丙酰左旋肉碱盐酸盐 | 20064-19-1

• 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: 丙酰左旋肉碱盐酸盐
• 英文名称: propionyl-L-carnitine
• 英文别名: (-)-Propionylcarnitine；L-propionylcarnitine；O-propanoylcarnitine；O-Propionyl-carnitin；Levocarnitine propionate；(3R)-3-propanoyloxy-4-(trimethylazaniumyl)butanoate
• CAS: 20064-19-1
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: UFAHZIUFPNSHSL-MRVPVSSYSA-N

物化性质

• 溶解度：
  氯仿（微溶）、甲醇（微溶）、水（微溶）
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

毒理性

• 相互作用

环孢素（CyA）是一种用于实体器官移植后的免疫抑制剂，但其临床应用受到副作用限制，其中最重要的是肾毒性。... 之前的一项工作... 证实了L-丙酰肉碱（L-PC），即L-肉碱的丙酰酯，能够通过减少在隔离和灌注的大鼠肾脏中的脂质过氧化来预防CyA引起的急性肾毒性。CyA给药与剂量依赖性的肾血管阻力增加相关，而预先使用L-PC可以预防这种情况。本研究的目的是在体内大鼠模型中证实L-PC的保护作用... 慢性肾毒性研究进行了28天。从第一天开始给予L-PC（ip 25 mg/kg bw），而CyA治疗在最后21天进行（口服给药25 mg/kg bw）。... L-PC能够显著降低CyA处理动物的血压，并预防CyA引起的肌酐清除率下降。此外，肾脏组织分析显示L-PC能够减少与慢性CyA给药相关的脂质过氧化物的含量和形态学异常。总之，我们的研究首次在体内证实，L-PC能够保护免受与慢性CyA给药相关的功能和组织损伤。

Cyclosporine (CyA) is an immunosuppressive agent used after solid organ transplantation, but its clinical use is limited by side effects, the most important of which is nephrotoxicity. ... A previous work ... demonstrated that L-propionylcarnitine (L-PC), a propionyl ester of L-carnitine, is able to prevent CyA-induced acute nephrotoxicity reducing lipid peroxidation in the isolated and perfused rat kidney. CyA administration was associated with a dose dependent increase in renovascular resistance prevented by a pretreatment with L-PC. The aim of the present study was to confirm L-PC protective effect ... in an in vivo rat model. Chronic nephrotoxicity study was carried out for 28 days. L-PC was administered (ip 25 mg/kg bw) since the first day, while CyA treatment was performed for the last 21 days (by oral administration 25 mg/kg bw). ... L-PC was able to significantly lower blood pressure in CyA treated animals and to prevent CyA induced decrease in creatinine clearance. Moreover renal tissue analysis revealed that L-PC was able to reduce lipid hydroperoxide content and morphological abnormalities associated to chronic CyA administration. In conclusion our study demonstrated for the first time in vivo that L-PC protects against functional and tissue damage associated to chronic CyA administration.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

肾毒性一直是环孢素A（CyA）使用的主要限制因素。在近端小管细胞层面上的结构异常包括坏死、空泡化和脂质滴，以及CyA引起的肾小球入球小动脉收缩和颗粒状近球细胞增生。血管收缩的作用机制尚不完全清楚，但似乎存在内皮细胞功能实质性损伤，导致诸如内皮素和血栓素等血管收缩剂的释放增加。L-丙酰肉碱（PC）是肉碱最有效的类似物之一，能够纠正并预防内皮膜渗透性的改变，并在多种动物物种的肾脏中发现。为了研究PC是否能够减少CyA引起的肾毒性，我们在给予CyA多个剂量的预处理前，使用PC对孤立灌注的大鼠肾脏进行了检查。组织学发现表明，用PC灌注可以减少CyA对肾小球毛细血管的收缩作用并保护小管上皮。肾小球毛细血管丛与鲍曼囊直径之比更高，而在小管层面，基底膜处内径/直径之比在PC + CyA灌注的肾脏中低于仅CyA灌注的肾脏。最终灌注压力在PC + CyA灌注的肾脏中低于仅CyA灌注的肾脏，证实了组织学发现。CyA诱导的丙氨酸氨基肽酶（AAP）和N-乙酰葡萄糖苷酶（NAG）的释放，作为小管损伤的标志物，通过PC预处理显著减少。这些数据表明，PC预处理可以减少孤立灌注大鼠肾脏中CyA诱导的肾毒性。

