烟酰胺 | 98-92-0

• 物质功能分类: 原料药 - 维生素类与矿物质类药 - 维生素B类药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 烟酰胺
• 中文别名: 维生素PP；维生素B3；3-吡啶甲酰胺；尼克酰胺；烟碱酰胺；VB3；VPP
• 英文名称: nicotinamide
• 英文别名: niacinamide；vitamin B3；3-pyridinecarboxamide；NAM；3-pyridinamide；niacin；NIC；pyridine-3-carboxamide
• CAS: 98-92-0；11032-50-1
• 化学式: C₆H₆N₂O
• mdl: MFCD00006395
• 分子量: 122.126
• InChiKey: DFPAKSUCGFBDDF-UHFFFAOYSA-N

物化性质

• 熔点：
  128-131 °C(lit.)
• 沸点：
  150-160 °C
• 密度：
  1.40
• 蒸气密度：
  4.22 (vs air)
• 闪点：
  182 °C
• 溶解度：
  691g/l
• LogP：
  -0.38 at 21℃
• 物理描述：
  Nicotinamide is a white powder. (NTP, 1992)
• 颜色/状态：
  White, powder, needles from benzene
• 气味：
  Odorless
• 味道：
  Bitter taste
• 蒸汽密度：
  Relative vapor density (air = 1): 4.2
• 蒸汽压力：
  4.2X10-4 mm Hg at 25 °C (est)
• 水溶性：
  0.61
• 稳定性/保质期：
  Stable under recommended storage conditions.
• 自燃温度：
  480 °C
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 折光率：
  Index of refraction: 1.466 at 25 °C/D
• 解离常数：
  pKa = 3.35 (conjugate acid)
• 碰撞截面：
  125.3 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]
• 保留指数：
  1426

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

在生理功能所需的辅酶量（每日12-18毫克）下，烟酸会转化为烟酰胺；大剂量的烟酸只有小部分转化为烟酰胺。烟酰胺在肝脏中代谢为N-甲基烟酰胺、其他N-甲基衍生物和烟尿酸（烟酸的甘氨酸结合物）。这些代谢物通过尿液排出。在给予生理剂量的烟酸或烟酰胺后，只有少量未改变的烟酰胺通过尿液排出；然而，在给予大剂量后，更大比例的烟酸和烟酰胺会以未改变的形式排出。

In amounts needed for physiologic function as a coenzyme (12-18 mg daily), niacin is converted to niacinamide; larger doses of niacin are converted to niacinamide to only a minor degree. Niacinamide is metabolized in the liver to N-methylniacinamide, other N-methylated derivatives, and nicotinuric acid (the glycine conjugate of niacin). These metabolites are excreted in urine. Following administration of physiologic doses of niacin or niacinamide, only a small amount of niacinamide is excreted unchanged in urine; however, following administration of larger doses, a greater proportion of niacin and niacinamide is excreted unchanged.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给两名受试者口服烟酰胺后，从血浆提取物的色谱图中检测到了N1-甲基-4-吡啶酮-3-甲酰胺。

N1-Methyl-4-pyridone-3-carboxamide was detected on chromatograms of plasma extracts after oral administration of niacinamide to two human subjects.

来源:Hazardous Substances Data Bank (HSDB)

代谢

6-羟基烟酰胺和6-羟基烟酸作为尿代谢物通过比较大鼠腹膜内注射14(C)烟酸或14(C)烟酰胺后的紫外光谱、红外光谱和质量光谱而被检测到。

6-Hydroxynicotinamide and 6-hydroxynicotinic acid /were detected/ as urinary metabolites by comparison of ultraviolet, infrared, and mass spectra following intraperitoneal injections of 14(C)Niacin or 14(C)Niacinamide into rats.

来源:Hazardous Substances Data Bank (HSDB)

代谢

N1-甲基-4-吡啶酮-3-甲酰胺是烟酸和烟酰胺的主要代谢物，它已被发现是由N1-甲基烟酰胺合成的。

N1-methyl-4- pyridone-3-carboxamide is a major metabolite of niacin and niacinamide which has been found to be synthesized from N1- methylnicotinamide.

