2-[(4R)-2,2-diphenyl-1,3-dioxolan-4-yl]piperidine | 4741-41-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(4R)-2,2-diphenyl-1,3-dioxolan-4-yl]piperidine
• CAS: 4741-41-7
• 化学式: C₂₀H₂₃NO₂
• 分子量: 309.4
• InChiKey: HGKAMARNFGKMLC-GGYWPGCISA-N

物化性质

• 沸点：
  449.68°C (rough estimate)
• 密度：
  1.1074 (rough estimate)
• 溶解度：
  In water, 19.2 mg/L at 25 °C (est)
• 蒸汽压力：
  8.26X10-8 mm Hg at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 相互作用

研究了苯环利定（PCP）和相关激动剂与假定的受体阻断剂之间的相互作用，使用电生理学技术在小脑浦肯野神经元上进行研究。由PCP或dexoxadrol（一种sigma受体激动剂）引起的抑制被PCP受体拮抗剂metaphit显著拮抗，后者通过其异硫氰酸酯部分使PCP受体乙酰化。相反，左氧沙醇（dexoxadrol的(-)异构体）的抑制效应不受metaphit的影响。进一步的数据表明，metaphit对dexoxadrol和PCP介导的抑制具有特异性拮抗作用，这些数据表明，分别对mu和delta阿片受体进行乙酰化的药物，如苯并咪唑异硫氰酸酯和芬太尼异硫氰酸酯，并不拮抗PCP或dexoxadrol的作用。此外，像PCP一样作为间接去甲肾上腺素激动剂的酪胺也不受metaphit的拮抗。这些观察结果支持了metaphit在小脑中对PCP和dexoxadrol的效果产生药理特异性和不可逆拮抗作用的概念。

The interactions of phencyclidine (PCP) and related agonists with putative receptor blockers were studied on cerebellar Purkinje neurons using electrophysiological techniques. Depressions induced by PCP or dexoxadrol, a sigma receptor agonist, were markedly antagonized by the PCP receptor antagonist metaphit, which acylates PCP receptors via its isothiocyanate moiety. Conversely, the depressant effect of levoxadrol, the (-) isomer of dexoxadrol, was not affected by metaphit. Further evidence that metaphit's specific antagonism of dexoxadrol- and PCP-mediated depressions was derived from data showing that drugs which respectively acylate mu and delta opioid receptors, benzimidazole isothiocyanate and fentanyl isothiocyanate, do not antagonize the actions of either PCP or dexoxadrol. Moreover, tyramine, which like PCP acts as an indirect norepinephrine agonist, is not antagonized by metaphit. These observations support the concept that metaphit causes a pharmacologically specific and irreversible antagonism of the effects of both PCP and dexoxadrol in the cerebellum. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

... 苯环己哌啶（PCP）诱导的鸽类强直是一种药理学上特异性和立体选择性的现象，被用来研究假设的甲磷脂与PCP位点共价结合的药理学后果。甲磷脂预处理增加了由累积剂量的PCP型药物（即PCP、氯胺酮和m-氨基PCP）以及具有PCP样作用的药物（即脱氧安定、LY 154716和环唑辛）诱导的强直效果...

... Phencyclidine (PCP)-induced catalepsy in pigeons, which is a pharmacologically specific and stereoselective phenomenon, was used to study pharmacological consequences of the proposed covalent bonding of metaphit to PCP sites. Metaphit pretreatment increased the cataleptic effects induced by cumulative doses of PCP-type drugs (ie, PCP, ketamine and m-amino PCP) and of drugs that have PCP-like actions (i.e., dexoxadrol, LY 154716 and cyclazocine)...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在大鼠大脑皮层中，[3H]苯环己哌啶（PCP）与受体的结合已被研究。已检测到两种受体，一种高亲和力受体位点，其解离常数KD为23.5 +/- 7.4 nM，以及一种低亲和力位点，其解离常数KD为7.6 +/- 1.8 microM。[3H]PCP与其受体的结合对pH和温度有依赖性，并且可以通过热变性而被破坏。[3H]PCP的结合可以被产生类似PCP行为效应的化合物抑制，包括.dexoxadrol、etoxadrol和ketamine，以及一系列新的苯(f)异喹啉类化合物。低亲和力位点可以被PCP、etoxadrol和(+)-SKF-10,047阻断，但吗啡或亮氨酸脑啡肽不能，这表明它也代表一个特定的PCP位点。在高亲和力受体上观察到PCP与cyclazocine、cyclorphan、SKF-10,047和dioxadrol（dexoxadrol和levoxadrol）的异构体之间的立体选择性位移。纳洛酮、4,5,6,7-四氢异噁唑啉(S,4-C)吡啶-3-醇（THIP）水合物和氟哌啶醇对结合的抑制作用较弱（Ki大于1 microM），这表明这些化合物在体内与高亲和力PCP受体的相互作用不明显。配体对苯环己哌啶受体的亲和力与其在鸽子上产生僵直症的效力高度相关（r = 0.714，P小于0.01）。

The binding of [3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a KD of 23.5 +/- 7.4 nM and a low affinity site with a KD of 7.6 +/- 1.8 microM. The binding of [3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo(S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly (Ki greater than 1 microM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated (r = 0.714, P less than 0.01) with their potency to produce catalepsy in pigeons.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽，有强烈的呕吐反射，并且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(3)H-Dexoxadrol，一种解离性麻醉剂，在大鼠大脑的特定部位具有高亲和力（膜结合和光镜放射自显影）。各种苯环利定类似物与(3)H-dexoxadrol位点的竞争方式与(3)H-phencyclidine结合位点的竞争方式略有不同。与(3)H-phencyclidine结合一样，(3)H-dexoxadrol结合位点在大脑区域如皮层和海马高度集中。然而，像下丘脑等其他区域仅在(3)H-dexoxadrol结合位点中富集。这表明(3)H-dexoxadrol结合到某些大脑区域的相关苯环利定位点，但不是在其他区域。在人类前脑中，(3)H-dexoxadrol结合位点的分布与大鼠大脑相似，主要发现于尾状核、壳核和皮层。

(3)H-Dexoxadrol, a dissociative anesthetic, binds with high affinity to specific sites in rat brain (membrane binding and light microscopic autoradiography). Various phencyclidine analogues compete for (3)H-dexoxadrol sites in a slightly different manner than against (3)H-phencyclidine binding sites. As for (3)H-phencyclidine binding, (3)H-dexoxadrol binding sites are highly concentrated in brain regions such as the cortex and the hippocampus. However, other areas such as the hypothalamus are enriched only in (3)H-dexoxadrol binding sites. This suggests that (3)H-dexoxadrol binds to phencyclidine-related sites in certain brain regions but not in others. In the human forebrain, (3)H-dexoxadrol binding sites are distributed as in the rat brain and mainly found in the caudate, putamen and cortex.

来源:Hazardous Substances Data Bank (HSDB)