4-(benzo[1,3]dioxol-5-yl)semicarbazide | 756791-27-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 4-(benzo[1,3]dioxol-5-yl)semicarbazide
• 英文别名: N-(benzo[1,3]dioxol-5-yl)hydrazinecarboxamide；3,4-(methylenedioxy)phenylsemicarbazide；LASSBio-1212；3-amino-1-(2H-1,3-benzodioxol-5-yl)urea；1-amino-3-(1,3-benzodioxol-5-yl)urea
• CAS: 756791-27-2
• 化学式: C₈H₉N₃O₃
• mdl: MFCD11212586
• 分子量: 195.178
• InChiKey: AEVPORUAGITDBX-UHFFFAOYSA-N

物化性质

• 密度：
  1.505±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  85.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(benzo[1,3]dioxol-5-yl)semicarbazide 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 3.0h， 生成 4-(benzo[d][1,3]dioxol-5-yl)-5-ethyl-2,4-dihydro-3H-1,2,4-triazol-3-one
  参考文献：
  名称：

  鉴定基于 2,4,5-三取代-2,4-二氢-3H-1,2,4-三唑-3-一的小分子作为选择性 BRD9 结合剂

  摘要：

  靶向含溴结构域蛋白 9 (BRD9) 代表了开发具有抗癌特性的新药物的有前途的策略。为此，采用依赖于计算机研究的组合方法研究了一组基于 2,4,5-三取代-2,4-二氢-3 H -1,2,4-三唑-3-酮的化合物、化学合成、生物物理和生物学评价最有前途的项目。该协议最初基于分子对接实验，计算了一个包含 1896 个可能可合成的项目的库，这些项目是在计算机上针对 BRD9 的溴域进行测试的。第一组 21 种化合物 ( 1 – 21) 被选中，并通过 AlphaScreen 分析评估了 BDR9 上的结合。获得的结果表明，化合物17和20能够在亚微摩尔范围内结合 BRD9（分别为 IC 50  = 0.35 ± 0.18 μM 和 IC 50  = 0.14 ± 0.03 μM），当针对另外九个溴结构域进行测试时显示出有希望的选择性特征。利用基于 3D 结构的药效团模型，在计算机中选择了另外

  DOI：

  10.1016/j.ejmech.2022.115018
• 作为产物：
  描述：

  phenyl benzo[d][1,3]dioxol-5-ylcarbamate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以85%的产率得到4-(benzo[1,3]dioxol-5-yl)semicarbazide
  参考文献：
  名称：

  Design, synthesis and in vitro trypanocidal and leishmanicidal activities of novel semicarbazone derivatives

  摘要：

  Trypanosomatids are protozoan parasites that cause various diseases in human, such as leishmaniasis, Chagas disease and sleeping sickness. The highly syntenic genomes of the trypanosomatid species lead the assumption that they can encode similar proteins, indicating the possibility to design new antitrypanosomatid drugs with dual trypanosomicidal and leishmanicidal activities. In this work a series of compounds (6a-h and 7a-h), containing a semicarbazone scaffold as a peptide mimetic framework, was designed and synthesized. From this series compound 7g (LASSBio-1483) highlighted, showing dual in vitro trypanosomicidal and leishmanicidal activities, with potency similar to the standard drugs nifurtimox and pentamidine. This data, taken together with its good in silico druglikeness profile and its great chemical and plasma stability, make LASSBio-1483 (7g) a new antitrypanosomatid lead-candidate. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.05.046

文献信息

• Facile one-pot synthesis of 4-substituted semicarbazides
  作者：Andrey V. Bogolubsky、Yurii S. Moroz、Pavel K. Mykhailiuk、Yurii V. Dmytriv、Sergey E. Pipko、Liudmyla N. Babichenko、Anzhelika I. Konovets、Andrey Tolmachev

  DOI：10.1039/c4ra12425a

  日期：——

  and disubstituted semicarbazides was prepared in a one-pot two-step approach. The method includes formation of a carbamate from bis(2,2,2-trifluoroethyl)carbonate or 2,2,2-trifluoroethylchloroformate and a primary or secondary amine and subsequent interaction of the carbamate with hydrazine to result in a semicarbazide. The approach allowed to obtain 4-substituted semicarbazides on a large scale in

