双氢速甾醇 | 67-96-9

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 维生素AD类药
• 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: 双氢速甾醇
• 中文别名: 多沙唑嗪杂质F；二氢速甾醇
• 英文名称: Dihydrotachysterol2
• 英文别名: dihydrotachysterol；(1S,3E,4S)-3-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5R)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylcyclohexan-1-ol
• CAS: 67-96-9
• 化学式: C₂₈H₄₆O
• 分子量: 398.673
• InChiKey: ILYCWAKSDCYMBB-OPCMSESCSA-N

物化性质

• 熔点：
  116-120°C
• 比旋光度：
  D22 +97.5° (chloroform)
• 沸点：
  461.8°C (rough estimate)
• 密度：
  0.9678 (rough estimate)
• 溶解度：
  几乎不溶于水，易溶于丙酮和己烷，微溶于乙醇（96%）。
• 物理描述：
  Solid
• 颜色/状态：
  Needles from 90% methanol
• 气味：
  ODORLESS
• 蒸汽压力：
  5.2X10-10 mm Hg at 25 °C (est)
• 旋光度：
  Specific Optical Rotation: +97.5 deg at 22 °C/D (chloroform)
• 碰撞截面：
  205.8 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

DHT3（二氢速留醇3）经历25-羟基化反应，生成25-羟基二氢速留醇3（25-OHDHT3），这被认为是DHT（二氢速留醇）在肠道和骨骼中的活性形式。

DHT3 /vitamin D3/ undergoes 25-hydroxylation to yield 25-hydroxydihydrotachysterol3 (25-OHDHT3), which appears to be active form of DHT (dihydrotachysterol) in both intestine & bone.

来源:Hazardous Substances Data Bank (HSDB)

代谢

高比活度(14)C-和(3)H-标记的二氢速留醇被制备出来，并在佝偻病鸡和小鼠中研究了它们的代谢物。在最初的24小时内，约20%的二氢速留醇随胆汁排出，其中约50%为羧酸衍生物。尽管在所有组织中都检测到了极性代谢物，但没有观察到C-1位的羟基化。与胆钙化醇相比，在组织中检测到更大比例的母体类固醇及其25-OH衍生物，但在胆钙化醇的细胞内作用位点没有检测到单一代谢物。

High specific radioactivity (14)C- and (3)H-labeled dihydrotachysterol were prepared and their metabolites studied in rachitic chicks and rats. 20% dihydrotachysterol was excreted in the bile in the first 24 hours, about 50% as a carboxylic acid derivative. No hydroxylation at C-1 was observed, although polar metabolites were detected in all tissues. Larger proportions of the parent steroid and its 25-OH derivative were detected in tissues compared with cholecalciferol but no single metabolite was detected at the intracellular site of action of cholecalciferol.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

一旦羟基化成为25-羟基二氢羊毛脂醇，改性的药物就会与维生素D受体结合。维生素D受体的结合形式作为骨骼基质蛋白的转录调节因子，诱导骨钙素的表达并抑制I型胶原的合成。维生素D（与维生素D受体结合时）刺激表达多种参与从肠道腔内运输钙的蛋白质，穿过上皮细胞进入血液。这刺激了肠道对钙的吸收并增加了肾脏对磷酸盐的排泄。这些都是通常由甲状旁腺激素执行的功能。

Once hydroxylated to 25-hydroxydihydrotachysterol, the modified drug binds to the vitamin D receptor. The bound form of the vitamin D receptor serves as a transcriptional regulator of bone matrix proteins, inducing the expression of osteocalcin and suppressing synthesis of type I collagen. Vitamin D (when bound to the vitamin D receptor)stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. This stimulates intestinal calcium absorption and increases renal phosphate excretion. These are functions that are normally carried out by the parathyroid hormone.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口腔

Oral

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

与二氢速甾醇相关的毒性类似于大剂量维生素D所见的毒性。

Toxicity associated with dihydrotachysterol is similar to that seen with large doses of vitamin D.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露处理

治疗过量包括停止使用二氢速甾醇，卧床休息，大量饮水，低钙饮食，并给予泻药。高钙血症危机伴脱水和昏迷，昏迷和氮质血症需要更积极的治疗。首先应该是病人的水合作用。静脉注射盐水可以快速显著增加尿钙排泄。在盐水输注过程中，可以给予环利尿剂（呋塞米或依他尼酸）以进一步增加肾钙排泄。其他报告的治疗措施包括透析或给予柠檬酸盐，硫酸盐，磷酸盐，皮质类固醇，EDTA（乙二胺四乙酸）和密特拉霉素。

