CN116768801A - 稠合的醌肟咪唑及其鎓衍生物与其制备和用途 - Google Patents
稠合的醌肟咪唑及其鎓衍生物与其制备和用途 Download PDFInfo
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- CN116768801A CN116768801A CN202210224058.9A CN202210224058A CN116768801A CN 116768801 A CN116768801 A CN 116768801A CN 202210224058 A CN202210224058 A CN 202210224058A CN 116768801 A CN116768801 A CN 116768801A
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种稠合的醌肟咪唑及其鎓衍生物与其制备和用途，其结构由下述通式(I)、(II)、(Ⅲ)和(Ⅳ)表示：
Description
技术领域
本发明属于医药领域，涉及一种稠合的醌肟咪唑及其鎓衍生物与其制备和用途；尤其涉及一类针对治疗癌症有用和抗菌抗病毒的醌肟咪唑鎓衍生物及其制备和其新的合成的中间体及其制备。
背景技术
含有醌类的化合物在自然界中广泛存在，其中很多具有良好的生物活性，如阿霉素和丝裂霉素C可以作为临床中应用的化疗药物用来治疗多种癌症，紫草素及其衍生物则具有抗炎，抗癌，抗病毒，抗血栓，降血糖，保护肝脏等多种生物活性。合成类含醌药物也有非常广泛的应用，如多柔比星和表柔比星也都是非常好的一线抗癌药物。近年来，含醌类活性物质抗癌活性研究引人关注。氮杂环卡宾是一类活性非常优异、应用非常广泛的金属有机催化剂配体及小分子催化剂，具有高效，易得，易修饰，廉价等特点。这与药物分子的特征高度重合。
现有文献报道的关于醌类咪唑衍生物的结构修饰主要有两种，一是偶然性的、不成系统的单取代咪唑产物的零星开发(美国专利，US 20090163545 A1 20090625；国际专利，WO 2009023773 A2 20090219，WO 2012149523 A1 20121101),二是在萘醌咪唑2位引入固定基团后再进行咪唑结构修饰，合成2-位取代的萘醌类咪唑非卡宾前体衍生物(日本专利，JP 2014156400 A 20140829；美国专利，US 20150086535 A1 20150326；国际专利，2001060803A1 20010823，2004092160A1 20041028，2012161177A1 20121129，2013148649A1 20131003，2014142220A1 20140918)。本发明运用学科融合思维，将醌类化合物与卡宾有机结合并进行肟化，首次设计并合成出一系列具有高效抗癌活性的醌肟咪唑鎓衍生物。
发明内容
目前癌症治疗主要以化疗为主，但是临床使用的化疗药物毒性不容忽视，因此研制出具有高活性且低毒安全可靠的抗癌药物迫在眉睫。本发明对醌类药物进行深入的研究发现，醌类化合物的毒性主要来自于醌转化成醌肟所产生的ROS，此外，天然的醌肟产物紫草素具有优良的抗癌活性。因此本发明的目的在于提供一类稠合的醌肟咪唑及其鎓衍生物与其制备和用途。这些化合物结构新颖，易于制备，体内体外试验显示出良好的抗肿瘤活性，且毒性较小安全可靠。
本发明的目的是通过以下的技术方案来实现的：
第一方面，本发明涉及一种有下述通式(Ⅰ)和(Ⅱ)表示的稠合的醌肟咪唑鎓衍生物；
其结构式如：
式中记号具有以下意思：
A环：选自无或有一个或多个取代基的芳环，或无或有一个或多个取代基的杂芳环；
R1、R2、R3和R4：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；
上述A环和R1、R2、R3和R4中的取代基可以选自B组的基团；
B组：-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-ORa、-SRa、-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-NRaRb、-O-低级亚烷基-O-低级亚烷基-NRaRb、-O-低级亚烷基-NRc-低级亚烷基-NRaRb、-O-CO-NRaRb、-SORa、-SO2Ra、-SO2NRaRb、-NRa-SO2Rb、-NRaRb、-NRc-低级亚烷基-NRaRb、-N(-低级亚烷基-NRaRb)2、-NO2、-CN、-卤素、-CO2Ra、-COO-、-CONRaRb、-CONRa-O-Rb、-NRa-CORb、-NRa-CO-NRbRc、-OCORa和-CORa；
Ra、Rb和Rc：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-低级亚烷基-(无或一个或多个取代基的5到7元饱和杂环)、-低级亚烷基-(无或一个或多个取代基的环烷基)、-低级亚烷基-(无或一个或多个取代基的芳基)、-低级亚烷基-(无或一个或多个取代基的杂芳基)；其中，取代基指低级烷基或杂烷基；
X-：抗衡阴离子，包括卤素离子、磺酸根离子(甲磺酸根离子、三氟甲磺酸根离子、苯磺酸根离子、对甲苯磺酸根离子等)、乙酸根离子、三氟乙酸根离子、碳酸根离子、硫酸根离子等；当取代基上阴离子与咪唑鎓阳离子形成内盐时，X-不存在。
作为本发明的一个实施方案，所述结构式中，
A环：选自无或一个或多个取代基的芳环；所述取代基为NO2；
R1：选自-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的芳基；
所述取代基选自-环烷基、-芳基、-ORa、-O-低级链烷基-ORa、-O-低级链烷基-O-低级链烷基-ORa、-ORa取代的芳基、-卤素取代的芳基、-CF3取代的芳基、-NO2取代的芳基、-NH2；其中，Ra为-氢原子、-芳基、-低级链烷基或芳基取代的低级链烷基；
R2：选自-无或一个或多个取代基的低级链烷基；
R3：选自-氢原子、-无或一个或多个取代基的低级链烷基、-环烷基、-芳基、-杂环基、-低级链烷基取代的芳基、-ORa和/或卤素取代的芳基、-杂芳基、-低级链烷基取代的杂芳基；
所述取代基为-杂芳基、-卤素、-低级链烷基取代的杂芳基；Ra为-低级链烷基；
R4：选自-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-环烷基、-无或一个或多个取代基的芳基；
所述取代基为-CN、低级链烷基、卤素、ORa取代的芳基、ORa、杂芳基、芳基、卤素取代的芳基、-CO2Ra、饱和杂环基、-O-低级链烷基-ORa；Ra为低级链烷基。
作为本发明的又一个实施方案，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-低级烷基，-低级炔基，-低级烯基、-低级链烷基-O-低级链烷基、-低级链烷基-O-芳基、-低级链烷基-O-低级链烷基-O-低级链烷基、-低级链烷基-O-低级链烷基-O-低级链烷基-O-低级链烷基、-芳基、-5到7元饱和杂环、-杂芳基；
R2：选自低级链烷基；
R3：选自-氢原子、-低级链烷基、-3到7元饱和环烷基、-杂环基、-芳基、-低级链烷基取代的芳基、-卤素取代的芳基、-杂芳基、-低级链烷基取代的杂芳基、-O-低级链烷基、-S-低级链烷基、-酰基、-低级烷基取代的酰基；
R4：选自-氢原子、-低级链烷基、-低级链烯基、-低级炔基、-芳基、-CN、-3到7元饱和环烷基、-卤素取代的芳基、-低级烷基取代的芳基、-杂芳基、-CO2Ra、-饱和杂环基、-低级链烷基-ORa、-低级链烷基-O-低级链烷基、-低级链烷基-S-低级链烷基、-低级链烷基-O-低级链烷基-ORa；Ra为-低级链烷基。
作为本发明的又一个实施方案，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-C1～C6的直链烷基或支链烷基、-苄基、-C4～C6的甲基环烷基、-C3～C6的烯基、-CH2(C6H5-m-Xm)(m＝1～5,X为卤素原子、NO2、氢原子或-OCnH2n+1，n＝1～6)、-CH2(C6H4-CHnX3-n)(n＝1～3,X为卤素原子)、-(CnH2n-O)y-CmH2m+1(n＝1～6、m＝1～6、y＝1～3)、-CnH2n-O-CmH2m-Ph(n＝1～6、m＝1～6)、-CnH2n-NH2(n＝1～6)或-CH2CH(-OCH2CH2O-)；
R2：选自低级链烷基；
R3：选自-氢原子、-C1～C6的直链烷基或支链烷基、-C4～C6的甲基环烷基、-杂芳基、-苯基或取代苯基；
R4：选自-C1～C6的直链烷基或支链烷基、-C3～C6的甲基环烷基、-低级亚烷基-0-低级烷基、-C3～C6的烯基、-苄基或取代苄基、-酯基或取代酯基、-苯基或取代苯基、-CH2(thienyl)或-CH2CH(-OCH2CH2O-)。
