甘露糖醇六硝酸酯 | 15825-70-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 甘露糖醇六硝酸酯
• 中文别名: 甘露六硝酯；六硝基甘露醇
• 英文名称: mannitol hexanitrate
• 英文别名: d-mannitol hexanitrate；MHN；hexa-O-nitro-D-mannitol；Hexa-O-nitro-D-mannit；Mannithexanitrat；[(2R,3R,4R,5R)-1,2,4,5,6-pentanitrooxyhexan-3-yl] nitrate
• CAS: 15825-70-4
• 化学式: C₆H₈N₆O₁₈
• 分子量: 452.159
• InChiKey: DGMJZELBSFOPHH-KVTDHHQDSA-N

物化性质

• 熔点：
  106-108°
• 沸点：
  559.71°C (rough estimate)
• 密度：
  1.8000
• 颜色/状态：
  Colorless crystals
• 溶解度：
  In water, 54.8 mg/L at 25 °C (est)
• 蒸汽压力：
  2.98X10-8 mm Hg at 25 °C (est)
• 分解：
  Upon decomposition it emits toxic fumes of /nitroxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  330
• 氢给体数：
  0
• 氢受体数：
  18

ADMET

代谢

从硝基酯中形成亚硝酸盐离子的特性在兔子的血液和组织悬浮液中得到了研究。悬浮液是通过将白兔的新鲜组织与四部分水缓冲液均质化制成的。将等体积的组织匀浆和硝基酯溶液混合。移取样品并进行亚硝酸盐分析。当硝甘油与肝脏匀浆一起孵化时，会迅速形成无机亚硝酸盐，但与肌肉匀浆或稀释的全血一起孵化则不会。硝基甘油、L-葡萄糖三硝酸和己糖醇六硝酸形成亚硝酸盐的速率受到pH值的影响。在pH值为8.4时，形成的体积最高。热对硝基甘油和己糖醇六硝酸有灭活作用，但在低温下对L-葡萄糖三硝酸仅部分灭活，而在60至100摄氏度之间，活性增加。对于己糖醇六硝酸，释放的亚硝酸盐量随着酯浓度的增加而增加。作者得出结论，无机亚硝酸盐是通过正常兔组织中的两个系统从多元醇的硝基酯形成的。第一个主要发生在肝脏，对热不稳定，而第二个在肝脏、肌肉和血液中，可被热激活。

The nature of the formation of nitrite ion from nitrate esters in the presence of blood and tissue suspensions from rabbits was examined. Suspensions were made by homogenizing one part fresh tissue from white-rabbits and four parts aqueous buffer. Equal volumes of the homogenate and a solution of nitrate ester were mixed. Samples for nitrite assay were removed and analyzed. Inorganic nitrite was formed rapidly when glycerol-trinitrate was incubated with the liver homogenate but not with muscle homogenate or diluted whole blood. The rate of nitrite formation from glycerol-trinitrate, l-glucosan-trinitrate, and mannitol-hexanitrate was influenced by pH. Highest volumes formed when the pH was 8.4. Heat had an inactivation effect for glycerol-trinitrate and mannitol-hexanitrate but only partial inactivation took place at low temperatures for l-glucosan-trinitrate while at temperatures between 60 and 100 degrees-C, activity increased. For mannitol-hexanitrate, the amount of nitrite liberated increased with increasing ester concentration. The authors conclude that inorganic nitrite is formed from nitrate esters of polyhydric alcohols by two systems occurring in normal rabbit tissues. The first, occurring principally in the liver, is heat labile while the second, found in liver, muscle, and blood, is activated by heat.