Nephrotoxicity has represented the major limitation in the use of cyclosporine A (CyA). The structural abnormalities at the level of the proximal tubular cells are necrosis, vacuolization and lipid droplets, as well as CyA-induced glomerular afferent arteriole constriction and granular juxtaglomerular cell hyperplasia. The mode of action of vasoconstriction is not well known, but there appears to be substantial impairment of endothelial cell function leading to enhanced release of vasoconstrictors such as endothelin and thromboxane. L-propionylcarnitine (PC), one of the most potent analogues of carnitine, is able to correct and to prevent alterations in endothelial membrane permeability and it has been identified in the kidney of various animal species. To investigate a possible reduction of CyA-induced nephrotoxocity ... the effects of a pretreatment with PC before administering several doses of CyA /were examined/ n an isolated and perfused rat kidney. The histological findings showed that the perfusion with PC reduces the vasoconstrictive effect of CyA on the glomerular capillaries and preserves the tubular epithelium. The ratio of the diameter between the glomerular capillary tuft and Bowman's capsule was higher, while at the tubular level the ratio internal-diameter/diameter evaluated at the level of the basal membrane was lower in PC + CyA perfused kidneys than in only CyA perfused ones. The final value of perfusion pressure was lower in PC + CyA perfused kidneys than in only CyA perfused ones, confirming the histological findings. The release induced by CyA of alanine aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG), markers of tubular damage, was significantly reduced by pretreatment with PC. These data suggest that the pretreatment with PC reduces the CyA-induced nephrotoxicity in an isolated and perfused rat kidney.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究旨在评估丙酰-L-肉碱这一肉碱衍生物预防亚麻酸和链脲佐菌素处理诱导的大鼠心肌功能障碍的能力。大鼠在10天内被喂食正常饮食或富含10%亚麻酸的饮食，并伴有或不伴有丙酰-L-肉碱腹腔注射（每天1 mM/kg）。另一组大鼠在8-10周内注射链脲佐菌素（65 mg/kg），并伴有或不伴有相同剂量的丙酰-L-肉碱腹腔注射。之后，动物被牺牲，心脏被隔离并在有氧条件下灌流。当应用等容测量左心室功能时，治疗组和对照组心脏的机械活动没有差异。相反，当在起搏心脏中确定压力-容积曲线时，来自亚麻酸处理或糖尿病大鼠的心脏产生的压力降低。丙酰-L-肉碱总是产生正性肌力作用。这对于接受药物的对照组-盐水处理的大鼠以及从心肌病动物隔离的心脏都是正确的。这些数据表明，当长期给予丙酰-L-肉碱时，它能够克服由亚麻酸处理或糖尿病引起的心肌功能障碍。

