CN107245050B - 香草醛异羟肟酸类衍生物及其应用 - Google Patents
香草醛异羟肟酸类衍生物及其应用 Download PDFInfo
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- CN107245050B CN107245050B CN201611103571.3A CN201611103571A CN107245050B CN 107245050 B CN107245050 B CN 107245050B CN 201611103571 A CN201611103571 A CN 201611103571A CN 107245050 B CN107245050 B CN 107245050B
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
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- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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Abstract
本发明公开了一类香草醛异羟肟酸类衍生物及其应用，其为式(I)所示的化合物或其药学上可接受的盐，其中，R1为氢或羟基；R2为C1～4烷基；X为C1～4亚烷基或共价键；Y为取代或非取代的如下基团：苯基、吡嗪基、苯并咪唑基或吡啶‑2‑基，其取代基选自C1～4烷基、C1～4卤代烷基、卤素、氨基、羧基中的一种或几种。本发明中的化合物或其药学上可接受的盐可应用于抗菌剂或由细菌感染所引起的疾病的治疗方面，为抗生素药物提供了新的选择。
Description
技术领域
本发明属于药物化合物领域，具体涉及一种香草醛异羟肟酸类衍生物及其应用。
背景技术
肽脱甲酰基酶(Peptide deformylase，PDF)是一类广泛存在于真核生物和原核生物体内的含铁金属蛋白酶，在体内蛋白质合成中脱去新生成的N-甲酰甲硫氨酸多肽的N-甲酰基，是原核生物蛋白质合成过程中必不可少的一种酶。在过去的几十年，由于抗生素的大量使用，导致越来越多的微生物产生了耐药性，甚至有些微生物产生了多重耐药，因此寻找全新的靶点是如今抗菌药物研究的首要问题，而PDF也被认为是极具潜力的抗菌靶标和抗肿瘤靶标。放线酰胺素是天然存在已被报道的PDF抑制剂，尽管它的生物学活性低，但却为后来PDF结构的设计提供了框架，基于放线酰胺素的结构，大量的抗菌，抗肿瘤和抗癌类的PDF抑制剂已经被报道。
肽脱甲酰基酶作为新的抗生素靶标，具有全新的抗菌机理。它存在微生物体内且易于进行体外检测，因此是一个很有潜力的靶点。抗菌类的PDF抑制剂有肽类，拟肽类和非肽类抑制剂，肽脱甲酰基酶抑制剂按照不同结构骨架分为异羟肟酸类、N-甲酰羟胺类、甲状丙酸类、联芳酸类和其他类型。异羟肟酸类和N-甲酰羟胺类与酶结合是二齿螯合，具有结合强度大、稳定性高的特点，是目前最具研究潜力的两种金属螯合基团。典型的有BB-3497，作为大肠杆菌体内PDF酶的抑制剂，实验发现BB-3497在体内和体外都有良好的抗菌活性。肽脱甲酰基酶抑制剂作为抗菌剂具有广谱性，对革兰氏阳性菌和革兰氏阴性菌也显示出了良好的抗菌活性。目前已经有GSK-1322322，BB-83698和LBM-415三种具有抗菌活性的PDF抑制剂进入了临床试验阶段。GSK-1322322是拟肽类的新型PDF抑制剂，在菌类引起的皮肤感染的静脉治疗方面有作用。GSK-1322322在临床第一阶段已显示出了良好的活性指标，目前也进入了临床第二阶段。BB-83698目前还在临床第一阶段，正在调查其对抗细菌感染的静脉治疗方面疗效。临床研究发现它对肺炎链球菌引起的感染显示出较高的活性，而对葡萄球菌的活性则较低。LBM-415是拟肽类的新型PDF抑制剂，在大多数细菌体内都存在它的靶点，具有广泛的杀菌作用。LBM-415对肺炎链球菌和葡萄球菌都显示出了良好的活性，目前正处于临床第一阶段。目前应用于临床的抗生素对肽脱甲酰基酶均没有抑制作用，即其抑制剂与其他抗生素不产生交叉耐药。综上可知，肽脱甲酰基酶是一个理想的新一代广谱抗生素药物筛选的靶点，对肽脱甲酰基酶抑制剂的结构优化和全新活性骨架筛选将是今后该类抗生素的发展趋势。
