cysteamine bitartrate | 27761-19-9

• 物质功能分类: 生物化工 - 氨基酸及其衍生物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: cysteamine bitartrate
• 英文别名: 2-Sulfanylethylazanium;2,3,4-trihydroxy-4-oxobutanoate；2-sulfanylethylazanium;2,3,4-trihydroxy-4-oxobutanoate
• CAS: 27761-19-9
• 化学式: C₂H₇NS*C₄H₆O₆
• 分子量: 227.238
• InChiKey: NSKJTUFFDRENDM-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMSO：45 mg/mL (198.03 mM)；乙醇：不溶

计算性质

• 辛醇/水分配系数(LogP)：
  -2.25
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  142
• 氢给体数：
  6
• 氢受体数：
  8

ADMET

毒理性

• 肝毒性

在预注册研究的长期使用胱胺期间，一小部分接受治疗的患者出现了血清ALT升高的情况，但这一人群的血清酶升高背景率很高，在开放标签研究中并未明确定义。有报告称，在接受高剂量胱胺治疗期间，出现了更为显著的酶水平升高，并在重新接触时复发。这些异常始终无症状，并在调整剂量后迅速逆转。此外，胱氨酸病患者似乎有发展结节性再生性增生和非肝硬化性门脉高压的风险。长期胱胺治疗在这些肝脏并发症中的作用尚不清楚。尽管胱胺的使用范围有限，但尚未有临床明显的急性肝损伤导致黄疸归因于胱胺的报告。

During long term use of cysteamine in preregistration studies, serum ALT elevations occurred in a small proportion of treated subjects, but the background rate of serum enzyme elevations in this population is high and was not defined in the open label studies. There have been reports of more marked enzyme elevations during high dose therapy with cysteamine, with recurrence on reexposure. These abnormalities were invariably asymptomatic and rapidly reversed with dose adjustment. In addition, patients with cystinosis appear to be at risk for developing nodular regenerative hyperplasia and noncirrhotic portal hypertension. The role of long term cysteamine therapy in these hepatic complications is not clear. There have been no reports of clinically apparent, acute liver injury with jaundice attributable to cysteamine, although it has had only limited wide scale use.

来源:LiverTox

毒理性

• 肝毒性

在使用半胱胺的长期使用过程中，在预注册研究的受试者中，一小部分人的血清ALT水平升高，但这一人群的血清酶升高背景率很高，在开放标签研究中没有明确定义。有报道称，在使用高剂量半胱胺治疗期间，酶水平升高更为明显，再次接触后复发。这些异常始终无症状，并在调整剂量后迅速逆转。此外，胱氨酸病患者似乎有发展结节性再生性增生和非肝硬化门静脉高压的风险。长期半胱胺治疗在这些肝脏并发症中的作用尚不清楚。尽管半胱胺的使用范围有限，但尚未有报道称因半胱胺导致明显的急性肝损伤和黄疸的临床报告。

During long term use of cysteamine in preregistration studies, serum ALT elevations occurred in a small proportion of treated subjects, but the background rate of serum enzyme elevations in this population is high and was not defined in the open label studies. There have been reports of more marked enzyme elevations during high dose therapy with cysteamine, with recurrence on reexposure. These abnormalities were invariably asymptomatic and rapidly reversed with dose adjustment. In addition, patients with cystinosis appear to be at risk for developing nodular regenerative hyperplasia and noncirrhotic portal hypertension. The role of long term cysteamine therapy in these hepatic complications is not clear. There have been no reports of clinically apparent, acute liver injury with jaundice attributable to cysteamine, although it has had only limited wide scale use.