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、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，让患者前倾或将其置于左侧（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。 /硝酸盐、亚硝酸盐及相关化合物/

/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Nitrates, nitrites, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有必要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测休克迹象，并在必要时进行治疗……预见癫痫发作并视需要进行治疗……对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……/硝酸盐、亚硝酸盐及相关化合物/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat as necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Nitrates, nitrites, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于失去意识或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。监测心率和必要时治疗心律失常。开始静脉输注5%葡萄糖溶液（D5W）/SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。如果对这些措施无反应，血管加压药可能有所帮助。注意观察液体过载的迹象...。用地西泮或劳拉西泮治疗癫痫...。如果病人在严重低氧血症、发绀和心脏受累（对氧气无反应）出现症状，给予1%亚甲蓝溶液...。使用丙美卡因氢氯化物协助眼部冲洗... /硝酸盐、亚硝酸盐及相关化合物/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary. Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. If unresponsive to these measures, vasopressors may be helpful. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Nitrates, nitrites, and related compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

/替代和体外测试/ 研究了甘油三硝基酯（GTN）、甘露醇六硝基酯（MHN）和赤藓糖醇四硝基酯（ETN）对电子传递和氧化磷酸化的作用模式。大鼠肝脏线粒体被分离出来，在有机硝酸盐酯的存在下，通过光谱法测量了氧气的消耗量。GTN的主要作用是阻断线粒体对腺苷二磷酸（ADP）的反应，并在ADP存在时降低氧气消耗率。相比之下，MHN导致氧气消耗率增加。当氧化与磷酸化解耦时，GTN抑制了解耦速率，MHN也在较小程度上如此。当使用琥珀酸而不是3-羟基丁酸作为底物时，GTN没有抑制呼吸作用，尽管MHN有抑制作用。以3-羟基丁酸为底物的受控呼吸也被ETN释放，但浓度高于MHN，0.5毫摩尔溶液与0.1毫摩尔溶液相比。以琥珀酸为底物时，ETN没有抑制电子传递。

/ALTERNATIVE and IN VITRO TESTS/ The mode of action of glycerol-trinitrate (GTN), mannitol-hexanitrate (MHN), and erythritol-tetranitrate (ETN) on electron transport and on oxidative phosphorylation were studied in rats. Rat liver mitochondria were isolated, and oxygen consumption was measured spectrometrically in the presence of the organic nitrate esters. The primary action of GTN was to block the response of mitochondria to adenosine-diphosphate (ADP) and to lower the rate of oxygen consumption when ADP was present. In contrast, MHN resulted in an increase in the rate of oxygen consumption. When oxidation was uncoupled from phosphorylation, GTN inhibited the uncoupled rate, as did MHN, to a smaller extent. When succinate, instead of 3-hydroxybutyrate, was used as substrate, GTN did not inhibit respiration, although MHN did. Controlled respiration with 3-hydroxybutyrate as substrate was also released by ETN, but at higher concentrations than MHN, 0.5 millimolar solution compared to 0.1 millimolar solution. With succinate as substrate, ETN did not inhibit electron transport.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

/替代性和体外试验/ 甘露醇六硝酸酯（MANHN）、iditol六硝酸酯和山梨坦四硝酸酯，三者均在442微摩尔浓度下，能刺激离体兔心房组织的摄氧量。在同一浓度下，甘油三硝酸酯减少了摄氧量，而异山梨醇二硝酸酯和赤藓糖醇四硝酸酯没有影响。这些化合物的脂溶性或硝化百分比与它们对摄氧量的影响之间没有发现简单的相关性。

/ALTERNATIVE and IN VITRO TESTS/ Mannitol hexanitrate (MANHN), iditol hexanitrate and sorbitan tetranitrate, all at 442 uM, stimulate oxygen uptake by isolated rabbit atrial tissue. At the same concentration, glyceryl trinitrate decreased oxygen uptake, while isosorbide dinitrate and erythrityl tetranitrate had no effect. No simple correlation was found between the lipoid solubility or percent nitration of these compounds and their effects on oxygen uptake.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

