乙酸茶碱哌嗪盐 | 18833-13-1

• 物质功能分类: 医药中间体 - 杂环化合物 - 哌嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 乙酸茶碱哌嗪盐
• 中文别名: 1,2,3,6-四氢-1,3-二甲基-2,6-二氧代-7H-嘌呤-7-乙酸哌嗪盐(2:1)；1,2,3,6-四氢-1,3-二甲基-2,6-二氧代-7H-嘌呤-7-乙酸哌嗪盐 (2:1)
• 英文名称: acepifylline piperazine
• 英文别名: acefylline piperazine；Acepifylline；(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetic acid ; piperazine salt；(1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-essigsaeure; Piperazin-Salz；1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid, compound with piperazine (2:1)；2-(1,3-dimethyl-2,6-dioxopurin-7-yl)acetic acid;piperazine
• CAS: 18833-13-1
• 化学式: C₄H₁₀N₂*2C₉H₁₀N₄O₄
• 分子量: 562.542
• InChiKey: SKKLFJHESZIVKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  120
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  哌嗪 、 茶碱乙酸 以 乙腈 为溶剂， 反应 0.5h， 生成 乙酸茶碱哌嗪盐
  参考文献：
  名称：

  Synthesis of Ternary Cocrystals, Salts, and Hydrates of Acefylline with Enhanced Dissolution and High Permeability

  摘要：

  乙酰茶碱（ACF）是一种黄嘌呤衍生物兴奋剂，以哌嗪盐的形式配制，用于治疗支气管哮喘。ACF属于BCS IV类，具有低溶解度和低渗透性，这限制了药物的生物利用度和疗效。在这项工作中，通过共结晶与几种共成型剂合成ACF二元和三元共晶、盐-共晶及其多晶型物。采用两种不同的方法对三元系统A.B.C进行超分子组装：（1）首先，在合适的溶剂中研磨组分的浆液，使二元加合物A.B或A.C结晶，然后加入C并继续研磨；（2）将所有三种组分一起放入溶剂浆液中研磨。发现前一种方法在提供三元盐/共晶方面更胜一筹。实验室种子在项目不同阶段结晶结果的变化中起着重要作用。通过单晶X射线衍射和粉末X射线衍射数据解决了产品的二元和三元系统的晶体结构。晶体结构显示，在二元和三元加合物中，羧酸根-吡啶和咪唑-酸杂合成物反复出现。通过Hirshfeld表面、二维指纹图和能量框架分析了ACF与共成型剂之间的分子间相互作用。在二元和三元系统中，ACF的渗透性随着所选共成型剂的增加而增加。ACF

  DOI：

  10.1021/acs.cgd.2c00184

文献信息

• 複数標的ハイブリダイゼーション用核酸、その調製、組成物、製剤、キット及び応用
  申请人：——

  公开号：JP2003517428A

  公开（公告）日：2003-05-27

  \n (57)【要約】\n二以上のＲＮＡ標的に結合するアンチセンスオリゴヌクレオチドが開示される。\n

  \(57)/n (57) [摘要] 公开了与两个或多个 RNA 靶标结合的反义寡核苷酸。\n
• COMPOSITION, FORMULATIONS & METHOD FOR PREVENTION & TREATMENT OF DISEASES AND CONDITIONS ASSOCIATED WITH BRONCHOCONSTRICTION, ALLERGY(IES) & INFLAMMATION
  申请人：——

