(3S,4R)-(-)-α-prodine | 77-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,4R)-(-)-α-prodine
• 英文别名: (-)-α-prodine；alphaprodine；trans-1,3-Dimethyl-4-propionyloxy-4-phenylpiperidin, α-Prodin；trans-3-Methyl-4-phenyl-1-methyl-4-propionyloxy-piperidin；trans-3-Methyl-4-phenyl-1-methyl-piperidinol-4-propionat；1,3ref-Dimethyl-4trans-phenyl-4-propionoxypiperidin；Nisintil；[(3S,4R)-1,3-dimethyl-4-phenylpiperidin-4-yl] propanoate
• CAS: 77-20-3
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: UVAZQQHAVMNMHE-XJKSGUPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

在给狗静脉注射后，从尿液中唯一可提取的代谢物是去甲阿尔法普罗定。

FOLLOWING IV ADMIN TO DOGS THE ONLY EXTRACTABLE METABOLITE FROM URINE WAS NORALPHAPRODINE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

盐酸阿普罗定的镇静作用会被巴比妥类药物、全身麻醉剂和某些吩噻嗪类药物增强。因此，在与这些药物同时使用时应减少剂量。/盐酸阿普罗定/

DEPRESSANT EFFECTS OF ALPHAPRODINE HYDROCHLORIDE ARE POTENTIATED BY BARBITURATES, GENERAL ANESTHETIC AGENTS, & SOME PHENOTHIAZINES. THUS, THE DOSE SHOULD BE REDUCED WHEN USED CONCOMITANTLY WITH SUCH AGENTS. /ALPHAPRODINE HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用美沙酮和苯乙肼或其他单胺氧化酶抑制剂可能导致中枢神经系统的兴奋和抑制效果，从而导致深度昏迷和死亡。/美沙酮/

CONCURRENT ADMIN OF MEPERIDINE & PHENELZINE OR OTHER MONOAMINE OXIDASE INHIBITORS MAY RESULT IN EXCITATORY & DEPRESSANT EFFECTS ON THE CNS LEADING TO DEEP COMA & DEATH. /MEPERIDINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

可能会形成习惯。

May be habit forming.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

不良影响包括偶尔的呼吸抑制、眩晕、嗜睡、出汗和荨麻疹；很少见的情况下，可能会出现恶心、呕吐、不安和混乱。/盐酸阿法罗定/

ADVERSE EFFECTS INCLUDE OCCASIONAL RESP DEPRESSION, DIZZINESS, DROWSINESS, SWEATING & URTICARIA; RARELY, NAUSEA, VOMITING, RESTLESSNESS, & CONFUSION MAY OCCUR. /ALPHAPRODINE HYDROCHLORIDE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

过敏现象在使用阿片类止痛药时会发生，但并不常见。它们通常表现为荨麻疹和其他类型的皮疹，如固定性药疹和接触性皮炎，在护士和制药工作者中也可能发生。吗啡及其相关药物注射部位的肿块可能是由于释放的组织胺引起的。/阿片类药物/

ALLERGIC PHENOMENA OCCUR WITH OPIOID ANALGESICS, BUT ... NOT COMMON. THEY ARE USUALLY MANIFESTED AS URTICARIA & OTHER TYPES OF SKIN RASHES SUCH AS FIXED ERUPTIONS CONTACT DERMATITIS IN NURSES & PHARMACEUTICAL WORKERS ALSO OCCURS. WHEALS @ SITE OF INJECTION OF MORPHINE ... & RELATED DRUGS ARE PROBABLY CAUSED BY THE RELEASED HISTAMINE. /OPIOIDS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在给狗静脉注射后，阿法罗定从血浆中迅速消失，并且具有较大的分布体积，这与它的快速起效和短时作用相符合。大脑和血浆之间似乎存在快速平衡。

FOLLOWING IV ADMIN TO DOGS, RAPID DISAPPEARANCE OF ALPHAPRODINE FROM PLASMA & LARGE DISTRIBUTION VOL WERE IN KEEPING WITH ITS RAPID ONSET & SHORT DURATION OF ACTION. THERE APPEARED TO BE RAPID EQUILIBRIUM BETWEEN BRAIN & PLASMA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿普洛丁的消除半衰期是131分钟（大约2小时），与美喷丁的247分钟相比。阿普洛丁和美喷丁的血浆清除率几乎相同：分别为1.04和1.01升/千克/分钟。尽管美喷丁在肝脏中广泛进行生物转化，形成去甲基衍生物和美喷丁酸（参见美喷丁），但目前没有关于阿普洛丁在人身上生物转化的信息。

The elimination half-life of alphaprodine is 131 minutes (approximately 2 hours) compared with 247 minutes for meperidine. Plasma clearances for alphaprodine and meperidine are nearly identical: 1.04 and 1.01 l/kg/min, respectively. Although meperidine undergoes extensive biotransformation in the liver to form N-demethylated derivatives and meperidinic acid (see Meperidine) no information is available relating to alphaprodine biotransformation in man.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿尔法普罗定从注射部位迅速吸收。35毫克阿尔法普罗定静脉给药产生的血药浓度与100毫克美沙酮后的血药浓度相似。阿尔法普罗定的半衰期（吸收）为4.6分钟，而美沙酮的半衰期为17.2分钟。

