3-(4-硝基苄基)-3H-咪唑-4-甲醛 | 85103-02-2

• 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: 3-(4-硝基苄基)-3H-咪唑-4-甲醛
• 英文名称: 1-(4-nitrobenzyl)-1H-imidazole-5-carbaldehyde
• 英文别名: 1-(4-nitrobenzyl)-5-imidazolecarboxaldehyde；5-formyl-1-(4-nitrobenzyl) imidazole；3-[(4-nitrophenyl)methyl]imidazole-4-carbaldehyde
• CAS: 85103-02-2
• 化学式: C₁₁H₉N₃O₃
• 分子量: 231.211
• InChiKey: XPSKUOKYICJVPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80.7
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  3-(4-硝基苄基)-3H-咪唑-4-甲醛 在 lithium perchlorate 、 四氯化钛 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 39.0h， 生成 4-(4-chlorophenyl)-2-(((1-(4-nitrobenzyl)-1H-imidazol-5-yl)methyl)amino)thiophene-3-carbonitrile
  参考文献：
  名称：

  Highly improved antiparasitic activity after introduction of an N-benzylimidazole moiety on protein farnesyltransferase inhibitors

  摘要：

  In our search for new protein farnesyltransferase inhibitors with improved antiparasitic activities, we modified our previously developed 3-aryithiophene series of inhibitors by replacing the thioisopropyl group by different substituted imidazolylmethanamino moieties. Twenty four new derivatives were synthesized and evaluated against human and parasite farnesyltransferases, and their anti-parasitic activity was determined against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi, and Leishmania donovani. Introduction of a N-p-substituted-benzylimidazole led to significantly increase the inhibition of parasite proliferation in the submicromolar range. The structure of the best inhibitors was parasite dependent. Three compounds possess IC50 values at the same range as the reference miltefosine against L donovani proliferation and other new derivatives display high level of anti-trypanosomal activity against T cruzi, higher or in the same order of magnitude as the reference compounds benznidazole and nifurtimox. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.045
• 作为产物：
  描述：

  4-硝基苄胺盐酸盐 在 manganese(IV) oxide 、 硝酸 、 溶剂黄146 、 sodium nitrite 作用下， 以 氯仿 、 正丁醇 为溶剂， 反应 121.0h， 生成 3-(4-硝基苄基)-3H-咪唑-4-甲醛
  参考文献：
  名称：

  Zarghi; Derakhshandeh; Roshanzamir, Bollettino Chimico Farmaceutico, 2002, vol. 141, # 1, p. 15 - 20

  摘要：

  DOI：

文献信息

• [EN] CONDENSED HETEROCYCLIC SYSTEM DERIVATIVES, PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] DERIVES DE SYSTEMES HETEROCYCLIQUES CONDENSES, LEUR PREPARATION, LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：AVENTIS PHARMA S.A.

  公开号：WO1999041248A1

  公开（公告）日：1999-08-19

  (EN) The invention concerns novel products of general formula (I), their preparation, pharmaceutical compositions containing them and the use thereof for preparing medicines. In general formula (I) R1 represents a -CO-CH(NH2)-CH2SH, or -CH2-CH(NH2)-CH2SH, or -CHRi1Ri2 radical; R2 represents a hydrogen atom, an alkyl, aralkyl, aryl, alkylcarbonyl, aralkylcarbonyl, heterocycloalkyl radical; R3 represents a hydrogen atom or a halogen atom or an alkyl, aryl, aralkyl radical; R4 represents a -CHRi3Ri4 radical; R5 represents a hydrogen atom, or a -C(O)-Ri5 radical; R6 represents a hydrogen atom or an alkyl, aryl, aralkyl radical; R7, R8 represent a hydrogen atom or an alkyl, aryl, aralkyl radical; X represents a hydrogen atom or a -S(O)1 radical.(FR) Nouveaux produits de formule générale (I), leur préparation, les compositions pharmaceutiques qui les contiennent et leur utilisation pour la préparation de médicaments. Dans la formule générale (I), R1 représente un radical -CO-CH(NH2)-CH2SH, ou -CH2-CH(NH2)-CH2SH, ou -CHRi1Ri2; R2 représente un atome d'hydrogène, un radical alkyle, aralkyle, aryle, alkylcarbonyle, aralkylcarbonyle, arylcarbonyle, hétérocyclalkyle; R3 représente un atome d'hydrogène ou un atome d'halogène ou un radical alkyle, aryle, aralkyle; R4 représente un radical -CHRi3Ri4; R5 représente un atome d'hydrogène, ou un radical -C(O)-Ri5; R6 représente un atome d'hydrogène ou un radical alkyle, aryle, aralkyle; R7, R8 représentent un atome d'hydrogène ou un radical alkyle, aryle, aralkyle; X représente un atome d'oxygène ou un radical -S(O)1.

