3-甲基-6-(1-甲基肼基)-2,4(1H,3H)-嘧啶二酮 | 42747-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 3-甲基-6-(1-甲基肼基)-2,4(1H,3H)-嘧啶二酮
• 英文名称: 3-methyl-6-(1-methylhydrazino)uracil
• 英文别名: 3-methyl-6-(1-methylhydrazinyl)pyrimidine-2,4(1H,3H)-dione；6-[amino(methyl)amino]-3-methyl-1H-pyrimidine-2,4-dione
• CAS: 42747-84-2
• 化学式: C₆H₁₀N₄O₂
• 分子量: 170.171
• InChiKey: VQUOCQPUWMVVJV-UHFFFAOYSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-甲基-6-(1-甲基肼基)-2,4(1H,3H)-嘧啶二酮 在 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Study on glycosylated prodrugs of toxoflavins for antibody-directed enzyme tumor therapy

  摘要：

  Eight novel toxoflavin glycosides, which are potential prodrugs in antibody directed enzyme prodrug therapy (ADEPT), were synthesized. The structures of all toxoflavin glycosides were characterized by C-13 NMR spectroscopy, elemental analysis, and MS. Their enzymatic hydrolysis activities were tested against P-glucosidase (EC.3.2.1.21). (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2007.03.006
• 作为产物：
  描述：

  6-氯-3-甲基尿嘧啶 、 甲基肼 以 乙醇 为溶剂， 反应 2.0h， 以65%的产率得到3-甲基-6-(1-甲基肼基)-2,4(1H,3H)-嘧啶二酮
  参考文献：
  名称：

  靶向β-Catenin/ Tcf4信号传导活性的毒素黄素的便捷合成

  摘要：

  描述了一种快速且改进的合成毒素和抗肿瘤药毒素黄素的途径。该方法使用容易获得的材料和简单而实用的反应（包括氯化，缩合和重氮化），分五个步骤生产毒黄素，产率为14.2％，纯度为98.6％（HPLC）。这种合成的黄素毒素有效抑制β-catenin/ Tcf4驱动的TOP荧光素酶活性，IC 50小于0.5μM，并以剂量​​依赖性方式诱导结肠癌细胞死亡，IC 50为0.29μM。

  DOI：

  10.1002/jhet.1111

文献信息

• Rational design, synthesis and biological profiling of new KDM4C inhibitors
  作者：Vatroslav Letfus、Dubravko Jelić、Ana Bokulić、Adriana Petrinić Grba、Sanja Koštrun

  DOI：10.1016/j.bmc.2019.115128

  日期：2020.1

  diseases such as prostate and breast cancer. Majority of currently known inhibitors suffer from the low permeability and low selectivity between the enzyme isoforms. In this study, toxoflavin motif was used to design and synthesize new KDM4C inhibitors with improved biological activity and in vitro ADME properties. Inhibitors displayed good passive cellular permeability and metabolic stability. However

  KDM4家族的人组蛋白脱甲基酶已经与诸如前列腺癌和乳腺癌的疾病有关。当前已知的大多数抑制剂都遭受酶同工型之间的低渗透性和低选择性。在这项研究中，毒素黄素被用于设计和合成具有改善的生物活性和体外ADME特性的新型KDM4C抑制剂。抑制剂表现出良好的被动细胞通透性和代谢稳定性。然而，减少氧化还原责任并因此对细胞生存力的非特异性影响仍然是一个挑战。
• AUTORECYCLING OXIDATION OF AMINES TO CARBONYL COMPOUNDS CATALYZED BY 3,4-DISUBSTITUTED 4-DEAZATOXOFLAVIN DERIVATIVES
  作者：Tomohisa Nagamatsu、Yuko Hashiguchi、Yoshiharu Sakuma、Fumio Yoneda

  DOI：10.1246/cl.1982.1309

  日期：1982.9.5

  3,4-Disubstituted 4-deazatoxoflavin derivatives (II) were prepared by the condensation of 6-(1-methylhydrazino)uracils (I) with appropriate α-diketones. The compounds II oxidized long-chain alkylamines such as n-octylamine and n-dodecylamine besides benzylamine and cyclohexylamine to yield the corresponding carbonyl compounds via imines, catalytically with a markedly high turnover number.

  3,4-二取代的 4-脱氮氧代黄素衍生物 (II) 是通过 6-(1-甲基肼基) 尿嘧啶 (I) 与适当的 α-二酮缩合制备的。除了苄胺和环己胺外，化合物II氧化长链烷基胺如正辛胺和正十二胺，通过亚胺产生相应的羰基化合物，催化转化率显着高。
• [EN] 3-FURANYL ANALOGS OF TOXOFLAVINE AS KINASE INHIBITORS<br/>[FR] ANALOGUES DE 3-FURANYLE DE TOXOFLAVINE EN TANT QU'INHIBITEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004007499A1