血液样本取自接受放射性甘油三硝酸盐（C-14-GTN）、异山梨醇二硝酸盐（C-14-ISD）或甘露醇六硝酸盐（C-14-MHN）处理的大鼠的颈动脉。测定了标记有机硝酸盐的半衰期。在另一项实验中，雌性大鼠静脉注射了一种放射性硝酸盐。每小时收集尿液，并计数样本中的放射性物质。用人类肝脏匀浆进行了另一项实验，并测量了有机硝酸盐还原酶活性。在第四项实验中，大鼠口服C-14-GTN，并收集淋巴液。血液清除调查的结果显示，母体化合物的血液浓度最初急剧下降，半衰期约为10到14秒。C-14-MHN的消失在90秒内超过99%。1分钟内，血液清除了超过80%的C-14-GTN或C-14-ISD。在尿液样本中，C-14-ISD和C-14-MHN代谢物的总和接近给药量的100%。然而，C-14-GTN并未接近100%。人类肝脏具有与大鼠肝脏相同的脱硝酶能力。在第四项实验中，口服给药7小时后，在淋巴液中回收的C-14-GTN不到1%。

... Blood samples were drawn from the carotid artery of rats treated with radioactive glyceryl-trinitrate (C-14-GTN), isosorbide-dinitrate (C-14-ISD) or mannitol-hexanitrate (C-14-MHN). The lifetime of the labeled organic nitrates was determined. In another experiment, female rats were intravenously administered one of the radioactive nitrates. Urine was collected hourly, and the samples were counted for radioactive material. A separate experiment was conducted with human liver homogenate, and organic nitrate-reductase activity was measured. In a fourth experiment, rats were treated orally with C-14-GTN and the lymph was collected. Results from the blood clearance investigations showed an extremely rapid initial fall in the blood concentration of the parent compound, with a half life of about 10 to 14 seconds. The disappearance of C-14-MHN was more than 99 percent complete by 90 seconds. Blood was cleared of more than 80 percent of C-14-GTN or C-14-ISD by 1 minute. In the urine samples, the sum of C-14-ISD and C-14-MHN metabolites approached 100 percent of the administered amount. However, the C-14-GTN did not approach 100 percent. The human liver contained the same enzyme capacity for denitration as the rat liver. In the fourth experiment, less than 1 percent of orally administered C-14-GTN was recovered in the lymph after 7 hours.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  1.1D
• 海关编码：
  2920909090

制备方法与用途

类别：爆炸物品

爆炸物危险特性

• 摩擦、震动、火花及冲击均可能引发灵敏爆炸

可燃性危险特性

• 可燃，在燃烧时会分解并释放有毒的氮氧化物气体

储运特性

• 应存放在通风良好且低温干燥的库房中
• 注意防明火、摩擦和火花，同时与氧化剂分开储存运输

灭火剂

• 水、二氧化碳、干粉及泡沫

反应信息

• 作为反应物：
  描述：

  甘露糖醇六硝酸酯 在 吡啶 、 ammonium carbonate 、 丙酮 作用下， 生成 O3-acetyl-O1,O2,O4,O5,O6-pentanitro-D-mannitol
  参考文献：
  名称：

  Derivatives of D-Mannitol 1,2,3,5,6-Pentanitrate¹

  摘要：

  DOI：

  10.1021/ja01530a043
• 作为产物：
  描述：

  甘露醇 在 硫酸 、 硝酸 作用下， 生成 甘露糖醇六硝酸酯
  参考文献：
  名称：

  Clerodendron serratum分离物的化学检查和d-甘露醇的表征

  摘要：

  D-甘露醇是从Clerodendron serratum的根皮中分离得到的，产率为10.9％，并通过混合熔点，分析，色谱行为以及制备六乙酰基，六硝基，六苯甲酰基衍生物和苯甲醛缩合产物来鉴定。

