吡维铵 | 7187-62-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 吡维铵
• 英文名称: pyrvinium pamoate
• 英文别名: pyrvinium；2-[(Z)-2-(2,5-dimethyl-1-phenylpyrrol-3-yl)ethenyl]-N,N,1-trimethylquinolin-1-ium-6-amine
• CAS: 7187-62-4
• 化学式: C₂₆H₂₈N₃
• 分子量: 382.528
• InChiKey: QMHSXPLYMTVAMK-UHFFFAOYSA-N

物化性质

• 颜色/状态：
  DEEP-RED CRYSTALLINE SOLID
• 稳定性/保质期：

  STABLE TO HEAT, LIGHT & AIR /PAMOATE/

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  12
• 氢给体数：
  0
• 氢受体数：
  1

ADMET

毒理性

• 人类毒性摘录

治疗的一小部分患者报告了包括恶心、呕吐和腹痛在内的副作用；这些患者中的大多数是较大的儿童或成人，他们接受了相对较大剂量的悬浮液或片剂。呕吐...是最常见的与悬浮液相关的副作用，但是...并没有在接受片剂的患者中发生。/PAMOATE/

SIDE EFFECTS REPORTED IN SMALL PROPORTION OF TREATED PT INCL NAUSEA, VOMITING, & CRAMPING; MAJORITY OF THESE PT WERE OLDER CHILDREN OR ADULTS WHO HAD RECEIVED RELATIVELY LARGE DOSE OF EITHER SUSPENSION OR TABLETS. EMESIS...MOST FREQUENT SIDE EFFECT ASSOC WITH SUSPENSION, BUT...DID NOT OCCUR IN PT...GIVEN TABLETS. /PAMOATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

...短暂的 光敏作用.../已经/ 有报道。

...TRANSIENT PHOTOSENSITIZATION.../HAS/ BEEN REPORTED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

阿苯达唑双羟萘酸盐（500、1000或3000毫克/千克，口服1个月）在大鼠中没有导致毒性效应。双羟萘酸吡维铵比阿苯达唑双羟萘酸盐更具毒性；在给予3000毫克/千克的13只雌性大鼠中，有6只在1个月内死亡。

ADMIN OF PYRANTEL PAMOATE (500, 1000, OR 3000 MG/KG, ORALLY FOR 1 MO) DID NOT RESULT IN TOXIC EFFECTS IN RATS. PYRVINIUM PAMOATE WAS MORE TOXIC THAN PYRANTEL PAMOATE; 6 OF 13 FEMALE RATS GIVEN 3000 MG/KG DIED WITHIN 1 MO.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

邻苯二甲酸二异丙酯通过大鼠肝脏微粒体混合物激活，能够引起沙门氏菌属的TA100菌株碱基对替换和TA98菌株的移码突变。使用了改良的艾姆斯试验。

PYRVINIUM EMBONATE WAS ACTIVATED BY RAT LIVER MICROSOMAL PREPN TO MUTAGEN CAPABLE OF CAUSING BOTH BASE-PAIR SUBSTITUTION IN SALMONELLA TYPHIMURIUM TA100 & FRAMESHIFT MUTATIONS IN TA98 STRAIN. MODIFIED AMES TEST WAS USED.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

吡vinium从胃肠道吸收不显著。

Pyrvinium is not significantly absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

通过口服途径给予时，PYRVINIUM PAMOATE不会从胃肠道吸收到任何可观的程度。/PAMOATE/

WHEN GIVEN BY ORAL ROUTE, PYRVINIUM PAMOATE IS NOT ABSORBED FROM GI TRACT TO ANY APPRECIABLE EXTENT. /PAMOATE/

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  5-氯-2-硝基苯甲醛 在 盐酸 、 氢气 、 sodium 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 38.0h， 生成 吡维铵
  参考文献：
  名称：

  New Synthesis of Pyrvinium That inhibits the β-Catenin/Tcf4 Pathway

  摘要：

  A new and converged route is described for synthesis of pyrvinium, an anthelmintic and antitumor agent. This method uses easily obtained materials and simple and practical reactions, including the key Friedlander condensation, to form the quinoline ring. The final product is generated through eight steps, with 23% yield and 96.6% purity (HPLC). This synthetic pyrvinium effectively inhibits beta-catenin/Tcf4 driven TOP-luciferase activity, with an IC50 value < 1 mu M, and induces colon cancer cell death in a dose-dependent manner with an IC50 of 0.54 +/- 0.06 mu M.