Treatment of overdosage consists of withdrawal of dihydrotachysterol, bed rest, liberal intake of fluids, a low-calcium diet, and administration of a laxative. Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment. The first step should be hydration of the patient. Intravenous saline may quickly and significantly increase urinary calcium excretion. A loop diurectic (furosemide or ethacrynic acid) may be given with the saline infusion to further increase renal calcium excretion. Other reported therapeutic measures include dialysis or the administration of citrates, sulfates, phosphates, corticosteroids, EDTA (ethylenediaminetetraacetic acids), and mithramycin via appropriate regimens. (L1712)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

起效时间：高钙血症：数小时（最大效果在1到2周后）。

Onset of action: Hypercalcemic: Several hours (maximal after 1 to 2 weeks).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

...二氢速甾醇及其代谢物的主要排泄途径可能是分泌到胆汁中并通过粪便排出...二氢速甾醇也通过乳汁排出...

...Major path of elimination of dihydrotachysterol & its metabolites is probably secretion into bile & excretion in feces ... dihydrotachysterol /is also/ excreted in breast milk ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

作用持续时间：口服给药后：长达9周。

Duration of action: following oral administration: Up to 9 weeks.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

维生素D的主要排泄途径是胆汁；只有很小一部分摄入剂量会出现在尿液中。

The primary route of excretion of vitamin D is the bile; only a small percentage of an administered dose is found in urine. /Vitamin D/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2936299055
• 危险品运输编号：
  UN 2811 6.1/PG 3
• 包装等级：
  III
• 危险类别：
  6.1(b)

反应信息

• 作为反应物：
  描述：

  双氢速甾醇 在 chromium(VI) oxide 、 溶剂黄146 作用下， 生成 (1R,3AR,7AR)-1-(((2R,5R,E)-5,6-二甲基庚-3--烯-2-基)-7A-甲基八氢-4H-茚满-4-酮
  参考文献：
  名称：

  v. Werder, Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1939, vol. 260, p. 119,126, 133

  摘要：

  DOI：
• 作为产物：
  描述：

  麦角固醇 在 sodium 、 N-甲基苯胺 作用下， 生成 双氢速甾醇
  参考文献：
  名称：

  Westerhof; Buisman, Recueil des Travaux Chimiques des Pays-Bas, 1956, vol. 75, p. 453,461

  摘要：

  DOI：

文献信息

• ANTHELMINTIC COMPOUNDS AND COMPOSITIONS AND METHOD OF USING THEREOF
  申请人：Meng Charles Q.

  公开号：US20140142114A1

  公开（公告）日：2014-05-22

  The present invention relates to novel anthelmintic compounds of formula (I) below: wherein Y and Z are independently a bicyclic carbocyclic or a bicyclic heterocyclic group, or one of Y or Z is a bicyclic carbocyclic or a bicyclic heterocyclic group and the other of Y or Z is alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, heterocyclyl or heteroaryl, and variables X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 and X 8 are as defined herein. The invention also provides for veterinary compositions comprising the anthelmintic compounds of the invention, and their uses for the treatment and prevention of parasitic infections in animals.

  本发明涉及以下式（I）的新型驱虫化合物： 其中 Y和Z分别是双环碳环或双环杂环基团，或者Y或Z中的一个是双环碳环或双环杂环基团，另一个是烷基，烯基，炔基，环烷基，苯基，杂环基或杂芳基，以及变量X 1 ，X 2 ，X 3 ，X 4 ，X 5 ，X 6 ，X 7 和X 8 如本文所定义。本发明还提供了包含本发明的驱虫化合物的兽药组合物，以及它们用于治疗和预防动物寄生虫感染的用途。
• [EN] ANTHELMINTIC DEPSIPEPTIDE COMPOUNDS<br/>[FR] COMPOSÉS DEPSIPEPTIDIQUES ANTHELMINTHIQUES
  申请人：MERIAL INC

  公开号：WO2018093920A1

  公开（公告）日：2018-05-24

  The present invention provides cyclic depsipeptide compounds of formula (I) wherein the stereochemical configuration of at least one carbon atom bearing the groups Cy1, Cy2, R1, R2, R3, R4, Ra and Rb is inverted compared with the naturally occurring cyclic depsipeptide PF1022A. The invention also provides compositions comprising the compounds that are effective against parasites that harm animals. The compounds and compositions may be used for combating parasites in or on mammals and birds. The invention also provides for an improved method for eradicating, controlling and preventing parasite infestation in birds and mammals.

