L-乙酰基肉碱 | 3040-38-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: L-乙酰基肉碱
• 英文名称: Acetyl-L-carnitine
• 英文别名: L-acetylcarnitine；acetylcarnitine；O-acetyl-L-carnitine；(3R)-3-acetyloxy-4-(trimethylazaniumyl)butanoate
• CAS: 3040-38-8
• 化学式: C₉H₁₇NO₄
• 分子量: 203.238
• InChiKey: RDHQFKQIGNGIED-MRVPVSSYSA-N

物化性质

• LogP：
  -4.031 (est)
• 物理描述：
  Solid
• 熔点：
  145°C
• 溶解度：
  In water, 1X10+6 mg/L at 25 °C (est)
• 碰撞截面：
  143 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)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

L-肉碱参与一个可逆的转酯化反应，其中酰基团从辅酶A转移到L-肉碱的羟基上... 乙酰-L-肉碱... 以这种方式生物合成。

L-carnitine participates in a reversible transesterification reaction, in which an acyl group is transferred from coenzyme A to the hydroxyl group of L-carnitine ... Acetyl-L-carnitine ... is biosynthesized in this manner.

来源:Hazardous Substances Data Bank (HSDB)

代谢

乙酰-L-肉碱（ALC）是三甲基氨基酸L-肉碱的酯，通过ALC转移酶在人脑、肝脏和肾脏中合成。

Acetyl-L-carnitine (ALC) is an ester of the trimethylated amino acid, L-carnitine, and is synthesized in the human brain, liver, and kidney by the enzyme ALC-transferase.

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 实验研究表明，在大鼠和人类中，肾脏能够从L-肉碱和乙酰乙酸或β-羟基丁酸合成乙酰-L-肉碱 ...

... Experimental studies have shown that in rats and humans, kidneys are able to synthesize acetyl-L-carnitine from L-carnitine and either acetoacetate or beta-hydroxybutyrate ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

对56名不育男性进行研究，发现L-肉碱和乙酰-L-肉碱的组合能显著提高精子活力。

... A ... study on 56 infertile males ... found the combination of L-carnitine ... and acetyl-L-carnitine ... led to significant improvement in sperm motility.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

N-乙酰半胱氨酸（一种抗氧化剂和谷胱甘肽前体，可保护免受Aβ神经毒性的侵害）、乙酰-L-肉碱（可以提高ATP水平，保护线粒体，并缓冲Aβ神经毒性）和S-腺苷甲硫氨酸（促进谷胱甘肽的使用并维持乙酰胆碱水平）的联合给药，在衰老和神经退行性小鼠模型中增强了或维持了认知功能，并减轻或预防了攻击性行为。停止该配方给药后，认知功能的增强迅速逆转，并在补充给药后恢复。行为异常与乙酰胆碱的下降相关，这也被这种营养补充剂的组合预防，表明神经递质失衡可能有助于它们的表现。这种营养补充剂组合的治疗能够补偿饮食中叶酸和维生素E的不足，并结合作为促氧化剂的食物铁的给药（这些因素共同增加了同型半胱氨酸和大脑组织的氧化损伤），表明它提供了抗氧化神经保护。

... combined administration of N-acetyl cysteine (an antioxidant and glutathione precursor that protects against A beta neurotoxicity), acetyl-L-carnitine (which raises ATP levels, protects mitochondria, and buffers A beta neurotoxicity), and S-adenosylmethionine (which facilitates glutathione usage and maintains acetylcholine levels) enhanced or maintain cognitive function, and attenuated or prevented aggression, in mouse models of aging and neurodegeneration. Enhancement of cognitive function was rapidly reversed upon withdrawal of the formulation and restored following additional rounds of supplementation. Behavioral abnormalities correlated with a decline in acetylcholine, which was also prevented by this nutriceutical combination, suggesting that neurotransmitter imbalance may contribute to their manifestation. Treatment with this nutriceutical combination was able to compensate for lack of dietary folate and vitamin E, coupled with administration of dietary iron as a pro-oxidant (which collectively increase homocysteine and oxidative damage to brain tissue), indicating that it provided antioxidant neuroprotection. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