  DOI：

  10.3987/com-12-12446

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] GLUCOSE UPTAKE INHIBITORS<br/>[FR] INHIBITEURS D'ABSORPTION DU GLUCOSE
  申请人：KADMON CORP LLC

  公开号：WO2016210330A1

  公开（公告）日：2016-12-29

  Provided hererin are compounds that modulate glucose uptake activityand are useful for treating cancer, autoimmune diseases, inflammation, infectious diseases, and metabolic diseases. In certain embodiments, the compounds modulate glucose uptake activity by modulating cellular components, including, but not limited to those related to glycolysis and known transporters/co-transporters of glucose such as GLUT1 and other GLUT family members/alternative hexose transporters. In certain embodiments, the compounds have the structure of formula I: Formula (I) wherein the variables have the values disclosed herein.

  本文提供了调节葡萄糖摄取活性的化合物，可用于治疗癌症、自身免疫疾病、炎症、传染病和代谢性疾病。在某些实施例中，这些化合物通过调节细胞组分来调节葡萄糖摄取活性，包括但不限于与糖酵解和已知的葡萄糖转运蛋白/共转运蛋白（如GLUT1和其他GLUT家族成员/替代己糖转运蛋白）有关的组分。在某些实施例中，这些化合物具有以下结构的结构：公式（I）其中变量具有此处披露的值。
• [EN] COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING CANCER<br/>[FR] COMPOSITIONS ET MÉTHODES POUR TRAITER ET PRÉVENIR LE CANCER
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2016187544A1

  公开（公告）日：2016-11-24

  This invention is in the field of medicinal chemistry. In particular, the invention relates to novel small molecule compounds having a quinolin-8-yl-nicotinamide structure which are useful in treating, ameliorating, or preventing various forms of cancer (e.g., pancreatic cancer).

  这项发明属于药物化学领域。具体来说，该发明涉及具有喹啉-8-基-烟酰胺结构的新型小分子化合物，可用于治疗、改善或预防各种癌症（例如胰腺癌）。
• SMALL-MOLECULE INHIBITORS OF THE ANDROGEN RECEPTOR
  申请人：Diamond Marc

  公开号：US20080293766A1

  公开（公告）日：2008-11-27

  The present invention provides a method of inhibiting an androgen receptor by administering a compound of Formula I: or a compound of Formula II: wherein R 1 , R 2 , R 3 and R 8 are each independently hydrogen or C 1-6 alkyl. R 4 is absent or is hydrogen, C 1-6 alkyl or C 1-6 alkyl-OH. R 5 is hydrogen, C 1-6 alkyl or —NR 6 R 7 . R 6 and R 7 are each independently hydrogen or C 1-6 alkyl, or are combined with the nitrogen to which they are attached to form a heterocycloalkyl having from 5 to 7 ring members. L is a linker of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene or C 3-6 cycloalkylene. The compounds of Formula I include the salts, hydrates and prodrugs thereof. Each R 9 is H, C 1-6 alkyl, —OH or —O—C 1-6 alkyl. The compounds of Formulas I and II include the salts, hydrates and prodrugs thereof. By administering the compound of Formula I or II, the method inhibits the androgen receptor.

  本发明提供了通过给予式I的化合物或式II的化合物来抑制雄激素受体的方法：其中R1、R2、R3和R8分别独立地为氢或C1-6烷基。R4不存在或为氢、C1-6烷基或C1-6烷基-OH。R5为氢、C1-6烷基或-NR6R7。R6和R7分别独立地为氢或C1-6烷基，或与它们连接的氮原子结合形成具有5至7个环成员的杂环烷基。L为C1-6烷基、C2-6烯基、C2-6炔基或C3-6环烷基的连接剂。式I的化合物包括其盐、水合物和前药。每个R9为H、C1-6烷基、-OH或-O-C1-6烷基。式I和II的化合物包括其盐、水合物和前药。通过给予式I或II的化合物，该方法抑制雄激素受体。