The purpose of this study is to evaluate the ability of propionyl-L-carnitine, a carnitine derivative to prevent cardiac dysfunction induced by erucic acid and streptozotocin treatment in rats. Rats were fed for 10 days with normal or 10% erucic-acid-enriched diet with or without propionyl-L-carnitine injected intraperitoneally (1 mM/kg daily). Another group of rats was injected for 8-10 weeks with streptozotocin (65 mg/kg) with or without propionyl-L-carnitine intraperitoneally injected at the same dosage. Thereafter the animals were sacrificed and the hearts isolated and perfused aerobically. When isovolumic measurements of left ventricular function were applied, there was no difference in mechanical activity between treated and control hearts. On the contrary, when pressure-volume curves were determined in the paced hearts, the pressure developed by hearts from erucic acid-treated or diabetic rats was reduced. Propionyl-L-carnitine always produced positive inotropy. This was true for the control-saline treated rats that received the drug, as well as for the hearts isolated from cardiomyopathic animals. These data suggest that propionyl-L-carnitine, when given chronically, is able to overcome myocardial dysfunction caused either from erucic acid treatment or diabetes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在这项研究中，我们探讨了丙酰-L-肉碱（PLC）可能保护阿霉素（ADR）诱导的心肌病的机制。ADR（3毫克/千克）每隔一天通过腹腔注射给药，持续2周，导致血清中肌酸磷酸激酶、乳酸脱氢酶和谷氨酸草酰乙酸转氨酶水平显著增加两倍，而每天注射PLC（250毫克/千克），腹腔注射2周，引起的变化不显著。将PLC每天给予接受ADR治疗的大鼠，完全逆转了ADR引起的心脏酶增加，除了乳酸脱氢酶只逆转了66%。在心脏组织匀浆中，ADR导致丙二醛（MDA）显著增加53%，还原型谷胱甘肽（GSH）水平显著降低50%，而PLC导致MDA显著降低33%，GSH水平显著增加41%。每天给接受ADR治疗的大鼠注射PLC，完全逆转了ADR引起的MDA增加和GSH减少，恢复到正常水平。在大鼠心脏线粒体中，ADR在最后一次给药后24小时导致从[1-14C]棕榈酰辅酶A和[1-14C]棕榈酰肉碱的氧化中释放的14CO2显著减少48%和42%，而PLC导致两种底物的氧化显著增加66%和54%。有趣的是，给接受ADR治疗的大鼠注射PLC，完全恢复了ADR引起的两种底物氧化的减少。此外，在大鼠心脏线粒体中，[1-14C]丙酮酸、[1-14C]丙酮酸和[1-14C]辛酸酸的氧化不受ADR和/或PLC治疗的影响。此外，ADR引起了严重的心脏病理损伤，表现为毒性心肌炎，而PLC对此有保护作用。值得一提是，PLC对ADR在实体艾氏癌中的抗肿瘤活性没有影响。这项研究的结果表明：(1) 在心脏中，PLC治疗完全防止了ADR对长链脂肪酸线粒体β-氧化的抑制；(2) PLC具有并/或诱导了对抗ADR引起的心脏膜脂质过氧化的强大抗氧化防御机制；最后(3) PLC对ADR的抗肿瘤活性没有影响。

In this study, the possible mechanisms whereby propionyl-l-carnitine (PLC) could protect against adriamycin (ADR)-induced cardiomyopathy were carried out. Administration of ADR (3 mg/kg) ip, every other day over a period of 2 weeks) resulted in a significant two-fold increase in serum levels of creatine phosphokinase, lactate dehydrogenase and glutamic oxaloacetic transaminase, whereas daily administration of PLC (250 mg/kg), ip for 2 weeks) induced non-significant change. Daily administration of PLC to ADR-treated rats resulted in complete reversal of ADR-induced increase in cardiac enzymes except lactate dehydrogenase which was only reversed by 66%. In cardiac tissue homogenate, ADR caused a significant 53% increase in malonedialdehyde (MDA) and a significant 50% decrease in reduced glutathione (GSH) levels, whereas PLC induced a significant 33% decrease in MDA and a significant 41% increase in GSH levels. Daily administration of PLC to ADR-treated rats completely reversed the increase in MDA and the decrease in GSH induced by ADR to the normal levels. In rat heart mitochondria isolated 24 h after the last dose, ADR induced a significant 48% and 42% decrease in(14)CO(2)released from the oxidation of [1-(14)C]palmitoyl-CoA and [1-(14)C]palmitoylcarnitine, respectively, whereas PLC resulted in a significant 66% and 54% increase in the oxidation of both substrates, respectively. Interestingly, administration of PLC to ADR-treated rats resulted in complete recovery of the ADR-induced decrease in the oxidation of both substrates. In addition, in rat heart mitochondria, the oxidation of [1-(14)C]pyruvate, [1-(14)C]pyruvate and [1-(14)C]octanoate were not affected by ADR and/or PLC treatment. Moreover, ADR caused severe histopathological lesions manifested as toxic myocarditis which is protected by PLC. Worth mentioning is that PLC had no effect on the antitumor activity of ADR in solid Ehrlich carcinoma. Results from this study suggest that: (1) in the heart, PLC therapy completely protects against ADR-induced inhibition of mitochondrial beta -oxidation of long-chain fatty acids; (2) PLC has and/or induces a powerful antioxidant defense mechanism against ADR-induced lipid peroxidation of cardiac membranes; and finally (3) PLC has no effect on the antitumor activity of ADR.

