3-[N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]propionic acid | 599-54-2

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 其它维生素类药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-[N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]propionic acid
• 英文别名: panthothenic acid；D,L-pantothenate；pantothenic acid；vitamin B5；N-DL-pantoyl-β-alanine；DL-pantothenic acid；3-[(2,4-dihydroxy-3,3-dimethylbutanoyl)amino]propanoic acid
• CAS: 599-54-2
• 化学式: C₉H₁₇NO₅
• mdl: MFCD00459547
• 分子量: 219.238
• InChiKey: GHOKWGTUZJEAQD-UHFFFAOYSA-N

物化性质

• 沸点：
  551.5±50.0 °C(Predicted)
• 密度：
  1.266±0.06 g/cm3(Predicted)
• 颜色/状态：
  Yellow viscous oil
• 溶解度：
  Very soluble in water, benzene, ethyl ether
• 蒸汽压力：
  5.14X10-9 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Unstable ... easily destroyed by acids, bases, heat

• 旋光度：
  Specific optical rotation: 37.5 deg at 25 °C/D
• 分解：
  When heated to decomposition it emits toxic vapors of /nitric oxide/.

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.777
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  5

ADMET

代谢

泛酸激酶是泛酸（pantothenate）合成辅酶A（CoA）的主要调节酶，该酶可被途径的终产物辅酶A和酰基辅酶A抑制。

The synthesis of Coenzyme A (CoA) from pantothenate is regulated primarily by pantothenate kinase, an enzyme that is inhibited by the pathway end products, CoA and acyl CoA.

来源:Hazardous Substances Data Bank (HSDB)

代谢

泛酸是碳水化合物、蛋白质和脂质中介代谢所必需的。泛酸是辅酶A的前体，它在糖异生中的作用是乙酰化（酰基团激活）反应，以及在碳水化合物释放能量、脂肪酸的合成和降解、固醇和类固醇激素、卟啉、乙酰胆碱以及其他化合物的合成中都是必需的。

/P/antothenic acid is required for intermediary metabolism of carbohydrates, proteins, and lipids. Pantothenic acid is a precursor of coenzyme A which is required for acetylation (acyl group activation) reactions in gluconeogenesis, in the release of energy from carbohydrates, the synthesis and degradation of fatty acids, and the synthesis of sterols and steroid hormones, porphyrins, acetylcholine, and other compounds.

来源:Hazardous Substances Data Bank (HSDB)

代谢

吸收辅酶A（CoA）。饮食中的CoA在小肠腔中被水解为去磷酸CoA、磷酸泛酰巯基乙胺和泛酰巯基乙胺，随后泛酰巯基乙胺被水解为泛酸。在研究各种形式吸收的大鼠实验中，泛酸是这些含泛酸化合物中唯一被吸收的一种。在动物模型中，泛酸的吸收是通过在低浓度下的主动运输和高浓度下的被动运输实现的。由于主动运输系统是可饱和的，因此在摄入浓度较高时，吸收效率会降低，但在人类中吸收效率降低的摄入水平尚不清楚。

Absorption Coenzyme A (CoA). CoA in the diet is hydrolyzed in the intestinal lumen to dephospho CoA, phosphopantetheine, and pantetheine, with the pantetheine subsequently hydrolyzed to pantothenic acid. Pantothenic acid was the only one of these pantothenate-containing compounds absorbed by rats in studies on absorption of the various forms. Absorption is by active transport at low concentrations of the vitamin and by passive transport at higher concentrations in animal models. Because the active transport system is saturable, absorption will be less efficient at higher concentrations of intake, but the intake levels at which absorptive efficiency decreases in humans are not known.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肠道微生物群在小鼠中已被观察到能够合成泛酸，但是细菌合成对人类体内泛酸水平或粪便中泛酸损失的贡献尚未被量化。如果微生物合成相当大，那么在人类中的平衡研究可能低估了泛酸的吸收和需求。

Intestinal microflora have been observed to synthesize pantothenic acid in mice, but the contribution of bacterial synthesis to body pantothenic acid levels or fecal losses in humans has not been quantified. If microbial synthesis is substantial, balance studies in humans may have underestimated pantothenic acid absorption and requirements.

