(+/-)-INCB9471 | 925701-76-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (+/-)-INCB9471
• 英文别名: 5-[(4-(3S)-4-[(1R,2R)-2-ethoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl-4-methylpiperidin-1-yl)carbonyl]-4,6-dimethylpyrimidine；Piperidine, 1-((4,6-dimethyl-5-pyrimidinyl)carbonyl)-4-((3S)-4-((1R,2R)-2-ethoxy-2,3-dihydro-5-(trifluoromethyl)-1H-inden-1-yl)-3-methyl-1-piperazinyl)-4-methyl-；(4,6-dimethylpyrimidin-5-yl)-[4-[(3S)-4-[(1R,2R)-2-ethoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazin-1-yl]-4-methylpiperidin-1-yl]methanone
• CAS: 925701-76-4；869769-98-2
• 化学式: C₃₀H₄₀F₃N₅O₂
• 分子量: 559.675
• InChiKey: ZMCJFJZOSKEMOM-DNKZPPIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-tert-butyl 4-(4-benzyl-3-methylpiperazin-1-yl)-4-cyanopiperidine-1-carboxylate 在 盐酸 、 20 % Pd(OH)2/C 、 氢气 、 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 20.0~70.0 ℃ 、413.7 kPa 条件下， 反应 71.0h， 生成 (+/-)-INCB9471
  参考文献：
  名称：

  发现INCB9471，这是一种具有有效抗HIV-1活性的有效，选择性和口服生物利用CCR5拮抗剂。

  摘要：

  为了将CCR5拮抗剂鉴定为HIV-1进入抑制剂，我们基于构象考量设计了一系列新型的茚满衍生物。茚满环上的修饰导致发现化合物22a（INCB9471）对CCR5表现出高亲和力，有效的抗HIV-1活性，高受体选择性，出色的口服生物利用度和可耐受的安全性。INCB9471已进入人体临床试验。

  DOI：

  10.1021/ml1001536

文献信息

• PIPERAZINYLPIPERIDINE DERIVATIVES AS CHEMOKINE RECEPTOR ANTAGONISTS
  申请人：Xue Chu-Biao

  公开号：US20120295912A1

  公开（公告）日：2012-11-22

  The present invention relates to compounds of Formula I: wherein variable substituents are defined herein, that modulate the activity of or bind to chemokine receptors such as CCR5. In some embodiments, the compounds of the invention are selective for CCR5. The compounds can be used, for example, to treat diseases associated with chemokine receptor expression or activity such as inflammatory diseases, immune diseases and viral infections.

  本发明涉及式I的化合物：其中变量取代基在此定义，可调节或结合于趋化因子受体如CCR5的活性。在某些实施例中，本发明的化合物对CCR5具有选择性。这些化合物可用于治疗与趋化因子受体表达或活性相关的疾病，如炎症性疾病、免疫性疾病和病毒感染。
• METHODS FOR DETECTING CANCER-RELATED CELL POPULATIONS, SCREENING FOR METASTATIC CANCER AND TREATMENTS THEREOF
  申请人：IncellDx, Inc.

  公开号：EP3818171A1

  公开（公告）日：2021-05-12
• COMBINATION THERAPY FOR HUMAN IMMUNODEFICIENCY VIRUS INFECTION
  申请人：Friedman A. Paul

  公开号：US20080108586A1

  公开（公告）日：2008-05-08

  The present invention is directed to combination therapies for treatment of Human Immunodeficiency Virus (HIV) infection comprising administration of a CCR5 antagonist in combination with other therapeutic agents.
• Methods of Treating Cytokine Storm Infections, Including COVID-19, By Inhibiting CCR5/CCL5 (RANTES) Interaction, and Compositions for Practicing the Same
  申请人：IncellDx, Inc.

  公开号：US20200362044A1

  公开（公告）日：2020-11-19

  Methods of treating a subject suffering from COVID-19 are provided. Aspects of the methods including administering to the subject an effective amount of an inhibitor of CCR5/CCL5 interaction, such as a CCR5 antagonist. Also provided are methods of assessing severity of a disease involving hypercytokinemia, such as COVID-19, by determining the level of CCL5/RANTES in a subject, as well as compositions for use in such methods.
• METHODS OF INHIBITING CEREBRAL INFLAMMATION
  申请人：UNIVERSITÉ DE GENÈVE

  公开号：US20210205412A1

  公开（公告）日：2021-07-08

  The present invention provides methods of inhibiting cerebral inflammation comprising administering a CCR5 inhibitor to a subject.