N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate | 136849-72-4

• 物质功能分类: 生物化工 - 缩合剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate
• 英文别名: TOTU；O-((cyano-(ethoxycarbonyl)-methylidene)amino)-1,1,3,3-tetramethyluronium tetrafluoroborate；O-{[cyano(ethoxycarbonyl)-methyliden]-amino}-1,1,3,3-tetramethyluronium tetrafluoroborate；O-[(cyano(ethoxycarbonyl)methylidene)amino]-1,1,3,3-tetramethyluronium tetrafluoroborate；O-((cyano(ethoxycarbonyl)methylene)-amino)-1,1,3,3-tetramethyluronium tetrafluoroborate；O-((cyano(ethoxycarbonyl)methylene)amino)-1,1,3,3-tetramethyluronium tetrafluoroborate；[[(E)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate
• CAS: 136849-72-4
• 化学式: BF₄*C₁₀H₁₇N₄O₃
• 分子量: 328.075
• InChiKey: FPQVGDGSRVMNMR-MXZHIVQLSA-N

物化性质

• 熔点：
  145 °C (dec.)(lit.)
• 溶解度：
  溶于水或1%醋酸

计算性质

• 辛醇/水分配系数(LogP)：
  0.94
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  10

安全信息

• 危险等级：
  8
• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S37/39
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  29280000
• 危险品运输编号：
  HAZARD
• 包装等级：
  III
• 危险类别：
  8
• 危险性防范说明：
  P501,P260,P270,P264,P280,P303+P361+P353,P301+P330+P331,P363,P301+P312+P330,P304+P340+P310,P305+P351+P338+P310,P405
• 危险性描述：
  H302,H314

制备方法与用途

用途：这种新型脲正离子型多肽缩合剂适用于苛刻的反应条件，产物的消旋率较低。

反应信息

• 作为反应物：
  描述：

  N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate 、 (S)- 3 -氨基- 2 -羰基氨基丙酸叔丁酯 、 (甲醇)(氧代)铕-苯甲酸(1:1) 在 N,N-二异丙基乙胺 作用下， 以 N-甲基乙酰胺 、 乙酸乙酯 为溶剂， 以770 mg (93%)的产率得到tert-butyl (2S)-2-benzyloxycarbonylamino-3-(4-(2-methoxycarbonyl-ethyl)-benzoylamino)propionate
  参考文献：
  名称：

  Acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists

  摘要：

  本发明涉及式(I)的酰基胍衍生物，其中R1、R2、R4、R5、R6、A、m和n具有专利要求中指示的含义，它们的生理耐受盐和前药。式(I)化合物是有价值的药用活性成分。它们是维脱内钙蛋白受体拮抗剂，能抑制破骨细胞对骨骼的吸收，例如，适用于治疗或预防至少部分由于不良骨吸收引起的疾病，例如骨质疏松症。该发明还涉及制备式(I)化合物的方法，它们的使用，特别是作为药用活性成分，并包含它们的药物制剂。

  公开号：

  US06492356B1
• 作为产物：
  描述：

  哌啶 、 甲基叔丁基醚 、 三甲基溴硅烷 、 间甲酚 在 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate
  参考文献：
  名称：

  Coupling reagent for peptide synthesis

  摘要：

  本发明涉及一种式子为I的新型化合物##STR1##其中X为阴离子，并描述了其制备方法。式I的化合物可用作肽合成中的偶联试剂。

  公开号：

  US05166394A1
• 作为试剂：
  描述：

  环丙沙星 在 4-二甲氨基吡啶 、 三甲基氯硅烷 、 N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)-methylidene]-N-methylmethanaminium tetrafluoroborate 、 苯甲醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 52.42h， 生成 ethyl 1-cyclopropyl-6-fluoro-4-oxo-7-(4-(3-((3R,6R,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)propanoyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis of Novel Artemisinin, Ciprofloxacin, and Norfloxacin Hybrids with Potent Antiplasmodial Activity

  摘要：

  The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures of artemisinin, ciprofloxacin or norfloxacin, and 7-chloroquinoline are reported in this study. The first step for all of the syntheses is the obtainment of key piperazine esters intermediates bearing the drugs ciprofloxacin and norfloxacin. Using these platforms, 18 final compounds were synthesized through a multistep procedure with overall yields ranging between 8 and 20%. All compounds were screened for their antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum FcB1 strain. Compounds 20, 21, 22, and 28, bearing an artesunate fragment with ciprofloxacin, exhibited IC50 values in the range of 3.5–5.4 nM and excellent selectivity indices. Among the compounds bearing the artesunate moiety on the norfloxacin, two of them, 23 and 24, afforded IC50 values of 1.5 nM and 1.9 nM, respectively. They also showed excellent selectivity indices. The most potent compounds were also evaluated against the CQ-resistant Dd2 strain of Plasmodium falciparum, demonstrating that those compounds incorporating the artesunate fragment were the most potent. Finally, the combination of artesunate with either ciprofloxacin or norfloxacin moieties in a single molecular entity proved to substantially enhance the activity and selectivity when compared to the administration of the unconjugated counterparts artesunate/ciprofloxacin and artesunate/norfloxacin.