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

大多数（54-86%）的饮食肉碱在小肠被吸收并进入血液。肾脏有效地保留肉碱，因此即使肉碱含量较低的饮食对身体总肉碱含量影响也很小。过量的肉碱不是通过代谢消耗，而是根据需要通过肾脏随尿液排出，以维持血液中肉碱的稳定浓度。/肉碱/

Most (54-86%) dietary carnitine is absorbed in the small intestine and enters the bloodstream. The kidneys efficiently conserve carnitine, so even carnitine-poor diets have little impact on the body's total carnitine content. Rather than being metabolized, excess carnitine is excreted in the urine as needed via the kidneys to maintain stable blood concentrations. /Carnitine/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

L-肉碱和酰基肉碱酯存在于所有组织中。在大多数组织和细胞中，它们的浓度高于血液中的浓度……L-肉碱和乙酰-L-肉碱通过高亲和力、钠依赖性有机阳离子转运体OCTN2在大多数组织中积聚……OCTN2与乙酰-L-肉碱和丙酰-L-肉碱具有相似的亲和力。这种蛋白质在心脏、胎盘、骨骼肌、肾脏、胰腺、睾丸和附睾中高度表达，在大脑、肺和肝脏中弱表达……/酰基肉碱酯/

L-Carnitine and acylcarnitine esters are present in all tissues. In most tissues and cells, they are present in higher concn than in the circulation ... L-carnitine and acetyl-L-carnitine are concn in most tissues via the high-affinity, Na+-dependent organic cation transporter OCTN2 ... OCTN2 binds acetyl-L-carnitine and propionyl-L-carnitine with comparable affinity. This protein is highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, testis, and epididymis and weakly expressed in brain, lung, and liver ... /Acylcarnitine esters/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在50微摩尔/升的过滤负荷下，L-肉碱和酰基肉碱酯的重吸收效率在肾脏中为90至98%。然而，随着L-肉碱过滤负荷的增加，例如在摄入膳食补充剂或静脉输液后，重吸收效率会迅速下降。酰基肉碱酯的清除率通常高于非酯化L-肉碱在肾脏中的清除率。在快速细胞内合成酰基肉碱酯或直接从循环中积累的条件下，尿液中酰基肉碱酯的比例高于血液中的比例。肾脏可能在调节循环中酰基肉碱酯浓度方面发挥重要作用。

... At a filtered load of 50 umol/L, the efficiency of L-carnitine and acylcarnitine ester reabsorption is 90 to 98% /in kidneys/. However, as the filtered load of L-carnitine incr, as, eg after consumption of a dietary supplement or after iv infusion, the efficiency of reabsorption declines rapidly ... Clearance of acylcarnitine esters is often higher than that of nonesterified L-carnitine /in kidneys/ ... Under conditions of rapid intracellular synth of acylcarnitine esters or direct accumulation from the circulation ... a higher proportion of acylcarnitine esters in urine compared to that in the circulation /is achieved/ ... Kidneys may be substantially involved in the regulation of circulating acylcarnitine ester concn. /Aacylcarnitine ester/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在血浆中，酰基肉碱酯/非酯化L-肉碱的比值达到0.4或更高时，被认为是异常的。

... A concn ratio of acylcarnitine esters/nonesterified L-carnitine of 0.4 or greater in plasma is ... considered abnormal ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2932999099
• WGK Germany：
  3
• 储存条件：
  2-8°C

制备方法与用途

丙酮基-L-肉碱是左旋肉碱的一种衍生物，能够高度亲和地与肌肉左旋肉碱转移酶结合。它能增加细胞内左旋肉碱的含量，促进游离脂肪酸进入线粒体进行代谢。通过这一途径，丙酮基-L-肉碱可以缓解外周动脉疾病(PAD)的症状，并改善运动表现。