  DOI：

  10.1002/jps.2600560520

文献信息

• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
  申请人：——

  公开号：US20010041726A1

  公开（公告）日：2001-11-15

  The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

  本发明描述了新颖的硝化和/或亚硝化环氧合酶2（COX-2）抑制剂以及包含至少一种硝化和/或亚硝化环氧合酶2（COX-2）抑制剂的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或可选地，至少一种治疗剂，如类固醇、非甾体抗炎化合物（NSAID）、5-脂氧合酶（5-LO）抑制剂、白三烯B4（LTB4）受体拮抗剂、白三烯A4（LTA4）水解酶抑制剂、5-HT激动剂、3-羟基-3-甲基戊二酰辅酶A（HMGCoA）抑制剂、H受体拮抗剂、抗肿瘤药物、抗血小板药物、解充血剂、利尿剂、镇静或非镇静抗组胺药、诱导型一氧化氮合酶抑制剂、阿片类药物、镇痛剂、幽门螺杆菌抑制剂、质子泵抑制剂、异前列腺素抑制剂以及其混合物。本发明还提供了包含至少一种母体COX-2抑制剂和至少一种一氧化氮供体的新型组合物，以及可选地，至少一种治疗剂。本发明还提供了用于治疗炎症、疼痛和发热的工具和方法；用于治疗和/或改善COX-2抑制剂的胃肠道特性；用于促进伤口愈合；用于治疗和/或预防肾毒性；以及用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病的工具和方法。
• Nitrosated proton pump inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040024014A1

  公开（公告）日：2004-02-05

  The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated proton pump inhibitor compound, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti- Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections.

  该发明描述了新颖的亚硝化质子泵抑制剂化合物及其药用盐，以及包含至少一种亚硝化质子泵抑制剂化合物的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或至少一种治疗剂。该发明还提供了包含至少一种亚硝化质子泵抑制剂化合物和至少一种捐赠、转移或释放一氧化氮、提高内源性内皮源性舒张因子水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或至少一种治疗剂的新型组合物。该发明还提供了包含至少一种亚硝化质子泵抑制剂化合物，可选地至少一种一氧化氮供体和/或至少一种治疗剂的新型套装。该发明还提供了治疗胃肠道疾病的方法；促进溃疡愈合；减少溃疡复发；改善质子泵抑制剂的胃保护性能、抗幽门螺杆菌性能或抗酸性能；减少或减轻与非甾体类抗炎化合物使用相关的胃肠毒性；治疗细菌感染和/或病毒感染。
• SUBSTITUTED AMIDE COMPOUNDS
  申请人：Pfizer Inc.

  公开号：US20140315928A1

  公开（公告）日：2014-10-23

  The present invention is directed at substituted amide compounds, pharmaceutical compositions containing such compounds and the use of such compounds to reduce plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

  本发明涉及替代酰胺化合物，含有这种化合物的药物组合物以及利用这种化合物降低血浆脂质水平，如LDL-胆固醇和甘油三酯，并据此治疗由高水平的LDL-胆固醇和甘油三酯加重的疾病，如动脉粥样硬化和心血管疾病，在哺乳动物，包括人类中的应用。
• Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040006133A1

  公开（公告）日：2004-01-08

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors having at least one oxime group or hydrazone group and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor having at least one oxime group or hydrazone group, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor having at least one oxime group or hydrazone group, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention having at least one oxime group or hydrazone group can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  该发明描述了具有至少一个肟基团或缩醛基团的新型环氧合酶2（COX-2）选择性抑制剂，以及包含至少一个具有至少一个肟基团或缩醛基团的环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选地至少一个供体、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或至少一个治疗剂。该发明还提供了包含至少一个具有至少一个肟基团或缩醛基团的COX-2选择性抑制剂的新型试剂盒，可选地硝化和/或亚硝化，以及可选地至少一个一氧化氮供体，和/或，可选地至少一个治疗剂的试剂盒。该发明的新型环氧合酶2选择性抑制剂具有至少一个肟基团或缩醛基团，可选地硝化和/或亚硝化。该发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠特性；促进伤口愈合；用于治疗和/或预防肾脏和/或呼吸道毒性；用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病；以及用于改善COX-2选择性抑制剂的心血管特性的方法。