HIV感染本身以及抗逆转录病毒药物可能会增加氧化应激和线粒体功能障碍。这项研究评估了齐多夫定、司他夫定和地丹诺辛对U937和CEM细胞系的影响。所有这些药物都诱导了凋亡并增加了细胞内过氧化氢的产生，但没有增加超氧阴离子。添加乙酰左旋肉碱（ALC）能够预防测试药物的促氧化作用。在HIV感染者中，特别是接受高效抗逆转录病毒治疗的人群中，ALC的补充与积极效果有关。这些数据表明，其中一种效果可能是直接的抗氧化作用。

Both HIV infection per se and antiretroviral drugs might contribute to oxidative stress and mitochondrial dysfunctions. ... /This/ study ... assessed zidovudine, stavudine and didanosine on U937 and CEM cell lines. All these drugs induced apoptosis and increased intracellular hydrogen peroxide but not superoxide anions. The addition of acetyl-l-carnitine (ALC) was able to prevent the pro-oxidant effect of the drugs tested. Supplementation with ALC, deficient in certain cohorts of HIV-infected individuals, especially on high active antiretroviral therapy regimen, has been associated with favorable effects. These data suggest that one of these effects could be a direct anti-oxidant action.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

7.6至8.8岁的比格犬每天两次服用α-硫辛酸（LA）和乙酰左旋肉碱（ALC）补充剂，持续约2个月，在两个地标识别任务上达到学习标准的错误次数显著少于服用甲基纤维素安慰剂的对照组。测试在5天的洗入期后开始。这些狗还接受了一个之前学过的空间记忆任务的变延迟版本的测试；结果并不显著。补充了LA + ALC的狗在地标任务上的表现改善，提供了证据表明这种补充剂在提高识别和中心空间学习能力方面的有效性。/有建议/长期维持服用LA和ALC可能通过减缓线粒体衰减和细胞衰老的速度，有效减缓与年龄相关的认知衰退。

Beagle dogs between 7.6 and 8.8 years of age administered a twice daily supplement of alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC) over approximately 2 months made significantly fewer errors in reaching the learning criterion on two landmark discrimination tasks compared to controls administered a methylcellulose placebo. Testing started after a 5 day wash-in. The dogs were also tested on a variable delay version of a previously acquired spatial memory task; results were not significant. The improved performance on the landmark task of dogs supplemented with LA + ALC provides evidence of the effectiveness of this supplement in improving discrimination and allocentric spatial learning. /It was suggested/ that long-term maintenance on LA and ALC may be effective in attenuating age-associated cognitive decline by slowing the rate of mitochondrial decay and cellular aging.

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。如果患者呕吐，让患者向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。 /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

乙酰左旋肉碱补充剂以与L-肉碱类似的方式被吸收。

Acetylcarnitine supplements are absorbed in a similar manner to L-carnitine.

来源:DrugBank

吸收、分配和排泄

• 消除途径

Acetylcarnitine与L-carnitine以类似方式被消除。两者都通过肾脏消除并涉及肾小管的分泌。

Acetylcarnitine is eliminated in a similar manner as L-carnitine. Both of which are eliminated by the kidneys and involve tubular secretion.