来源:LiverTox

毒理性

• 肝毒性

在预注册研究的长期使用胱胺期间，一小部分接受治疗的患者出现了血清ALT升高的情况，但这一人群的血清酶升高背景率很高，在开放标签研究中并未明确定义。有报告称，在接受高剂量胱胺治疗期间，出现了更为显著的酶水平升高，并在重新接触时复发。这些异常始终无症状，并在调整剂量后迅速逆转。此外，胱氨酸病患者似乎有发展结节性再生性增生和非肝硬化性门脉高压的风险。长期胱胺治疗在这些肝脏并发症中的作用尚不清楚。尽管胱胺的使用范围有限，但尚未有临床明显的急性肝损伤导致黄疸归因于胱胺的报告。

During long term use of cysteamine in preregistration studies, serum ALT elevations occurred in a small proportion of treated subjects, but the background rate of serum enzyme elevations in this population is high and was not defined in the open label studies. There have been reports of more marked enzyme elevations during high dose therapy with cysteamine, with recurrence on reexposure. These abnormalities were invariably asymptomatic and rapidly reversed with dose adjustment. In addition, patients with cystinosis appear to be at risk for developing nodular regenerative hyperplasia and noncirrhotic portal hypertension. The role of long term cysteamine therapy in these hepatic complications is not clear. There have been no reports of clinically apparent, acute liver injury with jaundice attributable to cysteamine, although it has had only limited wide scale use.

来源:LiverTox

安全信息

• 海关编码：
  2930909090
• 储存条件：
  2-8℃

反应信息

• 作为反应物：
  描述：

  金刚烷酮 、 cysteamine bitartrate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以97%的产率得到adamantane-2-spiro(2'-thiazolidine)
  参考文献：
  名称：

  Synthesis of adamantane-2-apiro-[2′-thiazolidine] derivatives and their biological activity

  摘要：

  DOI：

  10.1007/bf00773002
• 作为产物：
  描述：

  半胱胺盐酸盐 、 酒石酸 在 三正丁胺 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 0.5h， 以111 g的产率得到cysteamine bitartrate
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF A SULFUR-AMINE

  摘要：

  本发明涉及一种合成半胱胺或其盐的方法。

  公开号：

  US20180111897A1

文献信息

• [EN] MODULATORS OF HSD17B13 AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE HSD17B13 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：REGENERON PHARMA

  公开号：WO2021003295A1

  公开（公告）日：2021-01-07

  The disclosure relates to compounds and pharmaceutical compositions capable of modulating the hydroxysteroid 17-beta dehydrogenase (HSD17B) family member proteins including inhibiting the HSD17B member proteins, e.g. HSD17B13. The disclosure further relates to methods of treating liver diseases, disorders, or conditions with the compounds and pharmaceutical compositions disclosed herein, in which the HSD17B family member protein plays a role.

  本公开涉及能够调节羟基类固醇17-β脱氢酶（HSD17B）家族成员蛋白的化合物和药物组合物，包括抑制HSD17B家族成员蛋白，例如HSD17B13。本公开还涉及使用此处披露的化合物和药物组合物治疗肝脏疾病、障碍或状况的方法，其中HSD17B家族成员蛋白发挥作用。
• [EN] METHODS FOR THE TREATMENT OF CYSTEAMINE SENSITIVE DISORDERS<br/>[FR] MÉTHODES DE TRAITEMENT DES TROUBLES SENSIBLES À LA CYSTÉAMINE
  申请人：THIOGENESIS THERAPEUTICS INC

  公开号：WO2019060634A1

  公开（公告）日：2019-03-28

  The invention features methods for the treatment of cystinosis and other cysteamine sensitive disorders in a subject including administration of a disulfide convertible to cysteamine in vivo. The methods can include the separate administration of a reducing agent to the subject to increase the bioavailablity and extend the plasma pharmacokinetic profile of the cysteamine produced following administration of the disulfide. The methods permit sustained cysteamine plasma concentrations in a subject.

  这项发明涉及治疗囊性氨基酸病和其他对半胱氨酸敏感的疾病的方法，包括在体内给予可转化为半胱氨酸的二硫化物。该方法可以包括向受试者单独给予还原剂，以增加半胱氨酸在给予二硫化物后产生的生物利用度，并延长血浆药代动力学特性。该方法允许受试者体内维持持续的半胱氨酸血浆浓度。
• [EN] INHIBITORS OF CITRATE TRANSPORTER AND THEIR USE IN THERAPY<br/>[FR] INHIBITEURS D'UN TRANSPORTEUR DE CITRATE ET LEUR UTILISATION EN THÉRAPIE
  申请人：ETERNYGEN GMBH

  公开号：WO2018172251A1

  公开（公告）日：2018-09-27

  The present invention relates to a compound of general formula (I) for use in treating diseases depending on the activity of a citrate transporter, wherein the compound has the general formula (I) wherein Rl is aryl, substituted aryl, styryl, or bicyclic; V is SO2; W is N with n and n1 are 1 and X is C=O, or W is C with n and n1 are 0 or 1 and X is CH2 or C=O, Y is N-H or N-methyl and R2 is benzyl, substituted benzyl or CH2(2-pyridyl). Further, it relates to the use of a compound of general formula (I) for preparing a medicament and its use for the treatment of obesity and diabetes, in particular type 2 diabetes and other metabolic diseases as well as for the treatment of age related diseases.

