4-[6-(4-Hydroxyphenyl)-1,2-dihydro-1,2,4,5-tetrazin-3-yl]phenol | 53876-71-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-[6-(4-Hydroxyphenyl)-1,2-dihydro-1,2,4,5-tetrazin-3-yl]phenol
• 英文别名: 4-[6-(4-hydroxyphenyl)-1,4-dihydro-1,2,4,5-tetrazin-3-yl]phenol
• CAS: 53876-71-4
• 化学式: C₁₄H₁₂N₄O₂
• 分子量: 268.275
• InChiKey: KRINQQLIUFMQAX-UHFFFAOYSA-N

物化性质

• 沸点：
  477.1±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)
• 溶解度：
  2.4 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  89.2
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[6-(4-Hydroxyphenyl)-1,2-dihydro-1,2,4,5-tetrazin-3-yl]phenol 在 吡啶 、 溶剂黄146 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Mesogenic 3,6-bis(4-hydroxyphenyl)-1,2,4,5-tetrazine alkanoate esters

  摘要：

  A novel series of 3,6-bis(4-hdroxyphenyl)-1,2,4,5-tetrazine alkanoate esters were synthesized and their mesogenic properties were studied using differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). The impact of changing the tail-core linkage from alkyl or alkoxy to ester is profound. Compared to the alkyl or alkoxy linkages, the ester linkage reduced mesogenic properties. Short-tailed compounds are non mesogenic (4a-4e), while long-tailed compounds (4f-4r) exhibit nematic phases. Unlike the alkyl or alkoxy tail series, none of the 18 presented esters in this series exhibits a smectic phase.

  DOI：

  10.1080/15421406.2018.1499700
• 作为产物：
  描述：

  4-羟基苯甲腈 在 肼 作用下， 生成 4-[6-(4-Hydroxyphenyl)-1,2-dihydro-1,2,4,5-tetrazin-3-yl]phenol
  参考文献：
  名称：

  3,6-Substituted-1,2,4,5-tetrazines: tuning reaction rates for staged labeling applications

  摘要：

  涉及四氮杂环的环加成反应已被证明是多种应用的强大生物正交工具。可以想象，通过调整反应速率，可以实现基于四氮杂环的顺序和选择性标记。通过改变四氮杂环上的取代基，已实现与相同的二烯亲和体相比超过200倍的环加成速率变化。与不同的二烯亲和体（如诺尔本烯）耦合时，反应速率差异可超过14,000倍。这些取代的四氮杂环在不同条件下的选择性标记中非常有用。

  DOI：

  10.1039/c4ob00280f

文献信息

• BIO-ORTHOGONAL DRUG ACTIVATION
  申请人：KONINKLIJKE PHILIPS N.V.

  公开号：US20160106859A1

  公开（公告）日：2016-04-21

  The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

  该发明涉及一种用于治疗学的原药激活方法，其中使用了表现出彼此生物正交反应性的非生物活性化学基团。该发明还涉及一种包含至少一种原药和至少一种激活剂的试剂盒，其中原药包含药物和第一个生物正交反应基团（触发器），而激活剂包含第二个生物正交反应基团。该发明还涉及在上述方法和试剂盒中使用的靶向治疗剂。该发明特别适用于抗体药物偶联物和双特异性及三特异性抗体衍生物。
• 3,6-Substituted-1,2,4,5-tetrazines: tuning reaction rates for staged labeling applications
  作者：Danzhu Wang、Weixuan Chen、Yueqin Zheng、Chaofeng Dai、Ke Wang、Bowen Ke、Binghe Wang

  DOI：10.1039/c4ob00280f

  日期：——

  Cycloaddition reactions involving tetrazines have proven to be powerful bioorthogonal tools for various applications. Conceivably, sequential and selective labeling using tetrazine-based reactions can be achieved by tuning the reaction rate. By varying the substituents on tetrazines, cycloaddition rate variations of over 200 fold have been achieved with the same dienophile. Upon coupling with different dienophiles, such as norbornene, the reaction rate difference can be over 14 000 fold. These substituted tetrazines can be very useful for selective labeling under different conditions.

  涉及四氮杂环的环加成反应已被证明是多种应用的强大生物正交工具。可以想象，通过调整反应速率，可以实现基于四氮杂环的顺序和选择性标记。通过改变四氮杂环上的取代基，已实现与相同的二烯亲和体相比超过200倍的环加成速率变化。与不同的二烯亲和体（如诺尔本烯）耦合时，反应速率差异可超过14,000倍。这些取代的四氮杂环在不同条件下的选择性标记中非常有用。
• 4-(Cyclic Amidino)phenols - Preparation and Use In A Diamidine Synthesis
  作者：Jaroslaw Spychala

  DOI：10.1080/00397910008087126

  日期：2000.3

  Abstract The Pinner synthesis was applied to the preparation of 4-(cyclic amidino)phenols in high yields from readily available 4-hydroxybenzimidic acid methyl ester hydrochloride and diaminoalkanes. An alternative attempt was made to convert 4-(hydroxy)thiobenzamide to 4-(1,4,5,6-tetrahydro-5-hydroxy-2-pyrimidiyl)phenol. A procedure for the preparation of 3,6-bis(4-hydroxyphenyl)- 1,2,4,5-tetrazine

  摘要 Pinner 合成法用于从易得的 4-羟基苯甲酸甲酯盐酸盐和二氨基烷烃中以高收率制备 4-（环脒基）苯酚。另一种尝试是将 4-(羟基) 硫代苯甲酰胺转化为 4-(1,4,5,6-四氢-5-羟基-2-嘧啶基)苯酚。此处报道了制备 3,6-双(4-羟基苯基)-1,2,4,5-四嗪的程序。2,4-双[4-(4,5-二氢-1H-咪唑-2-基)苯氧基]嘧啶和2-氯-4-[4-(4,5-二氢-1H-咪唑- 2-基)-苯氧基嘧啶举例说明了标题合成中间体的使用。
• Bio-orthogonal drug activation
  申请人：TAGWORKS PHARMACEUTICALS B.V.

  公开号：US10004810B2

  公开（公告）日：2018-06-26

  The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

  本发明涉及一种用于治疗的原药活化方法，其中使用了相互之间具有生物正交反应性的非生物活性化学基团。本发明还涉及一种原药试剂盒，包括至少一种原药和至少一种活化剂，其中原药包括药物和第一生物正交反应基团（触发器），活化剂包括第二生物正交反应基团。本发明还涉及上述方法和试剂盒中使用的靶向治疗药物。本发明尤其涉及抗体-药物共轭物以及双特异性和三特异性抗体衍生物。
• US9421274B2
  申请人：——

  公开号：US9421274B2

  公开（公告）日：2016-08-23