  公开号：US20030087845A1

  公开（公告）日：2003-05-08

  A pharmaceutical composition effective for preventing and alleviating bronchoconstriction, allergy(ies) and/or inflammation comprises a surfactant and a nucleic acid comprising an oligonucleotide anti-sense to an adenosine A1, A2a, A2b or A3 receptor gene, mRNA, flanking regions or regions bridging the intro/exon borders, analogues which bind thymidine but have low adenosine content or exhibit lower or no adenosine receptor agonist activity, combinations thereof, physiologically acceptable salts thereof or mixtures thereof, and optionally a carrier and other agents such as therapeutic agents and formulation products known in the art. The composition is formulated for administration by a multiplicity of routes for the prevention or alleviation of diseases and conditions associated with breathing difficulties, impeded and obstructed airways, bronchoconstriction, allergy and/or inflammation. Among the appplications of this technology are the prevention and treatment of diseases and conditions such as asthma, kidney damage or failure, ARDS, pulmonary vasoconstriction, inflammation, allergies, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), and cancers such as leukemias, lymphomas, carcinomas, and the like, e.g. colon cancer, breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, kidney cancer, melanoma, hepatic, lung, breast, and prostate metastases, etc., to counter the renal damage and failure associated with ischemic conditions and the administration of certain drugs and radio active diagnostic and therapeutic agents, as well as a joint therapy with the administration of adenosine and adenosine-like agents in the treatment of arrhythmias such as SVT and in cardiovascular function tests (stress tests). The present agent(s) is (are) also suitable for administration before, during and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery. Alternatively, the present agent may be effectively administered preventatively, prophylactically or therapeutically, and in conjunction with other therapies, or by itself for conditions without known therapies or as a substitute for therapies that have significant negative side effects.

  一种可有效预防和缓解支气管收缩、过敏和/或炎症的药物组合物包含一种表面活性剂和一种核酸，该核酸包含与腺苷 A1、A2a、A2b 或 A3 受体基因、mRNA、侧翼区域或连接前导子/外显子边界的区域反义的寡核苷酸、结合胸苷但腺苷含量低或表现出较低或无腺苷受体激动剂活性的类似物、它们的组合、它们的生理上可接受的盐或它们的混合物，以及可选的载体和其他制剂，如治疗剂和本领域已知的制剂产品。配制成的组合物可通过多种途径给药，用于预防或缓解与呼吸困难、气道受阻、支气管收缩、过敏和/或炎症有关的疾病和病症。该技术的应用包括预防和治疗以下疾病和病症：哮喘、肾损伤或肾衰竭、急性呼吸衰竭、肺血管收缩、炎症、过敏、呼吸受阻、呼吸窘迫综合征、疼痛、囊性纤维化、肺动脉高压、肺血管收缩、肺气肿、慢性阻塞性肺病（COPD），以及白血病、淋巴瘤、癌等癌症，如结肠癌、乳腺癌、乳腺癌、肺癌、肺癌等。如结肠癌、乳腺癌、肺癌、胰腺癌、肝细胞癌、肾癌、黑色素瘤、肝转移、肺转移、乳腺癌和前列腺癌等、在治疗 SVT 等心律失常和心血管功能测试（压力测试）时，与服用腺苷和类腺苷制剂联合治疗。本制剂还适用于其他治疗，包括放疗、化疗、抗体治疗、光疗和癌症治疗以及其他类型的手术之前、期间和之后。另外，本制剂还可有效地用于预防、预防性或治疗性用药，并可与其他疗法联合使用，或单独用于没有已知疗法的病症，或作为具有明显负面影响的疗法的替代品。
• Composition & methods for treatment and screening
  申请人：——

  公开号：US20040049022A1

  公开（公告）日：2004-03-11

  This invention relates to single or multiple target anti-sense oligonucleotides (STA or MTA oligos) of low or no adenosine content for respiratory disease-relevant genes, composition thereof and method for manufacturing the composition. The compositions are effective in the prophylaxis and treatment of diseases and conditions associated with the up-regulated expression of one or more different combination of the genes, including airway inflammation, allergy(ies), asthma, impeded respiration, cystic fibrosis (CF), Chronic Obstructive Pulmonary Diseases (COPD), allergic rhinitis (AR), Acute Respiratory Distress Syndrome (ARDS), pulmonary hypertension, lung inflammation, bronchitis, airway obstruction, and bronchoconstriction, among others. This invention further relates to a method for screening candidate compounds useful for the prevention and/or treatment of respiratory diseases which binds to gene(s), EST(s), cDNA(s), mRNA(s), or their expresed product(s).

