CORT113176 | 1496508-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: CORT113176
• 英文别名: (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone；dazucorilant；Dazucorilant；[(4aR)-1-(4-fluorophenyl)-6-[4-(trifluoromethyl)phenyl]sulfonyl-4,5,7,8-tetrahydropyrazolo[3,4-g]isoquinolin-4a-yl]-pyridin-2-ylmethanone
• CAS: 1496508-34-9
• 化学式: C₂₉H₂₂F₄N₄O₃S
• 分子量: 582.578
• InChiKey: VXOBXKQLNWYQPQ-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  93.5
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (R)-6-tert-butyl 4a-methyl 1-(4-fluorophenyl)-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-4a,6(4H)-dicarboxylate 在 盐酸 、 正丁基锂 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 CORT113176
  参考文献：
  名称：

  [EN] HETEROARYL-KETONE FUSED AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  [FR] MODULATEURS DES RÉCEPTEURS DE GLUCOCORTICOÏDES CONSISTANT EN AZADÉCALINES À HÉTÉROARYLE CÉTONE FUSIONNÉ

  摘要：

  公开号：

  WO2013177559A3

文献信息

• Heteroaryl-Ketone Fused Azadecalin Glucocorticoid Receptor Modulators
  申请人：Corcept Therapeutics, Inc.

  公开号：US20140038926A1

  公开（公告）日：2014-02-06

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂环基酮融合的氮杂十环化合物，以及使用这些化合物作为糖皮质激素受体调节剂的方法。
• Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators
  申请人：Corcept Therapeutics, Inc.

  公开号：US08859774B2

  公开（公告）日：2014-10-14

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂环基酮融合的氮杂藤黄内酯化合物，并提供了使用这些化合物作为糖皮质激素受体调节剂的方法。
• HETEROARYL-KETONE FUSED AZADECALIN GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Corcept Therapeutics, Inc.

  公开号：US20150080389A1

  公开（公告）日：2015-03-19

  The present invention provides heteroaryl ketone fused azadecalin compounds and methods of using the compounds as glucocorticoid receptor modulators.

  本发明提供了杂环酰酮融合的氮杂十二烷化合物以及使用这些化合物作为糖皮质激素受体调节剂的方法。
• Therapeutic uses of relacorilant, a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator
  申请人：Corcept Therapeutics Incorporated

  公开号：US11058670B2

  公开（公告）日：2021-07-13

  Methods and compositions are disclosed for diagnosing a patient suspected of suffering from, and for treating a patient suffering from, a disorder such as hypercortisolemia, metabolic syndrome, pre-diabetes, diabetes, Cushing's syndrome, Cushing's Disease, hyperglycemia secondary to hypercortisolemia, a liver disease, a cardiac disorder, high blood pressure, a blood clotting disorder, a cancer, a psychological disorder, weight gain, a disorder of glucose control, a bone disorder (e.g., osteoporosis), hypogonadism, pseudoacromegaly, pituitary tumors, functional hypercortisolism, ACTH secreting tumors, peripheral neuropathy, dyslipidemia and other disorders. The methods and compositions include administration of a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (GRM). The preferred heteroaryl-ketone fused azadecalin GRM is relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone). In some cases, the GRM (e.g., relacorilant) is orally administered. In some cases, the GRM (e.g., relacorilant) is orally administered without food.

  本发明公开了用于诊断疑似高皮质醇血症、代谢综合征、糖尿病前期、糖尿病、库欣综合征、库欣病、继发于高皮质醇血症的高血糖症、肝脏疾病、心脏疾病、高血压、凝血障碍、癌症、心理障碍、体重增加、血糖控制障碍、骨骼障碍（例如，骨质疏松症）等疾病的患者和治疗患者的方法和组合物。g.,骨质疏松症）、性腺功能减退症、假性肢端肥大症、垂体瘤、功能性皮质醇过多症、促肾上腺皮质激素分泌肿瘤、周围神经病变、血脂异常和其他疾病。 这些方法和组合物包括施用杂芳基酮融合氮杂萘糖皮质激素受体调节剂（GRM）。优选的杂芳基酮融合氮杂十环素 GRM 是 relacorilant（(R)-(1-(4-氟苯基)-6-((1-甲基-1H-吡唑-4-基)磺酰基)-4,4a,5,6,7,8-六氢-1H-吡唑并[3,4-g]异喹啉-4a-基)(4-(三氟甲基)吡啶-2-基)甲酮）。在某些情况下，口服 GRM（例如 relacorilant）。在某些情况下，GRM（如抗逆转录酶药）不经食物口服给药。
• Methods of treating cancer comprising administration of a glucocorticoid receptor modulator and a cancer chemotherapy agent
  申请人：Corcept Therapeutics Incorporated

  公开号：US11234971B2

  公开（公告）日：2022-02-01

  Novel methods for treating cancer include: measuring the expression level of a gene; administering a glucocorticoid receptor modulator (GRM) to a patient; again measuring the expression level of a gene; identifying a patient in whom the expression level of the gene is decreased following GRM administration (compared to the baseline gene expression level) as likely to benefit from treatment by combined cancer chemotherapy plus GRM administration; and administering to the identified patient a combination of the GRM and cancer chemotherapy, whereby the cancer is treated in the patient. The GRM may be selected from relacorilant, CORT125281, CORT122928, and CORT113176. The cancer chemotherapy agent may be a taxane. The genes whose expression level is measured may be selected from COX2, DUSP1, GSK3b, MCL-1, PIK3CG, RGS-2, SGK1, and STAT3, and may be selected from FCGRT, C5, MAP3K7, TP53, BBC3, THBD, PRR5, RICTOR, and EIF2B4.

  治疗癌症的新方法包括：测量基因的表达水平；对患者施用糖皮质激素受体调节剂（GRM）；再次测量基因的表达水平；将施用 GRM 后基因表达水平下降（与基线基因表达水平相比）的患者确定为可能从癌症化疗加 GRM 联合施用的治疗中获益的患者；以及对确定的患者施用 GRM 和癌症化疗的组合，从而治疗患者的癌症。 GRM可选自relacorilant、CORT125281、CORT122928和CORT113176。癌症化疗剂可以是紫杉类药物。测量其表达水平的基因可选自 COX2、DUSP1、GSK3b、MCL-1、PIK3CG、RGS-2、SGK1 和 STAT3，也可选自 FCGRT、C5、MAP3K7、TP53、BBC3、THBD、PRR5、RICTOR 和 EIF2B4。