来源:Hazardous Substances Data Bank (HSDB)

代谢

辅酶A（CoA）通过多步反应水解成泛酸。泛酸以完整形式从尿液中排出……排出的量与饮食摄入量成正比，在一段离散但广泛的摄入值范围内变化。

Coenzyme A (CoA) is hydrolyzed to pantothenate in a multiple-step reaction. The pantothenic acid is excreted intact in urine, ... . The amount excreted varies proportionally with dietary intake over a discrete yet wide range of intake values.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

尽管其临床重要性尚未确立，但据报道，抗胆碱酯酶眼科制剂（例如，碘化乙氧噻吩（在美国已不再商业销售），异氟磷酸）的缩瞳作用可能会被泛酸增强。

Although the clinical importance has not been established, the miotic effects of anticholinesterase ophthalmic preparations (eg, echothiophate iodide (no longer commercially available in the US), isoflurophate) reportedly may be potentiated by pantothenic acid.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

泛酸衍生物（磷酸泛酸、泛醇和泛硫乙胺）的降血脂作用在小鼠下丘脑性肥胖模型上进行了研究，该模型是通过单次注射金硫葡萄糖（300 mg/kg体重，腹腔注射）诱导的。所有测试物质均在处死前最后10天内给药（肌肉注射，剂量相当于150 mg/kg体重的磷酸泛酸）。研究发现，这些物质抑制了下丘脑性肥胖动物在实验最后10天的体重增加。金硫葡萄糖治疗增加了食物摄入量、平均体重、血糖水平；胰岛素、血清总胆固醇、甘油三酯、LDL+VLDL之和以及LDL-胆固醇浓度；肝脏中的甘油三酯和胆固醇组分；以及实验小鼠脂肪组织中的甘油三酯和游离脂肪酸含量以及脂蛋白脂肪酶活性。给药测试化合物降低了食物摄入量、平均体重、胰岛素和葡萄糖水平，并减少了血清和脂肪组织中的甘油三酯、总胆固醇和胆固醇酯含量，同时提高了脂肪组织中的脂蛋白脂肪酶活性和肥胖小鼠血清中的脂解活性。在研究的化合物中，泛醇的逆转效果尤为显著。泛酸衍生物的降血脂作用机制可能与提高对胰岛素的敏感性以及血清和脂肪组织中脂解作用的激活有关。/泛醇、磷酸泛酸、泛硫乙胺/

The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity ... induced by single injection of aurothioglucose (300 mg/kg body wt, ip). All the tested substances were administered during the last 10 days before decapitation (im, of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue. /Panthenol, Phosphopantothenate, Pantethine/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

1.2克钙泛酸、0.6克吡哆醇、3克烟酰胺和3克抗坏血酸每日服用6周与儿童血清转氨酶水平升高有关。因此，这些剂量中的一种或组合可能会导致肝毒性，但仅凭这项研究无法将报告的肝功能不良反应归因于泛酸。

A combination of 1.2 g of calcium pantothenate, 0.6 g of pyridoxine, 3 g of niacinamide, and 3 g of ascorbic acid taken daily for 6 weeks was associated with elevations in serum transaminase levels in children. One of these doses or the combination may therefore cause hepatotoxicity, but it is not possible from this study alone to ascribe to pantothenic acid the reported adverse effect in liver function.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在神经管闭合前，给怀孕的CD-1小鼠施用致畸剂量的丙戊酸（VPA），并分析了胚胎蛋白水平。与对照组相比，VPA（400 mg/kg）诱导的神经管缺陷（NTD）占24%，暴露于VPA并出现神经管缺陷的胚胎p53蛋白水平增加了2倍，而NF-kappaB、Pim-1和c-Myb蛋白水平下降了4倍（P<0.05）。此外，VPA增加了胚胎Bax/Bcl-2蛋白水平的比率（P<0.05）。在VPA处理前，给怀孕的母鼠预先施用叶酸或泛酸可以显著防止VPA诱导的NTD（P<0.05）。叶酸还减少了VPA诱导的p53、NF-kappaB、Pim-1、c-Myb和Bax/Bcl-2蛋白水平的改变，而泛酸则预防了VPA诱导的NF-kappaB、Pim-1和c-Myb的改变...