作为本发明的又一个实施方案，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-C1～C6的直链烷基或支链烷基、-苄基、-C4～C6的甲基环烷基、-C3～C6的烯基、-CH2(C6H5-m-Xm)(m＝1～5,X为卤素原子、NO2、氢原子或-O-CnH2n+1(n＝1～6)、-CH2(C6H4-CHnX3-n)(n＝1～3,X为卤素原子)、-(CnH2n-O)y-CmH2m+1(n＝1～6、m＝1～6、y＝1～3)、-CnH2n-O-CmH2m-Ph(n＝1～6、m＝1～6)、-CnH2n-NH2(n＝1～6)或-CH2CH(-OCH2CH2O-)；
R2：选自低级链烷基；
R3：选自-氢原子、-甲基、-苯基或取代苯基；
R4：选自-C1～C6的直链烷基或支链烷基；
X：选自Br、I、OMs、OTs。
作为本发明的又一个实施方案，所述衍生物包括,
(E)-或(Z)-4-(羟基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-乙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-丙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-丁基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-异丙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-异丁基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2-甲基丁基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-叔丁基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-环丙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2-甲氧基乙基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(3-甲基-2-烯-1-基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-苄基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2-乙氧基-2-氧乙基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-苯基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2,4,6-三甲基苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(噻吩-2-甲基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-((1,3-二氧杂环-2-基)甲基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(4-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(3-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(2-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(3-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(4-甲氧基苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(4-甲氧基苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(3-氯-4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-(3-溴-4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑-3-鎓、(E)-或(Z)-1-丁基-4-(甲氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-1-丁基-4-(乙氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-1-丁基-4-(苄氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-1-丁基-4-(甲氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-1-丁基-4-(甲氧基亚氨基)-3-乙基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(甲氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(乙氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(苄氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-3-乙基-4-(甲氧基亚氨基)-1-甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(异丙氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(丁氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(异丁氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(叔丁氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(环丙甲氧基亚氨基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((烯丙氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((4-甲氧基苄氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((4-苄氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((4-三氟甲基苄氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((4-氟苄氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-(全氟苄氧基亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((4-硝基苄氧基)亚胺基)-1，3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((2-甲氧基乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((2-(苄氧基)乙氧基)亚胺基))-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((2-(2-甲氧基乙氧基)乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((2-(2-(2-甲氧基乙氧基)乙氧基)乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚并[2,3-d]咪唑鎓、(E)-或(Z)-4-((苄氧基)亚胺基)-1-丁基-3-甲基-9-氧代-2-(3,4,5-三甲氧基苯基)-4,9-二氢-1H-萘酚[2,3-d]咪唑鎓等。
第二方面，本发明还涉及一种药物组合物，包括前述的一种或多种醌肟咪唑鎓衍生物和制药学上所容许的载体。
第三方面，本发明还涉及一种所述的药物组合物在制备抗癌、抗菌或抗病毒药物中的用途。
第四方面，本发明还涉及一种由下述通式(Ⅲ)和(Ⅳ)表示的(Z)或(E)稠合的醌肟咪唑衍生物及其盐酸盐；
其结构式如：
A环：选自无或有一个或多个取代基的芳环，或无或有一个或多个取代基的杂芳环；
R1、R3和R4：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；
上述A环和R1、R2、R3和R4中的取代基可以选自B组的基团；
