碘美普尔 | 78649-41-9

• 物质功能分类: 原料药 - 诊断用药 - 影象检查用药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 碘美普尔
• 英文名称: iomeprol
• 英文别名: iomeron；1-N,3-N-bis(2,3-dihydroxypropyl)-5-[(2-hydroxyacetyl)-methylamino]-2,4,6-triiodobenzene-1,3-dicarboxamide
• CAS: 78649-41-9
• 化学式: C₁₇H₂₂I₃N₃O₈
• mdl: MFCD00867961
• 分子量: 777.09
• InChiKey: NJKDOADNQSYQEV-UHFFFAOYSA-N

物化性质

• 熔点：
  263-265?C
• 沸点：
  813.2±65.0 °C(Predicted)
• 密度：
  d420 1.166; d437 1.161; d420 1.334; d437 1.329; d420 1.446; d437 1.441
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 碰撞截面：
  211.2 Ų [M-H]-; 221.61 Ų [M+H]+

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  180
• 氢给体数：
  7
• 氢受体数：
  8

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：碘美普尔在美国尚未获得食品药品监督管理局的上市批准，但在其他国家有售。在英国，该药物的标签以及几个专业组织制定的指南指出，在接受碘美普尔等含碘对比剂后，哺乳期母亲无需中断哺乳。 ◉ 对哺乳婴儿的影响：一名早产儿，出生时孕周为31周4天，在17天大时被发现促甲状腺激素（TSH）值显著升高，为87.6 mUI/L（正常范围：0.27至4.20 mUI/L）。出生时TSH值正常。甲状腺球蛋白也升高至811 ng/mL（正常范围：3.5至77 ng/mL），但游离T4正常。该婴儿从出生起就接受了母乳喂养（具体程度未说明），但在生命的前10天也接受了部分肠外营养。婴儿的母亲在产后第4天接受了350 mg/kg碘的碘美普尔剂量，并在给药后停止哺乳24小时。母亲有亚临床甲状腺功能减退病史，并接受左甲状腺素治疗。婴儿的短暂性甲状腺功能减退，表现为TSH和甲状腺球蛋白升高，可能是由于对比剂中碘在乳汁中的含量所致。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Iomeprol is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Labeling for the drug in the United Kingdom and guidelines developed by several professional organizations state that breastfeeding need not be disrupted after a nursing mother receives an iodine-containing contrast medium such as iomeprol. ◉ Effects in Breastfed Infants:A preterm infant, born at 31 weeks 4 days, was noted at 17 days of age to have a markedly elevated thyrotropin (TSH) value of 87.6 mUI/L (normal range: 0.27 to 4.20 mUI/L). TSH had been normal at birth. Thyroglobulin was also elevated at 811 ng/mL (normal range: 3.5 to 77 ng/mL), but free T4 was normal. The infant had been breastfed (extent not stated) from birth, but also received partial parenteral nutrition until day 10 of life. The infant’s mother had received iomeprol in a dose of 350 mg/kg of iodine at day 4 postpartum and discontinued breastfeeding for 24 hours after the dose. The mother had a history of subclinical hypothyroidism and was treated with levothyroxine. The infant’s transient hypothyroidism, indicated by elevations in TSH and thyroglobulin, was probably caused by the iodine in milk from the contrast medium. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 储存条件：
  -20°C freezer

制备方法与用途

适应症

静脉尿路造影（适用于成人，包括肾脏损害或糖尿病患者）、CT（躯干）、常规血管造影、动脉DSA、心血管造影（成人和儿童）、常规选择性冠状动脉造影、介入性冠状动脉造影、瘘管造影、乳管造影、泪囊造影、涎管造影。

不良反应

1. 过敏反应：可能表现为各种症状，典型者包括感觉异常、焦虑、潮红、发热感、出汗、头晕、流泪增多、鼻炎、心悸、感觉倒错、瘙痒、头部跳痛、咽喉痛和紧缩感、吞咽困难、咳嗽、打喷嚏、荨麻疹、皮疹、轻度局部水肿或血管性水肿。严重者可能出现舌及咽喉部水肿，导致呼吸困难，伴随气喘和支气管哮喘的喉头痉挛。较少病人会出现恶心、呕吐、腹痛和腹泻。

2. 严重的不良反应可能累及心血管系统，包括外周血管扩张，伴有显著低血压、心动过速或心动过缓、紫绀、意识模糊，甚至呼吸和/或心跳停止导致死亡。这些反应可能会迅速发生，需要立即进行心肺复苏抢救治疗。

药理作用

碘美普尔是一种三碘化非离子型水溶性X线造影剂，与其它非离子型造影剂相比，具有极低的渗透压和黏滞度。

注意事项

尽管碘美普尔对X线的敏感性较低，仍建议将其保存在电离辐射范围之外。

反应信息

• 作为产物：
  描述：

  5-[[2-(乙酰氧基)乙酰基]氨基]-2,4,6-三碘-1,3-苯二甲酰氯 在 水 、 三乙胺 、 sodium hydroxide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 23.0h， 生成 碘美普尔
  参考文献：
  名称：