  本发明涉及一种通式（I）的化合物，用于治疗依赖于柠檬酸盐转运蛋白活性的疾病，其中该化合物具有通式（I），其中R1为芳基、取代芳基、亚烯基或双环；V为SO2；W为N，n和n1为1，X为C=O；或W为C，n和n1为0或1，X为CH2或C=O；Y为N-H或N-甲基，R2为苄基、取代苄基或 （2-吡啶基）。此外，涉及使用通式（I）的化合物制备药物，并将其用于治疗肥胖和糖尿病，特别是2型糖尿病和其他代谢性疾病以及老年相关疾病的治疗。
• [EN] COMBINATION THERAPY USING ENANTIOPURE, OXY-SUBSTITUTED, DEUTERIUM-ENRICHED 5-(BENZYL)-5-DEUTERO-THIAZOLIDINE-2, 4-DIONES FOR TREATMENT OF MEDICAL DISORDERS<br/>[FR] POLYTHÉRAPIE UTILISANT DES 5-(BENZYL)-5-DEUTÉRO-THIAZOLIDINE-2,4-DIONES OXY-SUBSTITUÉES ÉNANTIOPURES, ENRICHIES EN DEUTÉRIUM POUR LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：DEUTERX LLC

  公开号：WO2016153948A1

  公开（公告）日：2016-09-29

  The invention provides combination therapy using enantiopure deuterium-enriched pioglitazone, pharmaceutical compositions, and methods of treating nonalcoholic steatohepatitis, diabetes, fibrotic disorders, and other disorders using the combination therapy.

  这项发明提供了使用对映纯的富氘吡格列酮的联合疗法，以及使用该联合疗法治疗非酒精性脂肪性肝炎、糖尿病、纤维化疾病和其他疾病的药物组合和治疗方法。
• PROCESS FOR PREPARATION OF CYSTEAMINE BITARTRATE
  申请人：LUPIN LIMITED

  公开号：US20180193292A1

  公开（公告）日：2018-07-12

  The present invention provides process for preparation of cysteamine bitartrate comprising reacting cysteamine or its salt with tartaric acid. The present invention further provides crystalline form L1 of cysteamine bitartrate having characteristic diffraction peaks at 10.36, 14.54, 17.23, 18.03, 19.24, 20.76, 21.20, 22.02, 23.37, 23.64, 27.71, 28.28, 29.26, 31.33, 32.84, 33.83, 35.51, 36.74±0.2 degree two theta in an X-ray diffraction pattern and process for preparation thereof. The present invention provides crystalline form L2 of cysteamine bitartrate having characteristic diffraction peaks at 7.4, 10.3, 11.0, 11.4, 14.4, 14.9, 18.6, 19.4, 20.1, 20.8, 21.9, 22.3, 22.5, 23.5±0.2 degree two theta in an X-ray diffraction pattern and process for preparation thereof.

  本发明提供一种制备硫醇双酒石酸盐的方法，包括将硫醇或其盐与酒石酸反应。本发明还提供硫醇双酒石酸盐的结晶形态L1，其在X射线衍射图谱中具有特征衍射峰，分别为10.36、14.54、17.23、18.03、19.24、20.76、21.20、22.02、23.37、23.64、27.71、28.28、29.26、31.33、32.84、33.83、35.51、36.74±0.2度二θ，并提供其制备方法。本发明还提供硫醇双酒石酸盐的结晶形态L2，其在X射线衍射图谱中具有特征衍射峰，分别为7.4、10.3、11.0、11.4、14.4、14.9、18.6、19.4、20.1、20.8、21.9、22.3、22.5、23.5±0.2度二θ，并提供其制备方法。