曲吡那敏 | 91-81-6

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 曲吡那敏
• 英文名称: tripelennamine
• 英文别名: N'-benzyl-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine
• CAS: 91-81-6
• 化学式: C₁₆H₂₁N₃
• 分子量: 255.363
• InChiKey: UFLGIAIHIAPJJC-UHFFFAOYSA-N

物化性质

• 熔点：
  25°C
• 沸点：
  bp0.1 138-142°; bp1.7 185-190°; bp20 193-205°
• 密度：
  1.0683 (rough estimate)
• 物理描述：
  Tripelenamine is an oily liquid with an amine odor. (NTP, 1992)
• 颜色/状态：
  YELLOW OIL
• 气味：
  AMINE ODOR
• 溶解度：
  587 mg/L (at 30 °C)
• 水溶性：
  -2.64
• 稳定性/保质期：

  SLOWLY DARKENS ON EXPOSURE TO LIGHT /HYDROCHLORIDE/

• 折光率：
  INDEX OF REFRACTION: 1.5759-1.5765 @ 25 °C/D
• 解离常数：
  PKB= 4.93
• 保留指数：
  1976;1961;1961;1949;1975;1974;1980;1960;1960;1970.3;1970;1980;1949;1980;1980;1975;1975

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  19.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

从人类尿液中口服三丙胺，次要代谢物被识别为N-氧化物，主要的结合物是一种独特的季铵N-葡萄糖苷酸，另外两个是羟基化衍生物的O-葡萄糖苷酸。羟基三丙胺的葡萄糖苷酸是主要的代谢物。

FROM URINE OF HUMAN ORALLY ADMIN TRIPELENNAMINE, MINOR METAB IDENTIFIED AS N-OXIDE, MAJOR CONJUGATE WAS A UNIQUE QUATERNARY AMMONIUM N-GLUCURONIDE, 2 OTHERS WERE O-GLUCURONIDE OF HYDROXYLATED DERIV. GLUCURONIDE OF HYDROXYTRIPELENNAMINE BEING PRINCIPAL METAB.

来源:Hazardous Substances Data Bank (HSDB)

代谢

主要代谢转化部位是肝脏。/抗组胺药/

MAIN SITE OF METABOLIC TRANSFORMATION IS LIVER. /ANTIHISTAMINES/

来源:Hazardous Substances Data Bank (HSDB)

代谢

H1受体拮抗剂是诱导肝微粒体酶的许多药物之一，它们可能促进自身的代谢。/组胺拮抗剂：H1拮抗剂/

H1 blockers are among the many drugs that induce hepatic microsomal enzymes, and they may facilitate their own metabolism. /Histamine Antagonists: H1 Antagonists/

来源:Hazardous Substances Data Bank (HSDB)

代谢

Tripelennamine 已知的人类代谢物包括 Tripelennamine N-葡萄糖苷酸。

Tripelennamine has known human metabolites that include Tripelennamine N-glucuronide.

来源:NORMAN Suspect List Exchange

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：偶尔小剂量的曲普利定不会预期对哺乳婴儿产生任何不利影响。较大剂量或更长时间的使用可能会导致婴儿昏昏欲睡或其他影响，或者减少奶量，特别是在与伪麻黄碱等拟交感神经药合用或在哺乳期尚未建立时。首选非镇静抗组胺药作为替代品。 对哺乳婴儿的影响：截至修订日期，没有找到关于曲普利定的相关已发布信息。在一项电话随访研究中，母亲报告有10%的婴儿接触到各种抗组胺药后出现烦躁和肠绞痛症状，1.6%的婴儿出现嗜睡。所有反应均无需医疗关注。 对泌乳和母乳的影响：在非哺乳期妇女和产后早期妇女中，通过注射给予相对高剂量的抗组胺药可以降低基础血清催乳素。然而，产后母亲在接受抗组胺药预处理后，吮吸诱导的催乳素分泌不受影响。尚未研究较低口服剂量的抗组胺药是否对血清催乳素有相同的影响，或者催乳素的影响是否对哺乳成功有任何后果。在已建立哺乳的母亲中，催乳素水平可能不会影响她的哺乳能力。

