美吡拉敏 | 91-84-9

• 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: 美吡拉敏
• 英文名称: pyrilamine
• 英文别名: mepyramine；N-[(4-methoxyphenyl)methyl]-N',N'-dimethyl-N-2-pyridinyl-1,2-ethanediamine；[3H]-pyrilamine；[3H]-mepyramine；N-[(4-methoxy phenyl)methyl]-N’,N’-dimethyl-N-pyridin-2-yl ethane-1,2-diamine；N'-[(4-methoxyphenyl)methyl]-N,N-dimethyl-N'-pyridin-2-ylethane-1,2-diamine
• CAS: 91-84-9
• 化学式: C₁₇H₂₃N₃O
• 分子量: 285.389
• InChiKey: YECBIJXISLIIDS-UHFFFAOYSA-N

物化性质

• 熔点：
  131-132 °C
• 沸点：
  bp5 201°; bp0.06 168-172°
• 密度：
  1.0141 (rough estimate)
• 物理描述：
  Pyrilamine is a viscous brown liquid. (NTP, 1992)
• 颜色/状态：
  OILY LIQUID
• 溶解度：
  less than 1 mg/mL at 68° F (NTP, 1992)
• 稳定性/保质期：

  STABLE IN AIR /MALEATE/

• 折光率：
  INDEX OF REFRACTION: 1.5760-1.5765 @ 25 °C/D
• 碰撞截面：
  169.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2228.9;2200;2235;2225;2250;2204;2216.5;2230;2230;2220;2235;2235

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  28.6
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

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)

毒理性

• 在妊娠和哺乳期间的影响

哺乳期使用总结：在哺乳期间，偶尔使用小剂量的吡咯胺可能是可接受的。较大剂量或更长时间的使用可能会对婴儿产生影响或减少乳汁供应，尤其是与伪麻黄碱等拟交感神经药联合使用或在哺乳尚未建立时。首选非镇静抗组胺药作为替代。 对哺乳婴儿的影响：截至修订日期，未找到关于吡咯胺的相关已发布信息。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腹痛症状，1.6%的婴儿出现嗜睡。所有反应均无需医疗注意，且没有婴儿接触过吡咯胺。 对哺乳和乳汁的影响：在非哺乳期妇女和产后早期妇女中，相对高剂量的抗组胺药通过注射可以降低基础血清催乳素。然而，哺乳诱导的催乳素分泌不受产后母亲抗组胺药预处理的影响。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 pyrilamine are probably acceptable during breast feeding. Larger doses or more prolonged use may cause 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 pyrilamine 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 and none of the infants were exposed to pyrilamine. ◉ 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；此外，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效果。/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

抗胆碱能效果可能会在使用抗组胺药时与具有抗胆碱能活性的抗胆碱药或其他药物同时使用时增强；患者应被告知及时报告胃肠道问题的发生，因为在使用联合疗法时可能会出现麻痹性肠梗阻。/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

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)

安全信息

• 储存条件：
  -20°C下密封保存于干燥环境

制备方法与用途

Mepyramine是一种组胺H1受体拮抗剂。它具有轻微的镇静作用和局部麻醉效果，常用于治疗过敏症状（包括皮肤疹），既可以通过注射也可以局部使用。此外，它也是许多感冒药中的常见成分。

反应信息

• 作为反应物：
  描述：

  美吡拉敏 在 1-氯乙基氯甲酸酯 、 sodium carbonate 作用下， 以 1,2-二氯乙烷 、 甲醇 为溶剂， 反应 2.0h， 以15%的产率得到N-去甲基吡拉明
  参考文献：
  名称：

  Mepyramine–JNJ7777120-hybrid compounds show high affinity to hH1R, but low affinity to hH4R

  摘要：

  In literature, a synergism between histamine H-1 and H-4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H-1 antagonist and JNJ7777120, a H-4 receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H-1 and one H-4 pharmacophor, connected by an appropriate spacer, in order to address both, H1R and H4R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.001
• 作为产物：
  描述：

  N-(4-methoxybenzyl)methanimine oxide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2-(二环己基膦)3,6-二甲氧基-2′,4′,6′-三异丙基-1,1′-联苯 、 [Ir(dF(CF₃)ppy)₂(dtbbpy)](PF₆) 、 sodium tert-pentoxide 、 lithium carbonate 、 溶剂黄146 、 锌 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 47.0h， 生成 美吡拉敏
  参考文献：
  名称：

