2-Methylene-18,19-dinor-(20S)-1alpha,25-dihydroxyvitamin D3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-Methylene-18,19-dinor-(20S)-1alpha,25-dihydroxyvitamin D3
• 英文别名: (20S)-1α,25-dihydroxy-2-methylene-18,19-dinorvitamin D3；(20S)-2-methylene-1α,25-dihydroxy-18,19-dinor-vitamin D₃；2-methylene-18,19-dinor-(20S)-1α,25-dihydroxyvitamin D3；(20S)-1alpha,25-Dihydroxy-2-methylene-18,19-dinorvitamin D3；(1R,3R)-5-[(2E)-2-[(1R,3aR,7aR)-1-[(2S)-6-hydroxy-6-methylheptan-2-yl]-1,2,3,3a,5,6,7,7a-octahydroinden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol
• 化学式: C₂₆H₄₂O₃
• 分子量: 402.618
• InChiKey: LTTDETGPYPVMCP-QOFIXJPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

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 、 二异丁基氢化铝 、 苯基锂 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 5.33h， 生成 2-Methylene-18,19-dinor-(20S)-1alpha,25-dihydroxyvitamin D3
  参考文献：
  名称：

  Vitamin D analogs for obesity prevention and treatment

  摘要：

  治疗和预防肥胖的方法，抑制脂肪细胞分化，抑制增加的SCD-1基因转录，和/或减少受试者体脂肪的方法包括向需要的受试者施用至少一种1α,25-二羟基维生素D3或1α,25-二羟基维生素D2的类似物或包含这种类似物的药物组合物。该类似物可以是19-去甲基维生素D类似物，如式IA的化合物，式IB的化合物，或其中的混合物，其中变量R1、R2和R3具有此处描述的值。

  公开号：

  US20050119242A1

文献信息

• Removal of the 20-methyl group from 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) selectively eliminates bone calcium mobilization activity
  作者：Rafal Barycki、Rafal R. Sicinski、Lori A. Plum、Pawel Grzywacz、Margaret Clagett-Dame、Hector F. DeLuca

  DOI：10.1016/j.bmc.2009.09.047

  日期：2009.11

  convergent syntheses. The known phosphine oxide 10 was coupled by the Wittig–Horner process with the corresponding C,D-fragments (13–15), obtained by a multi-step procedure from commercial vitamin D2. The goal of our studies was to examine the influence of removal of the methyl groups located at carbons 13 and 20 on the biological potency of 2MD in the hope of finding analogs with improved therapeutic

  (20 S )-1α,25-dihydroxy-2-methylene-19-norvitamin D 3 ( 6 , 2MD )的 18-nor ( 7 )、21-nor ( 8 ) 和 18,21-dinor ( 9 ) 类似物由收敛合成制备。已知的氧化膦10与相应的C，d-片段（偶联通过维蒂希-霍纳过程13 - 15，从商业维生素d通过多步骤方法获得）2。我们研究的目的是检查去除位于碳 13 和 20 上的甲基对 2MD 的生物效力的影响，希望找到具有改进治疗特性的类似物。 在 2-methylene-19- nor- (20 S )-1α,25-dihydroxyvitamin D 3 (2MD)中用氢取代 20-甲基不影响与大鼠维生素 D 受体的结合，对转录活性几乎没有影响， HL-60 分化。然而，骨骼中钙的动员在很大程度上被消除，而肠道钙转运仍然很强。奇怪的是，去除 C-13-甲基和
• 2-alkylidene-18,19-dinor-vitamin D compounds
  申请人：DeLuca F. Hector

  公开号：US20050227950A1

  公开（公告）日：2005-10-13

  2-alkylidene-18,19-dinor-vitamin D compounds are disclosed as well as pharmaceutical uses for these compounds and methods of synthesizing these compounds. These compounds are characterized by low bone calcium mobilization activity and high intestinal calcium transport activity. This results in novel therapeutic agents for the treatment and prophylaxis of diseases where bone formation is desired, particularly osteoporosis, as well as autoimmune diseases such as multiple sclerosis, diabetes mellitus and lupus. These compounds also exhibit pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis. These compounds also increase both breaking strength and crushing strength of bones evidencing use in conjunction with bone replacement surgery such as hip and knee replacements.

  披露了2-烷基亚烯基-18,19-二诺尔维生素D化合物，以及这些化合物的药用途和合成这些化合物的方法。这些化合物的特点是低骨钙动员活性和高肠道钙运输活性。这导致了用于治疗和预防骨形成期望的疾病的新型治疗剂，特别是骨质疏松症，以及自身免疫疾病，如多发性硬化症、糖尿病和红斑狼疮。这些化合物还表现出明显的活性，可以阻止未分化细胞的增殖，并诱导它们分化为单核细胞，从而表明其用作抗癌剂和用于治疗银屑病等皮肤疾病。这些化合物还增加了骨骼的抗折强度和抗压强度，表明它们可与骨骼置换手术（如髋关节和膝关节置换）结合使用。
• Use of calcitonin and calcitonin-like peptides to treat and prevent multiple sclerosis
  申请人：DeLuca F. Hector

  公开号：US20070105774A1

  公开（公告）日：2007-05-10

  Methods for treating and preventing multiple sclerosis by administering to a patient an effective amount of calcitonin, calcitonin-like peptides or calcitonin mimetics to a patient. Additionally, 1,25-dihydroxyvitamin D analogs can be used in combination with the calcitonin, calcitonin-like peptides or calcitonin mimetics.
• USE OF CALCITONIN AND CALCITONIN-LIKE PEPTIDES TO TREAT AND PREVENT MULTIPLE SCLEROSIS
  申请人：DeLuca Hector F.

  公开号：US20080146491A1

  公开（公告）日：2008-06-19

  Methods for treating and preventing multiple sclerosis by administering to a patient an effective amount of calcitonin, calcitonin-like peptides or calcitonin mimetics to a patient. Additionally, 1,25-dihydroxyvitamin D analogs can be used in combination with the calcitonin, calcitonin-like peptides or calcitonin mimetics.
• US7566696B2
  申请人：——

  公开号：US7566696B2

  公开（公告）日：2009-07-28