来源:Hazardous Substances Data Bank (HSDB)

代谢

尿素毒素倾向于通过饮食过量或肾脏过滤不良在血液中积聚。大多数尿素毒素是代谢废物，通常通过尿液或粪便排出。

Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

识别和使用：烟酰胺是一种白色结晶性粉末。烟酰胺用于预防烟酸缺乏和治疗糙皮病。烟酰胺还用作化妆品中的发用和护肤调理剂。它被用于增强面包、面粉和其他谷物制品的营养。动物饲料通常会添加烟酰胺。它也用于多种维生素制剂中。烟酰胺和烟酸作为维生素同样有效，因为它们可以在体内相互转化。维生素 B(3) 是烟酸和烟酰胺的统称。烟酰胺是参与氢转移的重要辅酶的组成部分。人体研究：在人体中，烟酰胺对脂质代谢、组织呼吸和糖原分解是必需的。在活体内，烟酰胺是由烟酸转化形成的。此外，一些饮食中的色氨酸会在活体内氧化成烟酸，然后转化为烟酰胺。烟酰胺被并入两种辅酶：烟酸腺嘌呤二核苷酸 (NAD) 和烟酸腺嘌呤二核苷酸磷酸 (NADP)。NAD 和 NADP 在糖原分解、组织呼吸和脂质代谢中充当氢载体分子。在一项研究中，6名志愿者（单次剂量在3到9克/天之间）服用了烟酰胺，与烟酰胺相关的毒性症状温和，主要表现为恶心。研究了2 mM 烟酰胺对静止人淋巴细胞非计划性 DNA 合成的影响。在用紫外线照射或用 N-甲基-N-硝基- N-硝基胍处理的细胞中，烟酰胺导致非计划性 DNA 合成增加两倍。动物研究：将0.1克烟酰胺应用于兔子的眼睛，引起了可逆性的刺激。在豚鼠试验中没有产生致敏作用。给雄性大鼠单次腹腔注射烟酰胺（100毫克/千克）显著诱导了肝微粒体混合功能氧化酶系统的所有组分以及药物代谢酶的活性。将12只雄性大鼠分成几组，在它们的饮食中添加烟酰胺，持续8到12周。在饮食中的含量为0.1%（相当于每千克体重100毫克/天）时，烟酰胺没有显著改变生长速度；在0.2%时，生长速度提高；但在0.4%时，生长速度明显受到抑制。几乎完全的生长抑制发生在喂食1%烟酰胺的大鼠中。终身喂食1%烟酰胺对小鼠没有致癌作用。然而，烟酰胺促进了二乙基亚硝胺诱导的大鼠肾小管细胞肿瘤的发生。在给小鼠喂食500-2000毫克/千克的烟酰胺剂量时，会降低定向反射和探索行为，并具有抗攻击性和抗惊厥性质。给怀孕大鼠补充烟酰胺导致胎盘和胎儿肝基因组 DNA 甲基化和基因组尿嘧啶含量（一种改变 DNA 多样性的因素）在胎盘和胎儿肝脑中完全或部分降低，这可以通过补充甜菜碱来预防。此外，烟酰胺补充剂诱导了胎盘和胎儿肝中编码烟酰胺 N-甲基转移酶、DNA 甲基转移酶 1、过氧化氢酶和肿瘤蛋白 p53 的基因的 mRNA 表达的特定组织改变。高剂量烟酰胺补充剂增加了胎儿肝 a-胎蛋白 mRNA 水平，这可以通过补充甜菜碱来预防。因此，母体烟酰胺补充剂可以诱导胎儿表观遗传修饰和 DNA 碱基组成的改变。在用鼠伤寒沙门氏菌 TA 98、TA 100、TA 1535、TA 1537 和 TA 1538 菌株进行的 Ames 测试中，烟酰胺在加和不加代谢激活的情况下均为阴性。烟酰胺在酿酒酵母 D4 菌株中不具有诱变性。据报道，在体外实验中，浓度为3毫克/毫升（25 mM）的烟酰胺在中国仓鼠卵巢细胞中诱导了大型的结构染色体畸变。

