CN104530008B - 一种含1,2,3-三唑的苯并咪唑类化合物及其应用 - Google Patents
一种含1,2,3-三唑的苯并咪唑类化合物及其应用 Download PDFInfo
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- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 title description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 19
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 9
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- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
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- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract 1
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- UYGKMSUDBLULNG-UHFFFAOYSA-N 3-[(2-oxo-1,3-oxazolidin-5-yl)methyl]thiophene-2-carboxamide Chemical class S1C=CC(CC2OC(=O)NC2)=C1C(=O)N UYGKMSUDBLULNG-UHFFFAOYSA-N 0.000 description 1
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- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
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- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种含1,2,3‑三唑的苯并咪唑类化合物及其应用，所述含1,2,3‑三唑的苯并咪唑类化合物是式(Ⅰ)所示的1‑((1‑R‑1H‑1,2,3‑三唑‑4‑基)甲基)‑2‑(三氟甲基)‑1H‑苯并咪唑[d]，其中R取代基为苄基、邻氯苄基、C1‑C12烷基或‑R1COOR2，其中R1选自直链或支链的C1～C4亚烷基，R2选自直链或支链的C1～C4烷基。所述含1,2,3‑三唑的苯并咪唑类化合物可应用于制备抗菌剂。本发明提供的1‑((1‑R‑1H‑1,2,3‑三唑‑4‑基)甲基)‑2‑(三氟甲基)‑1H‑苯并咪唑[d]对多种菌体菌(枯草芽孢杆菌、大肠杆菌、金黄色葡萄球菌、烟曲霉)有抑制作用，且合成工艺简单，易于产业化。
Description
(一)技术领域
本发明涉及一种新型的含1,2,3-三唑的苯并咪唑类化合物及其应用。
(二)背景技术
抗菌药物是目前医药行业中使用最广泛的一类药物，也是药物开发与研究的重点领域之一。目前临床上的抗菌药物种类有β-内酰胺类、磺胺类、四环素类、氨基糖苷类、大环内酯类、喹诺酮类和几年来临床上用的噁唑烷酮类等。
但由于抗菌药物的滥用，导致病菌耐药性日益增加，死亡率也随之上升并引起全球性的健康危机。目前，抗菌药的耐药性问题以及如何提高对耐药细菌的抗菌活性已成为迫切需要关注的课题。为此已有许多科研工作者致力于这一方面的努力，例如科研制订一些措施用于防止滥用抗菌药从而降低耐药菌的出现、对现有药物的靶位进行修饰或改造、探讨耐药菌耐药性的原因和机制等等。这些工作的侧重点都在于防止耐药菌的出现，但是开发新的抗菌药可以更本质的解决问题，包括对已有抗菌药物结构的改造和全新结构的抗菌药物的研究与开发。全新结构的抗菌药可能对病菌具有不同的靶向作用，有望在一定程度上解决细菌的药耐药性问题，增强抗菌活性。
苯并咪唑衍生物作为是天然产物中常见的结构之一，具有多种生物活性和生物相容性(Yeong K Y,et al.Synthesis and evaluation of antimycobacterial activityof new benzimidazole aminoesters[J].European Journal of Medicinal Chemistry.201310:1-11.)，同时又因为其化学结构和目前临床上使用的抗菌药不同，有望能够解决抗菌药的耐药性问题。1,2,3-三唑类衍生物具有强内吸性、长效性、广谱性、高效性和立体选择性等特性，并且具有非常好的环境相容性，由于生物相似性，使其具有较高的生物活性以及较小的人体细胞毒性，得到很多生物、医药等相关领域的专家的广泛关注(Holla B S,Manjathuru M,Karthikeyan M S,eta1.Synthesis characterization and antimicrobial activity of some substituted1,2,3-triazoles[J.European Journal of Medicinal Chemistry,2005,40:1173-1177.Mishra R,Kumar R,Kumar S,et al.Synthesis and in vitro antimicrobial activity ofsome triazole derivatives[J].Chilean Chemical Society,2010,55:359-362.)。