来源:DrugBank

吸收、分配和排泄

在哺乳动物中，肉碱池由非酯化L-肉碱和许多酰基肉碱酯组成。在这些酯中，乙酰-L-肉碱在数量和功能上最为重要。肉碱的稳态通过饮食吸收、适度的合成速率以及高效的肾重吸收来维持。饮食中的L-肉碱通过跨肠细胞膜的主动和被动转运被吸收。饮食L-肉碱的生物利用度为54-87%，并取决于餐中L-肉碱的量。L-肉碱膳食补充剂（0.5-6克）的吸收主要是被动的；生物利用度为剂量的14-18%。未吸收的L-肉碱大部分在大肠中被微生物降解。循环中的L-肉碱分布到两个动力学定义的隔室：一个较大且周转慢的（可能是肌肉），另一个相对较小且周转快的（可能是肝脏、肾脏和其他组织）。在正常饮食L-肉碱摄入量下，人体的全身体周转时间为38-119小时。体外实验表明，乙酰-L-肉碱在吸收过程中部分被肠细胞水解。在体内，口服乙酰-L-肉碱补充剂2克/天后，循环中的乙酰-L-肉碱浓度增加了43%，这表明乙酰-L-肉碱至少部分未水解就被吸收了。单次静脉给药（0.5克）后，乙酰-L-肉碱迅速但未完全水解，乙酰-L-肉碱和L-肉碱的浓度在12小时内恢复到基线。在正常循环L-肉碱浓度下，肾L-肉碱重吸收非常高效（滤过负荷的90-99%；清除率，1-3 mL/min），但表现出饱和动力学。因此，随着循环L-肉碱浓度的增加（如静脉注射或口服高剂量L-肉碱后），重吸收效率降低，清除率增加，导致循环L-肉碱浓度迅速下降到基线。乙酰-L-肉碱的消除动力学与L-肉碱相似。有证据表明肾小管分泌L-肉碱和乙酰-L-肉碱。未来的研究应该解决补充剂量、组织和乙酰-L-肉碱浓度的变化和维护、以及代谢和功能变化及结果的相关性。

In mammals, the carnitine pool consists of nonesterified L-carnitine and many acylcarnitine esters. Of these esters, acetyl-L-carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary L-carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary L-carnitine is 54-87% and is dependent on the amount of L-carnitine in the meal. Absorption of L-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose. Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine. Circulating L-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues). At normal dietary L-carnitine intake, whole-body turnover time in humans is 38-119 h. In vitro experiments suggest that acetyl-L-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-L-carnitine concentration was increased 43% after oral acetyl-L-carnitine supplements of 2 g/day, indicating that acetyl-L-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-L-carnitine is rapidly, but not completely hydrolyzed, and acetyl-L-carnitine and L-carnitine concentrations return to baseline within 12 h. At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating L-carnitine concentration increases (as after high-dose intravenous or oral administration of L-carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating L-carnitine concentration to baseline. Elimination kinetics for acetyl-L-carnitine are similar to those for L-carnitine. There is evidence for renal tubular secretion of both L-carnitine and acetyl-L-carnitine. Future research should address the correlation of supplement dosage, changes and maintenance of tissue L-carnitine and acetyl-L-carnitine concentrations, and metabolic and functional changes and outcomes.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

乙酰左旋肉碱（ALC），作为左旋肉碱家族的一个生理成分，已被提议用于在药理剂量下治疗阿尔茨海默病。由于这种状况需要长期治疗，因此研究了多次给药方案后的动力学，该方案涉及11名患有阿尔茨海默型老年痴呆症的患者不同的给药途径。研究设计包括3天的基线观察期，重复采血的安慰剂治疗；连续10天以30毫克/千克静脉注射（血浆动力学在第7天进行研究），以及连续50天每天1.5克口服，分三次给予。使用enantioselective radioenzyme assay评估了血浆和脑脊液中的总可溶性左旋肉碱、左旋肉碱和乙酰左旋肉碱。短链左旋肉碱酯作为总左旋肉碱和游离左旋肉碱之差计算。在基线期的三天内，左旋肉碱家族各个成分的血浆浓度没有变化，在安慰剂治疗期间也未受影响。静脉注射后，血浆浓度显示出双相曲线，平均t1/2分别为0.073小时和1.73小时。口服治疗结束时，血浆中的乙酰左旋肉碱和左旋肉碱短链酯显著高于运行期。脑脊液中的浓度与血浆中的浓度平行，表明ALC容易穿过血脑屏障。...