IDENTIFICATION AND USE: Nicotinamide is a white, crystalline powder. Nicotinamide is used to prevent niacin deficiency and to treat pellagra. Nicotinamide is also used in cosmetics as a hair and skin conditioning agent. It has been used in the enrichment of bread, flour, and other grain-derived products. Animal feed is routinely supplemented with nicotinamide. It is also used in multi-vitamin preparations. Nicotinamide and niacin are similarly effective as a vitamin because they can be converted into each other within the organism. The blanket term vitamin B(3) is used for both. Niacinamide is a component of important coenzymes involved in hydrogen transfer. HUMAN STUDIES: In humans, nicotinamide is required for lipid metabolism, tissue respiration, and glycogenolysis. In vivo, nicotinamide is formed from conversion of niacin. In addition, some dietary tryptophan is oxidized to niacin and then to nicotinamide in vivo. Nicotinamide is incorporated into 2 coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP act as hydrogen-carrier molecules in glycogenolysis, tissue respiration, and lipid metabolism. In a study with 6 volunteers (single dose between 3 and 9 g/day) toxic symptoms associated with nicotinamide were mild and consisted mainly of nausea. The effect of 2 mM nicotinamide on unscheduled DNA synthesis on resting human lymphocytes was studied. In cells treated with UV irradiation or with N-methyl-N-nitro- N-nitrosoguanidine, nicotinamide caused a two-fold stimulation of unscheduled DNA synthesis. ANIMAL STUDIES: Application of 0.1 g nicotinamide to the eyes of rabbits induced reversible irritation. It did not produced sensitization in guinea pig test. Single ip injection of nicotinamide (100 mg/kg) to male rats was shown to significantly induce all components of the hepatic microsomal mixed function oxidase system as well as activities of drug-metabolizing enzymes. Groups of 12 male rats were fed nicotinamide in their diet for a period of 8 to 12 weeks. At 0.1% of the diet (100 mg/kg bw per day), nicotinamide caused no significant change in the growth rate, at 0.2%, growth rate was enhanced, but at 0.4%, a marked inhibition of growth rate resulted. Almost complete growth inhibition occurred in rats fed 1% nicotinamide. Lifelong treatment with 1% nicotinamide had no carcinogenic effect in mice. However, nicotinamide promoted diethylnitrosamine-induced renal tubular cell tumorigenesis in rats. In mice nicotinamide in doses of 500-2000 mg/kg depresses orientation reflexes and exploring behavior, and has antiaggressive and anticonvulsant properties. Nicotinamide supplementation in pregnant rats led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamide N-methyltransferase, DNA methyltransferase 1, catalase and tumor protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic a-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. Nicotinamide was negative in an Ames test performed with Salmonella strains TA 98, TA 100, TA 1535, TA 1537 and TA 1538 both with and without metabolic activation. Nicotinamide was not mutagenic in Saccharomyces stain D4. It was reported that nicotinamide at concentrations of 3 mg/mL (25 mM) induced large structural chromosome aberrations in vitro in Chinese hamster ovary cells.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

尿毒症毒素如烟酰胺通过有机离子转运体（特别是OAT3）被积极运输到肾脏中。尿毒症毒素水平的升高可以刺激活性氧种类的产生。这似乎是通过尿毒症毒素直接结合或抑制NADPH氧化酶酶（特别是肾脏和心脏中丰富的NOX4）（A7868）来介导的。活性氧种类可以诱导几种不同的DNA甲基转移酶（DNMTs），这些酶参与沉默一种被称为KLOTHO的蛋白质。KLOTHO已被确认为在抗衰老、矿物质代谢和维生素D代谢中具有重要作用。许多研究表明，在急性或慢性肾脏疾病中，由于局部活性氧种类水平升高，KLOTHO mRNA和蛋白质水平会降低（A7869）。

