(+)-喷他佐辛 | 7488-49-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 6,7-苯并吗啡烷
• 中文名称: (+)-喷他佐辛
• 英文名称: pentazocin
• 英文别名: pentazocine；(-)-trans-pentazocine；[³H]Pentazocine；(1R,9R,13R)-1,13-dimethyl-10-(3-methylbut-2-enyl)-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol
• CAS: 7488-49-5；359-83-1；7361-76-4
• 化学式: C₁₉H₂₇NO
• 分子量: 285.429
• InChiKey: VOKSWYLNZZRQPF-GDIGMMSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.578
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

戊唑辛产生1,2,3,4,5,6-六氢-8-羟基-α,6(等价),11(轴)-三甲基-2,6-亚甲基-3-苯并唑嗪-3-顺-2-丁烯-1-醇和1,2,3,4,5,6-六氢-8-羟基-α,6(等价),11(轴)-三甲基-2,6-亚甲基-3-苯并唑嗪-3-反-2-丁烯-1-醇，在猴子和老鼠中。/来自表格/

PENTAZOCINE YIELDS 1,2,3,4,5,6-HEXAHYDRO-8-HYDROXY- ALPHA,6(EQ),11(AX)-TRIMETHYL-2,6-METHANO-3-BENZAZOCINE-3-CIS-2-BUTEN-1-OL & 1,2,3,4,5,6-HEXAHYDRO-8-HYDROXY-ALPHA,6(EQ),11(AX)- TRIMETHYL-2,6-METHANO-3-BENZAZOCINE-3-TRANS-2-BUTEN-1-OL IN MONKEY & MOUSE. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

代谢

... 喷他佐辛的代谢速率已显示出吸烟者与非吸烟者之间存在差异。

... RATE OF METABOLISM OF PENTAZOCINE HAS BEEN SHOWN TO DIFFER /BETWEEN/ SMOKERS & NON-SMOKERS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠口服喷他佐辛后，尿液中发现的主要是喷他佐辛及其葡萄糖醛酸苷结合物。尽管从尿液中提取并鉴定了八种代谢物，但它们的量很小，表明了芳香环的羟基化和甲氧基化，以及一些二甲基丙烯侧链的氧化。

IN THE RAT, AFTER ORAL ADMIN OF PENTAZOCINE, MAINLY PENTAZOCINE & ITS GLUCURONIDE CONJUGATES WERE FOUND IN URINE. ALTHOUGH EIGHT METABOLITES WERE EXTRACTED FROM URINE & CHARACTERIZED ... THE AMOUNTS WERE SMALL AND INDICATED HYDROXYLATION AND METHOXYLATION OF THE AROMATIC RING, WITH SOME OXIDN OF THE DIMETHYLALLYL SIDE-CHAIN.

来源:Hazardous Substances Data Bank (HSDB)

代谢

戊唑辛在肝脏中被代谢，主要是通过氧化二甲烷基侧链的末端甲基团，形成醇和羧酸代谢物；葡萄糖醛酸苷结合也会发生。

Pentazocine is metabolized in the liver, mainly by oxidation of the terminal methyl groups of the dimethyl alkyl side chain to form alcoholic and carboxylic acid metabolites; glucuronide conjugation also occurs.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

证据显示，戊唑辛通过竞争同一受体位点，特别是阿片μ受体，从而拮抗阿片类药物的效果。

The preponderance of evidence suggests that pentazocine antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 肝毒性

戊唑辛治疗并未与血清酶水平升高或特异质急性、临床上明显的肝损伤相关联。 可能性评分：E（不太可能是药物诱导肝损伤的原因）。 关于戊唑辛的安全性和潜在肝毒性的参考资料，请参见阿片类药物概述部分。 药物类别：阿片类药物

Therapy with pentazocine has not been linked to serum enzyme elevations or to idiosyncratic acute, clinically apparent liver injury. Likelihood score: E (unlikely cause of drug-induced liver injury). References on the safety and potential hepatotoxicity of pentazocine are given in the Overview section of the Opioids. Drug Class: Opioids

来源:LiverTox

毒理性

• 药物性肝损伤

戊唑辛

Compound:pentazocine

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注释：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：无匹配

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

从胃肠吸收良好。

Well absorbed from the gastro-intestinal tract.