◉ Summary of Use during Lactation:Small occasional doses of tripelennamine would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. The nonsedating antihistamines are preferred alternatives. ◉ Effects in Breastfed Infants:Relevant published information on tripelennamine was not found as of the revision date. In one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention. ◉ Effects on Lactation and Breastmilk:Antihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women. However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers. Whether lower oral doses of antihistamines have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

同时使用具有耳毒性的药物和抗组胺药可能会掩盖耳毒性的症状，如耳鸣、头晕或眩晕。/抗组胺药/

Concurrent use /of ototoxic medications/ with antihistamines may mask the symptoms of ototoxicity such as tinnitus, dizziness, or vertigo. /Antihistamines/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

单胺氧化酶（MAO）抑制剂与抗组胺药的并用可能会延长并增强抗组胺药的抗胆碱能和中枢神经系统抑制作用；不建议同时使用。/抗组胺药/

Concurrent use of monoamine oxidase (MAO) inhibitors with antihistamines may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines; concurrent use is not recommended. /Antihistamines/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与酒精或其他能产生中枢神经系统抑制的药物同时使用，可能会增强这些药物或抗组胺药的中枢神经系统抑制作用；同时，与马普替林或三环类抗抑郁药同时使用，可能会增强抗组胺药或这些药物的的抗胆碱能作用。/抗组胺药/

Concurrent use /with alcohol or other CNS depression-producing medications/ may potentiate the CNS depressant effects of either these medications or antihistamines; also, concurrent use of maprotiline or tricyclic antidepressants may potentiate the anticholinergic effects of either antihistamines or these medications. /Antihistamines/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

抗胆碱能作用可能会在使用抗组胺药的同时使用抗胆碱药或其他具有抗胆碱活性的药物时增强；患者应该被告知立即报告出现的胃肠道问题，因为在使用联合疗法时可能会发生麻痹性肠梗阻。/抗组胺药/

Anticholinergic effects may be potentiated when /anticholinergics or other medications with anticholinergic activity/ are used concurrently with antihistamines; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy. /Antihistamines/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

消化道吸收良好。

Well absorbed in the digestive tract.

来源:DrugBank

吸收、分配和排泄

H1拮抗剂从胃肠道吸收良好。口服给药后，血浆浓度在2到3小时内达到峰值，效果通常持续4到6小时；然而，一些药物的药效持续更长时间... /组胺拮抗剂：H1拮抗剂/

The H1 antagonists are well absorbed from the gi tract. Following oral administration, peak plasma concn are achieved in 2 to 3 hr and effects usually last 4 to 6 hr; however, some of the drugs are much longer acting ... . /Histamine Antagonists: H1 Antagonists/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

H1拮抗剂在儿童体内的消除速度比成人快，而在严重肝病患者体内的消除速度则较慢。/组胺拮抗剂：H1拮抗剂/

... H1 antagonists are eliminated more rapidly by children than by adults and more slowly in those with severe liver disease. /Histamine Antagonists: H1 Antagonists/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

功效作用

曲吡那敏是一种乙二胺类抗组胺药，属于乙二胺类组胺H1受体拮抗剂。它的抗组胺作用略强于苯海拉明，并且持续时间更长，引起的嗜睡等副作用较少。

适应症

曲吡那敏主要用于治疗过敏性皮炎、湿疹、过敏性鼻炎以及哮喘等症状。

反应信息

• 作为反应物：
  描述：

  曲吡那敏 在 乙醇 、 双氧水 作用下， 生成 N'-benzyl-N,N-dimethyl-N'-[2]pyridyl-ethylenediamine-N-oxide
  参考文献：
  名称：

  2-[benzyl (2-dimethylaminoethyl) amino]-pyridine nu-oxides

  摘要：

  公开号：

  US02785170A1
• 作为产物：
  描述：

  2-氯吡啶 在 lithium amide 作用下， 以 乙腈 为溶剂， 反应 20.08h， 生成 曲吡那敏
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel FAK scaffold inhibitors targeting the FAK–VEGFR3 protein–protein interaction