反应信息

• 作为反应物：
  描述：

  丙酰左旋肉碱盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 propionyl-L-carnitine oxylactone
  参考文献：
  名称：

  Characterization of acylcarnitines using fast atom bombardment mass spectrometry and gas chromatography/mass spectrometry

  摘要：

  报告了一系列合成酰基肉碱的质谱数据。采用快速原子轰击离子化技术结合高能碰撞激发和B/E连扫的直接质谱方法。数据显示，可以使用该技术区分异构化合物。报告了以酰氧乳酸酯衍生物形式的酰基肉碱的气相色谱/质谱分析数据。使用了电子轰击和化学电离两种模式，这使得各种化合物的特征和鉴定变得明确无误。鉴于最近酰基肉碱分析活动的显著增加，详细报告的质谱和气相色谱数据可能对参考目的有所帮助。

  DOI：

  10.1002/jms.1190300112
• 作为产物：
  描述：

  左旋肉碱 、 propanoyl-CoA 生成 coenzyme A 、 丙酰左旋肉碱盐酸盐
  参考文献：
  名称：

  Substrate specificity of human carnitine acetyltransferase: Implications for fatty acid and branched-chain amino acid metabolism

  摘要：

  Carnitine acyltransferases catalyze the reversible conversion of acyl-CoAs into acylcarnitine esters. This family includes the mitochondrial enzymes carnitine palmitoyltransferase 2 (CPT2) and carnitine acetyltransferase (CrAT). CPT2 is part of the carnitine shuttle that is necessary to import fatty acids into mitochondria and catalyzes the conversion of acylcarnitines into acyl-CoAs. In addition, when mitochondrial fatty acid P-oxidation is impaired, CPT2 is able to catalyze the reverse reaction and converts accumulating long- and medium-chain acyl-CoAs into acylcarnitines for export from the matrix to the cytosol. However, CPT2 is inactive with short-chain acyl-CoAs and intermediates of the branched-chain amino acid oxidation pathway (BCAAO). In order to explore the origin of short-chain and branched-chain acylcarnitines that may accumulate in various organic acidemias, we performed substrate specificity studies using purified recombinant human CrAT. Various saturated, unsaturated and branched-chain acyl-CoA esters were tested and the synthesized acylcarnitines were quantified by ESI-MS/MS. We show that CrAT converts short- and medium-chain acyl-CoAs (C2 to C10-00A), whereas no activity was observed with long-chain species. Trans-2-enoyl-00A intermediates were found to be poor substrates for this enzyme. Furthermore, CrAT turned out to be active towards some but not all the BCAAO intermediates tested and no activity was found with dicarboxylic acyl-CoA esters. This suggests the existence of another enzyme able to handle the acyl-CoAs that are not substrates for CrAT and CPT2, but for which the corresponding acylcarnitines are well recognized as diagnostic markers in inborn errors of metabolism. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbadis.2013.02.012

文献信息

• [EN] 2-(1H-INDOLE-3-CARBONYL)-THIAZOLE-4-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS<br/>[FR] DÉRIVÉS DE 2-(1H-INDOLE-3-CARBONYL)-THIAZOLE-4-CARBOXAMIDE ET COMPOSÉS CORRESPONDANTS UTILISÉS EN TANQUE QUE AGONISTES DU RÉCEPTEUR D'HYDROCARBURE ARYLE (AHR) UTILISÉS POUR LE TRAITEMENT DE, P.EX., DE L'ANGIOGENÈSE IMPLIQUÉE OU DE TROUBLES INFLAMMATOIRES
  申请人：IKENA ONCOLOGY INC

  公开号：WO2021127302A1

  公开（公告）日：2021-06-24

  2-(1H-lndole-3-carbonyl)-thiazole-4-carboxamide derivatives and the corresponding imidazole, oxazole and thiophene derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 27 to 32 and 59 to 219; examples 1 to 8; compounds 1-1 to 1-97; tables 1-a, 2 and 3).

