ADP-ribose)synthase and poly(ADP-ribosyl)transferase. The compounds of the present invention are useful as mono-therapies in tumors with specific defects in DNA-repair pathways and as enhancers of certain DNA -damaging agents such as anticancer agents and radiotherapy. Further, the compounds of the present invention are useful for reducing cell necrosis (in stroke and myocardial infarction), down regulating inflammation and tissue injury, treating retroviral infections and protecting against the toxicity of chemotherapy.

  本发明涉及一种酰胺取代吲唑的药用可接受盐，它们是酶聚(ADP-核糖)聚合酶（PARP）的抑制剂，此前被称为聚(ADP-核糖)合酶和聚(ADP-核糖)转移酶。本发明的化合物可用作特定DNA修复途径缺陷肿瘤的单独治疗，以及作为某些DNA损伤剂（如抗癌剂和放疗）的增效剂。此外，本发明的化合物可用于减少细胞坏死（在中风和心肌梗死中）、下调炎症和组织损伤、治疗逆转录病毒感染以及保护免受化疗毒性的影响。
• Amide substituted indazoles as poly(ADP-ribose)polymerase(PARP) inhibitors
  申请人：Jones Philip

  公开号：US20080167345A1

  公开（公告）日：2008-07-10

  The present invention relates to compounds of formula I: and pharmaceutically acceptable salts, stereoisomers or tautomers thereof which are inhibitors of poly (ADP-ribose) polymerase (PARP) and thus useful for the treatment of cancer, inflammatory diseases, reperfusion injuries, ischemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes, neurodegenerative diseases, retroviral infection, retinal damage or skin senescence and UV-induced skin damage, and as chemo- and/or radiosensitizers for cancer treatment.

  本发明涉及式I的化合物及其药物可接受的盐、立体异构体或互变异构体，其为多聚（ADP核糖）聚合酶（PARP）的抑制剂，因此用于治疗癌症、炎症性疾病、再灌注损伤、缺血症、中风、肾衰竭、心血管疾病、除心血管疾病外的其他血管疾病、糖尿病、神经退行性疾病、逆转录病毒感染、视网膜损伤或皮肤衰老和紫外线诱导的皮肤损伤，并作为癌症治疗的化疗和/或放射增敏剂。
• PHARMACEUTICALLY ACCEPTABLE SALTS OF 2--2H-INDAZOLE-7-CARBOXAMIDE
  申请人：Foley Jennifer R.

  公开号：US20100286203A1

  公开（公告）日：2010-11-11

  The present invention relates to pharmaceutically acceptable salts of an amide substituted indazole which are inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), previously known as poly(ADP-ribose)synthase and poly(ADP-ribosyl) transferase. The compounds of the present invention are useful as mono-therapies in tumors with specific defects in DNA-repair pathways and as enhancers of certain DNA-damaging agents such as anticancer agents and radiotherapy. Further, the compounds of the present invention are useful for reducing cell necrosis (in stroke and myocardial infarction), down regulating inflammation and tissue injury, treating retroviral infections and protecting against the toxicity of chemotherapy.

  本发明涉及一种酰胺取代吲唑的药物可接受的盐，该药物是多聚腺苷酸核苷酸聚合酶（PARP）的抑制剂，以前称为多聚腺苷酸合成酶和多聚腺苷酸基转移酶。本发明的化合物可用作单一治疗法，用于具有特定DNA修复途径缺陷的肿瘤，并作为某些DNA损伤剂（如抗癌剂和放射治疗）的增效剂。此外，本发明的化合物还可用于减少细胞坏死（在中风和心肌梗死中），下调炎症和组织损伤，治疗逆转录病毒感染，并保护化疗的毒性。
• Combinations containing amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors
  申请人：Istituto di ricerche di Biologia Molecolare P. Angeletti S.R.L.

  公开号：EP2336120A1

  公开（公告）日：2011-06-22

  The present invention relates to combinations of compounds of formula I: and other anti-cancer agents which are useful for the treatment of cancer, inflammatory diseases, reperfusion injuries, ischemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes, neurodegenerative diseases, retroviral infection, retinal damage and skin senescence and UV-induced skin damage.

  本发明涉及式 I 化合物的组合： 和其他抗癌剂的组合，它们可用于治疗癌症、炎症性疾病、再灌注损伤、缺血性疾病、中风、肾功能衰竭、心血管疾病、心血管疾病以外的血管疾病、糖尿病、神经退行性疾病、逆转录病毒感染、视网膜损伤和皮肤衰老以及紫外线引起的皮肤损伤。
• [EN] POLYETHYLENE GLYCOL CONJUGATE DRUG SYNERGIST, PREPARATION METHOD THEREFOR, AND USE THEREOF<br/>[FR] AGENT SYNERGISTE DE MÉDICAMENT CONJUGUÉ AU POLYÉTHYLÈNE GLYCOL, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 聚乙二醇偶联药物增效剂、其制备方法及用途
  申请人：CHONGQING UPGRA BIOTECHNOLOGY CO LTD

  公开号：WO2022022354A1

  公开（公告）日：2022-02-03

  一种聚乙二醇偶联药物增效剂、其制备方法及用途，具体涉及式I所示的聚乙二醇偶联药物增效剂或其药学上可接受的盐，所述聚乙二醇偶联药物增效剂或其药学上可接受的盐的制备方法，用于制备所述聚乙二醇偶联药物增效剂或其药学上可接受的盐的中间体，包含所述聚乙二醇偶联药物增效剂或其药学上可接受的盐的组合物，以及所述聚乙二醇偶联药物增效剂或其药学上可接受的盐在制备药物中的用途。