Uremic toxins such as nicotinamide are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

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

• 健康影响

长期暴露于尿毒症毒素可能会导致多种疾病，包括肾脏损伤、慢性肾病和心血管疾病。

Chronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

内源性的，摄入，皮肤（接触）

Endogenous, Ingestion, Dermal (contact)

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

14(C)烟酰胺被添加到水包油（o/w）型皮肤霜中，并加入到30%（w/w）的皂基中，然后涂抹到雌性科沃斯威斯大鼠的皮肤上。在皂液中烟酰胺的最终浓度大约是0.3%（w/v），在皮肤霜中是1%（w/w）。将皮肤霜和皂膏涂抹到大鼠皮肤上，用量大约为每平方厘米20毫克。将霜仔细按摩到10平方厘米的皮肤上，持续5分钟，然后覆盖上聚乙烯衬里的密封保护贴。在大鼠被放置在代谢笼中48小时期间，收集所有排泄物。在48小时时，处死动物，并对贴片、尸体以及处理过的皮肤区域进行14(C)的检测。从接受含有14(C)烟酰胺皮肤霜治疗的大鼠中，最多有32%的14(C)在排泄物和尸体中被回收，而从接受皂膏治疗的大鼠中，最多有30%被回收。

14(C)Niacinamide was incorporated into an oil-in-water (o/w) skin cream and into a 30% (w/w) soap base and applied to the skin of female Colworth Wistar rats. The final concentration of niacinamide in the soap solution was approximately 0.3% (w/v) and was 1% (w/w) in the skin cream. Application of the skin cream and soap paste was made to rat skin at approximately 20 mg/sq cm. The cream was carefully massaged over 10 sq cm of skin for up to 5 min before covering with polythene-lined occlusive protective patches. The rats were placed in metabolism cages for 48 hr during which time all excreta was collected. At 48 hr, the animals were killed and the patch, carcass, and treated area of skin were assayed for 14(C). Up to 32% 14(C) was recovered in excreta and in the carcasses from rats treated with skin cream containing 14(C)Niacinamide and up to 30% from those treated with soap paste.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

烟酰胺从胃肠道被有效吸收。在低剂量时，吸收通过钠依赖性的促进扩散介导。在高剂量时，被动扩散是吸收的主要机制。高达三到四克的烟酰胺剂量几乎被完全吸收。烟酰胺通过门静脉循环运输到肝脏，并通过系统循环运输到身体的各种组织。烟酰胺通过被动扩散进入大多数细胞，并通过促进运输进入红细胞。

Nicotinamide is efficiently absorbed from the gastrointestinal tract. At low doses, absorption is mediated via sodium-dependent facilitated diffusion. Passive diffusion is the principal mechanism of absorption at higher doses. Doses of up to three to four grams of nicotinamide are almost completely absorbed. Nicotinamide is transported via the portal circulation to the liver and via the systemic circulation to the various tissues of the body. Nicotinamide enters most cells by passive diffusion and enters erythrocytes by facilitated transport.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

烟酸胺在身体各组织中广泛分布。

Niacinamide is widely distributed /throughout/ body tissues.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

烟酸和烟酰胺口服给药后可从胃肠道被迅速吸收，烟酰胺（在美国已不再商业可用）也可以从皮下和肌内注射部位被迅速吸收。

Niacin and niacinamide are readily absorbed from the GI tract following oral administration, and niacinamide (no longer commercially available in the US) is readily absorbed from subcutaneous and IM injection sites.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi,T,F
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  1
• 海关编码：
  2933399090
• 危险品运输编号：
  NONH for all modes of transport
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