来源:DrugBank

吸收、分配和排泄

单次给药后，可以在尿液中检测到喷他佐辛及其代谢物的痕迹量，持续数天。/喷他佐辛乳酸盐/

TRACE AMT OF PENTAZOCINE AND ITS METABOLITES CAN BE DETECTED IN URINE FOR SEVERAL DAYS AFTER A SINGLE ADMIN OF THE DRUG. /PENTAZOCINE LACTATE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

剂量的剂量、血液浓度和尿排泄率均低于口服和直肠给药，低于静脉给药。即使经直肠给药，粪便回收率也较低，这表明可用性降低可能是由于吸收过程中肠道或肝脏清除所致。

... DOSE FOR DOSE, BLOOD CONCN & URINARY EXCRETION RATES OF PENTAZOCINE WERE LOWER AFTER ORAL & RECTAL DOSAGE THAN AFTER IV DOSAGE TO MAN. FECAL RECOVERY WAS LOW EVEN AFTER RECTAL DOSING, SUGGESTING THAT REDUCED AVAILABILITY MAY BE DUE TO INTESTINAL OR HEPATIC CLEARANCE DURING ABSORPTION.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

戊唑辛迅速从血浆进入脑脊液，脑脊液与血浆的比值在静脉给药后2到3小时内从0.2变化到0.6，与血浆中游离戊唑辛与总戊唑辛的比值相符。

PENTAZOCINE ENTERS THE CSF RAPIDLY FROM PLASMA AND CSF:PLASMA RATIOS, WHICH VARIED FROM 0.2 TO 0.6 BETWEEN 2 AND 3 HR AFTER IV DOSES, AGREED WELL WITH THE RATIO OF UNBOUND:TOTAL PENTAZOCINE IN PLASMA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

戊唑辛通过各种给药途径都能很好地吸收，但个体间的差异较大。口服给药的生物利用度为18.4% +/- 7.8%；这种减少是由于首次通过代谢。

PENTAZOCINE IS WELL ABSORBED BY ALL ROUTES OF ADMIN, BUT THERE IS CONSIDERABLE INDIVIDUAL VARIATION. BIOAVAILABILITY AFTER ORAL ADMIN IS 18.4% +/- 7.8%; THE REDUCTION IS DUE TO FIRST-PASS METABOLISM.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (+)-喷他佐辛 在 三乙胺 、 N,N-二乙基苯胺 作用下， 以 甲苯 为溶剂， 反应 8.5h， 生成
  参考文献：
  名称：

  一种喷他佐辛前药、其制备方法及其用途

  摘要：

  本发明公开了一种式(Ⅰ)喷他佐辛前药、其制备方法、并包含其药物制剂的医药用途，其中R为氢或氘。本发明的前药化合物，室温下水溶解度提高20倍以上且化学稳定，延迟了起效时间及延长了药效，同时较低的剂量产生相同的母体药物血液浓度，具体广阔的临床运用前景。

  公开号：

  CN111349111A
• 作为产物：
  描述：

  ((R)-7-Methoxy-1-methyl-2-methylene-1,2,3,4-tetrahydro-naphthalen-1-yl)-acetaldehyde 在 正丁基锂 、 四甲基乙二胺 、 magnesium sulfate 、 二异丙胺 、 乙硫醇钠 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (+)-喷他佐辛
  参考文献：
  名称：

  迁移性氢化胺化：苯并吗啡类的简便对映选择性合成

  摘要：

  我们描述了一种高效、通用的对映选择性合成苯并吗啡烷的策略（市售材料的总产率为 45-46%）。新的合成证明了在复杂合成的背景下，通过迁移加氢胺化和钯催化的简单酮烯醇化物的不对称烯丙基烷基化 (AAA) 的能力，前所未有的非对映选择性环异构化的有效性。这里概述的三个连续立体中心的对映选择性合成和新型环异构化的策略应该在生物碱合成中具有许多应用。

  DOI：

  10.1021/ja0360539

文献信息

• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2013181135A1

  公开（公告）日：2013-12-05

  The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.

