ICI 192605 | 117621-64-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ICI 192605
• 英文别名: (Z)-6-((2R,4R,5S)-2-(2-chlorophenyl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl)hex-4-enoic acid；4-(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl)hexenoic acid；6-(2-(2-Chlorophenyl-4-hydroxyphenyl)-1,3-dioxan-5-yl)hexenoic acid；(Z)-6-[(2R,4R,5S)-2-(2-chlorophenyl)-4-(2-hydroxyphenyl)-1,3-dioxan-5-yl]hex-4-enoic acid
• CAS: 117621-64-4
• 化学式: C₂₂H₂₃ClO₅
• 分子量: 402.875
• InChiKey: WHUIENZXNGAHQI-YGPRPMEGSA-N

物化性质

• 熔点：
  124-126 °C
• 沸点：
  540.1±50.0 °C(Predicted)
• 密度：
  1.262±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

ICI 192605是一种有效的TXA2R（血栓素A2受体）拮抗剂，作为细胞信号前列腺素。研究显示，它能够阻断U-46619诱导的离体豚鼠气管收缩。

反应信息

• 作为反应物：
  描述：

  ICI 192605 在 咪唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Design of dual-acting thromboxane antagonist-synthase inhibitors by a mutual prodrug approach

  摘要：

  A mutual prodrug approach to dual acting thromboxane receptor antagonist - thromboxane synthase inhibitor compounds is reported in which TXA(2) antagonist and inhibitory 19-dioxanes with hexenoic acid side chains, were linked by diester and diamide groups. When linking of the components was achieved via di O-alkyl carboxylic esters of catechol, both TXA(2) receptor antagonist activity and TXA(2) synthase inhibition were observed for a single enantiomer (16) in ex vivo tests following oral dosing to dogs at 5 mg/kg.

  DOI：

  10.1016/0960-894x(96)00004-2
• 作为产物：
  描述：

  4(Z)-6-(2-chlorophenyl-4-o-methoxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid 在 乙硫醇钠 作用下， 以 various solvent(s) 为溶剂， 反应 6.0h， 以42%的产率得到ICI 192605
  参考文献：
  名称：

  新型血栓烷受体拮抗剂ICI 192605的改进合成途径：合成1,3-二恶烷中间体的活性。

  摘要：

  描述了对血栓烷受体拮抗剂ICI 192605 4（Z）-6-（2-o-氯苯基-4-o-羟基苯基-1,3-二恶烷-顺-5-基）己烯酸的合成途径的研究，该方法导致总的合成产率从20％提高到55％。报道了新型1，3-二恶烷合成中间体的体外血栓烷受体拮抗剂数据。这些数据表明，在适当取代的2,2-二甲基-1,3-二恶烷（例如ICI 180080）中从庚烯酸缩短为己烯酸的侧链对血栓烷受体拮抗剂的效力影响不大（pA2 =庚烯酸ICI 180080为7.5兔胸主动脉，相应己烯酸为pA2 = 6.9，人血小板聚集pA2值分别为6.7和7.0。

  DOI：

  10.1111/j.2042-7158.1990.tb05349.x

文献信息

• PPAR Modulators
  申请人：Kristiansen Karsten

  公开号：US20110178112A1

  公开（公告）日：2011-07-21

  1,3-dioxane derivatives are described and their use in the treatment of a disease or condition dependent on PPAR modulation, such as diabetes, cancer, inflammation, neurodegenerative disorders and infections.

  1,3-二噁烷衍生物被描述，并且它们在治疗依赖于PPAR调节的疾病或病况中的应用被提及，比如糖尿病、癌症、炎症、神经退行性疾病和感染。
• [EN] DUAL TNFR1 ANTAGONISTS AND TNFR2 AGONISTS FOR USE IN RENAL DISEASES<br/>[FR] COMPOSÉS À DOUBLE ACTION ANTAGONISTES DU TNFR1 ET AGONISTES DU TNFR2 DESTINÉS À ÊTRE UTILISÉS DANS DES NÉPHROPATHIES
  申请人：SERODUS ASA

  公开号：WO2022101389A1

  公开（公告）日：2022-05-19

  The present invention relates to certain 2,4-diphenyl-1,3-dioxanes that are capable of reducing Tumor necrosis factor receptor 1 (sTNFR1) and capable of increasing Tumor necrosis factor receptor 2 (sTNFR2) and their use in the treatment of specific subpopulations with a renal disease such as diabetic nephropathy.