发明内容
本发明的目的是在现有技术的基础上，提供一类具有抑菌活性的香草醛异羟肟酸类衍生物。
本发明的另一目的是提供上述香草醛异羟肟酸类衍生物在医药方面的用途。
本发明的目的可以通过以下措施达到：
式(I)所示的化合物或其药学上可接受的盐，
其中，
R1为氢或羟基；
R2为C1～4烷基；
X为C1～4亚烷基或共价键；
Y为取代或非取代的如下基团：苯基、吡嗪基、苯并咪唑基或吡啶-2-基，其取代基选自C1～4烷基、C1～4卤代烷基、卤素、氨基、羧基中的一种或几种。
在一种优选方案中，R1为羟基。
在一种优选方案中，R2为甲基、乙基、正丙基或异丙基。
在一种优选方案中，X为亚甲基、亚乙基、亚丙基或共价键。
在一种优选方案中，Y为取代或非取代的如下基团：苯基、吡嗪基、苯并咪唑基或吡啶-2-基，其取代基选自甲基、乙基、正丙基、异丙基、三氟甲基、氟、氯、溴、氨基、羧基中的一种或几种。
在一种更优选方案中，Y为苯基、卤代苯基、氨基苯基、甲酸基苯基、吡嗪基、卤代吡嗪基、氨基吡嗪基、苯并咪唑基、卤代苯并咪唑基或吡啶-2-基。
在一种更优选方案中，当X为共价键时，Y不含有吡啶-2-基基团。
本发明的化合物或其药学上可接受的盐，具体化合物可选自：
本发明的化合物，当X为共价键时，其结构为式(II)所示，
本发明进一步提供了一种药物组合物，该组合物以上述的化合物或其药学上可接受的盐为活性成分或主要活性成分，辅以药学上可接受的辅料。
本发明中的吡嗪基为基团。
本发明中的苯并咪唑基为含有的基团，其具体可以为苯并咪唑-1-基、苯并咪唑-2-基、苯并咪唑-3-基、苯并咪唑-4-基、苯并咪唑-5-基、苯并咪唑-6-基、苯并咪唑-7-基。
本发明中的吡啶-2-基为
本发明中的C1～4烷基是指含有1～4个碳原子的直链或支链的饱和烃基，具体可选自甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基。
本发明中的卤素是指氟、氯、溴和碘。
本发明中的卤代烷基是指含有至少一个卤素取代基的烷基。
本发明中的氨基是指-NH2基团。
本发明中的羧基是指-COOH基团。
本发明中的药学上可接受的盐表示保留母体化合物的生物有效性和性质的那些盐。这类盐包括：
(1)与酸成盐，通过母体化合物的游离碱与无机酸或有机酸的反应而得，无机酸包括盐酸、氢溴酸、硝酸、磷酸、偏磷酸、硫酸、亚硫酸和高氯酸等，有机酸包括乙酸、三氟乙酸、丙酸、丙烯酸、己酸、环戊烷丙酸、羟乙酸、丙酮酸、草酸、(D)或(L)苹果酸、富马酸、马来酸、苯甲酸、羟基苯甲酸、γ-羟基丁酸、甲氧基苯甲酸、邻苯二甲酸、甲磺酸、乙磺酸、萘-1-磺酸、萘-2-磺酸、对甲苯磺酸、水杨酸、酒石酸、柠檬酸、乳酸、肉桂酸、十二烷基硫酸、葡糖酸、谷氨酸、天冬氨酸、硬脂酸、扁桃酸、琥珀酸或丙二酸等。
(2)存在于母体化合物中的酸性质子被金属离子代替或者与有机碱配位化合所生成的盐，金属例子例如碱金属离子、碱土金属离子或铝离子，有机碱例如乙醇胺、二乙醇胺、三乙醇胺、氨丁三醇、N-甲基葡糖胺、奎宁等。
本发明中的药物组合物是指将本发明中的化合物中的一个或多个或其药学上可接受的盐、溶剂化物、水合物或前药与别的化学成分，例如药学上可接受的载体，混合。药物组合物的目的是促进给药给动物的过程。
本发明中的化合物或其药学上可接受的盐可应用于抗菌剂或由细菌感染所引起的疾病的治疗方面，为抗生素药物提供了新的选择。
具体实施方式
以下结合实施例对本发明的内容做进一步说明，但本发明的范围并不局限于以下所提供的各实施例。
制备实施例
化合物2a和2b按下式合成。
化合物1的合成
香兰素(1000mg,6.58mmol)，溴乙酸乙酯(1649mg,9.87mmol)，无水碳酸钾(1816mg,13.18mmol)，无水DMF(10ml)作溶剂，60℃加热搅拌5h。反应结束后，向反应液中加入适量蒸馏水(100ml)，混合物用乙酸乙酯萃取，有机层再用无水硫酸镁干燥，溶剂低压浓缩得到白色固体1(90％)。
1H NMR(400MHz,CDCl3):δ9.87(s,1H),7.45(dd,J1＝1.6,J2＝4.4,1H),7.42(s,1H),6.89(d,J＝8,1H),4.79(s,2H),4.29(q,J＝7.2,2H),3.97(s,3H),1.30(t,J＝7.2,3H).MS(ESI)m/z＝239[M+1]+.