  该披露涉及喹唑啉衍生物、组合物以及相关方法。在某些实施例中，该披露涉及NADPH-氧化酶（Nox酶）和/或髓过氧化物酶的抑制剂。
• [EN] AZOLE COMPOUNDS AS PIM INHIBITORS<br/>[FR] COMPOSÉS D'AZOLE UTILISÉS EN TANT QU'INHIBITEURS DES PIM
  申请人：AMGEN INC

  公开号：WO2012129338A1

  公开（公告）日：2012-09-27

  The invention relates to bicyclic compounds of formulas I and Ia, and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of Pim-1 and/or Pim-2, and/or Pim-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of Pim kinase related conditions and diseases, preferably cancer.

  该发明涉及公式I和Ia的双环化合物及其盐。在某些实施例中，该发明涉及Pim-1和/或Pim-2和/或Pim-3蛋白激酶活性或酶功能的抑制剂或调节剂。在更进一步的实施例中，该发明涉及包含本文所披露的化合物的药物组合物，以及它们在预防和治疗Pim激酶相关疾病和病症，尤其是癌症中的用途。
• [EN] COMBINATIONS OF INHIBITORS OF IRAK4 WITH INHIBITORS OF BTK<br/>[FR] COMBINAISONS D'INHIBITEURS DE L'IRAK4 À L'AIDE D'INHIBITEURS DE LA BTK
  申请人：BAYER PHARMA AG

  公开号：WO2016174183A1

  公开（公告）日：2016-11-03

  The present application relates to novel combinations of at least two components, component A and component B: · component A is an IRAK4-inhibiting compound of the formula (I) as defined herein, or a diastereomer, an enantiomer, a metabolite, a salt, a solvate or a solvate of a salt thereof; · component B is a BTK-inhibiting compound, or a pharmaceutically acceptable salt thereof; and, optionally, · one or more components C which are pharmaceutical products; in which one or two of the above-defined compounds A and B are optionally present in pharmaceutical formulations ready for simultaneous, separate or sequential administration, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of endometriosis, lymphoma, macular degeneration, COPD, neoplastic disorders and psoriasis.

  本申请涉及至少两种组分的新型组合，组分A和组分B：·组分A是根据本文所定义的式(I)的IRAK4抑制化合物，或其对映体、对映异构体、代谢物、盐、溶剂合物或其盐的溶剂合物；·组分B是BTK抑制化合物，或其药学上可接受的盐；以及，可选地，·一种或多种组分C，它们是药用产品；其中上述定义的化合物A和B中的一种或两种可选择地存在于用于治疗和/或预防疾病的制剂中，准备用于同时、分开或顺序给药，用于治疗和/或预防疾病，以及用于生产用于治疗和/或预防疾病的药物的用途，特别是用于治疗和/或预防子宫内膜异位症、淋巴瘤、黄斑变性、慢性阻塞性肺病、肿瘤性疾病和牛皮癣。
• Sustained-release analgesic compounds
  申请人：——

  公开号：US20030022876A1

  公开（公告）日：2003-01-30

  A pharmaceutically active inventive compound comprises two independently active analgesic moieties covalently conjoined through a physiologically labile linker. A preferred embodiment comprises an opioid, such as morphine, covalently linked to at least one analgesic compound selected from the group consisting of an opioid or a non-opioid compound through a physiologically labile linker. Suitable covalent linkers are covalently bonded to the two independently active analgesic compounds through one or more lactone, lactam, or sulfonamido linkages. Suitable linkers include endogenous carboxylate, amido, and sulfonamido moieties, and exogenous moieties that form the aforementioned lactone, lactam or sulfonamido linkages.

  一种药理活性的创新化合物包括通过生理易降解的连接物共价连接的两个独立活性镇痛基团。一种首选实施例包括阿片类药物，如吗啡，通过生理易降解的连接物与来自阿片类或非阿片类化合物组成的群中选择的至少一种镇痛化合物共价连接。适当的共价连接物通过一个或多个内源的内酯、内酰胺或磺酰胺连接而与这两个独立活性的镇痛化合物共价结合。适当的连接物包括内源的羧酸酯、酰胺和磺酰胺基团，以及形成上述内酯、内酰胺或磺酰胺连接的外源基团。