((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate | 1622180-48-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: ((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate
• 英文别名: [(1R,3S)-1-amino-3-[(6R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl]cyclopentyl]methyl dihydrogen phosphate
• CAS: 1622180-48-6
• 化学式: C₂₂H₃₆NO₄P
• 分子量: 409.506
• InChiKey: BWKSEIHXZRSETR-VOQZNFBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  92.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  BMS-986104 在 四磷十氧化物 、 磷酸 作用下， 生成 ((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate
  参考文献：
  名称：

  可伸缩合成（（1 R，3 S）-1-氨基-3-（（R）-6-己基-5,6,7,8-四氢萘-2-基）环戊基）甲醇（ BMS-986104）作为有效的S1P 1受体调制器

  摘要：

  我们描述了合成4a（BMS-986104）的高效途径。合成中的关键步骤是三取代烯烃6的不对称氢硼化。特别是考虑到这种类型的转化（6 → 7）涉及的已知困难，当前的方法学提供了制备此类化合物的有效方法。此外，我们公开了4a在小鼠EAE模型中的功效，可与4c（FTY720）媲美。从机理上讲，在三维脑细胞培养测定中，4a对溶血磷脂酰胆碱（LPC）诱导的脱髓鞘表现出优异的髓鞘再生作用。

  DOI：

  10.1021/acs.jmedchem.6b01433

文献信息

• BICYCLIC COMPOUNDS
  申请人：Bristol-Myers Squibb Company

  公开号：US20140235591A1

  公开（公告）日：2014-08-21

  Disclosed are compounds of Formula (I) and/or a salt thereof; wherein R is —OH or —OP(O)(OH) 2 . Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P 1 , and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  公开了化合物Formula (I)及/或其盐；其中R为—OH或—OP(O)(OH)2。还公开了使用这些化合物作为G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或紊乱方面具有用途，如自身免疫疾病和血管疾病。
• Tetrahydronaphthalenyl compounds useful as sipi agonists
  申请人：Bristol-Myers Squibb Company

  公开号：US09115054B2

  公开（公告）日：2015-08-25

  Disclosed are compounds of Formula (I) and/or a salt thereof; wherein R is —OH or —OP(O)(OH)2. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  公开了式(I)的化合物和/或其盐；其中R为—OH或—OP(O)(OH)2。还公开了使用这些化合物作为选择性G蛋白偶联受体S1P1激动剂的方法，以及包含这些化合物的制药组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病的进展方面有用，例如自身免疫性疾病和血管疾病。
• Bicyclic compounds
  申请人：Bristol-Myers Squibb Company

  公开号：US09359286B2

  公开（公告）日：2016-06-07

  Disclosed are compounds of Formula (I) and/or a salt thereof; wherein R is —OH or —OP(O)(OH)2. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

  本发明涉及化合物(I)和/或其盐；其中R为—OH或—OP(O)(OH)2。本发明还涉及使用这种化合物作为选择性G蛋白偶联受体S1P1的激动剂的方法，以及包含这种化合物的药物组合物。这些化合物可用于治疗、预防或减缓多种治疗领域的疾病或障碍，如自身免疫疾病和血管疾病。
• Identification and Preclinical Pharmacology of BMS-986104: A Differentiated S1P₁ Receptor Modulator in Clinical Trials
  作者：T. G. Murali Dhar、Hai-Yun Xiao、Jenny Xie、Lois D. Lehman-McKeeman、Dauh-Rurng Wu、Marta Dabros、Xiaoxia Yang、Tracy L. Taylor、Xia D. Zhou、Elizabeth M. Heimrich、Rochelle Thomas、Kim W. McIntyre、Bethanne Warrack、Hong Shi、Paul C. Levesque、Jia L. Zhu、James Hennan、Praveen Balimane、Zheng Yang、Anthony M. Marino、Georgia Cornelius、Celia J. D’Arienzo、Arvind Mathur、Ding Ren Shen、Mary Ellen Cvijic、Luisa Salter-Cid、Joel C. Barrish、Percy H. Carter、Alaric J. Dyckman

  DOI：10.1021/acsmedchemlett.5b00448

  日期：2016.3.10

  Clinical validation of SIP receptor modulation therapy was achieved with the approval of fingolimod (Gilenya, 1) as the first oral therapy for relapsing remitting multiple sclerosis. However, 1 causes a dose-dependent reduction in the heart rate (bradycardia), which occurs within hours after first dose. We disclose the identification of clinical compound BMS-986104 (3d), a novel S1P(1) receptor modulator, which demonstrates ligand-biased signaling and differentiates from 1 in terms of cardiovascular and pulmonary safety based on preclinical pharmacology while showing equivalent efficacy in a T-cell transfer colitis model.
• US9115054B2
  申请人：——

  公开号：US9115054B2

  公开（公告）日：2015-08-25