二乙基1-苯甲基-2,6-二甲基-4-(3-硝基苯基)-1,4-二氢吡啶-3,5-二羧酸酯 | 141286-14-8

• 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: 二乙基1-苯甲基-2,6-二甲基-4-(3-硝基苯基)-1,4-二氢吡啶-3,5-二羧酸酯
• 中文别名: 2-[4-[2-[(4-氯苯基)磺酰基氨基]乙硫基]-2,6-二氟苯氧基]乙酸
• 英文名称: ON 579
• 英文别名: 2,6-difluoro-4-[2-(4-chlorophenylsulfonylamino)ethylthio]phenoxyacetic acid；2-[4-[2-[(4-Chlorophenyl)sulfonylamino]ethylsulfanyl]-2,6-difluorophenoxy]acetic acid
• CAS: 141286-14-8
• 化学式: C₁₆H₁₄ClF₂NO₅S₂
• 分子量: 437.873
• InChiKey: FEYKNJZBWNIWJD-UHFFFAOYSA-N

物化性质

• 沸点：
  595.0±60.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ethyl 4-<2-(4-chlorophenylsulfonylamino)ethylthio>-2,6-difluorophenoxyacetate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以89.8%的产率得到二乙基1-苯甲基-2,6-二甲基-4-(3-硝基苯基)-1,4-二氢吡啶-3,5-二羧酸酯
  参考文献：
  名称：

  Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists

  摘要：

  A series of sulotroban-related arylsulfonamide derivatives possessing a fluorinated phenoxyacetic acid moiety was synthesized and tested for TXA(2) antagonizing ability on U-46619-induced platelet aggregation of rabbit platelet-rich plasma. Introduction of one or more fluorine atoms to the phenoxyacetic acid moiety increased this activity. The most potent compound among these compounds was 10c, which was 40-fold more potent (IC50 3.4 x 10(-7) M) than sulotroban. 10c exhibited high activity (ID50, 0.14 mg/kg) against a U-46619-induced acute thrombocytopenia model in mice when orally administrated. These findings and those of radioligand binding assays with various ligands showed 10c to be a potent and selective systemic TXA, receptor antagonist.

  DOI：

  10.1016/0223-5234(96)88250-x

文献信息

• Sulfonamide derivatives
  申请人：TAISHO PHARMACEUTICAL CO. LTD

  公开号：EP0469901A1

  公开（公告）日：1992-02-05

  Sulfonamide derivative, useful as blood platelet aggregation inhibitors, have the formula: in which A is a naphthyl group, a pyridyl group, a phenyl group, a phenyl group substituted by 1 to 5 substituents selected from halogen atoms, alkyl groups having 1 to 4 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, nitro groups and acetamido groups, or an alkyl group having 1 to 20 carbon atoms; B is an alkylene group having 1 to 3 carbon atoms, a group -OCH₂- or a group -CH=CH-; X and Y are the same or different, and each is a hydrogen or fluorine atom; R is a carboxy group, an alkyoxycarbonyl group having 2 to 5 carbon atoms, a hydroxymethyl group or a group of the formula (in which R¹ is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms; R² is a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 3 carbon atoms, a carboxymethyl group or an alkoycarbonylmethyl group having 3 to 6 carbon atoms); m is 0, 1 or 2; n is 0,1,2 or 3; or salts thereof. This invention also provided intermediates for the preparation of the sulfonamide, which intermediates are thiophenols of the formula: (in which R, X and Y are as defined above).

  磺酰胺衍生物可用作血小板聚集抑制剂，其化学式为 其中 A 是萘基、吡啶基、苯基、被 1 至 5 个取代基取代的苯基，取代基可选 自卤素原子、1 至 4 个碳原子的烷基、1 至 4 个碳原子的烷氧基、硝基和乙酰氨基， 或 1 至 20 个碳原子的烷基；B 是具有 1 至 3 个碳原子的亚烷基、基团-OCH₂- 或基团-CH=CH-； X 和 Y 相同或不同，各自是氢原子或氟原子； R 是羧基、具有 2 至 5 个碳原子的烷氧羰基、羟甲基或式如下的基团 (其中，R¹是氢原子或具有 1 至 3 个碳原子的烷基；R²是氢原子、羟基、具有 1 至 3 个碳原子的烷基、羧甲基或具有 3 至 6 个碳原子的烷酰基甲基）；m 是 0、1 或 2；n 是 0、1、2 或 3；或其盐。 本发明还提供了制备磺酰胺的中间体，这些中间体是式中的噻吩酚： (其中 R、X 和 Y 如上定义）。
• GLUTAMIC ACID RECEPTOR AGONIST
  申请人：NIPPON SUISAN KAISHA, LTD.

  公开号：EP0811375A1

  公开（公告）日：1997-12-10

  A glutamic acid receptor agonist which comprises as the active ingredient sulfonamide derivatives represented by general formula (I) or pharmaceutically acceptable salts thereof wherein A represents naphthyl, pyridyl, phenyl optionally having 1 to 5 substituents selected from the group consisting of halogeno, C1-4 alkyl, C1-4 alkoxy, nitro and acetamido, or C¿1-20 alkyl; B represents C¿1-3 alkylene, -OCH2- or -CH=CH-; X and Y are the same or different and each represents hydrogen or fluoro; R represents carboxy, C2-5 alkoxycarbonyl, hydroxymethyl or (a) (wherein R1 represents hydrogen or C1-3 alkyl; and R2¿ represents hydrogen, hydroxy, C1-3 alkyl, carboxymethyl or C¿3-6 alkoxycarbonyl); m represents an integer of 0 to 2 and n represents an integer of 0 to 3. The agonist is efficatious in the prevention and treatment of nerve degeneration in morbid conditions.

  一种谷氨酸受体激动剂，其活性成分包括通式(I)所代表的磺酰胺衍生物或其药学上可接受的盐 其中A代表萘基、吡啶基、苯基，可任选具有1至5个取代基，这些取代基选自由卤素、C1-4烷基、C1-4烷氧基、硝基和乙酰氨基或C¿1-20烷基组成的组；B代表C¿1-3亚烷基、-OCH2-或-CH＝CH-；X和Y相同或不同，各自代表氢或氟；R代表羧基、C2-5烷氧基羰基、羟甲基或(a)（其中R1代表氢或C1-3烷基；R2¿代表氢、羟基、C1-3烷基、羧甲基或C¿3-6烷氧基羰基）；m代表0至2的整数，n代表0至3的整数。该激动剂对预防和治疗病态情况下的神经变性具有疗效。
• 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。
• ENDOGENOUS NITRIC OXIDE SYNTHESIS UNDER CONDITIONS OF LOW OXYGEN TENSION
  申请人：Nitromed, Inc.

  公开号：EP1242068A1

  公开（公告）日：2002-09-25
• EP1242068A4
  申请人：——

  公开号：EP1242068A4

  公开（公告）日：2007-04-25