  本发明涉及针对呼吸道疾病相关基因的低腺苷含量或无腺苷含量的单靶或多靶反义寡核苷酸（STA 或 MTA 寡核苷酸）、其组合物和组合物的制造方法。囊性纤维化 (CF)、慢性阻塞性肺病 (COPD)、过敏性鼻炎 (AR)、急性呼吸窘迫综合征 (ARDS)、肺动脉高压、肺部炎症、支气管炎、气道阻塞和支气管收缩等。本发明还涉及一种筛选用于预防和/或治疗呼吸系统疾病的候选化合物的方法，该方法可与基因、EST、cDNA、mRNA 或其表达产物结合。
• Dry powder oligonucleotide formualtion, preparation and its uses
  申请人：——

  公开号：US20040092470A1

  公开（公告）日：2004-05-13

  A formulation consisting essentially of an oligo(s) and bearing greater than about 90% particles about 0.1&mgr; to about 1&mgr;, or about 10&mgr; to about 50&mgr; in diameter. A dry powder formulation consisting essentially of an oligo of particle size about 0.1&mgr; to about 100&mgr; micron in diameter. Methods of preparation and therapeutic and diagnostic use are disclosed. Kits for diagnosis or treatment of numerous diseases and conditions by administration into the respiratory tract.

  一种主要由寡聚物组成的制剂，其90%以上的颗粒直径约为0.1微米至约1微米，或约10微米至约50微米。一种干粉制剂，主要由粒径约 0.1&mgr; 至约 100&mgr; 微米的寡聚物组成。公开了制备方法以及治疗和诊断用途。通过给呼吸道给药诊断或治疗多种疾病和病症的试剂盒。
• Composition, formulations & methods for prevention and treatment of diseases and conditions associated with bronchoconstriction, allergy(ies) and inflammation
  申请人：Nyce W. Jonathan

  公开号：US20050014711A1

  公开（公告）日：2005-01-20

  A pharmaceutical composition effective for preventing and alleviating bronchoconstriction, allergy(ies) and/or inflammation comprises a surfactant and a nucleic acid comprising an oligonucleotide anti-sense to an adenosine A 1 , A 2a , A 2b or A 3 receptor gene, mRNA, flanking regions or regions bridging the intro/exon borders, analogues which bind thymidine but have low adenosine content or exhibit lower or no adenosine receptor agonist activity, combinations thereof, physiologically acceptable salts thereof or mixtures thereof. The composition is formulated for administration by a multiplicity of routes for the prevention or alleviation of diseases and conditions associated with breathing difficulties, impeded and obstructed airways, bronchoconstriction, allergy and/or inflammation. Among the applications of this technology are the prevention and treatment of diseases and conditions such as asthma, kidney damage or failure, ARDS, pulmonary vasoconstriction, inflammation, allergies, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), and cancers such as leukemias, lymphomas, carcinomas, and the like.

  一种可有效预防和缓解支气管收缩、过敏和/或炎症的药物组合物包含一种表面活性剂和一种核酸，该核酸包含一种反义于腺苷 A 1 , A 2a , A 2b 或 A 3 受体基因、mRNA、侧翼区域或连接前导子/外显子边界的区域、结合胸苷但腺苷含量低或表现出较低或无腺苷受体激动剂活性的类似物、它们的组合、它们的生理上可接受的盐或它们的混合物。配制的组合物可通过多种途径给药，用于预防或缓解与呼吸困难、呼吸道受阻、支气管收缩、过敏和/或炎症有关的疾病和病症。该技术的应用包括预防和治疗以下疾病和病症：哮喘、肾损伤或衰竭、急性呼吸衰竭、肺血管收缩、炎症、过敏、呼吸受阻、呼吸窘迫综合征、疼痛、囊性纤维化、肺动脉高压、肺血管收缩、肺气肿、慢性阻塞性肺疾病（COPD）以及白血病、淋巴瘤、癌等癌症。