异丁嗪 | 84-96-8

• 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 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 异丁嗪
• 中文别名: N,N,2-三甲基-3-吩噻嗪-10-基-1-丙胺；阿利马嗪
• 英文名称: Alimemazine
• 英文别名: Trimeprazine；10-[3-(dimethylamino)-2-methylpropyl]phenothiazine；N,N,2-trimethyl-3-phenothiazin-10-ylpropan-1-amine
• CAS: 84-96-8
• 化学式: C₁₈H₂₂N₂S
• 分子量: 298.452
• InChiKey: ZZHLYYDVIOPZBE-UHFFFAOYSA-N

物化性质

• 熔点：
  68°C
• 沸点：
  bp0.3 150-175°
• 密度：
  1.1163 (rough estimate)
• 物理描述：
  Solid
• 颜色/状态：
  CRYSTALS
• 溶解度：
  0.942 mg/L
• 稳定性/保质期：

  DARKENS ON EXPOSURE TO LIGHT /TARTRATE/

• 碰撞截面：
  166.8 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2283;2283;2300;2315;2343;2352;2309;2298.7;2292.1;2308.8;2354;2313;2320;2309;2298.5;2305;2305;2318.9

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  31.8
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

在大鼠中产生10-(3-二甲基氨基-2-甲基丙基)吩噻嗪砜和10-(3-甲基氨基-2-甲基丙基)吩噻嗪；HEWICK, DS, & BECKETT, AH, 生物化学杂志, 122, 56P (1971年)。/来自表格/

YIELDS 10-(3-DIMETHYLAMINO-2-METHYLPROPYL)PHENOTHIAZINE SULFOXIDE AND 10-(3-METHYLAMINO-2-METHYLPROPYL)PHENOTHIAZINE IN RAT; HEWICK, DS, & BECKETT, AH, BIOCHEM J, 122, 56P (1971). /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

主要通过肝脏代谢。肝脏的代谢反应包括氧化、羟基化、脱甲基、亚砜形成以及与葡萄糖醛酸的结合，侧链的代谢改变也可能发生/人类，口服/。/酒石酸/

METABOLIZED PRIMARILY BY THE LIVER. HEPATIC METABOLIC REACTIONS INCLUDE OXIDATION, HYDROXYLATION, DEMETHYLATION, SULFOXIDE FORMATION AND CONJUGATION WITH GLUCURONIC ACID, METABOLIC ALTERATIONS IN THE SIDE CHAIN MAY ALSO OCCUR /HUMAN, ORAL/. /TARTRATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

显著增强由美沙酮引起的呼吸抑制。增强多种药物的效果，尤其是中枢神经系统抑制剂，并不是由于抑制了肝脏微粒体酶。实际上，吩噻嗪类药物促进了这些酶的诱导。/吩噻嗪类药物/

...MARKEDLY ENHANCES RESPIRATORY DEPRESSION PRODUCED BY MEPERIDINE. ENHANCEMENT OF EFFECTS OF VARIETY OF DRUGS, PARTICULARLY CNS DEPRESSANTS, IS NOT DUE TO INHIBITION OF HEPATIC MICROSOMAL ENZYMES. IN FACT, PHENOTHIAZINES PROMOTE INDUCTION OF THESE ENZYMES. /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

可能会增加有机磷或其他乙酰胆碱酯酶抑制剂与普鲁卡因的毒性。不要使用肾上腺素来对抗其降压或抑制效果，因为它会增强这些效果。

MAY INCR TOXICITY OF ORGANOPHOSPHORUS OR OTHER ACETYLCHOLINESTERASE INHIBITORS & PROCAINE. DO NOT USE EPINEPHRINE TO COMBAT ITS HYPOTENSIVE OR DEPRESSANT EFFECTS AS IT POTENTIATES THEM.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

可能性严重的低温...在接受/同时/退热治疗的病人中...与中枢神经系统抑制剂的作用相加，或者可能增强其作用...阿托品，降压药，麻醉药，巴比妥类药物...其他镇静剂，麻醉剂，安眠药...酒精。/酒石酸/