制备方法与用途

根据上述内容，关于烟酰胺的性质和用途，我整理了一些关键点：

主要性质：

1. 化学名称：维生素B3以及PARP抑制剂的酰胺衍生物。
2. 溶解性：烟酰胺的水溶性较烟酸好。
3. 毒性：LD50 2.5～3.5g/kg (大鼠，经口)。GRAS(FDA)，ADI不作特殊规定。
4. 含量分析方法：
   • 滴定法：精确称取试样后溶于冰醋酸中，加苯和结晶紫滴定0.1mol/L高氯酸。
   • 高压液相色谱法。

用途与功能：

1. 营养强化剂：用于饼干等食品中。
2. 皮肤护理：用于护肤品防止皮肤粗糙、维护皮肤细胞健康，促进美白；护发中可促进头皮血液循环，健康毛囊，促进头发生长，防止秃发。
3. 临床应用：维生素类药，参与体内代谢过程，用于防治糙皮病及口炎、舌炎等病症的治疗。

生产方法：

1. 烟酸经空气氧化成烟酸，再与氢氧化铵作用，加热脱水制得。
2. 将烟酸、硼酸和氨水投入反应锅中，通入氨气溶解后蒸馏回收氨，浓缩后再加入液氨继续反应，稀释后脱色析晶干燥。

不良反应：

• 偶见头晕、恶心、上腹不适、食欲不振等。
• 在妊娠初期过量服用有致畸可能。肌注可引起疼痛，故少用。

希望这些信息对你有所帮助！如果需要更多细节或其他相关信息，请随时告知。

反应信息

• 作为反应物：
  描述：

  烟酰胺 在 盐酸 、 aluminum (III) chloride 、 四乙基氯化铵 、 sodium hydroxide 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 2.0h， 生成 2,3,6-三氯吡啶
  参考文献：
  名称：

  烟酰胺合成2,3,6-三氯吡啶的工艺研究

  摘要：

  本发明提供了一种烟酰胺合成2,3,6‑三氯吡啶的工艺研究，以烟酰胺为原料，碱性环境下加入次氯酸钠溶液，进行霍夫曼降级反应，得到3‑氨基吡啶，其在路易斯酸催化剂催化下，与浓盐酸/双氧水条件下进行氯化反应制得2，6‑二氯‑3‑氨基吡啶，再在低温、强酸条件下，经亚硝酸钠作用生成重氮盐溶液，最后经桑德迈尔反应生成目标产物—2,3，6‑三氯吡啶，本发明提供的工艺原料简单、易得并且价格便宜、反应条件简单容易操作、后处理简单、收率高，具有良好的工业开发前景。

  公开号：

  CN108484492A
• 作为产物：
  描述：

  L-鸟氨酸 生成 烟酰胺
  参考文献：
  名称：

  Nicotinamide biosynthesis by intestinal bacteria as influenced by methyltryptophans

  摘要：

  DOI：

  10.1042/bj0440506
• 作为试剂：
  描述：

  2-环己烯-1-酮 、 苯甲醛 在 novozyme 435 、 烟酰胺 、 β-环糊精 作用下， 反应 0.4h， 以43%的产率得到2-[羟基(苯基)甲基]环己-2-烯-1-酮
  参考文献：
  名称：

  一种采用微通道反应器催化获得MBH反应产物的方法

  摘要：

  本发明公开了一种采用微通道反应器催化获得MBH反应产物的方法，将含有式Ⅰ所示的苯甲醛类化合物、酰胺、环糊精和环己烯酮的混合溶液泵入微通道反应装置中，于填充有Novozym 435的填充柱式微反应器中进行反应，即得如式Ⅱ所示的Morita–Baylis–Hillman反应产物。本发明方法具有反应时间短，副反应少，毒性和污染小，生产成本低，产品质量好等优点，在反应过程中不使用有机催化剂催化，绿色环保且节能高效，适于推广应用，同时解决现有酶催化技术存在的反应时间长，反应条件苛刻的问题。

