D-泛酸 | 79-83-4

• 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 - 有机氧化合物
• 中文名称: D-泛酸
• 中文别名: (R)-N-(2,4-二羟基-3,3-二甲基-1-氧代丁基)-β-丙氨酸；本多生酸；N-(2,4-二羟基-3,3-二甲基丁酰)-β-丙氨酸；D(+)-N-(2,4-二羥-3,3-二甲丁醯基)-Β-胺丙酸；泛酸；D-泛酸钙；泛硫乙胺；维生素B5
• 英文名称: pantothenic acid
• 英文别名: vitamin B5；D-pantothenic acid；pantothenate；3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoic acid
• CAS: 79-83-4
• 化学式: C₉H₁₇NO₅
• 分子量: 219.238
• InChiKey: GHOKWGTUZJEAQD-ZETCQYMHSA-N

物化性质

• 熔点：
  178-179℃
• 比旋光度：
  D25 +37.5°
• 沸点：
  360.05°C (rough estimate)
• 密度：
  1.266
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）
• LogP：
  -0.856 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Yellow viscous oil
• 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/.
• 碰撞截面：
  148.1 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)：
  -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：
  0.78
• 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，它在糖异生的乙酰化（酰基团活化）反应中、从碳水化合物释放能量的过程中、脂肪酸的合成和降解中、以及固醇和类固醇激素、卟啉、乙酰胆碱和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。在关于各种形式吸收的研究中，泛酸是这些含有泛酸的物质中唯一被大鼠吸收的。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在较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，但尚不清楚在人类摄入水平上吸收效率降低的具体数值。

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

尽管尚未确定其临床重要性，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体重磷酸泛酸的剂量）。研究的物质在实验的最后10天内抑制了下丘脑性肥胖动物的体重增加。金硫葡萄糖治疗增加了食物摄入量和平均体重、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；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和平均体重、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的含量，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，泛醇的逆转效果尤其显著。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，这些剂量之一或联合用药可能会导致肝毒性，但仅凭这项研究无法将报告的肝功能不良影响归因于泛酸。

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，用叶酸或泛酸预先处理怀孕的母鼠，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，而泛酸阻止了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和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，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，让患者前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通并防止吸入。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

• 吸收

膳食中的泛酸主要以辅酶A（CoA）或酰基载体蛋白（ACP）的形式存在，必须转化为游离的泛酸才能被吸收。CoA和ACP被水解成4'-磷酸泛酰巯基乙胺，然后去磷酸化成泛硫乙胺，接着再次通过肠道腔内的泛硫乙胺酶水解成游离的泛酸。游离的泛酸通过一种可饱和的、钠依赖性的主动运输系统被吸收进入肠细胞，被动扩散作为次要途径。随着摄入量的增加，吸收率可降低至10%，因为运输蛋白会饱和。

Dietary pantothenic acid is primarily in the form of CoA or ACP and must be converted into free pantothenic acid for absorption. CoA and ACP are hydrolyzed into 4'-phosphopantetheine which is then dephosphorylated into pantetheine and subsequently hydrolyzed again to free pantothenic acid by Pantetheinase in the intestinal lumen. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system with passive diffusion acting as a secondary pathway. As intake increases up to 10-fold absorption rate can decrease to as low as 10% due to transporter saturation.

来源:DrugBank

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

泛酸能从胃肠道轻易吸收。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，大约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

泛酸口服给药后可从胃肠道被很好地吸收。正常的血清泛酸浓度应为100微克/毫升或更高。泛酸广泛分布于体内各组织中，主要以辅酶A的形式存在。在肝脏、肾上腺、心脏和肾脏中含量最高。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。口服的泛酸剂量中约有70%未经改变地在尿液中排出，约30%通过粪便排出。

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亲水平。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)

制备方法与用途

简介

D-泛酸是一种无色或淡黄色的黏性油状液体，易吸湿且不稳定。它在酸、碱和热的作用下会加速分解。D-泛酸难溶于苯和氯仿，微溶于乙醚和戊醇，但易溶于水、乙酸乙酯、二氧六环和冰醋酸。

生理功能与作用

D-泛酸在体内可以转化为辅酶A（CoA）或酰基载体蛋白（ACP），参与脂肪酸代谢反应。辅酶A是生物体内70多种酶的辅助因子之一，约占总酶量的4%，对于细菌构建细胞壁也有重要作用。在新陈代谢过程中，辅酶A主要发挥酰基载体的功能，参与糖、脂肪、蛋白质和能量代谢，并可通过修饰蛋白质影响其定位、稳定性和活性。辅酶A为生物体提供了90%的能量。

泛酸对脂肪酸合成类固醇、类固醇紫质、褪黑激素和亚铁血红素的合成至关重要。它还是体内柠檬酸循环、胆碱乙酰化及抗体合成等代谢过程中的中间物。因此，D-泛酸在体内可以作用于神经、肾上腺、消化道及皮肤等正常的上皮器官，提高动物对病原体的抵抗力。

