坡尔吲哚 | 60762-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 坡尔吲哚
• 中文别名: 吡吲哚；2,3,3a,4,5,6-六氢-8-甲基-1H-吡嗪并[3,2,1-j,k]咔唑甲磺酸
• 英文名称: (-)-8-methyl-2,3,3a,4,5,6,-hexahydro-1N-pyrazino<3,2,1-jk>carbazole
• 英文别名: (-)-8-methyl-2,3,3a,4,5,6,-hexahydro-1N-pyrazino(3,2,1-jk)carbazole；Pirlindole；12-methyl-1,4-diazatetracyclo[7.6.1.05,16.010,15]hexadeca-9(16),10(15),11,13-tetraene
• CAS: 60762-57-4
• 化学式: C₁₅H₁₈N₂
• 分子量: 226.321
• InChiKey: IWVRVEIKCBFZNF-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：1mg/mL；二甲基亚砜：5mg/mL
• 沸点：
  369
• 熔点：
  145

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  17
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

药物主要通过肝脏系统代谢。根据对狗和鼠的研究，由于肝脏的首过效应，匹林多尔的生物利用度在20%到30%之间。大鼠主要消除未结合的药物，而狗主要消除结合的药物。

The drug is metabolized significantly through the hepatic system. From studies in dogs and rats, pirlindole has a bioavailability of between 20 and 30% due to the hepatic first-pass effect on this medication. The rat eliminates mainly unconjugated drug while the dog eliminates mostly conjugated drug.

来源:DrugBank

毒理性

• 蛋白质结合

97%与血浆蛋白结合

97% binding to plasma proteins

来源:DrugBank

吸收、分配和排泄

• 吸收

吸收良好，生物利用度为90%。

Well absorbed with a bioavailability of 90%.

来源:DrugBank

吸收、分配和排泄

• 消除途径

主要经肾脏排泄，健康男性中有0.4-0.5%的药物以原形通过尿液排出。在人类中，肾脏排泄是代谢物消除的主要途径。

Mainly renal, with 0.4-0.5% being excreted in the urine as unchanged drug in healthy males. Renal excretion was the main route of elimination of the metabolites in man.

来源:DrugBank

吸收、分配和排泄

• 清除

在一项研究中，高血浆清除率（450-1000 1/小时）。

High plasma clearance (450–1000 1/h) in one study.

来源:DrugBank

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

制备方法与用途

吡林多是一种选择性可逆的MAO-A抑制剂[1]，同时也能够抑制肠病毒D68和柯萨奇病毒B3(CV-B3)[2]。

反应信息

• 作为反应物：
  描述：

  坡尔吲哚 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 216.0h， 生成 methyl 3-ethyl-10-methyl-2,3,5a,6,7,8-hexahydro-1H-[1,4]diazocino[7,8,1-jk]carbazole-5-carboxylate
  参考文献：
  名称：

  Synthesis of hexahydro[1,4]diazocino[7,8,1-jk]carbazoles and 1-methoxy-9-(β-vinylethylamino)ethylcarbazoles

  摘要：

  3-Ethylhexahydropyrazino[3,2,1-jk]carbazole is converted into hexahydro[1,4]diazocino[7,8,1-jk]carbazoles by the action of methyl propiolate and acetylacetylene in acetonitrile and into 1-methoxy9-(beta-vinylethylamino)ethylcarbazoles by the action of acetylenedicarboxylic ester and methyl propiolate in methanol. 3-Benzyl-substituted pyrazinocarbazole does not react with alkynes.

  DOI：

  10.1007/s10593-012-1035-x
• 作为产物：
  描述：

  (E)-((6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)amino)ethan-1-ol 在 甲醇 、 sodium tetrahydroborate 、 五氯化磷 、 sodium carbonate 、 calcium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 38.0h， 生成 坡尔吲哚
  参考文献：
  名称：

  坡尔吲哚的合成新方法

  摘要：

  本发明属于医药技术领域，涉及坡尔吲哚的合成方法。本方法以对甲基苯肼盐酸盐和1,2‑环己二酮为起始原料，经关环、缩合、氯代、烷基化、还原等常规方法合成坡尔吲哚。其中关键步骤为对甲基苯肼盐酸盐与1,2‑环己二酮在冰醋酸和盐酸作用下，通过关环反应得到关键中间体6‑甲基‑2,3,4,9‑四氢‑1H‑咔唑‑1‑酮。该方法收率高、原料便宜易得，降低了反应成本，适合工业化生产。