  本发明涉及某些能够减少肿瘤坏死因子受体1（sTNFR1）并能够增加肿瘤坏死因子受体2（sTNFR2）的2,4-二苯基-1,3-二噁烷，并且它们在治疗特定亚群的肾脏疾病（如糖尿病肾病）中的应用。
• DUAL TNFR1 ANTAGONISTS AND TNFR2 AGONISTS FOR USE IN RENAL DISEASES
  申请人：Serodus ASA

  公开号：EP4000615A1

  公开（公告）日：2022-05-25

  The present invention relates to certain 2,4-diphenyl-1,3-dioxanes that are capable of reducing Tumor necrosis factor receptor 1 (sTNFR1) and capable of increasing Tumor necrosis factor receptor 2 (sTNFR2) and their use in the treatment of specific subpopulations with a renal disease such as diabetic nephropathy.

  本发明涉及某些 2,4-二苯基-1,3-二噁烷，它们能够减少肿瘤坏死因子受体 1（sTNFR1），能够增加肿瘤坏死因子受体 2（sTNFR2），并可用于治疗患有肾病（如糖尿病肾病）的特定亚人群。
• Thromboxane inhibitors, compositions and methods of use
  申请人：——

  公开号：US20030050305A1

  公开（公告）日：2003-03-13

  The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxane inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflanmmatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulants, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles.

  本发明描述了治疗或预防男性和女性性功能障碍以及增强男性和女性性反应的方法，其方法是施用治疗有效量的至少一种血栓素抑制剂，以及可选的至少一种能捐献、转移或释放一氧化氮、提高内皮源性松弛因子的内源性水平、刺激一氧化氮的内源性合成或一氧化氮合酶底物的化合物和/或至少一种血管活性剂。男性或女性最好患有糖尿病。本发明还提供了新型组合物，其中包含至少一种血栓素抑制剂，以及至少一种能捐献、转移或释放一氧化氮、提高内皮源性松弛因子的内源性水平、刺激一氧化氮的内源性合成或作为一氧化氮合酶底物的化合物、以及至少一种治疗剂，如血管活性剂、非甾体抗炎化合物（NSAIDs）、选择性环氧化酶-2（COX-2）抑制剂、抗凝剂、血管紧张素转换酶（ACE）抑制剂、血管紧张素 II 受体拮抗剂、肾素抑制剂及其混合物。本发明还提供了治疗或预防缺血性心脏疾病、心肌梗塞、心绞痛、中风、偏头痛、脑出血、心脏病死亡、短暂性脑缺血发作、器官移植后并发症、冠状动脉搭桥术、血管成形术、动脉内膜切除术、动脉粥样硬化、肺栓塞、支气管哮喘、支气管炎、肺炎、各种器官的循环休克、肾衰竭、心肌梗塞、心绞痛、中风、偏头痛、脑出血、心肌梗塞、血管成形术、动脉内膜切除术、冠状动脉搭桥术、血管成形术、动脉内膜切除术、动脉粥样硬化、肺栓塞、支气管哮喘、支气管炎、肺炎的方法、各种器官的循环休克、肾炎、移植物排斥反应、癌症转移、妊娠高血压、子痫前期、子痫、血栓和血栓栓塞性疾病、宫内发育、胃肠功能紊乱、肾病和肾功能紊乱、尿酸水平升高引起的疾病和痛经，以及用于抑制血小板聚集或血小板粘附或松弛平滑肌。
• WO2008/89461
  申请人：——

  公开号：——

  公开（公告）日：——