B组：-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-ORa、-SRa、-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-NRaRb、-O-低级亚烷基-O-低级亚烷基-NRaRb、-O-低级亚烷基-NRc-低级亚烷基-NRaRb、-O-CO-NRaRb、-SORa、-SO2Ra、-SO2NRaRb、-NRa-SO2Rb、-NRaRb、-NRc-低级亚烷基-NRaRb、-N(-低级亚烷基-NRaRb)2、-NO2、-CN、-卤素、-CO2Ra、-COO-、-CONRaRb、-CONRa-O-Rb、-NRa-CORb、-NRa-CO-NRbRc、-OCORa和-CORa；
Ra、Rb和Rc：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；其中，取代基指低级烷基或杂烷基。
作为一个实施方案，所述结构式中，
A环：选自无或一个或多个取代基的芳环；所述取代基为NO2；
R1：选自-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基；
所述取代基选自-环烷基、-芳基、-ORa、-O-低级链烷基-ORa、-O-低级链烷基-O-低级链烷基-ORa、-ORa取代的芳基、-卤素取代的芳基、-CF3取代的芳基、-NO2取代的芳基、-NH2；其中，Ra为-氢原子、-芳基、-低级链烷基或芳基取代的低级链烷基；
R3：表示-氢原子、-无或一个或多个取代基的低级链烷基、-环烷基、-芳基、-低级链烷基取代的芳基、-ORa和/或卤素取代的芳基、-杂芳基；
所述取代基为-杂芳基、-卤素、-低级链烷基取代的杂芳基；Ra为-低级链烷基；
R4：表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-环烷基、-无或一个或多个取代基的芳基；
所述取代基为-CN、-低级链烷基、-卤素、-ORa取代的芳基、-ORa、-杂芳基、-芳基、-卤素取代的芳基、-CO2Ra、-饱和杂环基、-O-低级链烷基-ORa；Ra为-低级链烷基。
作为又一个实施方案，所述结构式中，
A环：选自无或一个或多个取代基的芳环；所述取代基为NO2；
R1：选自-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基；
所述取代基选自-环烷基、-芳基、-ORa、-O-低级链烷基-ORa、-O-低级链烷基-O-低级链烷基-ORa、-ORa取代的芳基、-卤素取代的芳基、-CF3取代的芳基、-NO2取代的芳基、-NH2；其中，Ra为-氢原子、-芳基、-低级链烷基或芳基取代的低级链烷基；
R3：表示-氢原子、-无或一个或多个取代基的低级链烷基、-环烷基、-芳基、-低级链烷基取代的芳基、-ORa和/或卤素取代的芳基、-杂芳基；
所述取代基为-杂芳基、-卤素、-低级链烷基取代的杂芳基；Ra为-低级链烷基；
R4：表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-环烷基、-无或一个或多个取代基的芳基；
所述取代基为-CN、-低级链烷基、-卤素、-ORa取代的芳基、-ORa、-杂芳基、-芳基、-卤素取代的芳基、-CO2Ra、-饱和杂环基、-O-低级链烷基-ORa；Ra为-低级链烷基。
作为本发明的又一个实施方案，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-C1～C6的直链烷基或支链烷基、-苄基、-C3～C6的甲基环烷基、-C3～C6的烯基、-CH2(C6H5-m-Xm)(X为卤素原子、NO2、氢原子或-O-CnH2n+1，n＝1～6)、-CH2(C6H4-CHnX3-n)(n＝1～3,X为卤素原子)、-(CnH2n-O)y-CmH2m+1(n＝1～6、m＝1～6、y＝1～3)、-CnH2n-O-CmH2m-Ph(n＝1～6、m＝1～6)或-CnH2n-NH2(n＝1～6)；
R3：选自-氢原子、-C1～C6的直链烷基或支链烷基、-苯基或取代苯基、-C4～C6的甲基环烷基、-杂芳基、-CHnX3-n(n＝1～3,X为卤素原子)、或-CH2CH2(2-CH3-furyl)；
R4：选自-C1～C6的直链烷基或支链烷基、-C3～C6的甲基环烷基、-低级亚烷基-0-低级烷基、-C3～C6的烯基、-炔基、-杂芳基、-苄基或取代苄基、-酯基或取代酯基、-苯基或取代苯基、-氰基、-CH2(thienyl)、-CH2CH(-OCH2CH2O-)或-CH2(pyrazinyl)。
作为本发明的又一个实施方案，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-C1～C6的直链烷基或支链烷基、-苄基、-C3～C6的甲基环烷基、-C3～C6的烯基、-CH2(C6H5-m-Xm)(X为卤素原子、NO2、氢原子或-O-CnH2n+1，n＝1～6)、-CH2(C6H4-CHnX3-n)(n＝1～3,X为卤素原子)、-(CnH2n-O)y-CmH2m+1(n＝1～6、m＝1～6、y＝1～3)、-CnH2n-O-CmH2m-Ph(n＝1～6、m＝1～6)或-CnH2n-NH2(n＝1～6)；
R3：选自-氢原子、-C1～C6的直链烷基或支链烷基；
R4：选自-C1～C6的直链烷基或支链烷基、-低级亚烷基-0-低级烷基、-C3～C6的烯基、-酯基或取代酯基、-苯基或取代苯基、-氰基。
作为本发明的又一个实施方案，所述衍生物包括(E)-9-(羟基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-乙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-异丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-异丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(2-甲基丁基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(4-甲氧基苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(2-甲氧基乙基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(3-甲基-2-烯-1-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(丙基-2-炔-1-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(噻吩-2-基甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-苄基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(2-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(3-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(4-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-2-(4-(羟基亚氨基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-1-基)乙酸酯、(E)-3-((1,3-二氧杂环-2-基)甲基)-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-11-(羟基亚氨基)-3-乙基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-3-环丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-叔丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(吡嗪-2-基甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-苄基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(2,4,6-三甲基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(2-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(3-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(4-甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(3-氯-4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-(3-溴-4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