化合物2的合成
化合物1(500mg,2.10mmol)，色胺(370mg,2.31mmol)，加入1,2-二溴乙烷10ml，搅拌溶解，再加入三乙酰氧基硼氢化钠(668mg,3.15mmol)。反应混合物在氮气保护下常温搅拌12h。反应结束后，反应液用饱和碳酸氢钠溶液淬灭，再用乙酸乙酯萃取(3次)，取乙酸乙酯层用无水硫酸镁干燥，再减压浓缩得到黄色固体；粗品用硅胶柱层析分离纯化得到2(60％)，TLC：(乙酸乙酯—乙酸乙酯：甲醇＝10:1)。
1H NMR(400MHz,DMSO):δ10.81(s,1H),7.50(d,J＝7.6,1H),7.33(d,J＝8.4,1H),7.13(s,1H),7.06(t,J＝7.2,1H),7.01(s,1H),6.96(t,J＝7.2,1H),6.83-6.81(m,2H),4.70(s,2H),4.16(q,J＝7.2,3H),2.89-2.83(m,4H),1.86(s,4H),1.20(t,J＝7.2,3H).MS(ESI)m/z＝383[M+1]+.
化合物2a的合成
金属钠(101mg,4.4mmol)溶解于无水甲醇3ml，盐酸羟胺(140mg,2.0mmol)溶解于无水甲醇5ml，将上述两种溶液混合，混合物室温下搅拌10min，出现白色浑浊，过滤除去白色固体，滤渣用无水甲醇洗涤，取滤液；将2(382mg,1.0mmol)加入到滤液中，混合物70℃下回流反应2h。反应结束后，将反应液低压浓缩，残渣用最少量的蒸馏水溶解，再用乙酸酸化溶液至pH 4，出现黄色浑浊，过滤，取滤渣，再用硅胶柱层析分离纯化得到2a(75％)，TLC(二氯甲醇：甲醇＝2:1)。
1H NMR(400MHz,DMSO):δ10.79(s,1H),7.50(d,J＝7.6,1H),7.32(d,J＝8.0,1H),7.11(s,1H),7.05(t,J＝7.6,1H),6.97-6.88(m,4H),4.34(s,2H),3.72(s,3H),3.67(s,2H),2.87-2.83(m,2H),2.80-2.77(m,2H).MS(ESI)m/z＝370[M+1]+.MP:104.1-106.8℃.
化合物2b的合成
化合物2(382mg,1.0mmol)，过量浓氨水(d＝0.88kg﹒dm-3)5ml，乙醇3ml，反应液室温搅拌14h。反应结束后将反应液低压浓缩，得到残渣，粗品用硅胶柱层析分离纯化得到2b(78％)，TLC(乙酸乙酯：甲醇＝2:1)。
1H NMR(400MHz,DMSO):δ10.78(s,1H),7.50(d,J＝8.0,1H),7.38-7.29(m,3H),7.12(s,1H),7.05(t,J＝7.6,1H),6.98-6.86(m,4H),4.38(s,2H),3.75(s,3H),3.68(s,2H),3.19(s,1H),2.86-2.84(m,2H),2.81-2.79(m,2H).MS(ESI)m/z＝354[M+1]+.MP:117.3-118.5℃.
化合物4a、5a、6a和8a可按下述反应式，并采用与合成化合物2a相同的方法进行合成。
化合物3的合成
乙基香兰素(5000mg,30.12mmol)，溴乙酸乙酯(7545mg,45.18mmol)，无水碳酸钾(8313mg,60.24mmol)，得到3(86％)。
1H NMR(400MHz,DMSO):δ9.85(s,1H),7.51(d,J＝2.0,1H),7.49(s,1H),7.07(d,J＝8.4,1H),4.94(s,2H),4.18(q,J＝7.2,2H),4.12(q,J＝7.2,2H),1.37(t,J＝7.2,3H),1.23(t,J＝7.2,3H).MS(ESI)m/z＝253[M+1]+.