本发明通过邻苯二胺与三氟乙酸发生缩合反应，在利用click反应合成含1,2,3-三唑杂环的苯并咪唑衍生物，这些化合物是一种具有显著抗菌活性的抑制剂药物，为抗菌药物的筛选提供了研究基础。
(三)发明内容
本发明目的是提供一种新型的含1,2,3-三唑的苯并咪唑类化合物及其在制备抗菌剂中的应用，该类化合物对多种菌体菌有抑制作用，且合成工艺简单，易于产业化。
本发明采用的技术方案如下：
一种含1,2,3-三唑的苯并咪唑类化合物，其化学名为1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]，其结构如式(Ⅰ)所示：
R取代基为苄基、邻氯苄基、C1-C12烷基或-R1COOR2，其中R1选自直链或支链的C1～C4亚烷基，R2选自直链或支链的C1～C4烷基。
进一步，C1-C12烷基优选C12H25。
更进一步，-R1COOR2优选下列之一：2-丁酸甲酯基、2-丙酸甲酯基、乙酸乙酯基、2-丙酸乙酯基。
再更进一步，所述1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]选自下列之一：
本发明所述的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]可通过常规方法制备，其反应式如下所示：
本发明提供了所述1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]在制备抗菌剂中的应用。
进一步，所述的抗菌剂是针对枯草芽孢杆菌、大肠杆菌、金黄色葡萄球菌或烟曲霉的抑制剂。
更进一步，用于制备针对枯草芽孢杆菌的抑制剂的是化合物Ⅰ-3、Ⅰ-4、或Ⅰ-6。
更进一步，用于制备针对大肠杆菌的抑制剂的是化合物Ⅰ-2。
更进一步，用于制备针对金黄色葡萄球菌的抑制剂的是化合物Ⅰ-2或Ⅰ-3。
更进一步，用于制备针对抗烟曲霉的抑制剂的是化合物Ⅰ-3、Ⅰ-5或Ⅰ-6。
与现有技术相比，本发明的有益效果在于：本发明提供的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]对多种菌体菌(枯草芽孢杆菌、大肠杆菌、金黄色葡萄球菌、烟曲霉)有抑制作用，且合成工艺简单，易于产业化。
(四)具体实施方式
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此：
中间体制备：
1)2-三氟甲基-1H-苯并咪唑(2)的制备
将邻苯二胺1(1.08g，10mmol)加入到10mL的微波反应管中，加入三氟乙酸(2mL)，加入搅拌子，反应30min(70℃，100W，高速)。反应结束冷却后将混合物倒入圆底烧瓶中，旋蒸除去多余的三氟乙酸，得到2-三氟甲基-1H-苯并咪唑1.35g，产率99.9％。
2)1-炔丙基-2-三氟甲基-1H-苯并咪唑的制备
将2-三氟甲基-1H-苯并咪唑2(1.35g，10mmol)加入到装有15mL丙酮的圆底烧瓶中，搅拌溶解后加入烯(炔)丙基溴(0.87mL，10mmol)和K2CO3(2.07g，15mmol)，加热回流，TCL检测，反应完全后，降温冷却，过滤除去固体，用二氯甲烷洗涤固体，丙酮溶液浓缩后与二氯甲烷溶液混合，用H2O洗(15mL×3)，有机相用无水MgSO4干燥，过滤浓缩后得到粗品。得到1-炔丙基-2-三氟甲基-1H-苯并咪唑(3)2.06g，产率91.96％。
实施例1：1-((1-十二烷基-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-1)
反应式如下：
称取0.211g(1.0mmol)1-十二烷基叠氮(4-1)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5ml水和5mL异丁醇，加入CuSO4 0.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品1-((1-十二烷基-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-1)0.275g，产率为63.4％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.83(dd,J＝8.4,2.7Hz,1H),7.71(dd,J＝8.1,0.9Hz,1H),7.43-7.38(m,1H),7.37-7.34(m,1H),5.61(d,J＝2.1Hz,2H),4.28-4.22(m,2H),1.82(dd,J＝13.8,6.9Hz,2H),1.21(d,J＝6.1Hz,19H),0.88-0.83(m,3H).IR(KBr,cm-1):2989,1518,1407,1326,1271,1101,750.HRMS(ESI):m/z calcd for C23H33F3N5 +[M+H]+:436.2683,found:436.2680.