-3-甲基-8-硝基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-(羟基亚氨基)-2,3-二甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-11-(羟基亚氨基)-2,3-二甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-3-乙基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-3-异丁基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-11-(羟基亚氨基)-2-甲基-3-(3-甲基-2-烯-1-基)-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-2-(4-(羟基亚氨基)-2-甲基-11-氧代-4,11-二氢-1H-蒽[2,3-d]咪唑-1-基)乙腈、(E)-3-苄基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-3-(4-氟苄基)-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-乙基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-丙基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-2-(仲丁基)-3-丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-异丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(戊烷-3-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-叔丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(2-(5-甲基呋喃-2-基)乙基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-环丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-苯基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(4-异丙基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(3,4,5-三甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-2-(3-氯-4-甲氧基苯基)-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-萘基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(三氟甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(呋喃-2-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-3-丁基-9-(羟基亚氨基)-2-(噻吩-2-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-2-乙基-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-2-(呋喃-2-基)-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)和(Z)-9-(甲氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(乙氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(苄氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(异丙氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(异丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-(叔丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-((环丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-((烯丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((4-甲氧基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((4-氯苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((4-三氟甲基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((4-氟苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((全氟苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-甲基-9-(((4-硝基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-11-(苄氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)和(Z)-11-(丁氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)和(Z)-11-(叔丁氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)-9-((2-甲氧基乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-((2-(苄氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-((2-(2-甲氧基乙氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-((2-(2-(2-甲氧基乙氧基)乙氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)-9-((3-氨基丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-丁基-9-(甲氧基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-3-丁基-9-(乙氧基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-9-((苄氧基)亚胺基)-3-丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-11-((甲氧基)亚胺基)-3-(2-(2-甲氧基乙氧基)乙基)-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)和(Z)-9-((苄氧基)亚胺基)-2,3-二甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-11-((苄氧基)亚胺基)-2,3-二甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮、(E)和(Z)-9-((苄氧基)亚胺基)-3-丁基-2-(3,4,5-三甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮、(E)和(Z)-2-环丙基-11-(甲氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮。
通式(Ⅲ)和(Ⅳ)表示的(Z)或(E)稠合的醌肟咪唑衍生物及其盐酸盐是上述通式(Ⅰ)和(Ⅱ)的合成中间体，且其本身具有优良的抗肿瘤活性。因此，第五方面，本发明还涉及一种药物组合物，包括该化合物或其盐酸盐，和制药学上所容许的载体。其具有抗癌、抗菌和抗病毒作用。
第五方面，本发明涉及一种上述药物组合物在制备抗癌、抗菌或抗病毒药物中的用途。
下面将进一步描述通式(I)、(II)、(Ⅲ)和(Ⅳ)的化合物。