  光氧化还原催化的α-氨基酸与硝酮的脱羧交叉偶联

  摘要：

  建立了α-氨基酸与硝酮通过可见光诱导的光氧化还原催化的脱羧交叉偶联反应，易于获得具有结构多样性的β-氨基羟胺和邻二胺，具有操作简单、条件温和、容易获得的特点。可用的α-氨基酸，以及广泛的硝酮底物。该协议的应用可以为一些有价值的含有连二胺的分子提供有效的合成策略。

  DOI：

  10.1021/acs.orglett.0c04101

文献信息

• Imidazole and benzimidazole derivatives useful as histamine H3 antagonists
  申请人：Aslanian G. Robert

  公开号：US20060166960A1

  公开（公告）日：2006-07-27

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: n is 2-5; R is R 3 -aryl, R 3 -heteroaryl, R 3 -cycloalkyl, R 3 -heterocycloalkyl, alkyl, haloalkyl, —OR 4 , —SR 4 or —S(O) 1-2 R 5 ; R 1 and R 2 are H or optionally substituted phenyl or optionally substituted and X is —O— or —S—; or R 1 and R 2 , together with the carbon atoms to which they are attached form optionally substituted and X is —O—, —S— or —NR 7 —; Z is and the remaining variables are as defined in the specification; also disclosed are pharmaceutical compositions comprising the compounds of formula I; also disclosed are methods of treating allergy, allergy-induced airway responses, congestion, obesity and metabolic syndrome using the compounds of Formula I, as well as combinations with other drugs useful for treating those diseases.

  揭示了以下公式化合物或其药学上可接受的盐或溶剂，其中：n为2-5；R为R3-芳基，R3-杂环芳基，R3-环烷基，R3-杂环烷基，烷基，卤代烷基，—OR4，—SR4或—S(O)1-2R5；R1和R2为H或可选择地取代的苯基或可选择地取代的，X为—O—或—S—；或R1和R2，连同它们连接的碳原子形成可选择地取代的，X为—O—，—S—或—NR7—；Z为，其余变量如规范中所定义；还揭示了包括公式I化合物的药物组合物；还揭示了使用公式I化合物治疗过敏、过敏引起的气道反应、充血、肥胖和代谢综合征的方法，以及与其他用于治疗这些疾病的药物的组合。
• [EN] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES AS HISTAMINE H3 ANTAGONISTS<br/>[FR] 1-(4-PIPERIDINYL) BENZIMIDAZOLONES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR H3 DE L'HISTAMINE
  申请人：SCHERING CORP

  公开号：WO2003103669A1

  公开（公告）日：2003-12-18

  Disclosed are histamine H3 antagonists of the formula (I) wherein R1 is benzimidazolone derivative, M1 and M2 are optionally substituted carbon or nitrogen, R2 includes optionally substituted aryl or heteroaryl, and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of Formula (I). Also disclosed are methods of treating various diseases or conditions, such as, for example, allergy, allergy-induced airway responses, and congestion (e.g., nasal congestion) using the compounds of formula (I) in combination with a H1 receptor antagonist.

  揭示了公式（I）中的组胺H3拮抗剂，其中R1是苯并咪唑酮衍生物，M1和M2是可选择地取代的碳或氮，R2包括可选择地取代的芳基或杂环基，其余变量如规范中所定义。还揭示了包括公式（I）化合物的药物组合物。还揭示了使用公式（I）化合物治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）的方法。还揭示了使用公式（I）化合物与H1受体拮抗剂结合治疗各种疾病或症状的方法，例如过敏、过敏引起的气道反应和充血（例如，鼻塞）。
• SUBSTITUTED INDOLES
  申请人：Gant Thomas G.

  公开号：US20090191183A1

  公开（公告）日：2009-07-30

  Disclosed herein are substituted indole cysteinyl leukotriene receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本文揭示了Formula I的替代吲哚半胱氨酸白三烯受体调节剂，其制备方法，药物组合物以及使用方法。
• [EN] TRICYCLIC TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY<br/>[FR] COMPOSÉS TRIAZOLES TRICYCLIQUES MODULANT L'ACTIVITÉ HSP90
  申请人：SYNTA PHARMACEUTICALS CORP

  公开号：WO2009139916A1

  公开（公告）日：2009-11-19

  The present invention relates to substituted tricyclic triazole compounds and compositions comprising substituted tricyclic triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a compound of the invention, or a composition comprising such a compound.

  本发明涉及替代三环三唑化合物和包含替代三环三唑化合物的组合物。该发明还涉及在需要的受体中抑制Hsp90活性的方法，以及预防或治疗高增殖性疾病（如癌症）的方法，其中包括向受体施用本发明的化合物或包含这种化合物的组合物。
• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。

表征谱图