  조영제 중간체의 신규 제조방법 및 이를 이용한 조영제의 제조방법

  摘要：

  本发明的制造方法通过简化造影剂的中间体或造影剂制造过程，减少废溶剂的生成，环保性强，并且可以显著降低制造成本。因此，本发明的制造方法可以大幅降低造影剂的生产成本，经济实惠，适合大规模生产。

  公开号：

  KR20200077744A

文献信息

• [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。
• [EN] TARGETED RADIOPHARMACEUTICALS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER<br/>[FR] PRODUITS RADIOPHARMACEUTIQUES CIBLÉS POUR LE DIAGNOSTIC ET LE TRAITEMENT DU CANCER DE LA PROSTATE
  申请人：BAYER AS

  公开号：WO2021013978A1

  公开（公告）日：2021-01-28

  A compound of general formula (I): wherein: n is 1, 2 or 3; R1, R2, R3 and R4, independently represent OH or Q; and 20 Q represents a tissue-targeting moeity selected from the group consisting of or a stereoisomer, a hydrate, a solvate, or a salt thereof, or a mixture of same, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said 25 compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of soft tissue diseases, as a sole agent or in combination with other active ingredients.

  通用式(I)的化合物：其中：n为1、2或3；R1、R2、R3和R4独立地代表OH或Q；Q代表从群组中选择的组织靶向基团，或其立体异构体、水合物、溶剂合物、盐或其混合物，制备所述化合物的方法，用于制备所述化合物的中间化合物，包含所述化合物的药物组合物和组合物，以及用于制造用于治疗或预防疾病的药物组合物的所述化合物的用途，特别是软组织疾病的治疗或预防，作为唯一药剂或与其他活性成分结合使用。
• [EN] TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS<br/>[FR] ADMINISTRATION CIBLÉE D'UN MÉDICAMENT FAISANT APPEL À DES COUPLEURS FONDÉS SUR L'AFFINITÉ
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2015148126A1

  公开（公告）日：2015-10-01

  The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.

  当前的发明揭示了包括通过具有与靶向基团亲和力的分子连接到药物的靶向药物传递共轭物。通常，该共轭物包括一个靶向配体和一个感兴趣的分子，例如，一个治疗剂。靶向配体和感兴趣的分子通过一个亲和配体相互连接。该亲和配体进一步以共价或非共价方式连接到药物或治疗剂。药物可以被修改以使其更溶解，并使其在靶点处从连接分子中解离。
• [EN] 2-HETEROARYL-3-OXO-2,3-DIHYDROPYRIDAZINE-4-CARBOXAMIDES FOR THE TREATMENT OF CANCER<br/>[FR] 2-HÉTÉROARYL-3-OXO-2,3-DIHYDROPYRIDAZINE-4-CARBOXAMIDES POUR LE TRAITEMENT DU CANCER
  申请人：BAYER AG

  公开号：WO2018146010A1

  公开（公告）日：2018-08-16

  The present invention covers 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide compounds of general formula (I), in which X, R1, R2, R3, R4 and R5 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的2-杂环芳基-3-酮基-2,3-二氢吡啶嗪-4-羧酰胺化合物，其中X、R1、R2、R3、R4和R5如本文所定义，制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是癌症或与异常AHR信号传导相关的疾病，或与失调免疫反应或其他与异常AHR信号传导相关的疾病，作为单一药剂或与其他活性成分组合使用。
• [EN] SPIRO-FUSED TRICYCLIC MAP4K1 INHIBITORS<br/>[FR] INHIBITEURS DE MAP4K1 TRICYCLIQUES SPIRO FUSIONNÉS
  申请人：BAYER AG

  公开号：WO2021074279A1

  公开（公告）日：2021-04-22

  The present invention relates to Map4K1 inhibitors of formula (I) to pharmaceutical compositions and combinations comprising the compounds according to the invention, and to the prophylactic and therapeutic use of the inventive compounds, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for neoplastic disorders, repectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant MAP4K1 signaling, as a sole agent or in combination with other active ingredients. The present invention further relates to the use, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of protein inhibitors in benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, in neurodegenerative disorders, in inflammatory disorders, in atherosclerotic disorders and in male fertility control.

  本发明涉及式(I)的Map4K1抑制剂，以及包含根据本发明的化合物的药物组合物和组合物，以及创新化合物的预防性和治疗性用途，分别用于制造用于治疗或预防疾病的药物组合物，特别是用于肿瘤性疾病，癌症或与异常MAP4K1信号相关的其他紊乱免疫反应或其他紊乱的疾病，作为单一药剂或与其他活性成分组合使用。本发明还涉及使用，分别用于制造用于治疗或预防良性增生、动脉粥样硬化疾病、败血症、自身免疫疾病、血管疾病、病毒感染、神经退行性疾病、炎症性疾病、动脉粥样硬化疾病和男性生育控制的蛋白抑制剂的药物组合物的用途。