术语“低级”指有1-6个碳原子直链或者支链烃链。“低级烷基”一般为1-4个碳原子的烷基，特别佳的是甲基、乙基、丙基、异丙基、丁基和异丁基。“低级链烯基”一般为乙烯基、烯丙基、1-丙烯基、异丙烯基、1-丁烯基、2-丁烯基、3-丁烯基和3-甲基-2丁烯基。“低级炔基”一般为乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔基、3-丁炔基和1-甲基-2-丙炔基。“芳基”指芳香族基团，比较佳的是有6-14个碳原子的芳基，最佳的是苯基、萘基和芴基。另外，A环是指形成上述芳基的环，最佳的是苯基和萘基。“杂芳环”是指具有1-4个选自N、S、O中一种或多种的杂原子的5-6元的单环杂芳基，以及它们与苯环或5-6元单环杂芳基稠合而成的双环杂芳基。在这种情况下，5-6元单环杂芳基宜为呋喃基、噻吩基、吡咯基、咪唑基、噻唑基、吡唑基、异噻唑基、噁唑基、异噁唑基、噁二唑基、噻二唑基、三唑基、四唑基、吡啶基、嘧啶基、吡嗪基、哒嗪基和三嗪基，双环杂芳基宜为苯并呋喃基、苯并噻吩基、苯并噻二唑基、苯并噻唑基、苯并噁唑基、苯并噁二唑基、苯并咪唑基、吲哚基、异吲哚基、吲唑基、喹啉基、异喹啉基、喹唑啉基、喹喔啉基、苯并间二氧杂环戊烯基、中氮茚基、咪唑并吡啶基和噌啉基。部分饱和的杂芳基例如1,2,3,4-四氢喹啉基。更佳的是呋喃基、噻吩基。
“低级杂烷基”是指具有1-4个选自N、S和O杂原子中的一种或几种的1-4个碳原子的烷基。
“环烷基”是指3-10个碳原子的环烷基，特别佳的是环丙基、环丁基、环戊基和环己基。“环烯基”宜为3-8个碳原子的环烯基。
“抗衡阴离子”没有特别的限制，只要它作为咪唑鎓阳离子的抗阴离子是制药学上所容许的阴离子即可，较佳的是单价或二价阴离子如卤素离子，有机磺酸根离子、乙酸根离子、三氟乙酸根离子、碳酸根离子和硫酸根离子等，其中最佳的是卤素离子。
“杂环基”是指具有1-4个选自N、S和O的杂原子的5-7元单环饱和杂环或其桥环。较佳的是四氢吡喃基、四氢呋喃基、吡咯烷基、哌嗪基、氮杂环庚烷基、二氮杂环庚烷基、奎宁环基、哌啶基和吗啉基。
本发明的化合物由于阳离子的非定域作用而存在下式所示的互变异构体，本发明也包括分离的互变异构体或其混合物。因此，在本发明中，用1H-咪唑-3-鎓衍生物表示的化合物也包括3H-咪唑-1-鎓衍生物这一互变异构体和两个异构体的混合物。
另外，本发明的(Ⅲ)和(Ⅳ)的盐酸盐也包括在本发明内。
在一些情况下，根据取代基的种类不同，本发明的化合物(Ⅰ)、(Ⅱ)、(Ⅲ)和(Ⅳ)存在几何异构体和互变异构体。这些异构体的分离形式或其混合物均包括在本发明内。而且，由于本发明的化合物有不对称碳原子情况，因此存在给予该不对称碳原子的异构体；本发明包括这些光学异构体的混合和分离形式。另外在一些情况下，由于取代基的种类，本发明化合物形成了N-氧化物，这些物质也包括在本发明中；本发明还包括本发明化合物(Ⅰ)、(Ⅱ)、(Ⅲ)和(Ⅳ)的各种水合物、溶剂化物和多晶型物质。
第六方面，本发明还涉及一种前述的醌肟咪唑鎓衍生物及其合成中间体的制备方法，所述方法包括如下步骤：
A、以质子溶剂为溶剂，取代的醌咪唑衍生物和R1ONH2·HCl在弱碱的催化作用下或和相应的R1ONH2在弱碱盐酸盐的作用下发生肟化反应，得到醌肟咪唑衍生物/>
B、醌肟咪唑衍生物(III)或(IV)在有机溶剂中与相应的卤代物试剂R2X发生N-烷基化反应，得到醌肟咪唑鎓衍生物(Ⅰ)或(Ⅱ)。
优选的，步骤A中，
所述取代萘醌咪唑、取代氧氨盐酸盐R1ONH2·HCl和弱碱的摩尔比为1：1.2～5：0.001～0.01。
优选的，所述取代氧氨盐酸盐选自羟胺盐酸盐、甲氧基胺盐酸盐、苯氧基胺盐酸盐、苄氧基胺盐酸盐。
优选的，步骤A中，所述弱碱选自碳酸钾、三乙胺、吡啶等。
优选的，步骤A中，所述质子溶剂选自甲醇、乙醇、异丙醇。
优选的，步骤A中，反应温度为90～125℃，反应时间为12～48小时。
优选的，步骤B中，所述醌肟咪唑衍生物(III)或(IV)、卤代物试剂R2X的摩尔比为1:1～1:100。
优选的，步骤B中，所述卤代烃选自碘甲烷、碘乙烷等。
优选的，步骤B中，所述有机溶剂选自乙腈、乙酸乙酯、四氢呋喃等。
优选的，步骤B中，反应温度50～120℃，反应时间为8～48小时。
本发明的化合物(Ⅲ)和(Ⅳ)可作为广谱抗癌药以及抗菌和抗病毒药物，且毒性低安全性好。因此，本发明化合物对所有的实体肿瘤和淋巴瘤，尤其是乳腺癌、宫颈癌、非小细胞肺癌、直肠癌、肝癌、白血病、前列腺癌、卵巢癌、骨髓瘤、食管癌、胰腺癌、膀胱癌、黑色素瘤、胃癌等肿瘤具有增殖抑制作用。
本发明的药物组合物可用通式(Ⅲ)和(Ⅳ)中所示的一种或两种以上化合物以及本领域中常用的制药学上所容许的载体(药物载体、赋形剂等)通过常用方法制得。给药通过片剂、丸剂、胶囊剂、颗粒剂、散剂、液剂、吸入剂等经口给予，或通过静脉注射、肌内注射等注射剂、栓剂、滴眼剂、眼膏、经皮用液剂、软膏、经皮用贴剂、经粘膜液剂、经粘膜贴剂等非经口给药的任何一种形态给予均可。
作为用于本发明经口给药的固体组合物，可用片剂、散剂、颗粒剂等。在这些固体组合物中，将一种或多种活性物质与至少一种惰性赋形剂(如乳糖、甘露糖醇、葡萄糖、羟丙基纤维素、微晶纤维素、淀粉、聚乙烯吡咯烷酮、偏硅酸铝镁等)混合。根据通常的步骤，该化合物可含有惰性添加剂如润滑剂(硬脂酸镁等)和崩解剂(羧甲基淀粉钠等)和助溶剂。根据需要，片剂或丸剂可用糖衣或胃溶性或肠溶性包衣剂来包衣。
用于口服给药的液体组合物包括药剂学上所容许的乳剂、液剂、悬浮剂、糖浆剂、酏剂等，并含有常用的惰性溶剂如纯化水或乙醇。除惰性溶剂外，该组合物还可含有增溶剂。润湿剂、悬浮剂等助剂、增甜剂、调味剂、芳香剂和防腐剂。
用于非经口给药的注射剂含有无菌水性或水性溶剂、悬浮剂和乳剂。水溶性剂的例子包括注射用蒸馏水和生理盐水。非水溶性剂有丙二醇、聚乙二醇、橄榄油等植物油、乙醇等醇类、聚山梨酯80等。这些组合物还可含有等渗剂、防腐剂、润湿剂、乳化剂、分散剂、稳定剂和助溶剂。这些组合物例如通过除菌膜过滤、与杀菌剂混合或辐照等方式来杀菌。此外，可以制成无菌固体组合物，在使用前用无菌水或无菌注射用溶剂溶解或悬浮使用。
与现有技术相比，本发明具有如下有益效果：
1、本发明系统性的对醌并咪唑骨架进行修饰，得到了一系列结构新颖的醌肟咪唑衍生物、醌肟醌咪唑衍生物。
2、本发明采用探索的新制备方法，合成更简单，原料更加易得，成本低廉且适宜大规模制备。
具体实施方式
以下实施例将有助于本领域的技术人员进一步理解本发明，但不以任何形式限制本发明。应当指出的是，对本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干调整和改进。这些都属于本发明的保护范围。本发明化合物绝非局限于下面实施例中记载的化合物。下列实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。另外，在实施例中显示了本发明化合物的原料化合物的合成。
实施例1
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升甲酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘甲烷(0.2毫升)，反应2小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-甲基-1,4-萘醌咪唑(0.31克)。将2-甲基萘醌咪唑(0.21克)、羟胺盐酸盐(0.35克)、吡啶(0.8毫升)溶于乙醇(70毫升)，在90摄氏度下反应48小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.15克)，即化合物1。
化合物1：
(E)-9-(羟基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.26(d,J＝0.8Hz,2H),8.07(dd,J＝8.0,4.0Hz,1H),7.72-7.64(m,1H),7.61-7.52(m,1H),4.00(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.27,145.22,140.18,139.62,133.71,133.06,131.04,129.58,127.17,126.12,123.92,34.14.
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+228.0768,实测值：228.0771.
1,4-萘醌咪唑和不同取代的卤代烃反应，用实施例1的方法可制得化合物2-20，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物2：
(E)-3-乙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.04(s,1H),8.36(s,1H),8.26(d,J＝8.0Hz,1H),8.10(d,J＝8.0Hz,1H),7.72-7.64(m,1H),7.60(t,J＝7.2Hz,1H),4.46(q,J＝7.2Hz,2H),1.39(t,J＝8.0Hz,3H).