  用一锅两步法制备了25种4-一元和二取代的氨基脲的多样化文库。该方法包括由碳酸双（2,2,2-三氟乙基）酯或氯甲酸2,2,2-三氟乙基酯与伯胺或仲胺形成氨基甲酸酯，以及随后使氨基甲酸酯与肼相互作用以生成氨基脲。该方法允许以高收率和高纯度大规模获得4-取代的氨基脲。
• Exploration of a Library of 3,4-(Methylenedioxy)aniline-Derived Semicarbazones as Dual Inhibitors of Monoamine Oxidase and Acetylcholinesterase: Design, Synthesis, and Evaluation
  作者：Rati K. P. Tripathi、Gopal K. Rai、Senthil R. Ayyannan

  DOI：10.1002/cmdc.201600128

  日期：2016.6.6

  A library of 3,4‐(methylenedioxy)aniline‐derived semicarbazones was designed, synthesized, and evaluated as monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors for the treatment of neurodegenerative diseases. Most of the new compounds selectively inhibited MAO‐B and AChE, with IC50 values in the micro‐ or nanomolar ranges. Compound 16, 1‐(2,6‐dichlorobenzylidene)‐4‐(benzo[1,3]dioxol‐5‐yl)semicarbazide

  设计，合成并评估了3,4-（亚甲二氧基）苯胺衍生的半咔唑文库，作为单胺氧化酶（MAO）和乙酰胆碱酯酶（AChE）抑制剂用于神经退行性疾病的治疗。大多数新化合物选择性抑制MAO-B和AChE，IC 50值在微摩尔或纳摩尔范围内。化合物16，1-（2,6-二氯苯基）-4-（苯并[1,3]二氧杂环戊烯-5-基）氨基脲呈现MAO-A的一个平衡的多官能轮廓（IC 50 = 4.52±0.032μ米），MAO -B（IC 50 = 0.059±0.002μ米），和乙酰胆碱（IC 50 = 0.0087±0.0002μ米）抑制无神经毒性。动力学研究表明该化合物16表现出对MAO-A和MAO-B的竞争性和可逆性抑制，以及对AChE的混合型抑制。分子对接研究进一步揭示了对酶抑制剂复合物中可能相互作用的见解。发现活性最高的化合物通过氢键和疏水相互作用与酶相互作用。此外，还对合成化合物的计算机分子特性和ADME特性进行了计算，以探索其类药物特性。
• Dérivés d'indane-1,3-dione et d'indane-1,2,3-trione, leurs procédés de préparation et leur application en thérapeutique
  申请人：INNOTHERA

  公开号：EP0566445B1

  公开（公告）日：1996-02-07
• [EN] INDAN-1,3-DIONE AND INDAN-1,2,3-TRIONE DERIVATIVES, PROCESSES FOR THE PREPARATION OF SAME AND THEIR APPLICATION AS THERAPEUTIC AGENTS<br/>[FR] DERIVES D'INDANE-1,3-DIONE ET D'INDANE-1,2,3-TRIONE, LEURS PROCEDES DE PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
  申请人：INNOTHERA