Acetyl-L-carnitine (ALC), a physiological component of the L-carnitine family, has been proposed for treating Alzheimer's disease in pharmacological doses. As this condition requires prolonged therapy, its kinetics has been examined after a multiple dose regimen, involving different routes of administration, in 11 patients suffering from Senile Dementia of Alzheimer Type. The study design comprised a 3-day basal observation period, sham treatment with repeated blood sampling; treatment with 30 mg/kg iv [corrected] for 10 days (plasma kinetics was studied on the 7th day), and 50 days of 1.5 g/day [corrected] po given in three daily doses. Total acid soluble L-carnitine, L-carnitine and acetyl-L-carnitine in plasma and CSF were evaluated using an enantioselective radioenzyme assay. Short chain L-carnitine esters were calculated as the difference between total and free-L-carnitine. The plasma concentrations of individual components of the L-carnitine family did not change during the three days of the basal period, nor were they affected during the sham therapy period. Following the iv.bolus injections, the plasma concentrations showed a biphasic curve, with average t1/2 of 0.073 hr and 1.73 hr, respectively. At the end of oral treatment, plasma acetyl-L-carnitine and L-carnitine short chain esters were significantly higher than during the run-in phase. The CSF concentrations paralleled those in plasma, suggesting that ALC easily crosses the blood-brain barrier. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

盐酸乙酰左旋肉碱的药代动力学在6名男女健康志愿者中进行了研究，在静脉注射500毫克药物（以内盐形式表达）后。在给药前24小时至给药后48小时的期间内，评估了乙酰左旋肉碱（A）、左旋肉碱（B）和总酸溶性左旋肉碱组分的血浆浓度和尿液排泄。给药后，A的血浆浓度迅速升高，然后在12小时内降至基础值。相反，B的血浆浓度升高较慢，在30-60分钟达到峰值，然后在24小时内降至基础值。大部分注射的乙酰左旋肉碱剂量在给药后前24小时内以B和A的形式从尿液中回收。注射后前12小时内A和B的平均肾清除率高于基础值，这表明存在一种可饱和的管状重吸收过程，这可能抵消左旋肉碱模式血浆浓度发生的主要变化。/盐酸乙酰左旋肉碱/

The pharmacokinetics of acetyl-L-carnitine hydrochloride were investigated in 6 healthy volunteers of both sexes after iv injection of 500 mg of the drug, expressed as inner salt. Plasma concentrations and urinary excretion of acetyl-L-carnitine (A), L-carnitine (B) and total acid soluble L-carnitine fraction were evaluated over a period lasting from 24 h before to 48 h after the administration. Plasma concentrations of A increased quickly after administration and then declined reaching base values within 12 h. Conversely, plasma concentrations of B rose more slowly, reaching a peak in 30-60 min, and then declined to base values within 24 h. Most of the injected dose of acetyl-L-carnitine was recovered in the urine during the first 24 h after administration as B and A. Mean renal clearance of both A and B during the first 12 h after injection was higher than the base values, suggesting the presence of a saturable tubular reabsorption process which may counterbalance major changes occurring in plasma concentrations of L-carnitine pattern. /Acetyl-L-carnitine hydrochloride/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  存储条件：2-8°C，密封保存，并保持干燥。

制备方法与用途

Acetyl-L-carnitine is a stimulator of α-secretase activity and amyloid precursor protein (APP) metabolism. It has been shown to induce the NF-κB-mediated upregulation of mGluR2 receptors, which confers antidepressant, neuroprotective, analgesic, and antinociceptive activities.

反应信息

• 作为反应物：
  描述：

  L-乙酰基肉碱 以 乙腈 为溶剂， 反应 24.0h， 以77%的产率得到2(5H)-呋喃酮
  参考文献：
  名称：

  Single Step Conversion of Chiral Carnitine and Derivatives into (S)- and (R)-β-Substituted-γ-Butyrolactones

  摘要：

  本文介绍了通过分子内亲核置换将手性肉碱和肉碱衍生物高效地一步转化为立体异构纯(S)-和(R)-δ-取代-δ³-丁内酯的方法。(S)-或(R)-肉碱和(R)-氨基肉碱内盐分别得到δ-羟基-δ³-丁内酯和δ-氨基-δ³-丁内酯（82%和 77%），其构型与起始原料相同。(在相同的反应条件下，(R)-乙酰基氨基肉碱内盐可以得到(R)-δ-乙酰氨基-δ-丁内酯（90%），而(R)-乙酰基肉碱通过环化和随后的消除反应可以得到 2(5H)-呋喃酮（77%）。(R)-N-苄氧基肉碱酰胺可以得到吡咯烷酮（11%）和呋喃酰亚胺酯（50%）衍生物的混合物。废(S)-卡尼汀直接转化为有价值的(S)-δ-羟基-δ-丁内酯或（乙酰化后）转化为珍贵的 2(5H)-呋喃酮特别令人感兴趣。