  摘要：

  Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor 3 (VEGFR3) are tyrosine kinases, which function as key modulators of survival and metastasis signals in cancer cells. Previously, we reported that small molecule chlorpyramine hydrochloride (C4) specifically targets the interaction between FAK and VEGFR3 and exhibits anti-tumor efficacy. In this study, we designed and synthesized a series of 1 (C4) analogs on the basis of structure activity relationship and molecular modeling. The resulting new compounds were evaluated for their binding to the FAT domain of FAK and anti-cancer activity. Amongst all tested analogs, compound 29 augmented anti-proliferative activity in multiple cancer cell lines with stronger binding to the FAT domain of FAK and disrupted the FAK-VEGFR3 interaction. In conclusion, we hope that this work will contribute to further studies of more potent and selective FAK-VEGFR3 protein-protein interaction inhibitors.

  DOI：

  10.1016/j.ejmech.2014.04.041

文献信息

• [EN] 3,5-DIAMINO-6-CHLORO-N-(N-(4-PHENYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2- CARBOXAMIDE COMPOUNDS<br/>[FR] COMPOSÉS 3,5-DIAMINO -6-CHLORO-N-(N- (4-PHÉNYLBUTYL)CARBAMIMIDOYL) PYRAZINE-2-CARBOXAMIDE
  申请人：PARION SCIENCES INC

  公开号：WO2014099673A1

  公开（公告）日：2014-06-26

  The present invention relates compounds of the formula: or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

  本发明涉及以下化合物的公式：或其药学上可接受的盐，用作钠通道阻滞剂，以及含有这些化合物的组合物，制备这些化合物的方法，以及在促进粘膜表面水合和治疗包括囊性纤维化、慢性阻塞性肺病、哮喘、支气管扩张、急性和慢性支气管炎、肺气肿和肺炎等疾病的治疗方法。
• CHLORO-PYRAZINE CARBOXAMIDE DERIVATIVES WITH EPITHELIAL SODIUM CHANNEL BLOCKING ACTIVITY
  申请人：Parion Sciences, Inc.

  公开号：US20140171447A1

  公开（公告）日：2014-06-19

  This invention provides compounds of the formula I: and their pharmaceutically acceptable salts, useful as sodium channel blockers, compositions containing the same, therapeutic methods and uses for the same and processes for preparing the same.

  这项发明提供了式I的化合物及其药用盐，可用作钠通道阻滞剂，包含这些化合物的组合物，以及用于这些化合物的治疗方法和用途，以及制备这些化合物的方法。
• Dual Pharmacophores - PDE4-Muscarinic Antagonistics
  申请人：Callahan James Francis

  公开号：US20090203657A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.

  本发明涉及具有式（I）的新化合物及其药用盐，药物组合物及其用作对PDE4和肌胆碱受体（mAChRs）具有抑制活性的双色素，因此可用于治疗呼吸道疾病。
• [EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2009100169A1

  公开（公告）日：2009-08-13

  The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.

  本发明涉及式(I) - (VI)的新化合物，以及其药学上可接受的盐、药物组合物及其在治疗中的应用，例如作为磷酸二酯酶IV (PDE4)的抑制剂和肌碱乙酰胆碱受体 (mAChRs)的拮抗剂，用于治疗和/或预防呼吸道疾病，包括炎症性和/或过敏性疾病，如慢性阻塞性肺病（COPD）、哮喘、鼻炎（例如过敏性鼻炎）、特应性皮炎或银屑病。
• 3-Aminocyclopentanecarboxamides as modulators of chemokine receptors
  申请人：Xue Chu-Biao

  公开号：US20060004018A1

  公开（公告）日：2006-01-05

  The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.

  本发明涉及以下式的化合物： 这些化合物是趋化因子受体的调节剂。本发明的化合物及其组合物在治疗与趋化因子受体表达和/或活性相关的疾病方面是有用的。

表征谱图