Alphaprodine is immediately absorbed from parenteral sites. Thirty-five milligrams of alphaprodine intravenously produces plasma concentrations similar to those following 100 mg meperidine. The half-life (absorption) is 4.6 minutes for alphaprodine compared with 17.2 minutes for meperidine.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (3S,4R)-(-)-α-prodine 在 氢氧化钾 、 potassium carbonate 、 溶剂黄146 、 锌 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 52.0h， 生成 (3S,4R)-4-hydroxy-3-methyl-4-phenylpiperidine
  参考文献：
  名称：

  苯环利定的一些异构衍生物的阿片样物质性质。

  摘要：

  苯环类类似物（+/-）-α-，（+/-）-β-和（+）-α-和（-）-α-4-羟基-3-甲基-4-苯基-1-已经制备了（1-苯基环己基）哌啶，均具有已知的相对和绝对立体化学，并且它们的镇痛作用与相应的脯氨酸有关。与脯氨酸相比，（+/-）-α-苯环利定类似物比其非对映异构体具有更强的镇痛作用，而与脯氨酸系列中的观察结果一致，3R，4S-α-对映异构体的药效远高于其非对映异构体。镜像形式。

  DOI：

  10.1111/j.2042-7158.1992.tb14356.x
• 作为产物：
  描述：

  (3S,4R)-4-hydroxy-3-methyl-4-phenylpiperidine 在 吡啶 、 甲酸 作用下， 反应 8.0h， 生成 (3S,4R)-(-)-α-prodine
  参考文献：
  名称：

  Common stereospecificity of opioid and dopamine systems for N-butyrophenone prodine-like compounds

  摘要：

  The two optical isomers of 1-[3-(p-fluorobenzoyl)propyl]-3-methyl-4-phenyl-4-propionoxypiperidine (FPP) were obtained by resolution of (+/-)-r-3-methyl-4-phenyl-c-4-piperidinol followed by N-alkylation and O-propionylation. These, as well as the racemate, were evaluated for their antinociceptive, opioid, and neuroleptic properties using in vivo and in vitro test systems. The results are remarkable in two respect, namely, the dextrorotatory isomer is consistently the most potent on all tests, and it acts on both opioid (mu) and neuroleptic (D2) receptors.

  DOI：

  10.1021/jm00105a029

文献信息

• Controlled-release compositions containing opioid agonist and antagonist
  申请人：——

  公开号：US20020010127A1

  公开（公告）日：2002-01-24

  Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.

  含有阿片激动剂、阿片拮抗剂和受控释放材料的控释剂型，其在给药间隔期间释放阿片激动剂的镇痛或亚镇痛量以及足以减轻所述阿片激动剂的副作用的阿片拮抗剂的量。当给予人类患者时，该剂型提供至少约8小时的镇痛作用。在其他实施例中，给药间隔期释放的拮抗剂剂量增强了阿片激动剂的镇痛效力。
• CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
  申请人：Cerulean Pharma Inc.

  公开号：US20130196906A1

  公开（公告）日：2013-08-01

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法，例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• 3,4,6-Substituted pyridazines for treating neuropathic pain and associated syndromes
  申请人：Sultzbaugh Lance

  公开号：US20070191365A1

  公开（公告）日：2007-08-16

  The present invention is directed to the use of 3,4,6-substituted pyridazines such as those characterized by structure I for treating conditions such as neuropathic pain among others.

  本发明涉及使用3,4,6-取代吡啶嗪，如结构I所示的化合物，用于治疗神经病痛等疾病。
• [EN] BUPRENORPHINE ANALOGS<br/>[FR] ANALOGUES DE BUPRÉNORPHINE
  申请人：PURDUE PHARMA LP

  公开号：WO2012038813A1

  公开（公告）日：2012-03-29

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R1, R2, R8, R 3a, R 3b, G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。
• PYRIDINE AND PIPERIDINE DERIVATIVES AND USE THEREOF
  申请人：Purdue Pharma L.P.

  公开号：US20150141434A1

  公开（公告）日：2015-05-21

  The invention provides compounds that are useful as sodium channel blockers. In one aspect, the invention provides compounds of Formula I: or pharmaceutically acceptable salts, solvates, hydrates, or diastereomers thereof, wherein R 1 , R 4 , X, G, n, p, W 1 , W 2 , W 3 , W 4 , and the E ring are defined in the disclosure. In certain embodiments, the invention provides compounds of Formulae II-XIII as set forth supra. The invention also provides the use of compounds of any of the above discussed formulae to treat a disorder responsive to blockade of sodium channels. In one embodiment, Compounds of the Invention are useful for treating pain.

  本发明提供了一种用作钠通道阻断剂的化合物。在一方面，本发明提供了公式I的化合物： 或其药用可接受的盐、溶剂化物、水合物或对映异构体，其中R1、R4、X、G、n、p、W1、W2、W3、W4和E环在公开中定义。在某些实施例中，本发明提供了上述公式II-XIII的化合物。本发明还提供了使用上述任何讨论公式的化合物来治疗对钠通道阻断有反应的疾病。在一个实施例中，发明化合物用于治疗疼痛。