  本发明涉及一般式（I）的新型产品，其制备，包含它们的药物组合物以及用于制备药物的它们的使用。在一般式（I）中，R1代表-CO-CH（NH2）-CH2SH或-CH2-CH（NH2）-CH2SH或-CHRi1Ri2基团；R2代表氢原子，烷基，芳基烷基，芳基，烷基羰基，芳基烷基羰基，杂环烷基基团；R3代表氢原子或卤素原子或烷基，芳基，芳基烷基基团；R4代表-CHRi3Ri4基团；R5代表氢原子或-C（O）-Ri5基团；R6代表氢原子或烷基，芳基，芳基烷基基团；R7，R8代表氢原子或烷基，芳基，芳基烷基基团；X代表氢原子或-S（O）1基团中的氧原子。
• Compounds and methods for the inhibition of compounds cruzi
  申请人：Hamilton D Andrew

  公开号：US20060167269A1

  公开（公告）日：2006-07-27

  The present invention relates to compounds according to the formula (I): Where R A is a C 1 -C 10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group according to the formula (II): R B is a C 1 -C 10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group of the formula (III): R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently selected from H, C 1 -C 10 (preferably a C 1 -C 4 ) alkyl or alkenyl group, CF 3 , F, Cl, Br, I, CN, NO 2 , NH 2 , NHR, NRR, COR (acyl group), OR (hydroxyl or ether group), CO 2 R (carboxylic acid or ester group), or COSR (thioester group) where R is H or a C 1 -C 10 (preferably a C 1 -C 4 ) alkyl or alkenyl group, an unsubstituted or substituted aryl (preferably, phenyl) or heterocycle group, or a (IV) group, where R 3 is H, a C 1 -C 10 (preferably a C 1 -C 4 ) alkyl, alkenyl, ether or a thioether group; and R 11 and R 12 are independently selected from H or a C 1 -C 3 alkyl or alkenyl group, or a pharmaceutically acceptable salt thereof and methods for treating infections caused by protozoal, fungal and/or bacterial agents such as Trypanosoma cruzi, Mycobacterium spp., Leishmania spp., Cryptococcus spp., Aspergillus spp., Histoplasma spp., Candida spp., especially Candida albicans, Pneumocystis carinii, Trichophyton spp., Microsporum spp., Malassezia spp., Rhizopus spp., Pseudallescheria spp., Blastomyces dermatitidis and Coccidiodes spp., among others.

  本发明涉及式(I)的化合物：其中RA是C1-C10取代或未取代的线性、支链或环烷基或烯基或式(II)的苯基：RB是C1-C10取代或未取代的线性、支链或环烷基或烯基或式(III)的苯基：R1、R2、R3、R4、R5、R6、R7、R8、R9和R10各自独立地选自H、C1-C10(优选为C1-C4)烷基或烯基、CF3、F、Cl、Br、I、CN、NO2、NH2、NHR、NRR、COR（酰基）、OR（羟基或醚基）、CO2R（羧酸或酯基）或COSR（硫酯基），其中R是H或C1-C10(优选为C1-C4)烷基或烯基、未取代或取代的芳基（优选为苯基）或杂环基，或式(IV)的基团，其中R3是H、C1-C10(优选为C1-C4)烷基、烯基、醚或硫醚基；R11和R12各自独立地选自H或C1-C3烷基或烯基，或其药学上可接受的盐，以及用于治疗由原虫、真菌和/或细菌引起的感染的方法，例如Trypanosoma cruzi，Mycobacterium spp.，Leishmania spp.，Cryptococcus spp.，Aspergillus spp.，Histoplasma spp.，Candida spp.，特别是Candida albicans，Pneumocystis carinii，Trichophyton spp.，Microsporum spp.，Malassezia spp.，Rhizopus spp.，Pseudallescheria spp.，Blastomyces dermatitidis和Coccidioides spp.等。
• Structurally Simple Inhibitors of Lanosterol 14α-Demethylase Are Efficacious In a Rodent Model of Acute Chagas Disease
  作者：Praveen Kumar Suryadevara、Srinivas Olepu、Jeffrey W. Lockman、Junko Ohkanda、Mandana Karimi、Christophe L. M. J. Verlinde、James M. Kraus、Jan Schoepe、Wesley C. Van Voorhis、Andrew D. Hamilton、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1021/jm900030h

  日期：2009.6.25

  We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14 alpha-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T cruzi amastigotes in vitro with values of EC50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.
• Synthesis of<i>N</i> ¹-Aryl- and<i>N</i> ¹-Benzyl Substituted Imidazole-4- and Imidazole-5-carbaldehydes
  作者：Ippolito Antonini、Gloria Cristalli、Palmarisa Franchetti、Mario Grifantini、Sante Martelli

  DOI：10.1055/s-1983-30217

  日期：——
• Design and Synthesis of Potent Nonpeptidic Farnesyltransferase Inhibitors Based on a Terphenyl Scaffold
  作者：Junko Ohkanda、Jeffrey W. Lockman、Mohit A. Kothare、Yimin Qian、Michelle A. Blaskovich、Said M. Sebti、Andrew D. Hamilton

  DOI：10.1021/jm0103099

  日期：2002.1.1

  By modification of key carboxylate, hydrophobic, and zinc-binding groups projected from a sterically restricted terphenyl scaffold, a series of simple and nonpeptide mimetics of the Cys-Val-Ile-Met tetrapeptide substrate of protein farnesyltransferase (FTase) have been designed and synthesized. A crystal structure of 4-nitro-2-phenyl-3'-methoxycarbonylbiphenyl shows that the triphenyl fragment provides a large hydrophobic surface that potentially mimics the hydrophobic side chains of the three terminal residues in the tetrapeptide. 2-Phenyl-3-(N-(1-(4-eyanobenzyl)-1H-imidazol-5-yl)methyl)amino-3'carboxylbiphenyl, in which the free thiol group was replaced with a 1-(4-cyanobenzyl)imidazole group, shows submicromolar inhibition activity against FTase in vitro and inhibits H-Ras processing in whole cells.