4-Methyl-3-[2-[7a-methyl-1-((E)-1,4,5-trimethyl-hex-2-enyl)-octahydro-inden-(4E)-ylidene]-eth-(E)-ylidene]-cyclohexanol | 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
• 英文名称: 4-Methyl-3-[2-[7a-methyl-1-((E)-1,4,5-trimethyl-hex-2-enyl)-octahydro-inden-(4E)-ylidene]-eth-(E)-ylidene]-cyclohexanol
• 英文别名: Calcamine；(3E)-3-[(2E)-2-[1-[(E)-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-ZJGOHBTISA-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%）。
• 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)

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

• 相互作用

皮质类固醇抵消维生素D类似物的作用。/维生素D类似物/

Corticosteroids counteract the effects of vitamin D analogs. /Vitamin D analogs/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

噻嗪类利尿剂和药理剂量的维生素D类似物在患有低甲状旁腺功能的病人中同时使用可能会导致高钙血症，这种情况可能是暂时的、自限性的，或者可能需要停止使用维生素D类似物。低甲状旁腺病人中由噻嗪类引起的高钙血症可能是由于骨骼中钙的释放增加所致。/维生素D类似物/

Concurrent administration of thiazide diuretics and pharmacologic doses of vitamin D analogs in patients with hypoparathyroidism may result in hypercalcemia which may be transient and self-limited or may require discontinuance of vitamin D analogs. Thiazide-induced hypercalcemia in hypoparathyroid patients is probably caused by increased release of calcium from bone. /Vitamin D analogs/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

过度使用矿物油可能会干扰肠道对维生素D类似物的吸收。/维生素D类似物/

Excessive use of mineral oil may interfere with intestinal absorption of vitamin D analogs. /Vitamin D analogs/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

奥利司他可能会导致脂肪溶性维生素（如维生素D类似物）的胃肠道吸收减少。在任何奥利司他剂量和维生素D类似物给药之间应至少间隔2小时……。/维生素D类似物/

Orlistat may result in decreased GI absorption of fat-soluble vitamins such as vitamin D analogs. At least 2 hours should elapse between (before or after) any orlistat dose and vitamin D analog administration ... . /Vitamin D analogs/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

药物治疗:立即停止服用维生素，低钙饮食，使用糖皮质激素，大量饮水。实验表明，氢化可的松可以减少钙的吸收，在人身上，它确实能更快地将升高的血钙浓度恢复到正常水平。/维生素D/

EXPL THER: ... Immediate withdrawal of vitamin, low-calcium diet, administration of glucocorticoids, & generous intake of fluid. ... Hydrocortisone has been shown exptl to decrease calcium absorption, & in man it does cause more rapid reversion of elevated plasma calcium concentration to normal. /Vitamin D/

来源:Hazardous Substances Data Bank (HSDB)

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)