13C NMR(101MHz,DMSO-d6)δ174.94,144.31,140.21,140.08,133.66,133.06,131.10,129.59,126.48,126.22,123.91,42.17,16.64.
HRMS(ESI):m/z理论值：C13H11N3O2[M+H]+242.0924,实测值：242.0927.
化合物3：
(E)-3-丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
(E)-3-propyl-9-(hydroxyimino)-3,9-dihydro-4H-naphtho[2,3-d]imidazol-4-one
1H NMR(400MHz,DMSO-d6)δ13.05(s,1H),8.34(s,1H),8.26(d,J＝8.0Hz,1H),8.09(dd,J＝8.0,1.0Hz,1H),7.72-7.65(m,1H),7.59(td,J＝8.0,1.0Hz,1H),4.39(t,J＝8.0Hz,2H),1.85-1.72(m,2H),0.83(t,J＝7.4Hz,3H).
13C NMR(101MHz,DMSO-d6)δ174.99,144.84,140.20,140.05,133.64,133.05,131.11,129.58,126.57,126.21,123.89,48.30,23.97,11.02.
HRMS(ESI):m/z理论值：C14H13N3O2[M+H]+256.1081,实测值：256.1084.
化合物4：
(E)-3-丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
(E)-3-butyl-9-(hydroxyimino)-3,9-dihydro-4H-naphtho[2,3-d]imidazol-4-one
1H NMR(400MHz,DMSO-d6)δ13.05(s,1H),8.34(s,1H),8.26(dd,J＝8.0,1.2Hz,1H),8.09(dd,J＝8.0,1.2Hz,1H),7.67(td,J＝4.0,1.6Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),4.42(t,J＝8.0Hz,2H),1.81-1.66(m,2H),1.30-1.19(m,2H),0.86(t,J＝8.0Hz,3H).
13C NMR(101MHz,DMSO-d6)δ174.97,144.77,140.20,140.03,133.63,133.04,131.11,129.57,126.54,126.22,123.89,46.55,32.70,19.48,13.84.
HRMS(ESI):m/z理论值：C15H15N3O2[M+H]+270.1237,实测值：270.1240.
化合物5：
(E)-3-异丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1H NMR(400MHz,DMSO-d6)δ13.12(s,1H),8.52(s,1H),8.26(d,J＝8.0Hz,1H),8.11(dd,J＝8.0,1.6Hz,1H),7.73-7.63(m,1H),7.59(td,J＝8.0,1.2Hz,1H),5.39-5.25(m,1H),1.51(d,J＝8.0Hz,6H).
13C NMR(101MHz,DMSO-d6)δ174.95,141.88,140.23,140.16,133.33,133.04,131.27,129.61,126.36,126.16,123.78,49.64,23.06.
化合物6：
(E)-3-异丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1H NMR(400MHz,DMSO-d6)δ13.05(s,1H),8.33(s,1H),8.27(dd,J＝8.0,1.2Hz,1H),8.10(dd,J＝8.0,1.4Hz,1H),7.68(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),4.26(d,J＝8.0Hz,2H),2.17-2.02(m,1H),0.84(d,J＝4.0Hz,6H).
13C NMR(101MHz,DMSO-d6)δ175.08,145.17,140.19,140.03,133.64,133.07,131.13,129.59,126.69,126.22,123.90,53.53,29.52,19.75.
HRMS(ESI):m/z理论值：C15H15N3O2[M+H]+270.1237,实测值：270.1237.
化合物7：
(E)-9-(羟基亚氨基)-3-(2-甲基丁基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1HNMR(400MHz,DMSO-d6)δ13.05(s,1H),8.33(s,1H),8.27(dd,J＝8.0,1.2Hz,1H),8.10(dd,J＝8.0,1.4Hz,1H),7.71-7.64(m,1H),7.60(td,J＝8.0,1.2Hz,1H),4.43-4.35(m,1H),4.24-4.16(m,1H),1.99-1.83(m,1H),1.37-1.20(m,1H),1.17-1.07(m,1H),0.85(t,J＝8.0Hz,3H),0.77(d,J＝4.0Hz,3H).
13C NMR(101MHz,DMSO-d6)δ175.08,159.51,145.25,140.19,140.05,133.65,133.08,131.14,129.60,126.72,126.25,123.90,52.24,35.68,26.51,16.57,11.31.
HRMS(ESI):m/z理论值：C16H17N3O2[M+H]+284.1394,实测值：284.1390.
化合物8：
(E)-9-(羟基亚氨基)-3-(4-甲氧基苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1H NMR(400MHz,DMSO-d6)δ13.03(s,1H),8.48(s,1H),8.27(d,J＝8.0Hz,1H),8.09(dd,J＝8.0,1.2Hz,1H),7.68(td,J＝8.0,1.2Hz,1H),7.62-7.55(m,1H),7.28(d,J＝8.0Hz,2H),6.86(d,J＝8.0Hz,2H),5.62(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.10,159.52,159.38,144.87,140.11,133.77,133.14,131.03,129.59,129.50,129.35,126.36,126.22,123.96,114.49,55.52,49.10.
HRMS(ESI):m/z理论值：C19H15FN3O3[M+H]+334.1186,实测值：334.1182.
化合物9：
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(E)-9-(羟基亚氨基)-3-(2-甲氧基乙基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1H NMR(400MHz,DMSO-d6)δ13.04(s,1H),8.30-8.23(m,2H),8.09(dd,J＝8.0,1.4Hz,1H),7.68(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),4.61(t,J＝5.2Hz,2H),3.68(t,J＝4.0Hz,2H),3.20(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.16,145.37,140.16,139.96,133.69,133.09,131.05,129.57,126.48,126.20,123.93,70.72,58.48,46.46.
HRMS(ESI):m/z理论值：C14H13N3O3[M+H]+272.1030,实测值：272.1032.