实施例2：1-((1-苯基-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-2)
反应式如下：
称取0.133g(1.0mmol)编辑叠氮(4-2)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO4 0.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品1-((1-苯基-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-2)0.263g，产率为73.7％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.85(d,J＝8.0Hz,1H),7.74(d,J＝8.0Hz,1H),7.43(t,J＝7.3Hz,1H),7.36(dd,J＝14.8,5.6Hz,4H),7.30(s,1H),7.23-7.18(m,2H),5.61(s,2H),5.46(s,2H).13C NMR(126MHz,CDCl3)δ142.57,141.08,139.85(m),135.32134.07,129.20,128.96,127.98,125.78,124.01,122.19,121.51,119.21(m),111.57,54.38,40.44.HRMS(ESI):m/z calcd for C18H15F3N5 +[M+H]+:358.1274,found:358.1277.
实施例3：2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)丙酸甲酯(Ⅰ-3)
反应式如下：
称取0.115g(1.0mmol)2-叠氮乙酸甲酯(4-3)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO4 0.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)乙酸甲酯(Ⅰ-3)0.195g，产率为57.8％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.84(d,J＝8.1Hz,1H),7.72(d,J＝8.2Hz,1H),7.61(s,1H),7.39(dt,J＝15.3,7.2Hz,2H),5.63(s,2H),5.22(dd,J＝9.4,5.8Hz,1H),3.71(s,3H),2.21(tt,J＝14.6,7.4Hz,2H),0.82(t,J＝7.4Hz,3H).IR(KBr,cm-1):2999,1531,1431,1321,1146,1061,740.HRMS(ESI):m/z calcd forC15H15F3N5O2 +[M+H]+:354.1172,found:354.1170.
实施例4：2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)乙酸乙酯(Ⅰ-4)
反应式如下：
称取0.129g(1.0mmol)2-叠氮乙酸乙酯(4-4)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO40.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-烯丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)乙酸乙酯(Ⅰ-4)0.227g，产率为64.3％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.85(d,J＝7.9Hz,1H),7.73(d,J＝8.1Hz,1H),7.53(s,1H),7.43(t,J＝8.1Hz,1H),7.37(t,J＝7.1Hz,1H),5.66(s,2H),5.09(s,2H),4.22(q,J＝7.1Hz,2H),1.25(t,J＝7.2Hz,3H).13C NMR(150MHz,CDCl3)δ165.88,142.60,141.07,139.90(m),135.28,125.81,124.02,123.80,121.52,119.23(m),111.49,62.56,50.95,40.36,13.95.IR(KBr,cm-1):2997,1747,1519,1472,1328,1230,1198,739.HRMS(ESI):m/z calcd for C15H15F3N5O2 +[M+H]+:354.1172,found:354.1176.
实施例5：2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)丙酸乙酯(Ⅰ-5)
反应式如下：
称取0.143g(1.0mmol)2-叠氮丙酸乙酯(4-5)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO40.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)丙酸乙酯(Ⅰ-5)0.224g，产率为61.0％。
1H NMR(600MHz,CDCl3,ppm-1)δ7.87(t,J＝9.3Hz,1H),7.77(t,J＝8.0Hz,1H),7.59(s,1H),7.45(q,J＝8.1Hz,1H),7.39(q,J＝8.0Hz,1H),5.67(d,J＝7.8Hz,2H),5.43-5.37(m,1H),4.19(p,J＝7.3Hz,2H),1.81-1.76(m,3H),1.21(q,J＝7.1Hz,3H).IR(KBr,cm-1):2908,1743,1527,1467,1316,1241,1187,751.HRMS(ESI):m/z calcd for C16H17F3N5O2 +[M+H]+:368.1329,found:368.1323.