化合物4的合成
化合物3(500mg,1.98mmol)，色胺(348mg,2.18mmol)，三乙酰氧基硼氢化钠(631mg,2.97mmol)，得到4(51％)。
1H NMR(400MHz,DMSO):δ10.79(s,1H),7.50(d,J＝8.0,1H),7.33(d,J＝8.0,1H),7.13(s,1H),7.06(t,J＝7.4,1H),6.97-6.94(m,2H),6.81-6.73(m,2H),4.73(s,2H),4.00(q,J＝7.2,2H),3.71-3.69(m,4H),3.18(s,3H),2.87-2.82(m,4H),1.32(t,J＝7.2,3H).MS(ESI)m/z＝397[M+1]+.
化合物4a的合成
化合物4(200mg,0.52mmol)，金属钠(101mg,4.4mmol)，NH2OH·HCl(140mg,2.0mmol)，得到4a(80％)。
1H NMR(400MHz,DMSO):δ10.78(s,1H),7.49(d,J＝7.6,1H),7.32(d,J＝8.0,1H),7.11(s,1H),7.05(t,J＝7.2,1H),6.97-6.93(m,4H),4.30(s,2H),3.96(q,J＝7.2,2H),3.65(s,2H),2.84-2.83(m,2H),2.79-2.78(m,2H),1.31(t,J＝6.0,3H).MS(ESI)m/z＝382[M-1]+.MP:103.3-105.3℃.
化合物5的合成
化合物3(500mg,1.98mmol)，2-(2-氨基乙基)吡啶(266mg,2.18mmol)，三乙酰氧基硼氢化钠(631mg,2.97mmol)，得到5(56％)。
1H NMR(400MHz,DMSO):δ8.45(d,J＝4.8,1H),7.67(t,J＝7.6,1H),7.25(d,J＝8.0,1H),7.19(t,J＝6.4,1H),6.93(s,1H),6.76(m,2H),4.72(s,2H),4.15(q,J＝7.2,2H),3.99(q,J＝7.2,2H),3.63(s,2H),2.89-2.81(m,4H),1.32(t,J＝6.8,3H),1.21(t,J＝6.8,3H).MS(ESI)m/z＝359[M+1]+.
化合物5a的合成
化合物5(200mg,0.56mmol)，金属钠(101mg,4.4mmol)，NH2OH·HCl(140mg,2.0mmol)，得到5a(76％)。
1H NMR(400MHz,DMSO):δ8.46(d,J＝4.8,1H),7.67(t,J＝7.6,1H),7.25(d,J＝7.6,1H),7.18(t,J＝6.4,1H),6.93(s,1H),6.87(d,J＝8.0,1H),6.78-6.76(s,1H),4.40(s,2H),4.00(q,J＝6.8,2H),3.64(s,2H),2.89-2.82(m,4H),1.77(s,2H),1.33(t,J＝6.8,3H).MS(ESI)m/z＝346[M+1]+.
化合物6的合成
化合物3(500mg,1.98mmol)，对氨基苯甲酸(299mg,2.18mmol)，三乙酰氧基硼氢化钠(631mg,2.97mmol)，得到6(60％)。
1H NMR(400MHz,DMSO):δ7.65(d,J＝8.8,2H),6.99(s,1H),6.89(m,1H),6.83-6.82(m,2H),6.60(d,J＝8.8,2H),4.72(s,2H),4.24(d,J＝5.6,2H),4.15(q,J＝7.2,2H),4.02(q,J＝7.2,2H),1.32(t,J＝7.2,3H),1.20(t,J＝7.2,3H).MS(ESI)m/z＝372[M-1]+.
化合物6a的合成
化合物6(200mg,0.54mmol)，金属钠(101mg,4.4mmol)，NH2OH·HCl(140mg,2.0mmol)，得到6a(76％)。
1H NMR(400MHz,DMSO):δ7.61(d,J＝7.6,2H),6.97-6.91(m,2H),6.83-6.81(m,1H),6.46(d,J＝8.4,2H),6.20(s,1H),4.34(s,2H),4.17(d,J＝5.6,2H),4.01(q,J＝7.2,2H),1.32(t,J＝7.2,3H).MS(ESI)m/z＝359[M-1]+.MP:139.9-141.4℃.
