盐酸尼拉帕尼 | 1038915-64-8

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 盐酸尼拉帕尼
• 中文别名: 尼拉帕尼盐酸盐
• 英文名称: 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide hydrochloride
• 英文别名: niraparib hydrochloride；niraparib；(3S)-3-[4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl]piperidinium chloride；2-[4-[(3S)-piperidin-1-ium-3-yl]phenyl]indazole-7-carboxamide;chloride
• CAS: 1038915-64-8
• 化学式: C₁₉H₂₀N₄O*ClH
• 分子量: 356.855
• InChiKey: YXYDNYFWAFBCAN-PFEQFJNWSA-N

物化性质

• 熔点：
  144 °C
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  25
• 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：
  3
• 氢受体数：
  3

安全信息

• 储存条件：
  2-8°C

制备方法与用途

简介

作为同类最优的PARP抑制剂，甲苯磺酸尼拉帕利凭借卓越的临床疗效、一天一次的给药方案以及优越的药代动力学特质，特别具备穿越血脑屏障的优势。

适应症

甲苯磺酸尼拉帕利适用于复发性上皮性卵巢癌、输卵管癌或原发性腹膜癌成年患者的维持治疗，要求患者对基于铂化疗有完全或部分缓解。

反应信息

• 作为反应物：
  描述：

  盐酸尼拉帕尼 、 对甲苯磺酸 以 甲醇 、 水 为溶剂， 反应 4.0h， 以100 g的产率得到(3S)-3-[4-[7-(氨基羰基)-2H-吲唑-2-基]苯基]哌啶对甲苯磺酸盐
  参考文献：
  名称：

  一种尼拉帕尼对甲苯磺酸盐水合物晶型及其制备方法

  摘要：

  本发明属于化学医药领域，具体涉及尼拉帕尼(2‑[4‑((3S)‑3‑哌啶基)苯基]‑2H‑吲唑‑7‑甲酰胺)对甲苯磺酸盐的晶型A及其制备方法，本发明中的晶型A，其X‑射线粉末衍射图在2theta值为9.5±0.2°、13.2±0.2°、15.1±0.2°、18.4±0.2°、19.4±0.2°、21.0±0.2°、24.6±0.2°和30.0±0.2°处有特征峰。本发明的尼拉帕尼对甲苯磺酸盐的晶型A具有极高的稳定性，无或者几乎无引湿性，其性质稳定，不易变质，有利于维持药效。

  公开号：

  CN108530425A
• 作为产物：
  描述：

  尼拉帕尼 在 盐酸 作用下， 以 水 为溶剂， 反应 0.25h， 生成 盐酸尼拉帕尼
  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

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。
• [EN] PHARMACEUTICAL COMPOSITIONS AND METHODS<br/>[FR] COMPOSITIONS PHARMACEUTIQUES ET MÉTHODES
  申请人：POP TEST ONCOLOGY LLC

  公开号：WO2017023694A1

  公开（公告）日：2017-02-09

  This invention relates the use of Cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.

  本发明涉及使用皮质醇阻断剂（例如，糖皮质激素受体[GR]拮抗剂）用于治疗或预防病毒感染，治疗或预防难治性前列腺癌，治疗或预防肿瘤，以及治疗或预防与急性或慢性损伤或疾病相关的感染。
• 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。