实施例6：2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)丁酸甲酯(Ⅰ-6)
反应式如下：
称取0.143g(1.5mmol)2-叠氮丁酸甲酯(4-6)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO40.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品2-(4-((2-(三氟甲基)-1H-苯并咪唑[d]-1-基)甲基)-1H-1,2,3-三唑-1-基)丁酸甲酯(Ⅰ-6)0.222g，产率为60.4％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.86(d,J＝8.0Hz,1H),7.74(d,J＝8.2Hz,1H),7.60(s,1H),7.44(t,J＝7.5Hz,1H),7.37(t,J＝7.9Hz,1H),5.65(s,2H),5.30(dd,J＝9.6,5.7Hz,1H),3.73(s,3H),0.81(t,J＝7.1Hz,3H).IR(KBr,cm-1):2985,1759,1521,1477,1321,1134,746.HRMS(ESI):m/z calcd for C16H17F3N5O2 +[M+H]+:368.1329,found:368.1331.
实施例7：1-((1-(2-氯苯基)-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-7)
反应式如下：
称取0.167g(1.0mmol)邻氯苄基叠氮(4-7)和0.224g(1.0mmol)1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)加入到圆底烧瓶中，加入5mL水和5mL异丁醇，加入CuSO4 0.005g(0.02mmol)和VC 0.0352g(0.2mmol)，25℃反应，TLC跟踪反应，1-炔丙基-2-三氟乙酸-1H-苯并咪唑(3)点消失，反应完全，过滤分出有机层，旋转蒸发浓缩，经硅胶板层析分离，得到精品1-((1-(2-氯苯基)-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d](Ⅰ-7)0.279g，产率为71.3％。
1H NMR(400MHz,CDCl3,ppm-1)δ7.85(d,J＝8.0Hz,1H),7.74(d,J＝8.1Hz,1H),7.46-7.34(m,4H),7.32-7.21(m,2H),7.12(d,J＝7.5Hz,1H),5.61(s,2H),5.59(s,2H).13C NMR(150MHz,CDCl3)δ142.42141.06,139.85(m),135.30,133.51,131.93,130.46,130.33,130.02,127.65,125.78,124.01,122.60,121.51,119.21(m),111.57,51.66,40.39.IR(KBr,cm-1):1517,1470,1325,1261,1194,1048,762,745.HRMS(ESI):m/z calcd for C18H14ClF3N5 +[M+H]+:392.0884,found:392.0889.
实施例8：抗菌活性的测定
(1)培养基的配制
肉汤培养基：牛肉膏1g，蛋白胨2g，NaCl 1g，加180ml水溶解，用1N NaOH调pH值7.0，加水定容至200ml，121℃灭菌20min。
琼脂培养基：牛肉膏1g，蛋白胨2g，NaCl 1g，琼脂4g，加180ml水溶解，用1N NaOH调pH值7.0，加水定容至200ml，121℃灭菌20min。
PDA固体培养基：马铃薯30g，葡萄糖2g，琼脂1.5-2g，水100ml，自然pH值，121℃灭菌20min。
PDA液体培养基：马铃薯30g，葡萄糖2g，水100ml，自然pH值，121℃灭菌20min。
(2)抗菌活性测定
1)菌液的制备
挑取形态相似的待检菌落(大肠杆菌、枯草芽孢杆菌、金黄色葡萄球菌)3-5个，接种于5ml普通肉汤培养基中，37℃培养2-6h，菌体繁殖后，测定其OD630值，控制其OD630值在0.1左右，用培养基稀释100倍备用。
