磷酸咯萘啶 | 74847-35-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 磷酸咯萘啶
• 中文别名: 磷酸咯奈啶
• 英文名称: pyronaridine
• 英文别名: 4-((7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino)-2,6-bis(pyrrolidin-1-ylmethyl)phenol；PND；4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]-2,6-bis(pyrrolidin-1-ylmethyl)phenol
• CAS: 74847-35-1
• 化学式: C₂₉H₃₂ClN₅O₂
• mdl: MFCD01748123
• 分子量: 518.058
• InChiKey: DJUFPMUQJKWIJB-UHFFFAOYSA-N

物化性质

• 沸点：
  621.3±55.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3 (20℃ 760 Torr)
• 溶解度：
  DMSO（少许）、水（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  73.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  磷酸咯萘啶 在 磷酸 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 以95%的产率得到4-[(7-氯-2-甲氧基-1,5-二氢吡啶并[3,2-b]喹啉-10-基)亚氨]-2,6-二(吡咯烷-1-基甲基)环己-2,5-二烯-1-酮磷酸盐 (1:4)
  参考文献：
  名称：

  Synthesis of [²H]- and [¹³C]-labeled pyronaridine tetraphosphate-an antimalarial drug

  摘要：

  恶性疟原虫对氯喹和其他抗疟药物的耐药性日益普遍，这迫切需要开发具有强效药理活性的新型抗疟药物。吡咯尼群四磷酸酯（PNDP）就是这样一种药物，目前正在进行用于疟疾化疗治疗的临床前和临床试验。本研究旨在合成用于研究药物ADME和药代动力学的碳-13（¹³C）和氘（²H）标记的PNDP。在此，我们介绍了一种使用微波辐照技术合成[¹³C]和[²H]PNDP的方法，因为这种方法比经典方法更有优势。合成的标记化合物通过HPLC测定的化学纯度>99%，并且在标准储存条件下发现相对稳定，可达3个月。此外，它们还显示出令人满意仪器分析数据。版权所有©2008 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1568
• 作为产物：
  描述：

  2-羟基-5-硝基吡啶 在 硫酸 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 copper(II) oxide 、 三氯氧磷 作用下， 以 乙醇 、 异戊醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 12.0h， 生成 磷酸咯萘啶
  参考文献：
  名称：

  Methnaridine is an orally bioavailable, fast‐killing and long‐acting antimalarial agent that cures Plasmodium infections in mice

  摘要：

  Background and PurposeMalaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.Experimental ApproachAn integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed.Key ResultsMethnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei‐infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg−1·day−1) and cured the established infection (CD50 = 10.13 mg·kg−1·day−1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four‐dose oral regimen at a dosage of 25 mg·kg−1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross‐resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long‐lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg−1). In addition, following methnaridine treatment, infection‐induced Th1 immune response was almost fully alleviated in mice.Conclusion and ImplicationsMethnaridine is an orally bioavailable, fast‐acting and long‐lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.

  DOI：

  10.1111/bph.15268

文献信息

• [EN] AZEPANYL-DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME WITH ANTIPARASITIC ACTIVITY<br/>[FR] DÉRIVÉS D'AZÉPANYLE ET COMPOSITIONS PHARMACEUTIQUES À ACTIVITÉ ANTI-PARASITAIRE LES CONTENANT
  申请人：MERCK PATENT GMBH

  公开号：WO2016000827A1

  公开（公告）日：2016-01-07

  The present invention provides compounds of Formula (i). Furthermore, pharmaceutical compositions are provided comprising at least one compound of Formula (i), for the treatment of parasitic diseases including malaria, as well as neurodegenerative diseases.

  本发明提供了化合物的结构式（i）。此外，提供了包含至少一种结构式（i）化合物的药物组合物，用于治疗包括疟疾在内的寄生虫病以及神经退行性疾病。
• SUBSTITUTED 2,4 DIAMINO-QUINOLINE AS NEW MEDICAMENT FOR FIBROSIS, AUTOPHAGY AND CATHEPSINS B (CTSB), L (CTSL) AND D (CTSD) RELATED DISEASES
  申请人：Genoscience Pharma SAS

  公开号：EP3620164A1

  公开（公告）日：2020-03-11

  The present invention relates to novel 2-primary amino-4-secondary amino-quinoline derivatives, their manufacture, pharmaceutical compositions comprising them and their use as medicaments. The active compounds of the present invention can be useful as a medicament in the treatment and/or the decreasing and/or the prevention of fibrosis and/or fibrosis related diseases, or for use as a medicament in the treatment and/or the decreasing and/or the prevention of the autophagy and/or autophagy related diseases and for the inhibition of the autophagy flux, or for use in the inhibition of cathepsins B (CTSB), L (CTSL) and/or D (CTSD) and/or cathepsins B (CTSB), L (CTSL) and/or D (CTSD) related diseases; with the proviso that said compounds are not to be used for the treatment of any forms of cancers.

  本发明涉及新型2-初级氨基-4-次级氨基喹啉衍生物，其制备方法，包含它们的药物组合物以及它们作为药物的用途。本发明的活性化合物可用作药物治疗和/或减少和/或预防纤维化和/或与纤维化相关疾病，或用作药物治疗和/或减少和/或预防自噬和/或与自噬相关疾病以及抑制自噬通量，或用于抑制蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）和/或与蛋白酶B（CTSB）、L（CTSL）和/或D（CTSD）相关疾病；但所述化合物不得用于治疗任何形式的癌症。
• [EN] NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES À BASE DE NUCLÉOTIDES ET NUCLÉOSIDES ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2017155923A1

  公开（公告）日：2017-09-14

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，在这些组合物中，核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。
• [EN] ALKYNE CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES À BASE DE NUCLÉOTIDES ET NUCLÉOSIDES CONTENANT UN ALCYNE ET UTILISATIONS ASSOCIÉES
  申请人：UNIV EMORY

  公开号：WO2017189978A1

  公开（公告）日：2017-11-02

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，其中核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。
• [EN] NUCLEOTIDE AND NUCLEOSIDE COMPOSITIONS AND USES RELATED THERETO<br/>[FR] COMPOSITIONS À BASE DE NUCLÉOTIDE ET DE NUCLÉOSIDE ET UTILISATIONS CORRESPONDANTES
  申请人：UNIV EMORY

  公开号：WO2015038596A1

  公开（公告）日：2015-03-19

  This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

  这份披露涉及到核苷酸和核苷类治疗组合物，用于治疗传染病、病毒感染和癌症，在这些组合物中，核苷酸或核苷的碱基至少含有一个硫醇、硫酮或硫醚。