  DOI：

  10.3390/antibiotics13020142

文献信息

• Factor VIIa inhibitory (thio)urea derivatives, their preparation and their use
  申请人：——

  公开号：US20020052417A1

  公开（公告）日：2002-05-02

  The present invention relates to compounds of the formula I, 1 in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A, X, m and n have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of thromboembolic diseases and restenoses. They are reversible inhibitors of the blood clotting enzyme factor VIIa and can in general be applied in conditions in which an undesired activity of factor VIIa is present or for the cure or prevention of which an inhibition of factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, for example as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及公式I的化合物，其中R1、R2、R3、R4、R5、R6、A、X、m和n具有所述声明中指示的含义。公式I的化合物是有价值的药理活性化合物。它们表现出强烈的抗血栓作用，适用于治疗和预防血栓栓塞病和再狭窄症等疾病。它们是血凝酶酶因子VIIa的可逆抑制剂，通常可以应用于存在不良VIIa活性的情况或者为治疗或预防需要抑制VIIa的情况。本发明还涉及制备公式I化合物的方法，以及它们的用途，例如作为药物的活性成分和包含它们的药物制剂。
• Malonamid and malonamic ester derivatives with antithrombotic activity, their preparation, and their use
  申请人：——

  公开号：US20030027828A1

  公开（公告）日：2003-02-06

  Compounds of formula I, 1 In which R 1 , R 2 , A, and B having the definitions set forth in the claims, are valuable pharmacologically active compounds, which exhibit a strong antithrombotic effect and are suitable, for example, for treating thromboembolic diseases and restenoses. They are reversible inhibitors of the blood clotting enzyme factor VIIa and can in general be applied in conditions in which an undesired activity of factor VIIa is present or for the cure or prevention of which an inhibition of factor VIIa is intended. Also disclosed are processes for the preparation of compounds of formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  化合物的公式I，其中R1、R2、A和B的定义如索赔中所述，是有价值的药理活性化合物，表现出强烈的抗血栓作用，适用于治疗血栓栓塞疾病和再狭窄等疾病。它们是血凝酶酶因子VIIa的可逆抑制剂，通常可用于存在血凝酶酶因子VIIa不良活性的情况或者用于治疗或预防需要抑制血凝酶酶因子VIIa的情况。还公开了化合物I的制备方法，它们的用途，特别是作为药物中的活性成分，并包括它们的制药制剂。
• N-[1,3,4]-THIADIAZOL-2-YL-BENZENE SULFONAMIDES, PHARMACEUTICAL COMPOSITIONS THEREOF AND METHODS FOR THEIR THERAPEUTIC USE
  申请人：KEIL Stefanie

  公开号：US20090054494A1

  公开（公告）日：2009-02-26

  The present invention comprises N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides, their physiologically acceptable salts and functional derivatives that exhibit peroxisome proliferator activated receptor (PPAR) PPARdelta and PPARgamma agonist activity. The structure of the compounds of the invention are defined by Formula I below, And the isomers thereof wherein the various substituents are defined herein, including their physiologically acceptable salts. Processes for the compounds preparation are also disclosed. The compounds are suitable for the treatment of fatty acid metabolism and glucose utilization disorders, disorders relating to insulin resistance are involved as well as demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.

  本发明涉及N-[1,3,4]-噻二唑-2-基苯磺酰胺、其生理上可接受的盐和功能衍生物，它们表现出过氧化物酶体增殖物激活受体(PPAR) PPARδ和PPARγ激动剂活性。发明中的化合物的结构由下式I定义，以及其异构体，其中各种取代基在此定义，包括其生理上可接受的盐。还公开了制备这些化合物的方法。这些化合物适用于治疗涉及脂肪酸代谢和葡萄糖利用障碍、涉及胰岛素抵抗的疾病，以及中枢和周围神经系统的脱髓鞘和其他神经退行性疾病的治疗。
• Acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US06492356B1

  公开（公告）日：2002-12-10

  The present invention relates to acylguanidine derivatives of formula (I) in which R1, R2, R4, R5, R6, A, m and n have the meanings indicated in the patent claims, their physiologically tolerable salts and their prodrugs. The compounds of formula (I) are valuable pharmaceutical active ingredients. They are vitronectin receptor antagonists and inhibitors of bone resorption by osteoclasts and are suitable, for example, for the therapy or prophylaxis of diseases which are caused at least partially by an undesired extend of bone resorption, for example of osteoporosis. The invention furthermore relates to processes for the preparation of compounds of formula (I), their use, in particular as pharmaceutical active ingredients, and pharmaceutical preparations comprising them.

  本发明涉及式(I)的酰基胍衍生物，其中R1、R2、R4、R5、R6、A、m和n具有专利要求中指示的含义，它们的生理耐受盐和前药。式(I)化合物是有价值的药用活性成分。它们是维脱内钙蛋白受体拮抗剂，能抑制破骨细胞对骨骼的吸收，例如，适用于治疗或预防至少部分由于不良骨吸收引起的疾病，例如骨质疏松症。该发明还涉及制备式(I)化合物的方法，它们的使用，特别是作为药用活性成分，并包含它们的药物制剂。
• Coupling reagent for peptide synthesis
  申请人：Hoechst Aktiengesellschaft

  公开号：US05166394A1

  公开（公告）日：1992-11-24

  Novel compounds of the formula I ##STR1## in which X is an anion, and a process for the preparation thereof, are described. Compounds of the formula I are used as coupling reagents in peptide synthesis.

  本发明涉及一种式子为I的新型化合物##STR1##其中X为阴离子，并描述了其制备方法。式I的化合物可用作肽合成中的偶联试剂。