化合物8的合成
化合物3(500mg,1.98mmol)，氨基吡嗪(207mg,2.18mmol)，三乙酰氧基硼氢化钠(631mg,2.97mmol)，得到8(71％)。
1H NMR(400MHz,DMSO):δ7.96(d,J＝1.2,1H),7.92(d,J＝1.6,1H),7.66(d,J＝2.8,1H),7.44(s,1H),6.98(s,1H),6.81(d,J＝1.2,2H),4.7(s,2H),4.39(d,J＝5.6,2H),4.15(q,J＝7.2,2H),4.02(q,J＝6.4,2H),1.32(t,J＝7.2,3H),1.23(t,J＝7.2,3H).MS(ESI)m/z＝332[M+1]+.
化合物8a的合成
化合物8(200mg,0.60mmol)，金属钠(101mg,4.4mmol)，NH2OH·HCl(140mg,2.0mmol)，得到8a(63％)。
1H NMR(400MHz,DMSO):δ10.68(s,1H),8.95(s,1H),7.96(d,J＝1.2,1H),7.92(d,J＝1.2,1H),7.66(d,J＝2.8,1H),7.46(s,1H),6.98(s,1H),6.90-6.81(m,2H),4.40-4.38(m,4H),4.0(q,J＝6.8,2H),1.33(t,J＝7.2,3H).MS(ESI)m/z＝319[M+1]+.MP:105.2-106.9℃.
抑菌活性实验实施例
用含有四种不同微生物的培养基分别测试这些样品。本次实验的菌种由中国科学院微生物研究所提供，分别为大肠杆菌(Escherichia coli，ATCC 8739)、金黄色葡萄球菌(Staphylococcus aureus，ATCC 25923)、米曲霉菌(Aspergillus oryzae，ATCC 42149)、臭曲霉菌(Aspergillus foetidus,ATCC 14916)。取大肠杆菌和金黄色葡萄球菌在Luria-Bertani培养基的营养琼脂中37℃恒温培养24小时，另取米曲霉菌和臭曲霉菌在察氏培养基的营养琼脂中28℃恒温培养48小时。
最低抑菌浓度(MIC)测试
最低抑菌浓度测试参考了基准法(Duraipandiyan et al.,2009)。向96孔板的各孔内加入100μL Luria-Bertani培养基培养液或察式培养基培养液以分别培养细菌和真菌。被测样品被事先用10％DMSO溶解于肉汤培养液中。将这些被测样品的两倍稀释溶液和100μL统一配制成浓度为106CFU/mL的真菌或细菌溶液一并加入每个孔中。装有细菌溶液的96孔板被放入摇床分别在37℃培养24小时以充分混合和培养，装有真菌溶液的则放入摇床在28℃培养48小时。某样品最低抑菌浓度即使孔内未出现明显变化的最低样品浓度，在此浓度下，微生物已停止增殖。所有以上测试均有三份实验组。
最低杀菌浓度(MBC)测试
最低杀菌浓度测试参考了基准法(CLSI 2003)。最低杀菌浓度指当以卡那霉素作为阳性对照组时使99.9％微生物死亡的样品浓度。所有以上测试均有三份实验组。
表1对不同菌株的体外抗菌活性
*化合物5a用水溶解.
"-"表示无数值，杀菌活性几乎没有。
从表1可知，6个小分子化合物对大肠杆菌、金黄色葡萄球菌、米曲霉菌和臭曲霉菌都具有明显的抗菌活性。其中，化合物5a的抗菌活性要强于其他5个化合物，而化合物6a显示出稍弱的抗菌活性，这可能是由于其本身的低溶解性。化合物5a对大肠杆菌和金黄色葡萄球菌的抗菌活性要弱于放线酰胺素，但其对米曲霉菌和臭曲霉菌的抗菌活性要强于放线酰胺素。本发明的化合物有望成为一类基于肽脱甲酰基酶的新型抗菌药物。
Claims (3)
1.化合物或其药学上可接受的盐，其中，化合物选自：
2.一种药物组合物，其特征在于该组合物以权利要求1所述的化合物或其药学上可接受的盐为活性成分或主要活性成分，辅以药学上可接受的辅料。
3.权利要求1所述的化合物或其药学上可接受的盐在制备抗菌剂或由细菌感染所引起的疾病的药物方面的应用。
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