POSSIBILITY OF SEVERE HYPOTHERMIA...IN PATIENTS RECEIVING /CONCOMITANT/ ANTIPYRETIC THERAPY...ADDITIVE WITH, OR MAY POTENTIATE, ACTION OF CNS DEPRESSANTS...ATROPINE, HYPOTENSIVE AGENTS, NARCOTICS, BARBITURATES...OTHER SEDATIVES, ANESTHETICS, TRANQUILIZERS...ALCOHOL. /TARTRATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

如果出现光敏感性，患者应避免日晒或穿着防护服以防止晒伤...严重的低血压效应...可以通过...左旋arterenol...或苯肾上腺素缓解。/酒石酸/

IF PHOTOSENSITIVITY DEVELOPS, PATIENT SHOULD STAY OUT OF THE SUN OR WEAR PROTECTIVE CLOTHING TO PREVENT SOLAR ERYTHEMA...SEVERE HYPOTENSIVE EFFECTS...ALLEVIATED BY...LEVARTERENOL...OR PHENYLEPHRINE. /TARTRATE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

严重的低血压/由于过量/可以通过...静脉注射左旋arterenol...或苯肾上腺素输注...可以使用麻黄碱、安非他命或咖啡因和苯甲酸钠/作为兴奋剂/。低体温...难以控制...交换输血可能有用...血液透析...价值不大。/酒石酸/

SEVERE HYPOTENSION /FROM OVERDOSAGE/ ALLEVIATED BY...IV LEVARTERENOL...OR PHENYLEPHRINE INFUSIONS...EPHEDRINE, AMPHETAMINES OR CAFFEINE & SODIUM BENZOATE MAY BE USED /AS STIMULANTS/. HYPOTHERMIA...DIFFICULT TO CONTROL... EXCHANGE TRANSFUSIONS MAY BE USEFUL...HEMODIALYSIS...OF LITTLE VALUE. /TARTRATE/

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

吩噻嗪类药物在体内的最终停留时间非常长。在停药六个月后，尿液中仍可检测到各种代谢物。/吩噻嗪类/

ULTIMATE SOJOURN OF PHENOTHIAZINE DRUGS IN BODY IS EXCEEDINGLY LONG. SIX MO AFTER DISCONTINUATION OF THESE DRUGS, VARIOUS METABOLITES ARE DETECTABLE IN URINE. /PHENOTHIAZINES/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• WGK Germany：
  3
• 危险类别：
  6.1(a)
• 安全说明：
  S22,S24/25,S26,S36
• 危险类别码：
  R20/21/22,R36/37/38
• 包装等级：
  II
• 危险品运输编号：
  2811
• 储存条件：
  库房应保持通风、低温和干燥，并与食品原料分开存放。

制备方法与用途

生物活性

Alimemazine 是一种通常用作止痒剂的吩噻嗪衍生物，同时也是血凝素（HA）受体拮抗剂。作为一种组胺H1受体 (H1R) 和其他G蛋白偶联受体 (GPCR) 的部分激动剂，它还具有镇静、抗血清素、抗痉挛和止吐作用。

靶点

HA receptor

类别

有毒物品

毒性分级

高毒

急性毒性

• 口服-大鼠 LD50: 210 毫克/公斤
• 口服-小鼠 LD50: 300 毫克/公斤

可燃性危险特性

可燃；燃烧时产生有毒氮氧化物和硫氧化物烟雾

储运特性

库房应通风、低温干燥，并与食品原料分开存放

灭火剂

干粉、泡沫、砂土、二氧化碳，以及雾状水

反应信息

• 作为反应物：
  描述：

  异丁嗪 在 soybean lipoxygenase 、 双氧水 作用下， 以 phosphate buffer 为溶剂， 反应 0.5h， 生成 聚合甲醛
  参考文献：
  名称：

  N-demethylation of phenothiazines by lipoxygenase from soybean and human term placenta in the presence of hydrogen peroxide

