US9527857, Ppp

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: US9527857, Ppp
• 英文别名: 4-[[5-[4-(3,3-dimethylbutyl)-3-methylpiperazin-1-yl]pyridin-2-yl]amino]spiro[1,3,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraene-13,1'-cyclopentane]-10-one
• 化学式: C₂₉H₄₀N₈O
• 分子量: 516.7
• InChiKey: FWURMUMMBPAZIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  91.2
• 氢给体数：
  2
• 氢受体数：
  7

文献信息

• Anti-neoplastic combinations and dosing regimens using CDK4/6 inhibitor compounds to treat RB-positive tumors
  申请人：G1 Therapeutics, Inc.

  公开号：US10231969B2

  公开（公告）日：2019-03-19

  This invention directed to methods for treating select RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.

  本发明涉及使用 CDK4/6 抑制剂以特定剂量和联合或交替方案治疗选择性 RB 阳性癌症和其他 Rb 阳性异常细胞增殖紊乱的方法。在一个方面，本发明公开了使用特定CDK4/6抑制剂与另一种化疗药物（例如，另一种激酶抑制剂、PD-1抑制剂或BCL-2抑制剂或其组合）联合或交替使用治疗选择性RB阳性癌症的方法。
• Treatment of Rb-negative tumors using topoisomerase with cyclin dependent kinase 4/6 inhibitors
  申请人：G1 Therapeutics, Inc.

  公开号：US10413547B2

  公开（公告）日：2019-09-17

  This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

  本发明涉及使用特定拓扑异构酶抑制剂和特异性细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂治疗特定视网膜母细胞瘤（Rb）阴性癌症和Rb阴性异常细胞增殖性疾病的改良治疗组合和方法领域。在一个方面，本文公开了使用本文公开的特定化合物与拓扑异构酶 I 抑制剂联合治疗特定 Rb 阴性癌症的改进方法。
• HSPC-sparing treatments for Rb-positive abnormal cellular proliferation
  申请人：G1 Therapeutics, Inc.

  公开号：US10434104B2

  公开（公告）日：2019-10-08

  This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

  本发明涉及用于治疗选定的 RB 阳性癌症和其它 Rb 阳性异常细胞增殖性疾病的改良化合物和方法，同时最大限度地减少与当前治疗方法相关的对健康细胞（例如健康的造血干细胞和祖细胞（HSPC））的有害影响。在一个方面，本文公开了使用本文公开的特定化合物改善对特定 RB 阳性癌症的治疗。在某些实施方案中，本文所述的化合物在给受试者用药时可作为高选择性、在某些实施方案中为短效、瞬时作用的细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂。
• HSPC-sparing treatments for RB-positive abnormal cellular proliferation
  申请人：G1 Therapeutics, Inc.

  公开号：US10925878B2

  公开（公告）日：2021-02-23

  This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

  本发明涉及用于治疗选定的 RB 阳性癌症和其它 Rb 阳性异常细胞增殖性疾病的改良化合物和方法，同时最大限度地减少与当前治疗方法相关的对健康细胞（例如健康的造血干细胞和祖细胞（HSPC））的有害影响。在一个方面，本文公开了使用本文公开的特定化合物改善对特定 RB 阳性癌症的治疗。在某些实施方案中，本文所述的化合物在给受试者用药时可作为高选择性、在某些实施方案中为短效、瞬时作用的细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂。
• Treatment of Rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors
  申请人：G1 Therapeutics, Inc.

  公开号：US11090306B2

  公开（公告）日：2021-08-17

  This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.

  本发明涉及使用特定拓扑异构酶抑制剂和特异性细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂治疗特定视网膜母细胞瘤（Rb）阴性癌症和Rb阴性异常细胞增殖性疾病的改良治疗组合和方法领域。在一个方面，本文公开了使用本文公开的特定化合物与拓扑异构酶 I 抑制剂联合治疗特定 Rb 阴性癌症的改进方法。