  公开号：WO1993020045A1

  公开（公告）日：1993-10-14

  (EN) Compounds of formula (I) used as therapeutic agents. R2 and R3 are independently H, C1-C4 alkoxy or OH and (A, B) = (oxygen, oxygen) in which case either R or R1 is OH, halogen, secondary amino or tertiary amine while the other denotes NHNHCONHR4 or R and R1 together form =N-NH-CX-NHR5, =N-NH-CX-N(phenyl)2, =N-NH-CX-NH-NH-R5, =N-NH-C(SCH3)=N-R6 or =N-N=C(SCH3)-NH-R6; or (A, B) = (N-OH, oxygen) in which case R and R1 together form =N-NH-CX-NHR5 or =N-NH-CX-N(phenyl)2; or (A, B) = (N-NH-CX-NHR5, oxygen) in which case R and R1 together form =N-NH-CX-NHR5; or (A, B) = (N-OH, N-OH) in which case R and R1 together form =N-NH-CX-NHR5 or =N-NH-CX-N(phenyl)2.(FR) Composés utiles en thérapeutique de formule (I) dans laquelle R2 et R3 représentent indépendamment l'un de l'autre H, alkoxy en C1-C4 ou OH et (A, B) = (oxygène, oxygène), auquel cas l'un parmi R et R1 représente OH, halogène, amino secondaire ou amine tertiaire et l'autre représente NHNHCONHR4 ou bien R et R1 forment ensemble =N-NH-CX-NHR5, =N-NH-CX-N(phényle)2, =N-NH-CX-NH-NH-R5, =N-NH-C(SCH3)=N-R6 ou =N-N=C(SCH3)-NH-R6; ou (A, B) = (N-OH, oxygène), auquel cas R et R1 forment ensemble =N-NH-CX-NHR5 ou =N-NH-CX-N(phényle)2; ou (A, B) = (N-NH-CX-NHR5, oxygène), auquel cas R et R1 forment ensemble =N-NH-CX-NHR5; ou (A, B) = (N-OH, N-OH), auquel cas R et R1 forment ensemble =N-NH-CX-NHR5 ou =N-NH-CX-N(phényle)2.
• [EN] HYDRAZIDE-N-ACYLHYDRAZONE COMPOUNDS, METHOD FOR PRODUCING HYDRAZIDE-N-ACYLHYDRAZONE COMPOUNDS, USE OF INTERMEDIATE COMPOUNDS FOR PRODUCING HYDRAZIDE-N-ACYLHYDRAZONES FOF THE TREATMENT OF LEISHMANIASIS AND CHAGAS DISEASE, AND THUS OBTAINED PHARMACEUTICAL COMPOSITIONS<br/>[FR] COMPOSÉS HYDRAZIDE-N-ACYLHYDRAZONES, PROCÉDÉ D'OBTENTION DE COMPOSÉS HYDRAZIDE-N-ACYLHYDRAZONES, UTILISATION DE COMPOSÉS INTERMÉDIAIRES POUR L'OBTENTION D'HYDRAZIDE-N-ACYLHYDRAZONES POUR LE TRAITEMENT DE LA LEISHMANIOSE ET DE LA MALADIE DE CHAGAS, ET COMPOSITION PHARMACEUTIQUES OBTENUES<br/>[PT] COMPOSTOS HIDRAZIDA-N-ACILIDRAZONAS, PROCESSO DE OBTENÇÃO DE COMPOSTOS HIDRAZIDA-N-ACILIDRAZONAS, USO DE COMPOSTOS INTERMEDIÁRIOS PARA A OBTENÇÃO DE HIDRAZIDA-N-ACILIDRAZONAS PARA TRATAMENTO DE LEISHMANIOSE E DOENÇA DE CHAGAS &Eacgr; COMPOSIÇÕES FARMACÊUTICAS OBTIDAS
  申请人：UNIV RIO DE JANEIRO

  公开号：WO2014019044A1

  公开（公告）日：2014-02-06

  Compostos hidrazida-n-acilidrazonas, processo de obtenção de compostos hidrazida-n-acilidrazonas, uso de compostos intermediários para a obtenção de hidrazida-n-acilidrazonas para tratamento de leishmaniose e doença de chagas e composições farmacêuticas obtidas, particularmente descreve a obtenção de compostos leismanicidas e/ou tripanomicidas, inibidores de cisteína proteinases envolvidas nos processos infecciosos causados pelos parasitas Trypanossoma cruzi e Leishmania sp. Ou seja, a invenção trata do planejamento da série de compostos hidrazida-N-acilidrazonas com o objetivo de gerar um princípio ativo para composições farmacêuticas voltadas ao tratamento das diferentes formas clínicas de Leishmaniose e Doença de Chagas; o planejamento da série de derivados hidrazida-N-acilidrazona funcionalizados (séries III e IV) é realizado mediante hibridação molecular entre os protótipos LASSBio-1111 (leishmanicida) e LASSBio-1064 (tripanomicida) mediante hibridação da subunidade aril-hidrazida de LASSBio-1111 com a acilidrazona funcionalizada de LASSBio-1064, obtendo-se um novo padrão molecular que conjugando as propriedades leishmanicida e/ou tripanomicida.