用接种圈从4℃保存的PDA培养基上挑取真菌珠菌少量(烟曲霉、黑曲霉)，接种至5ml PDA培养液，于37℃，在恒温培养箱培养18-25h。
2)受试药物的配制
待试药物用DMSO配成6.4mg/ml溶液，于1.5ml EP管中加入6.4mg样品和1ml DMSO，溶解后置于-20℃保存，实验前，取出药液取出37℃温箱融化备用。
3)药敏板的制备
取无菌96孔板，于每排1号孔加184μl新鲜菌液，2～12号孔各加新鲜配制的菌液100μl；1号孔加入16μl药液。2～11号10级倍比稀释，使各孔中的药物浓度分别为512、256、128、64、32、16、8、4、2、1和0.5μg/ml，12号孔不含药物，作阳性对照，另有一组为DMSO作为空白对照，各药敏板于37℃培养。
4)IC50值判定
大肠杆菌、枯草杆菌和金黄色葡萄球菌于37℃培养18h，烟曲霉菌、溜曲霉于37℃培养20h，用酶标仪测OD630。与12号孔对比，以OD值下降50％以上的最低浓度孔中的药物浓度为IC50(真菌或细菌生长50％被抑制时的浓度)。当测定的IC50高于最高浓度时，记为“>512μg/mL”；IC50值低于最低浓度时，记为“<0.5μg/mL”。
实施例1-7制得的化合物分别按上述方法进行测试，结果如下：
由表可知，衍生物Ⅰ-3、Ⅰ-4、Ⅰ-6对枯草芽孢杆菌显示出较好的活性。化合物Ⅰ-2对大肠杆菌具有较高的抑制活性，化合物Ⅰ-2、Ⅰ-3对金黄色葡萄球菌的具有较好的抑制效果。化合物Ⅰ-3、Ⅰ-5、Ⅰ-6对烟曲霉的抗菌效果要优于氟康唑。
Claims (10)
1.一种式(Ⅰ)所示的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]：
R取代基为苄基、邻氯苄基、C1-C12烷基或-R1COOR2，其中R1选自直链或支链的C1～C4亚烷基，R2选自直链或支链的C1～C4烷基。
2.如权利要求1所述的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]，其特征在于：C1-C12烷基为C12H25。
3.如权利要求1所述的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]，其特征在于：-R1COOR2选自下列之一：2-丁酸甲酯基、2-丙酸甲酯基、乙酸乙酯基、2-丙酸乙酯基。
4.如权利要求1所述的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]，其特征在于：所述1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]选自下列之一：
5.如权利要求1所述的1-((1-R-1H-1,2,3-三唑-4-基)甲基)-2-(三氟甲基)-1H-苯并咪唑[d]在制备抗菌剂中的应用。
6.如权利要求5所述的应用，其特征在于：所述的抗菌剂是针对枯草芽孢杆菌、大肠杆菌、金黄色葡萄球菌或烟曲霉的抑制剂。
7.如权利要求6所述的应用，其特征在于：用于制备针对枯草芽孢杆菌的抑制剂的是化合物Ⅰ-3、Ⅰ-4、或Ⅰ-6；
8.如权利要求6所述的应用，其特征在于：用于制备针对大肠杆菌的抑制剂的是化合物Ⅰ-2；
9.如权利要求6所述的应用，其特征在于：用于制备针对金黄色葡萄球菌的抑制剂的是化合物Ⅰ-2或Ⅰ-3；
10.如权利要求6所述的应用，其特征在于：用于制备针对抗烟曲霉的抑制剂的是化合物Ⅰ-3、Ⅰ-5或Ⅰ-6；
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| KR100314828B1 (ko) * | 1994-08-29 | 2002-02-19 | 유승렬 | 신규한벤즈이미다졸-2-카르바민산알킬에스터화합물및그의제조방법 |
| WO2013040647A1 (en) * | 2011-09-23 | 2013-03-28 | Adelaide Research & Innovation Pty Ltd | Novel antimicrobial compounds |
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