  2-(1H-吲哚-3-甲酰基)-噻唑-4-羧酰胺衍生物及相应的咪唑、噁唑和噻吩衍生物以及相关化合物作为芳香烃受体（AHR）激动剂，用于治疗涉及血管生成的疾病，例如视网膜病变、银屑病、类风湿性关节炎、肥胖和癌症，或炎症性疾病。本说明书揭示了示例化合物的合成和表征以及其药理数据（例如第27至32页和59至219页；示例1至8；化合物1-1至1-97；表1-a、2和3）。
• [EN] 4-PHENYL-N-(PHENYL)THIAZOL-2-AMINE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS<br/>[FR] DÉRIVÉS DE 4-PHÉNYL-N-(PHÉNYL)THIAZOL-2-AMINE ET COMPOSÉS ASSOCIÉS UTILISÉS COMME AGONISTES DU RÉCEPTEUR D'HYDROCARBURE ARYLE (AHR) POUR LE TRAITEMENT, PAR EX., DE TROUBLE LIÉS À L'ANGIOGENÈSE OU INFLAMMATOIRES
  申请人：IKENA ONCOLOGY INC

  公开号：WO2021127301A1

  公开（公告）日：2021-06-24

  4-phenyl-N-(phenyl)thiazol-2-amine and 4-(pyridin-3-yl)-N-( phenyl) thiazol-2-amine derivatives and the corresponding thiadiazole, thiophene, oxazole, oxadiazole, imidazole and triazole derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders.

  4-苯基-N-(苯基)噻唑-2-胺和4-(吡啶-3-基)-N-(苯基)噻唑-2-胺衍生物以及相应的噻二唑、噻吩、噁唑、噁二唑、咪唑和三唑衍生物和相关化合物作为芳香烃受体（AHR）激动剂，用于治疗涉及血管生成的疾病，例如视网膜病变、银屑病、类风湿性关节炎、肥胖和癌症，或炎症性疾病。
• [EN] COT MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE COT ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GILEAD SCIENCES INC

  公开号：WO2020252151A1

  公开（公告）日：2020-12-17

  The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) of generic Formula (I) and methods of use and manufacture thereof.

  本公开涉及一般性地与Cot（癌症大阪甲状腺）的通用化学式（I）的调节剂，以及其使用和制造方法。
• IMIDAZOLE AND TRIAZOLE CONTAINING BICYCLIC COMPOUNDS AS JAK INHIBITORS
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20200231590A1

  公开（公告）日：2020-07-23

  The invention provides compounds of formula (I): or a pharmaceutically-acceptable salt thereof, wherein the variables are defined in the specification, that are inhibitors of JAK kinases, particularly JAK3. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat gastrointestinal and other inflammatory diseases.

  这项发明提供了式(I)的化合物： 或其药用可接受的盐，其中变量在规范中定义，这些化合物是JAK激酶的抑制剂，特别是JAK3。该发明还提供了包括这些化合物的药物组合物，以及使用这些化合物治疗胃肠道和其他炎症性疾病的方法。
• Compositions and Methods for Affecting Mental State and Body Composition
  申请人：USPLABS. LLC

  公开号：US20140134283A1

  公开（公告）日：2014-05-15

  The invention discloses compositions, including nutritional products and dietary supplements, comprising aegeline, which is a compound that occurs naturally in the Bael plant. The invention also describes methods comprising the administration of aegeline to mammals. The methods result in increased mental stamina, focus, and energy level, improved mood, increased thermogenesis, increased libido, and anabolic effects and increased strength output and/or muscle mass. These effects can improve cognition, influence body composition, promote weight loss, and/or promote fitness and well-being. A novel method for the synthesis of aegeline is also provided.

  该发明披露了包括永利素的组合物，其中永利素是一种天然存在于木槿果植物中的化合物，这些组合物包括营养产品和膳食补充剂。该发明还描述了涉及将永利素用于哺乳动物的方法。这些方法导致了增加的精神耐力、专注力和能量水平，改善了情绪，增加了热能产生，增加了性欲，具有促进肌肉合成的作用以及增加了力量输出和/或肌肉质量。这些效应可以改善认知能力，影响体态构成，促进减重，以及促进健康和健身。该发明还提供了一种合成永利素的新方法。