  公开号：

  CN110950873A

文献信息

• [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] NUCLEOSIDE PRODRUGS AND USES RELATED THERETO<br/>[FR] PROMÉDICAMENTS NUCLÉOSIDIQUES ET LEURS UTILISATIONS
  申请人：UNIV EMORY

  公开号：WO2021035214A1

  公开（公告）日：2021-02-25

  Disclosed are acyclic nucleoside prodrugs with improved metabolic stability and oral bioavailability. In general, the prodrugs are derivatives of acyclic nucleoside phosphonates containing a lipid-like moiety that can increase oral absorption and subsequent stability in the liver and plasma. Preferably, the lipid-like moiety can resist enzyme-mediated ω-oxidation, such as ω -oxidation catalyzed by cytochrome P450 enzymes. Also disclosed are pharmaceutical formulations of the acyclic nucleoside prodrugs. The acyclic nucleoside prodrugs and pharmaceutical formulations thereof can be used to treat viral infections, such as HIV infections, and/or viral-associated cancer, such as HPV-associated cancers.

  揭示了具有改善代谢稳定性和口服生物利用度的非环核苷前药。一般来说，这些前药是非环核苷膦酸酯的衍生物，含有类似脂质的基团，可以增加口服吸收并在肝脏和血浆中提高稳定性。最好，类似脂质的基团可以抵抗酶介导的ω-氧化，例如细胞色素P450酶催化的ω-氧化。还揭示了非环核苷前药的药物配方。这些非环核苷前药及其药物配方可用于治疗病毒感染，如HIV感染，和/或病毒相关癌症，如HPV相关癌症。
• [EN] PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] ANTAGONISTES DU RÉCEPTEUR EP2 DES PROSTAGLANDINES, DÉRIVÉS, COMPOSITIONS ET UTILISATIONS ASSOCIÉS
  申请人：UNIV EMORY

  公开号：WO2015167825A1

  公开（公告）日：2015-11-05

  The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

  该披露涉及前列腺素受体EP2拮抗剂，衍生物，组合物以及相关方法。在某些实施例中，该披露涉及治疗或预防EP2受体激活在生理作用中起作用的疾病和疾病的方法，例如但不限于脑损伤，炎症性疾病，癫痫后的神经炎症，疼痛，子宫内膜异位症，癌症，类风湿性关节炎，皮肤炎症，血管炎症，结肠炎和神经系统疾病，通过向需要的受试者给予包含本文所披露的化合物的药物组合物进行治疗。
• [EN] MACROCYCLIC PANTETHEINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS MACROCYCLIQUES DE LA PANTÉTHÉINE ET LEURS UTILISATIONS
  申请人：COMET THERAPEUTICS INC

  公开号：WO2021108579A1

  公开（公告）日：2021-06-03

  The present disclosure relates to compounds of Formulae (I) or (II): and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.

  本公开涉及式(I)或(II)的化合物，以及其药学上可接受的盐或溶剂化合物。本公开还涉及包含这些化合物的药物组合物，以及这些化合物和药物组合物的治疗和诊断用途。
• AMINOTHIAZOLONES AS ESTROGEN RELATED RECEPTOR-ALPHA MODULATORS
  申请人：Bignan Gilles

  公开号：US20110200587A1

  公开（公告）日：2011-08-18

  The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

  本发明涉及式(I)的化合物，制备这些化合物的方法，组合物，中间体及其衍生物，并用于治疗包括但不限于强直性脊柱炎、动脉粥样硬化、关节炎（如类风湿关节炎、感染性关节炎、儿童关节炎、银屑病性关节炎、反应性关节炎）、与骨相关的疾病（包括与骨形成有关的疾病）、乳腺癌（包括对抗雌激素治疗无效的癌症）、心血管疾病、软骨相关疾病（如软骨损伤/丧失、软骨退化以及与软骨形成有关的疾病）、软骨发育不全、软骨肉瘤、慢性背部损伤、慢性支气管炎、慢性炎症性气道疾病、慢性阻塞性肺病、糖尿病、能量稳态紊乱、痛风、假性痛风、脂质紊乱、代谢综合征、多发性骨髓瘤、肥胖、骨关节炎、遗传性骨发育不全、骨溶解性骨转移、软骨软化症、骨质疏松症、帕金森病、牙周病、多肌痛风、Reiter综合征、重复性应激损伤、高血糖、血糖水平升高和胰岛素抵抗等疾病的方法。