  DOI：

  10.1055/s-1997-686
• 作为产物：
  描述：

  左旋肉碱盐酸盐 在 palladium on activated charcoal 吡啶 、 盐酸 、 Amberlite IRA-402 (ClO₄^- form) 、 氢气 、 碳酸氢钠 作用下， 以 二甲基亚砜 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 35.75h， 生成 L-乙酰基肉碱
  参考文献：
  名称：

  Bernabei, Ida; Castagnani, Roberto; Angelis, Francesco De, Chemistry - A European Journal, 1996, vol. 2, # 7, p. 826 - 831

  摘要：

  DOI：
• 作为试剂：
  描述：

  二氧化碳 、 邻甲苯缩水甘油醚 在 L-乙酰基肉碱 作用下， 120.0 ℃ 、1.0 MPa 条件下， 以99%的产率得到4-((o-tolyloxy)methyl)-1,3-dioxolan-2-one
  参考文献：
  名称：

  一种环状碳酸酯的制备方法

  摘要：

  本发明公开了一种环状碳酸酯的制备方法，采用式(I)～(IV)所示的天然生物来源肉碱中的一种或几种作为催化剂，催化环氧化物与二氧化碳发生环加成反应得到环状碳酸酯。本发明相比现有的催化体系具有绿色、温和、高效、无金属、无卤素、无溶剂等明显的优势。

  公开号：

  CN117534647A

文献信息

• [EN] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• [EN] HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143143A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• [EN] NITRIC OXIDE RELEASING PRODRUGS OF THERAPEUTIC AGENTS<br/>[FR] PROMÉDICAMENTS D'AGENTS THÉRAPEUTIQUES LIBÉRANT DE L'OXYDE NITRIQUE
  申请人：SATYAM APPARAO

  公开号：WO2014111957A1

  公开（公告）日：2014-07-24

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其中所述药物或治疗剂至少含有一个羧酸基团。发明还涉及制备这些一氧化氮释放前药的方法，包含它们的药物组合物以及使用这些前药的方法。
• SUBSTITUTED 6-ARYL-IMIDAZOPYRIDINE AND 6-ARYL-TRIAZOLOPYRIDINE CARBOXAMIDE ANALOGS AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR5
  申请人：Vanderbilt University

  公开号：US20160096833A1

  公开（公告）日：2016-04-07

  Disclosed are negative allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with glutamate dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention

  本文披露了代谢型谷氨酸受体亚型5（mGluR5）的负向变构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与谷氨酸功能障碍相关的神经和精神疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不旨在限制本发明。
• Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them
  申请人：Syngenta Limited

  公开号：US20030144263A1

  公开（公告）日：2003-07-31

  Compounds of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, 1 wherein, for example, X is —O— or —S—; HET is an optionally substituted C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S; Q is selected from, for example, Q1 and Q2 2 R 2 and R 3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, an N-linked (fully unsaturated) 5-membered heteroaryl ring system or a group of formula (TC5): 3 wherein Rc is, for example, R 13 CO—, R 13 SO 2 — or R 13 CS—; wherein R 13 is, for example, optionally substituted (1-10C)alkyl or R 14 C(O)O(1-6C)alkyl wherein R 14 is optionally substituted (1-10C)alkyl; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  式(I)的化合物，或其药学上可接受的盐，或其体内可水解的酯， 其中，例如，X为—O—或—S—； HET是一个可选择的取代的C-连接的含有2到4个异原子（独立选择自N、O和S）的5元杂芳环； Q从Q1和Q2中选择 R2和R3独立地为氢或氟； T从一系列基团中选择，例如，一个N-连接的（完全不饱和的）5元杂芳环系统或式(TC5)的基团： 其中Rc是，例如，R13CO—，R13SO2—或R13CS—； 其中R13是，例如，可选择的取代的(1-10C)烷基或R14C(O)O(1-6C)烷基 其中R14是可选择的取代的(1-10C)烷基；这些化合物可用作抗菌剂；并描述了其制备方法和含有它们的药物组合物。