N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluorophenoxy)-2-hydroxy-2-methylpropanamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluorophenoxy)-2-hydroxy-2-methylpropanamide
• 英文别名: N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenoxy)-2-hydroxy-2-methylpropanamide
• 化学式: C₁₈H₁₄F₄N₂O₃
• 分子量: 382.314
• InChiKey: PBDLETFMTMGDKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氟苯酚 、 N-[4-氰基-3-(三氟甲基)苯基]甲基环氧丙烯酰胺 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 以16.7%的产率得到N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-fluorophenoxy)-2-hydroxy-2-methylpropanamide
  参考文献：
  名称：

  Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog–Thalidomide PROTACs

  摘要：

  一系列由比卡鲁胺类似物和沙利度胺组成的PROTACs（PROteolysis-TArgeting Chimeras）被设计、合成并在生物学上评估，作为新型雄激素受体（AR）降解剂。特别地，我们发现PROTAC化合物13b能够成功地在AR阳性癌细胞中展示对AR的有针对性降解，并可能是一种用于研究AR依赖性癌细胞的有用化学探针，同时也是前列腺癌的潜在治疗候选药物。

  DOI：

  10.3390/molecules26092525

文献信息

• METHODS OF TREATING UROLOGICAL DISORDERS USING SARMs
  申请人：GTx, Inc.

  公开号：US20160106702A1

  公开（公告）日：2016-04-21

  The present invention is directed to methods of treating, preventing, suppressing and/or inhibiting urological disorders such as urinary incontinence including stress urinary incontinence and pelvic-floor disorders by administering a SARM compound of the invention.

  本发明涉及通过给予本发明的SARM化合物来治疗、预防、抑制和/或抑制尿路疾病，如尿失禁，包括压力性尿失禁和盆底障碍的方法。
• METHODS OF TREATING MEIBOMIAN GLAND DYSFUNCTION
  申请人：Dalton James T.

  公开号：US20110172302A1

  公开（公告）日：2011-07-14

  The present invention includes methods for treating Meibomian gland dysfunctions. The invention also includes methods for improving tear lipid composition, for treating abnormal Meibomian gland secretion and for normalizing Meibomian gland secretions.

  本发明涉及治疗美波腺功能障碍的方法。该发明还包括改善泪液脂质组成的方法，治疗异常的美波腺分泌以及规范美波腺分泌的方法。
• METHOD OF TREATING ESTROGEN RECEPTOR (ER) -POSITIVE BREAST CANCERS WITH SELECTIVE ANDROGEN RECEPTOR MODULATOR (SARMS)
  申请人：GTx, Inc.

  公开号：US20140080905A1

  公开（公告）日：2014-03-20

  This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and/or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

  本发明涉及治疗雄激素受体阳性乳腺癌的方法，例如治疗女性患者。因此，本发明提供了以下方法：a）治疗患有乳腺癌的患者；b）治疗患有转移性乳腺癌的患者；c）治疗患有难治性乳腺癌的患者；d）治疗患有AR阳性乳腺癌的患者；e）治疗患有AR阳性难治性乳腺癌的患者；f）治疗患有AR阳性转移性乳腺癌的患者；g）治疗患有AR阳性和ER阳性乳腺癌的患者；h）治疗患有三阴性乳腺癌的患者；i）治疗患有晚期乳腺癌的患者；j）治疗经SERM（他莫昔芬，托瑞米芬），芳香化酶抑制剂，曲妥珠单抗（赫赛汀，阿多曲妥珠单抗乳腺癌注射液），珀妥珠单抗（珀妥泽），拉帕替尼，依西美坦（阿罗马星），贝伐珠单抗（阿瓦斯汀）和/或富马酸雌二醇失败的患有乳腺癌的患者；k）治疗、预防、抑制或阻止患有乳腺癌的患者的转移；l）延长患有乳腺癌患者的生存期；和/或m）延长患有乳腺癌患者的无进展生存期；包括向患者施用本发明的选择性雄激素受体调节剂（SARM）化合物的治疗有效量。
• PHARMACEUTICAL COMPOSITIONS OF SELECTIVE ANDROGEN RECEPTOR MODULATORS AND METHODS OF USE THEREOF
  申请人：GTx, Inc.

  公开号：US20130122085A1

  公开（公告）日：2013-05-16

  This invention provides a pharmaceutical composition comprising Compound I-V, including inter alia solid dosage forms of powder-filled capsule formulations, liquid-filled softgel capsules (softgels), tablets, and sustained release dosage forms, and uses thereof in treating a variety of diseases or conditions in a subject, for example, treating a muscle wasting disease and/or disorder, a bone related disease and/or disorder, metabolic syndrome, diabetes and associated diseases, and others.

  本发明提供了一种药物组合物，包括化合物I-V，其中包括粉末填充胶囊制剂、液体填充软胶囊（软胶囊）、片剂和缓释剂型等固体剂型，以及在治疗受体内的多种疾病或病症方面的用途，例如治疗肌肉萎缩病和/或疾病、骨相关疾病和/或疾病、代谢综合征、糖尿病及相关疾病等。
• METHOD OF TREATING ANDROGEN RECEPTOR (AR) -POSITIVE BREAST CANCERS WITH SELECTIVE ANDROGEN RECEPTOR MODULATOR (SARMS)
  申请人：GTx, Inc.

  公开号：US20140018433A1

  公开（公告）日：2014-01-16

  This invention relates to the treatment of androgen receptor-positive breast cancer in a subject, for example a female subject. Accordingly, this invention provides methods of: a) treating a subject suffering from breast cancer; b) treating a subject suffering from metastatic breast cancer; c) treating a subject suffering from refractory breast cancer; d) treating a subject suffering from AR-positive breast cancer; e) treating a subject suffering from AR-positive refractory breast cancer; f) treating a subject suffering from AR-positive metastatic breast cancer; g) treating a subject suffering from AR-positive and ER-positive breast cancer; h) treating a subject suffering from triple negative breast cancer; i) treating a subject suffering from advanced breast cancer; j) treating a subject suffering from breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; k) treating, preventing, suppressing or inhibiting metastasis in a subject suffering from breast cancer; l) prolonging survival of a subject with breast cancer, and/or m) prolonging the progression-free survival of a subject with breast cancer; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound, comprising administering to the subject a therapeutically effective amount of a SARM compound of this invention.

  本发明涉及治疗雄激素受体阳性乳腺癌的方法，例如治疗女性患者。因此，本发明提供以下方法：a）治疗患有乳腺癌的患者；b）治疗患有转移性乳腺癌的患者；c）治疗患有难治性乳腺癌的患者；d）治疗患有AR阳性乳腺癌的患者；e）治疗患有AR阳性难治性乳腺癌的患者；f）治疗患有AR阳性转移性乳腺癌的患者；g）治疗患有AR阳性和ER阳性乳腺癌的患者；h）治疗患有三阴性乳腺癌的患者；i）治疗患有晚期乳腺癌的患者；j）治疗未能对SERM（他莫昔芬，托瑞米芬）、芳香化酶抑制剂、曲妥珠单抗（赫赛汀，阿多曲妥珠单抗乳腺癌）、珀妥珠单抗（珀妥珠单抗）、拉帕替尼、依西美坦（阿罗马星）、贝伐珠单抗（阿瓦斯汀）和/或富马酸霉环素治疗无效的乳腺癌患者；k）治疗、预防、抑制或阻止患有乳腺癌的患者的转移；l）延长患有乳腺癌患者的生存期；m）延长患有乳腺癌患者的无进展生存期；包括向患者施用本发明中的选择性雄激素受体调节剂（SARM）化合物的治疗有效量。