应用

D-泛酸广泛应用于生化研究和药物研发。

生产方法

由于泛酸具有很强的吸湿性，难以结晶，通常会将其制成钙盐或钠盐。D-泛酸自然存在且具生理活性，可通过异丁醛与甲醛在碳酸钾的存在下进行醛醇缩合反应生成dl-泛内酯，再与氨基丙酸钙反应得到。此外，也可以通过本多生酸钙与硫酸的反应制备。

食品添加剂最大允许使用量及残留标准

• 运动营养食品：泛酸作为营养强化剂的最大允许使用量为0.8至20毫克/公斤。
• 较大婴儿和幼儿配方食品：泛酸作为营养强化剂的最大允许添加量为1.5至8.5毫克/100克。
• 果汁（味）饮料、茶饮料及碳酸饮料：泛酸作为营养强化剂的最高允许使用量为每公斤2.2毫克（以泛酸计，具体数值可能根据不同标准略有差异）。

化学性质

D-泛酸是一种无色或淡黄色黏性油状液体，易吸湿且不稳定，在酸、碱和热的作用下会加速分解。它难溶于苯和氯仿，微溶于乙醚和戊醇，但易溶于水、乙酸乙酯、二氧六环和冰醋酸。

用途

D-泛酸主要用于生化研究及药物研发；也可作为饲料添加剂、医药和食品添加剂中的成分。泛酸钠因其吸湿性较强而较少使用，现在通常改用D-泛酸。

生产方法

由于泛酸具有很强的吸湿性，难以结晶，通常会制成钙盐或钠盐。D-泛酸在自然界中存在且具生理活性，其工业生产过程见相关文献资料。

反应信息

• 作为反应物：
  描述：

  D-泛酸 在 吡啶 、 disodium hydrogenphosphate 、 sodium hydride 、 lithium bromide 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 2.0h， 生成 S-phenyl (R)-3-(4-((bis((trimethylsilyl)oxy)phosphoryl)oxy)-2-hydroxy-3,3-dimethylbutanamido)propanethioate
  参考文献：
  名称：

  Martin, David P.; Drueckhammer, Dale G., Journal of the American Chemical Society, 1992, vol. 114, # 18, p. 7287 - 7288

  摘要：

  DOI：
• 作为产物：
  描述：

  D-泛醇 在 barium permanganate 、 硫酸 作用下， 生成 D-泛酸
  参考文献：
  名称：

  US2377814

  摘要：

  公开号：
• 作为试剂：
  描述：

  D-葡萄糖 在 ammonium dihydrogen phosphate 、 dipotassium hydrogenphosphate 、 potassium dihydrogenphosphate 、 2-甲基-3-羟基-4,5-二羟甲基吡啶 、 air 、 sodium 35S-sulphate 、 D-泛酸 、 Inositol 、 zinc diacetate 、 盐酸硫胺 、 三氯化铁 、 DL-asparagine monohydrate 、 柠檬酸 、 sodium chloride 、 copper dichloride 、 magnesium chloride 、 D-生物素 作用下， 反应 24.0h， 以7%的产率得到[35S]-L-cysteine
  参考文献：
  名称：

  Biotechnological production of high specific activity L-35 S-cysteine and L-35 S-methionine by using a diploid yeast Saccharomyces cerevisiae

  摘要：

  采用野生型二倍体面包酵母菌株——酿酒酵母合成了高比活性的L-35 S-半胱氨酸和L-35 S-蛋氨酸。酵母细胞在硫贫化的合成培养基中生长，其中补充Na2 35 SO4 (50 mCi/ml)作为唯一的硫源。合并水平平均为60%。对培养细胞的蛋白质水解产物进行纸色谱和柱色谱分离，得到单独的L-35 S-氨基酸。半胱氨酸和蛋氨酸的放射化学收率分别为6-7%和18-20%。产品放射化学纯度>95%。采用该方法获得的产物的最高比活度为1100 Ci/mmole，起始原料Na2 35 SO4，比活度为1350 Ci/mmole。

  DOI：

  10.1002/jlcr.2580340612

文献信息

• Additives and products including oligoesters
  申请人：——

  公开号：US20030199593A1

  公开（公告）日：2003-10-23

  The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.

  本发明涉及寡酯及其用途或添加剂的制备。含有寡酯的添加剂和/或寡酯本身可用于配制药物制剂、化妆品或个人护理产品，如洗发水和护发素。这些寡酯对于制备能够赋予调理、长效性和/或紫外线保护的多功能添加剂特别有用。描述了单独的寡酯和寡酯混合物。
• Novel indole derivatives as selective androgen receptor modulators (SARMS)
  申请人：Lanter C. James

  公开号：US20050245485A1

  公开（公告）日：2005-11-03

  The present invention is directed to novel indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by the androgen receptor.

  本发明涉及新型吲哚衍生物，含有它们的药物组合物以及它们在治疗由雄激素受体调节的疾病和症状中的应用。
• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。