细胞角蛋白15单克隆抗体 | 1469985-12-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 中文名称: 细胞角蛋白15单克隆抗体
• 英文名称: ((1R,3R)-5-((E)-2-((3αS,7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H,5H,6H,7H,7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol)
• 英文别名: 1,3-Cyclohexanediol, 2-methylene-5-((2E)-2-((1S,3aS,7aS)-octahydro-1-((1R)-1-((2S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7a-methyl-4H-inden-4-ylidene)ethylidene)-, (1R,3R)-；(1R,3R)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(1R)-1-[(2S)-3-hydroxy-2,3-dimethylbutoxy]ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• CAS: 1469985-12-3
• 化学式: C₂₇H₄₄O₄
• 分子量: 432.644
• InChiKey: UECLGFUOBJOZRT-PIOAYZOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  69.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl-2-((3R,5R)-3,5-bis(tertbutyldimethylsilyloxy)-4-methylenecyclohexylidene)acetate 在 正丁基锂 、 四丁基氟化铵 、 双氧水 、 二异丁基氢化铝 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 细胞角蛋白15单克隆抗体
  参考文献：
  名称：

  Synthesis of VS-105: A novel and potent vitamin D receptor agonist with reduced hypercalcemic effects

  摘要：

  We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2-((3 alpha S,7 alpha S)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7 alpha-methyldihydro-1H-inden-4(2H,5H,6H,7H,7 alpha H)-ylidene) ethylidene)-2-methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11, followed by Wittig-Horner coupling of 11 with the protected 25-hydroxy Grundmann's ketone 22 generated the precursor 12. Deprotection of the TBDMS groups of 12 produced the target compound VS-105. The biological profiles of VS-105 were evaluated using in vitro assays (VDR receptor binding, VDR reporter gene and HL-60 differentiation) in comparison to calcitriol (the endogenous hormone) or paricalcitol. Furthermore, the PTH suppressing potency and hypercalcemic side effects of VS-105 were evaluated in the 5/6 nephrectomized uremic rats in comparison to paricalcitol. Combining various changes at 20-epi, 22-oxa, 24-methyl, and 2-methylene yielded VS-105 that not only is highly potent in inducing functional responses in vitro, but also effectively suppresses PTH in a dose range that does not affect serum calcium in the 5/6 nephrectomized uremic rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.076

文献信息

• Vitamin D Receptor Agonists and Uses Thereof
  申请人：Kawai Megumi

  公开号：US20120115824A1

  公开（公告）日：2012-05-10

  Disclosed is a compound of Formula (I) in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, and a are defined herein, or a pharmaceutically acceptable salt thereof. Also disclosed are a pharmaceutical composition comprising a compound or salt thereof of Formula (I) and a method of treating a disease which benefits from the modulation of the vitamin D receptor, such as a bone disorder, cardiovascular disease, a cardiovascular complication associated with renal disease, endothelial dysfunction, hyperparathyroidism, hypocalcemia, an immune disorder, left ventricular hypertrophy, a proliferative disease, proteinuria, renal disease, and thrombosis.

  本发明公开了一种式（I）的化合物，其中R1、R2、R3、R4、R5、R6、X和a如本文所定义，或其药学上可接受的盐。本发明还公开了一种包括式（I）的化合物或其盐的制药组合物，以及一种治疗需要调节维生素D受体的疾病的方法，例如骨疾病、心血管疾病、与肾脏疾病相关的心血管并发症、内皮功能障碍、甲状旁腺功能亢进、低钙血症、免疫紊乱、左心室肥厚、增生性疾病、蛋白尿、肾脏疾病和血栓形成等疾病。