化合物10：
(E)-9-(羟基亚氨基)-3-(3-甲基-2-烯-1-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.03(s,1H),8.32(s,1H),8.26(dd,J＝8.0,1.2Hz,1H),8.10(dd,J＝8.0,1.4Hz,1H),7.68(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),5.44-5.35(m,1H),5.06(d,J＝8.0Hz,2H),1.77(s,3H),1.67(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.05,144.24,140.17,139.91,137.77,133.66,133.07,131.08,129.58,126.45,126.23,123.92,119.76,44.64,25.77,18.42.
HRMS(ESI):m/z理论值：C16H15N3O2[M+H]+282.1237,实测值：282.1239.
化合物11：
(E)-9-(羟基亚氨基)-3-(丙基-2-炔-1-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.02(s,1H),8.41(s,1H),8.28(d,J＝8.0Hz,1H),8.11(d,J＝8.0Hz,1H),7.73-7.64(m,1H),7.64-7.54(m,1H),5.35(s,2H),3.53(s,1H).
13C NMR(101MHz,DMSO-d6)δ175.02,144.29,139.99,133.91,133.22,130.86,129.61,129.58,126.61,126.12,124.05,78.38,77.22,36.50.
HRMS(ESI):m/z理论值：C14H9N3O2[M+H]+252.0768,实测值：252.0769.
化合物12：
(E)-9-(羟基亚氨基)-3-(噻吩-2-基甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.49(s,1H),8.27(d,J＝8.0,1H),8.12(dd,J＝7.9,1.5Hz,1H),7.69(t,J＝8.0,1H),7.60(t,J＝8.0Hz,1H),7.43(d,J＝8.0Hz,1H),7.19(d,J＝4.0Hz,1H),6.95(dd,J＝8.0,4.0Hz,1H),5.88(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.20,144.72,140.04,139.91,139.42,133.87,133.20,130.93,129.60,127.89,127.49,127.25,126.19,126.18,124.02,44.36.
HRMS(ESI):m/z理论值：C16H11N3O2S[M+H]+310.0645,实测值：310.0642.
化合物13：
(E)-9-(羟基亚氨基)-3-苄基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.05(s,1H),8.51(s,1H),8.27(dd,J＝8.0,1.2Hz,1H),8.07(dd,J＝8.0,1.4Hz,1H),7.67(td,J＝8.0 1.4Hz,1H),7.57(td,J＝8.0,1.2Hz,1H),7.39-7.10(m,5H),5.70(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.08,145.10,140.10,140.06,137.44,133.81,133.14,130.98,129.56,129.12,128.25,127.72,126.48,126.18,123.97,49.58.
HRMS(ESI):m/z理论值：C18H13N3O2[M+H]+304.1081,实测值：304.1082.
化合物14：
(E)-9-(羟基亚氨基)-3-(2-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.04(s,1H),8.41(s,1H),8.31-8.22(m,1H),8.04(dd,J＝8.0,1.4Hz,1H),7.70-7.64(m,1H),7.62-7.54(m,1H),7.35-7.27(m,1H),7.25-7.18(m,1H),7.10(td,J＝7.5,1.2Hz,1H),7.04(td,J＝8.0,1.8Hz,1H),5.77(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.00,163.05(160.71,J＝234.0Hz),145.45,140.08,139.99,133.88,133.16,130.90,130.45(130.37,J＝8.0Hz),129.56,129.35(129.31,J＝4.0Hz),126.66,126.15,125.19(125.15,J＝4.0Hz),124.45(124.31,J＝14.0Hz),123.99,115.92(115.71,J＝21.0Hz),44.17(44.12,J＝5.0Hz).
HRMS(ESI):m/z理论值：C18H12FN3O2[M+H]+322.0986,实测值：322.0984.
化合物15：
(E)-9-(羟基亚氨基)-3-(3-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.51(s,1H),8.27(d,J＝8.0Hz,1H),8.07(d,J＝8.0Hz,1H),7.68(t,J＝8.0Hz,1H),7.58(t,J＝8.0Hz,1H),7.40-7.30(m,1H),7.17-7.06(m,3H),5.71(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.12,163.82(161.39,J＝243.0Hz),145.17,140.22(140.15,J＝7.0Hz),140.10,133.87,133.17,131.22(131.14,J＝8.0Hz),130.95,129.56,126.63,126.47,126.18,123.99,123.75(123.72,J＝3.0Hz),115.21(115.00,J＝21.0Hz),114.78(114.56,J＝22.0Hz),49.06(49.05,J＝1.0Hz).
化合物16：
(E)-9-(羟基亚氨基)-3-(4-氟苄基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.04(s,1H),8.51(s,1H),8.27(dd,J＝8.0,1.2Hz,1H),8.07(dd,J＝8.0,1.4Hz,1H),7.68(td,J＝8.0,1.4Hz,1H),7.58(td,J＝8.0,1.2Hz,1H),7.39-7.31(m,2H),7.18-7.07(m,2H),5.68(s,2H).
13C NMR(101MHz,DMSO-d6)δ175.11,163.34(160.91,J＝243.0Hz),145.01,140.13,140.09,133.83,133.65(133.62,J＝3.0Hz),133.15,130.96,130.15(130.07,J＝8.0Hz),129.56,126.40,126.19,123.97,116.03(115.81,J＝22.0Hz),48.87.
HRMS(ESI):m/z理论值：C18H12FN3O2[M+H]+322.0986,实测值：322.0986.
化合物17：
(E)-2-(4-(羟基亚氨基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-1-基)乙酸酯
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.31-8.25(m,2H),8.06(dd,J＝8.0,0.8Hz,1H),7.70(td,J＝8.0,1.2Hz,1H),7.60(td,J＝8.0,0.8Hz,1H),5.32(s,2H),4.15(q,J＝7.2Hz,2H),1.19(t,J＝7.2Hz,3H).
13C NMR(101MHz,DMSO-d6)δ175.27,168.10,145.42,134.05,133.27,130.71,129.61,127.16,126.61,126.05,124.13,61.78,48.16,14.47.
HRMS(ESI):m/z理论值：C15H13N3O4[M+H]+300.0979,实测值：300.0981.