  本发明提供了公式（I）的环状脱氨肽化合物，其中至少一个碳原子的立体化学构型与自然存在的环状脱氨肽PF1022A的基团Cy1、Cy2、R1、R2、R3、R4、Ra和Rb相比发生了倒置。该发明还提供了包含这些化合物的组合物，对危害动物的寄生虫具有有效性。这些化合物和组合物可用于对抗哺乳动物和鸟类体内或体表的寄生虫。该发明还提供了一种改进的方法，用于根除、控制和预防鸟类和哺乳动物的寄生虫感染。
• [EN] BINDING-SITE MODIFIED LECTINS AND USES THEREOF<br/>[FR] LECTINES DE SITE DE LIAISON MODIFIÉES ET USAGE CORRESPONDANT
  申请人：SMARTCELLS INC

  公开号：WO2010088261A1

  公开（公告）日：2010-08-05

  In one aspect, the disclosure provides cross-linked materials that include multivalent lectins with at least two binding sites for glucose, wherein the lectins include at least one covalently linked affinity ligand which is capable of competing with glucose for binding with at least one of said binding sites; and conjugates that include two or more separate affinity ligands bound to a conjugate framework, wherein the two or more affinity ligands compete with glucose for binding with the lectins at said binding sites and wherein conjugates are cross-linked within the material as a result of non-covalent interactions between lectins and affinity ligands on different conjugates. These materials are designed to release amounts of conjugate in response to desired concentrations of glucose. Depending on the end application, in various embodiments, the conjugates may also include a drug and/or a detectable label.

  在一个方面，该公开提供了包括多价凝集素的交联材料，其中该多价凝集素具有至少两个葡萄糖结合位点，其中该凝集素包括至少一个与亲和配体共价连接的亲和配体，该亲和配体能够与至少一个所述结合位点中的葡萄糖竞争结合；以及包括绑定到共轭框架的两个或更多个独立亲和配体的共轭物，其中这两个或更多个亲和配体与葡萄糖在所述结合位点上与凝集素竞争结合，其中由于不同共轭物上的凝集素和亲和配体之间的非共价相互作用，共轭物在材料内交联。这些材料旨在根据所需葡萄糖浓度释放共轭物的量。根据最终应用，在各种实施例中，共轭物还可以包括药物和/或可检测标记。
• GLUTATHIONE-CHOLESTEROL DERIVATIVES AS BRAIN TARGETING AGENTS
  申请人：South Dakota Board of Regents

  公开号：US20200048305A1

  公开（公告）日：2020-02-13

  The present invention describes compositions containing cholesterol-linker-glutathione conjugates for targeting the brain by overcoming barrier entry to the CNS through the blood brain barrier (BBB), including micelle and liposome forms of such compositions. In addition, methods for treating subjects by administering such compositions are also disclosed.

  本发明描述了含有胆固醇-连接剂-谷胱甘肽共轭物的组合物，通过克服血脑屏障（BBB）进入中枢神经系统的屏障入口，包括这些组合物的胶束和脂质体形式。此外，还公开了通过给予这些组合物治疗受试者的方法。
• [EN] ANTI PARASITIC DIHYDROAZOLE COMPOUNDS AND COMPOSITIONS COMPRISING SAME<br/>[FR] DIHYDROAZOLES ANTIPARASITAIRES ET COMPOSITIONS LES INCLUANT
  申请人：MERIAL LTD

  公开号：WO2011075591A1

  公开（公告）日：2011-06-23

  The present invention relates to novel dihydroazole of formula (I) and salts thereof: Wherein R1, A1, A2, G, X and Y are as defined in the description, compositions thereof, processes for their preparation and their uses to prevent or treat parasitic infections or infestations in animals and as pesticides.

  本发明涉及式(I)的新型二氢咪唑及其盐：其中R1、A1、A2、G、X和Y如描述中所定义，以及它们的组合物、制备方法以及它们用于预防或治疗动物寄生虫感染或寄生虫侵袭以及作为杀虫剂的用途。