... Pregnant CD-1 mice were administered a teratogenic dose of valproic acid (VPA) prior to neural tube closure and embryonic protein levels were analyzed. ... VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with a neural tube defect (NTD) showed a 2-fold increase in p53, and 4-fold decreases in NF-kappaB, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P<0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P<0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P<0.05). Folic acid also reduced VPA-induced alterations in p53, NF-kappaB, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-kappaB, Pim-1, and c-Myb...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

泛酸在小肠中被吸收，低浓度时通过主动运输，高浓度时通过被动运输。由于主动运输系统是可饱和的，因此在高摄入浓度时吸收效率较低。然而，目前尚不清楚在摄入量达到何种水平时，人体内的吸收会减少。泛酸在尿液中的排泄量与饮食摄入量成比例，适用于广泛摄入值范围。

Pantothenic acid is absorbed in the small intestine by active transport at low concentrations of the vitamin and by passive transport at higher concentrations. Because the active transport system is saturable, absorption is less efficient at higher concentrations of intake. However, the exact intake levels at which absorption decreases in humans are not known. Pantothenic acid is excreted in the urine in amounts that are proportional with dietary intake over a wide range of intake values.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

泛酸可从胃肠道被很好地吸收。它存在于所有组织中，浓度从2-45微克/克不等。由于摄入和排出的泛酸量大约相等，泛酸在人体内似乎不会被破坏。大约70%的未改变的泛酸通过尿液排出，约30%通过粪便排出。

Pantothenic acid is readily absorbed from the GI tract. It is present in all tissues, in concentrations ranging from 2-45 ug/g. Pantothenic acid apparently is not destroyed in human body since intake and excretion ... are approximately equal. About 70% of unchanged pantothenic acid is excreted in urine and about 30% in feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

泛酸在口服给药后可从胃肠道被很好地吸收。正常的血清泛酸盐浓度应为100微克/毫升或更高。泛酸广泛分布到身体各组织中，主要以辅酶A的形式存在。在肝脏、肾上腺、心脏和肾脏中浓度最高。接受正常饮食的哺乳期母亲的乳汁中大约含有每毫升2微克的泛酸。口服的泛酸剂量中大约有70%以原形从尿液中排出，大约30%从粪便中排出。

Pantothenic acid is readily absorbed from the GI tract following oral administration. Normal serum pantothenate concentrations are 100 ug/mL or greater. /Pantothenic acid/ is widely distributed into body tissues, mainly as coenzyme A. Highest concentrations are found in the liver, adrenal glands, heart, and kidneys. Milk of nursing mothers receiving a normal diet contains about 2 ug of pantothenic acid per mL. About 70% of an oral dose of pantothenic acid is excreted unchanged in urine and about 30% in feces.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

新生儿泛酸水平显著高于母体水平。在足月时，174位母亲的平均泛酸水平为430 ng/mL（范围250-710），而他们新生儿为780 ng/mL（范围400-1480）。泛酸通过胎盘主动运输转移到胎儿，但这一过程比其他B族维生素的转移要慢。在一项报告中，低出生体重婴儿的泛酸水平显著低于正常体重婴儿。

... /N/ewborn pantothenic acid levels are significantly greater than maternal levels. At term, mean pantothenate levels in 174 mothers were 430 ng/mL (range 250-710) and in their newborns 780 ng/mL (range 400-1480). Placental transfer of pantothenate to the fetus is by active transport, but it is slower than transfer of other B complex vitamins. In one report, low-birth-weight infants had significantly lower levels of pantothenic acid than did normal weight infants.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2924199090
• 储存条件：
  存储条件：2-8°C，干燥，避光

制备方法与用途

泛酸((±)-PaNTothenate)，一种B族维生素，对于哺乳动物细胞中辅酶A(CoA)的生物合成是必需的。研究显示，泛酸能够保护丙戊酸(VPA)诱导的CD-1小鼠神经管缺陷(NTD)[1]。

反应信息

• 作为反应物：
  描述：

  3-[N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]propionic acid 在 pantothenate kinase 作用下， 生成 泛酸钙杂质
  参考文献：
  名称：

  Stable pantetheine derivatives for the treatment of pantothenate kinase associated neurodegeneration (pkan) and methods for the synthesis of such compounds

  摘要：

  该发明涉及(S)-酰基-4'-磷酰泛醇衍生物，其合成方法，以及这类化合物的相关医学用途。首选的医学用途与治疗神经退行性疾病有关，如PKAN。

  公开号：

  EP2868662A1
• 作为产物：
  描述：

  calcium pantothenate 在 硫酸 作用下， 以 水 为溶剂， 生成 3-[N-(2,4-dihydroxy-3,3-dimethyl-1-oxobutyl)amino]propionic acid
  参考文献：
  名称：

  WO2007/21219

  摘要：

  公开号：

文献信息

• Additives and products including oligoesters