2-[2-Chloro-6-(diethoxymethyl)-5-(2-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]ethylcarbamic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-[2-Chloro-6-(diethoxymethyl)-5-(2-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]ethylcarbamic acid
• 英文别名: 2-[2-chloro-6-(diethoxymethyl)-5-(2-methylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]ethylcarbamic acid
• 化学式: C₂₁H₂₅ClN₄O₄
• 分子量: 432.9
• InChiKey: GNQCDAOFHVFIRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  98.5
• 氢给体数：
  2
• 氢受体数：
  6

文献信息

• [EN] COMBINATIONS AND DOSING REGIMES TO TREAT RB-POSITIVE TUMORS<br/>[FR] COMBINAISONS ET RÉGIMES POSOLOGIQUES POUR TRAITER DES TUMEURS RB-POSITIVES
  申请人：G1 THERAPEUTICS INC

  公开号：WO2016040858A1

  公开（公告）日：2016-03-17

  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.

  这项发明涉及使用特定剂量和组合或交替方案中的CDK4/6抑制剂治疗选择性RB阳性癌症和其他RB阳性异常细胞增殖紊乱疾病的方法。在一个方面，揭示了使用特定CDK4/6抑制剂与另一种化疗药物（例如，额外的激酶抑制剂、PD-1抑制剂或BCL-2抑制剂，或其组合）组合或交替治疗选择性RB阳性癌症。
• [EN] TRANSIENT PROTECTION OF NORMAL CELLS DURING CHEMOTHERAPY<br/>[FR] PROTECTION TRANSITOIRE DE CELLULES NORMALES PENDANT UNE CHIMIOTHÉRAPIE
  申请人：G1 THERAPEUTICS INC

  公开号：WO2014144326A1

  公开（公告）日：2014-09-18

  This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

  该发明涉及改进化合物、组合物和方法的领域，用于短暂保护健康细胞，特别是造血干细胞和祖细胞（HSPC）以及肾细胞，免受与损伤有关的DNA损伤化疗药物。在一个方面，通过使用所述的化合物揭示了对健康细胞的改进保护，这些化合物在接受DNA损伤化疗方案治疗增殖性疾病的受试者时作为高度选择性和短暂作用的细胞周期依赖性激酶4/6（CDK 4/6）抑制剂。
• [EN] TREATMENT OF RB-NEGATIVE TUMORS USING TOPOISOMERASE INHIBITORS IN COMBINATION WITH CYCLIN DEPENDENT KINASE 4/6 INHIBITORS<br/>[FR] TRAITEMENT DE TUMEURS RB-NÉGATIVES EN UTILISANT DES INHIBITEURS DE LA TOPOISOMÉRASE EN ASSOCIATION AVEC DES INHIBITEURS DES KINASES CYCLINE-DÉPENDANTES 4/6
  申请人：G1 THERAPEUTICS INC

  公开号：WO2016040848A1

  公开（公告）日：2016-03-17

  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.

  这项发明涉及改进的治疗组合和方法，用于治疗选择性视网膜母细胞瘤（Rb）阴性癌症和Rb阴性异常细胞增殖障碍，使用特定的拓扑异构酶抑制剂和特定的细胞周期依赖性激酶4/6（CDK4/6）抑制剂。在一个方面，使用本文披露的特定化合物与拓扑异构酶I抑制剂结合，披露了对选择性Rb阴性癌症的改进治疗。
• HSPC-sparing treatments for RB-positive abnormal cellular proliferation
  申请人：G1 Therapeutics, Inc.

  公开号：US10076523B2

  公开（公告）日：2018-09-18

  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。
• Transient protection of normal cells during chemotherapy
  申请人：G1 THERAPEUTICS, INC.

  公开号：US10085992B2

  公开（公告）日：2018-10-02

  This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

  本发明涉及瞬时保护健康细胞，特别是造血干细胞和祖细胞（HSPC）以及肾脏细胞免受DNA损伤性化疗药物损害的改良化合物、组合物和方法。在一个方面，所公开的化合物可作为高选择性、短效、瞬时起作用的细胞周期蛋白依赖性激酶4/6（CDK 4/6）抑制剂，用于接受DNA损伤性化疗方案治疗增殖性疾病的受试者，从而改善对健康细胞的保护。