  摘要：

  Several phenothiazine derivatives have been shown to cause reproductive toxicity. The biochemical mechanisms responsible for these effects are not fully understood at present. In this study, we investigated hydrogen peroxide-dependent oxidation of six phenothiazines by purified lipoxygenase from soybean (SLO) and human term placenta (HTPLO). Chlorpromazine was employed as the prototype phenothiazine drug. Chlorpromazine was easily demethylated releasing formaldehyde when incubated at pH 7.0 and 6.5 with SLO or HTPLO, respectively, in the presence of hydrogen peroxide. The reaction was linear with respect to time, exhibited dependence on the amount of enzyme, and the concentration of chlorpromazine and hydrogen peroxide. Under the optimal assay conditions, the estimated Vmax values for chlorpromazine N-demethylation were 139 and 7.2 nmoles/min/mg of SLO and HTPLO, respectively. Collectively, the results suggest an enzymatic nature of the reaction. In the presence of gossypol and NDGA, the classical inhibitors of different Lipoxygenases, the formaldehyde production was significantly decreased, as expected. Similar to SLO, the generation of chlorpromazine cation radical, an initial oxidation product with an absorption maximum at 525 nm, was also observed with HTPLO. The radical generation was detectable only under acidic conditions (pH 3.5-4.5). The formaldehyde production was also decreased by BHT and BHA, suggesting a radical nature of the SLO-mediated chlorpromazine N-demethylation. Reduced glutathione, ascorbate, and dithiothreitol suppressed the rate of SLO-dependent formaldehyde generation, presumably due to the reduction of the cation radical back to chlorpromazine in a concentration-dependent manner. Besides chlorpromazine, SLO also oxidized promazine, triflupromazine, trifluperazine, trimeprazine, and perphenazine, albeit at different rates, in the presence of hydrogen peroxide. The evidence gathered in this in vitro study suggests that phenothiazines can undergo peroxidative N-demethylation via lipoxygenase pathway. The role of this biochemical mechanism in the in vivo developmental toxicity of phenothiazines remains to be established. Teratogenesis Carcinog. Mutagen. 19:211-222, 1999. (C) 1999 Wiley-Liss, Inc.

  DOI：

  10.1002/(sici)1520-6866(1999)19:3<211::aid-tcm4>3.0.co;2-m
• 作为产物：
  描述：

  吩噻嗪 在 chloro(1,5-cyclooctadiene)rhodium(I) dimer 、 氢气 作用下， 120.0 ℃ 、11.0 MPa 条件下， 反应 48.0h， 生成 异丁嗪
  参考文献：
  名称：

  通过铑催化杂环烯丙基胺的羰基化氢氨基甲基化一锅合成药理活性二胺

  摘要：

  吩噻嗪，亚氨基二苄基，咔唑和吡唑的药理活性衍生物是通过使相应的N-烯丙基或N-甲基烯丙基化合物，伯或仲胺，一氧化碳和氢在[Rh（cod）Cl通过一锅加氢甲酰化-胺缩合-还原顺序得到作为催化剂的] 2。图选项

  DOI：

  10.1016/s0040-4020(99)00536-0

文献信息

• 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。
• Benzoxazinyl-amidocyclopentyl-heterocyclic modulators of chemokine receptors
  申请人：Goble D. Stephen

  公开号：US20070238723A1

  公开（公告）日：2007-10-11

  Cyclopentyl compounds linked to a benzoxazinyl group through an amido moiety utilizing the ring nitrogen of the benzoxazine, and further substituted with a heterocyclic moiety, such compounds represented by formula I: which are used to modulate the CCR-2 chemokine receptor to prevent or treat inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis; and pharmaceutical compositions comprising these compounds and the use of these compounds and compositions.

  环戊基化合物通过酰胺基团与苯并噁唑基团相连，利用苯并噁唑环的环氮原子，并进一步用杂环基团取代，这些化合物由式I表示： 用于调节CCR-2趋化因子受体，以预防或治疗炎症和免疫调节性疾病和疾病，过敏性疾病，包括过敏性鼻炎，皮炎，结膜炎和哮喘，以及类风湿性关节炎和动脉粥样硬化等自身免疫病理病变；以及包含这些化合物的药物组合物和这些化合物和组合物的使用。
• 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。

表征谱图