  公开（公告）日：2004-01-22

  The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents an integer being 0 or 1; n represents an integer being 0, 1 or 2; R1 represents C1-4alkyl, C1-4alkyl substituted with pyridinyl, phenyl, piperidinyl or piperidinyl substituted with C1-4-alkyloxycarbonyl; R2 represents hydrogen or C1-4 alkyl; R3 represents hydrogen or C1-4alkyl; or R2 and R3 taken together with the carbon atom to which they are attached form cyclopentyl or piperidinyl wherein said cyclopentyl or piperidinyl each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from C1-4alkyloxycarbonyl, phenylcarbonyl or -C(=NH)-NH2; R4 represents halo or C1-4alkyloxy; R5 represents Het2, C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy, halo, Het3 or NR6R7, or C1-4alkyloxy substituted with one or where possible more substituents being selected from Het4 or -C(=O)-Het4; R6 and R7 are each independently selected from hydrogen, C1-4alkyl, Het5 or C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy or Het5; Het2 represents piperazinyl; Het3 represents a heterocycle selected from morpholinyl, pyrrolidinyl, piperidinyl, or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C1-4alkyl preferably methyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl, hydroxyC1 -4alkyloxyC1-4alkyl, C1-4alkyloxyC1-4alkyl or C1-4alkyloxy; Het4 represents a heterocycle selected from morpholinyl or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three C1-4alkyl substituents, preferably methyl; Het5 represents a heterocycle selected from pyridinyl, pyrrolidinyl or piperidinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from aminosulfonyl, C1-4alkyloxycarbonyl or mono- or di(C1-4alkyl)aminosulfonyl.

  本发明涉及具有式（I）的化合物，其N-氧化物形式，药用可接受的加合物盐及其立体化异构体形式，其中m代表为0或1的整数；n代表为0，1或2的整数；R1代表C1-4烷基，带有吡啶基，苯基，哌啶基或带有C1-4-烷氧羰基的C1-4烷基；R2代表氢或C1-4烷基；R3代表氢或C1-4烷基；或R2和R3与它们连接的碳原子一起形成环戊烷基或哌啶基，其中所述的环戊烷基或哌啶基各自可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自C1-4烷氧羰基，苯甲酰基或-C（=NH）-NH2；R4代表卤素或C1-4烷氧基；R5代表Het2，带有一个或在可能的情况下更多取代基的C1-4烷基，所选取的取代基包括羟基，卤素，Het3或NR6R7，或带有一个或在可能的情况下更多取代基的C1-4烷氧基，所选取的取代基包括Het4或-C（=O）-Het4；R6和R7各自独立选择自氢，C1-4烷基，Het5或带有羟基或Het5的C1-4烷基取代基；Het2代表哌嗪基；Het3代表从吗啉基，吡咯啉基，哌啶基或哌嗪基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自C1-4烷基（最好是甲基），氨基磺酰基，单烷基或双烷基氨基磺酰基，羟基C1-4烷氧基C1-4烷基，C1-4烷氧基C1-4烷基或C1-4烷氧基；Het4代表从吗啉基或哌嗪基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个C1-4烷基取代基取代，最好是甲基；Het5代表从吡啶基，吡咯啉基或哌啶基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自氨基磺酰基，C1-4烷氧羰基或单烷基或双烷基氨基磺酰基。
• Synthesis, Properties, and Redox Ability of Optically Active 3-Carba- moyl-1,6-dimethylpyrimido[4,5-c]-pyridazine-5,7(1H,6H)-dione and Related Pyrimido-annulated Pyridine Analogues
  作者：Makoto Nitta、Shin-ichi Naya、Kohtaro Shibayama

  DOI：10.3987/com-04-10063

  日期：——

  active 3-carbamoyl-1,6-dimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione (13a) and related pyrimido-annulated pyridine analogues (13b,c) were prepared via the corresponding 3-ethoxycarbonyl-1,6-dimethylpyrimido[4,5-c]pydazine-5,7(1H,6H)-dione (11a) and the related compounds (11b,c). The properties of lla-c, 13a-c, and the related 1,3,6-trimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione (18a) as well

  光学活性的 3-carbamoyl-1,6-dimethylpyrimido[4,5-c]pyridazine-5,7(1H,6H)-dione (13a) 和相关的嘧啶环化吡啶类似物 (13b,c) 是通过相应的3-乙氧羰基-1,6-二甲基嘧啶并[4,5-c]哒嗪-5,7(1H,6H)-二酮 (11a) 和相关化合物 (11b,c)。lla-c、13a-c 和相关的 1,3,6-三甲基嘧啶并[4,5-c]哒嗪-5,7(1H,6H)-二酮 (18a) 以及 7-苯基-的性质和 3,7,8-trimethyl-pyrido[2,3-d]pyrimidine-2,4(3H,8H)-dione (18b,c) 通过 UV-VIS 光谱和氧化还原进行了研究潜力。虽然哒嗪衍生物(13a)没有被还原，但吡啶衍生物(11b,c)、(13b)和(18b)被Na 2 S 2 O 4 还原得到二氢化合物(20b
• Microwave-assisted synthesis of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione libraries: derivatives of toxoflavin
  作者：Nick Todorovic、Andrew Giacomelli、John A. Hassell、Christopher S. Frampton、Alfredo Capretta

  DOI：10.1016/j.tetlet.2010.09.044

  日期：2010.11

  The parallel synthesis of a library of toxoflavin derivatives is described. The microwave-assisted approach involves the de novo generation of the heterocyclic scaffold and allows for facile introduction of a variety of fragments.

  描述了一种平行合成的毒素类黄素衍生物的文库。微波辅助方法涉及从头产生杂环支架，并允许容易地引入各种片段。