CP-394531 | 305822-63-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: CP-394531
• 英文别名: [2R-(2α,4aα,10aβ)]-2-(chloroethynyl)-1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2,7-phenanthrenediol；4a(S)-benzyl-2(R)-chloroethynyl-1,2,3,4,4a,9,10,10a(R)-octahydro-phenanthrene-2,7-diol；2,7-Phenanthrenediol, 2-(chloroethynyl)-1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-, (2R,4aS,10aR)-；(2R,4aS,10aR)-4a-benzyl-2-(2-chloroethynyl)-1,3,4,9,10,10a-hexahydrophenanthrene-2,7-diol
• CAS: 305822-63-3
• 化学式: C₂₃H₂₃ClO₂
• 分子量: 366.887
• InChiKey: CNOAOQSZNOTZLQ-OIBXWCBGSA-N

物化性质

• 熔点：
  230-232 °C (decomp)
• 沸点：
  530.9±50.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3,4-dihydro-6-methoxy-1-(phenylmethyl)-2(1H)-naphthalenone 在 lithium amide 、 sodium methylate 、 三氯化硼 、 四丁基碘化铵 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 9.75h， 生成 CP-394531
  参考文献：
  名称：

  Discovery of Potent, Nonsteroidal, and Highly Selective Glucocorticoid Receptor Antagonists

  摘要：

  An approach to the computer-assisted, pharmacophore design of nonsteroidal templates for the glucocorticoid receptor (GR) that contained an element of pseudo-C2 symmetry was developed. The enatiomer of the initial design, 1Ra, and not the designed molecule, 1S, showed the desired ligand binding to the GR. The pseudo-C2 symmetry of the template allowed for rapid improvements in GR activity resulting in potent, selective, nonsteroidal GR antagonists, CP-394531 and CP-409069.

  DOI：

  10.1021/jm0105530

文献信息

• Glucocorticoid receptor modulators
  申请人：Dow L. Robert

  公开号：US20070117805A1

  公开（公告）日：2007-05-24

  The present invention provides non-steroidal compounds of formula I which are selective modulators (i.e., agonists and antagonists) of a steroid receptor, specifically, the glucocorticoid receptor. The present invention also provides pharmaceutical compositions containing these compounds and methods for using these compounds to treat animals requiring glucocorticoid receptor agonist or antagonist therapy. Glucocorticoid receptor modulators are useful to the diseases, such as obesity, diabetes, inflammation and others as described below. The present invention also provides intermediates and processes for preparing these compounds.

  本发明提供公式I的非甾体化合物，它们是类固醇受体的选择性调节剂（即激动剂和拮抗剂），具体地，是糖皮质激素受体。本发明还提供含有这些化合物的药物组合物，并使用这些化合物治疗需要糖皮质激素受体激动剂或拮抗剂治疗的动物的方法。糖皮质激素受体调节剂对于肥胖症、糖尿病、炎症等疾病是有用的，如下所述。本发明还提供制备这些化合物的中间体和方法。
• Glucocorticoid receptor modulators to treat pancreatic cancer
  申请人：Corcept Therapeutics, Inc.

  公开号：US10646474B2

  公开（公告）日：2020-05-12

  Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

  本发明公开了用于治疗患有非 ACTH 分泌性胰腺肿瘤的受试者的方法和组合物。这些方法包括向受试者施用化疗剂和糖皮质激素受体调节剂（GRM），最好是选择性糖皮质激素受体调节剂（SGRM），以减少受试者体内的肿瘤负荷。GRM可以是非类固醇GRM，也可以是非类固醇SGRM。非 ACTH 分泌性胰腺肿瘤可以是外分泌性胰腺肿瘤。 非甾体 SGRM 可以是一种非甾体化合物，包括：融合氮杂环丁烷结构；杂芳酮融合氮杂环丁烷结构；或八氢融合氮杂环丁烷结构。公开了包含化疗药物和 GRM 的药物组合物。此类药物组合物中的 GRM 可以是非类固醇 GRM，也可以是 SGRM，例如非类固醇 SGRM。非甾体 SGRM 可包括：融合氮杂萘结构；杂芳酮融合氮杂萘结构；或八氢融合氮杂萘结构。
• Methods for inhibiting cognitive deterioration in adults with down's syndrome
  申请人：Corcept Therapeutics, Inc.

  公开号：US20030064974A1

  公开（公告）日：2003-04-03

  This invention generally pertains to the field of psychiatry. In particular, this invention pertains to the discovery that agents capable of inhibiting the binding of cortisol to its receptors can be used in methods for preventing or reversing cognitive deterioration in adults with Down's syndrome. Mifepristone, a potent specific glucocorticoid receptor antagonist, can be used in these methods. The invention also provides a kit for preventing or reversing cognitive deterioration in a DS patient including a glucocorticoid receptor antagonist and instructional material teaching the indications, dosage and schedule of administration of the glucocorticoid receptor antagonist.

  本发明一般涉及精神病学领域。特别是，本发明涉及发现能够抑制皮质醇与其受体结合的制剂可用于预防或逆转患有唐氏综合征的成年人认知功能退化的方法。米非司酮是一种强效的特异性糖皮质激素受体拮抗剂，可用于这些方法中。本发明还提供了一种用于预防或逆转唐氏综合征患者认知功能退化的试剂盒，包括一种糖皮质激素受体拮抗剂和教导糖皮质激素受体拮抗剂的适应症、剂量和给药计划的指导材料。
• GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：Pfizer Products Inc.

  公开号：EP1175383B1

  公开（公告）日：2018-03-14
• METHODS FOR INHIBITING COGNITIVE DETERIORATION IN ADULTS WITH DOWN'S SYNDROME
  申请人：Corcept Therapeutics, Inc.

  公开号：EP1432379A1

  公开（公告）日：2004-06-30