  公开号：

  CN114213201B

文献信息

• A highly efficient Pd–C catalytic hydrogenation of pyridine nucleus under mild conditions
  作者：Chuanjie Cheng、Jimin Xu、Rui Zhu、Lixin Xing、Xinyan Wang、Yuefei Hu

  DOI：10.1016/j.tet.2009.08.011

  日期：2009.10

  A synergistic Pd–C catalytic hydrogenation of 4-pyridinecarboxamides straightforward to 4-piperidinecarboxamide hydrochlorides was developed in the presence of ClCH2CHCl2. It provided a novel strategy for highly efficient hydrogenation of pyridine nuclear by using low-cost Pd–C catalyst under mild conditions.

  在存在ClCH 2 CHCl 2的情况下，开发了对4-吡啶羧甲酰胺盐酸盐直接作用的4-吡啶甲酰胺的Pd-C协同催化氢化反应。它通过在温和条件下使用低成本的Pd-C催化剂，为吡啶核的高效加氢提供了一种新的策略。
• [EN] IMIDAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS IMIDAZOLE UTILES COMME INHIBITEURS DE LA FAAH
  申请人：MERCK & CO INC

  公开号：WO2009152025A1

  公开（公告）日：2009-12-17

  The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.

  本发明涉及某些咪唑衍生物，其可用作脂肪酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病性神经病、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。
• [EN] PYRAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILES COMME INHIBITEURS DE FAAH
  申请人：MERCK & CO INC

  公开号：WO2009151991A1

  公开（公告）日：2009-12-17

  The present invention is directed to certain imidazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzheimer disease, and Parkinson's disease

  本发明涉及某些咪唑衍生物，其可用作脂肪酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病神经病变、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。
• Chemoselective Reactions of Tellurium Tetraethoxide towards Thioamides and Amides
  作者：Kazushi Omote、Yoshio Aso、Tetsuo Otsubo、Fumio Ogura

  DOI：10.1246/bcsj.67.1759

  日期：1994.6

  Tellurium tetraethoxide reacts with primary thioamides at room temperature, forming nitriles in high yields. On the other hand, the reactions with amides are largely temperature-dependent, giving predominantly esters at 80 °C and nitriles at a higher temperature. Similarly, tellurium tetraethoxide readily induces the C–N bond cleavage of ureas to give carbamates and amines.

  四乙氧基碲在室温下与伯硫酰胺反应，高效生成腈。另一方面，四乙氧基碲与酰胺的反应很大程度上依赖于温度，在80°C主要生成酯，而在更高温度下生成腈。同样，四乙氧基碲容易引发尿素中的C-N键断裂，生成氨基甲酸酯和胺。
• [EN] OXAZOLE DERIVATIVES USEFUL AS INHIBITORS OF FAAH<br/>[FR] DÉRIVÉS D'OXAZOLE UTILES COMME INHIBITEURS DE FAAH
  申请人：MERCK & CO INC

  公开号：WO2010017079A1

  公开（公告）日：2010-02-11

  The present invention is directed to certain oxazole derivatives which are useful as inhibitors of Fatty Acid Amide Hydrolase (FAAH). The invention is also concerned with pharmaceutical formulations comprising these compounds as active ingredients and the use of the compounds and their formulations in the treatment of certain disorders, including osteoarthritis, rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, skeletomuscular pain, and fibromyalgia, as well as acute pain, migraine, sleep disorder, Alzeimer Disease, and Parkinson's Disease.

  本发明涉及某些噁唑衍生物，其可用作脂肪酸酰胺水解酶（FAAH）的抑制剂。该发明还涉及包含这些化合物作为活性成分的药物配方，以及这些化合物及其配方在治疗某些疾病中的使用，包括骨关节炎、类风湿性关节炎、糖尿病神经病变、带状疱疹后神经痛、骨骼肌肉疼痛和纤维肌痛，以及急性疼痛、偏头痛、睡眠障碍、阿尔茨海默病和帕金森病。

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