化合物18：
(E)-3-((1,3-二氧杂环-2-基)甲基)-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.03(s,1H),8.30-8.20(m,2H),8.09(dd,J＝8.0,1.4Hz,1H),7.68(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),5.20(t,J＝4.0Hz,1H),4.67(d,J＝4.0Hz,2H),3.82-3.73(m,4H).
13C NMR(101MHz,DMSO-d6)δ175.26,145.49,140.06,139.55,133.72,133.12,131.03,129.58,126.88,126.19,123.95,101.10,65.05,48.12.
HRMS(ESI):m/z理论值：C15H13N3O4[M+H]+300.0979,实测值：300.0978.
化合物19：
(E)-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.09(s,1H),9.04(s,1H),8.77(d,J＝12.4Hz,2H),8.15(dd,J＝26.4,7.7Hz,2H),7.64(d,J＝20.0Hz,2H),4.03(s,3H).
HRMS(ESI):m/z理论值：C15H13N3O4[M+H]+278.0924,实测值：278.0922.
化合物20：
(E)-11-(羟基亚氨基)-3-乙基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.89(s,1H),8.93(s,1H),8.84(s,2H),8.21(dd,J＝22.4,8.2Hz,2H),7.82-7.64(m,2H),4.60(d,J＝7.8Hz,2H),1.41(t,J＝8.0Hz,3H).
HRMS(ESI):m/z理论值：C15H13N3O4[M+H]+292.1081,实测值：292.1078.
实施例2
将2,2'-(1,4-二氧基-1,4,6,7-四氢萘-2,3-二基)双(异吲哚啉-1,3-二酮)(13.3克)溶于200毫升二氯甲烷和20毫升甲醇里面，加入环丙基胺，反应2小时后除去溶剂，加100毫升水打浆10分钟后抽滤，得红色固体(10克)。直接把10克固体加入150毫升乙醇中，滴入8毫升水合肼(80％)，室温搅拌半小时候除去有机相，加入200毫升水打浆10分钟，过滤水洗至无色，真空干燥得蓝色固体2-氨基-3-环丙基-6,7-二氢萘-1,4-二酮(6.2克)。将2-氨基-3-环丙基-6,7-二氢萘-1,4-二酮(1克)在原甲酸价值(25毫升)中回流2.5小时，除去溶剂，用硅胶色谱柱分离的白色固体1-环丙基-6,7-二氢-1H-萘酚[2,3-d]咪唑-4,9-二酮(0.46克)。将3-环丙基萘醌咪唑(0.21克)、羟胺盐酸盐(0.35克)、吡啶(0.8毫升)溶于乙醇(70毫升)，在100摄氏度下反应36小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.15克)。
用实施例2的方法可制得化合物21：
化合物21：
(E)-3-环丙基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.00(s,1H),8.31(s,1H),8.25(dd,J＝8.0,1.2Hz,1H),8.11(dd,J＝8.0,1.4Hz,1H),7.67(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),3.93-3.86(m,1H),1.13-1.03(m,4H).
13C NMR(101MHz,DMSO-d6)δ174.50,143.32,140.18,139.97,133.46,132.97,131.25,129.58,128.36,126.23,123.86,29.61,7.44.
HRMS(ESI):m/z理论值：C14H11N3O2[M+H]+254.0924,实测值：254.0927.
实施例3
将氮-(3-氯-1,4-二氧-1,4,6,7-四氢萘-2-基)乙酰胺(0.25克)溶于20毫升四氢呋喃里面，反应液中依次加入三乙胺和叔丁基胺，氮气保护下回流反应26小时，冷却到室温后除去溶剂加入10毫升超纯水，打浆半小时得到氮-(3-(叔丁胺基)-1,4-二氧基-1,4,6,7-四氢萘-2-基)乙酰胺。将其分散在85毫升水合肼中(50％)，80摄氏度反应两小时，用二氯甲烷萃取，收集有机相，用饱和食盐水洗涤之后无水硫酸钠干燥，过滤，浓缩，硅胶层析柱分离的产物2-氨基-3-(叔丁胺基)-6,7-二氢萘-1,4-二酮。在2-氨基-3-(叔丁胺基)-6,7-二氢萘-1,4-二酮(1.63克)中加入50毫升原甲酸三乙酯，回流反应3小时后，冷却到室温，除去溶剂，用硅胶色谱柱分离纯化得到产物3-叔丁基萘醌咪唑。将3-叔丁基萘醌咪唑(0.21克)、羟胺盐酸盐(0.17克)、吡啶(0.4毫升)溶于乙醇(50毫升)，在110摄氏度下反应24小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.16克)。
加入不同取代的胺，用实施例3的方法可制得化合物22-32，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物22：
(E)-3-叔丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.55(s,1H),8.49(s,1H),8.23(d,J＝8.0Hz,1H),8.17(d,J＝7.4Hz,1H),7.68(t,J＝8.0Hz,1H),7.60(t,J＝8.0Hz,1H),1.72(s,9H).
13C NMR(101MHz,DMSO-d6)δ173.70,142.87,142.71,140.17,132.99,132.43,131.66,129.80,127.11,127.08,123.26,59.59,29.32.
HRMS(ESI):m/z理论值：C15H15N3O2[M+H]+270.1237,实测值：270.1241.
化合物23：
(E)-9-(羟基亚氨基)-3-(吡嗪-2-基甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.06(s,1H),8.71(s,1H),8.59-8.41(m,3H),8.27(d,J＝8.0Hz,1H),7.99(d,J＝8.0Hz,1H),7.72-7.51(m,2H),5.87(s,2H).
13C NMR(101MHz,DMSO-d6)δ174.99,151.72,145.78,144.60,144.34,143.98,140.12,139.84,133.89,133.16,130.80,129.55,126.79,126.08,124.01,49.11.
HRMS(ESI):m/z理论值：C16H11N5O2[M+H]+306.0986,实测值：306.0985.
化合物24：
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(E)-9-(羟基亚氨基)-3-苄基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.10(s,1H),8.47(s,1H),8.30(dd,J＝8.0,1.2Hz,1H),8.02(dd,J＝8.0,1.4Hz,1H),7.69(td,J＝8.0,1.4Hz,1H),7.63-7.48(m,6H).
13C NMR(101MHz,DMSO-d6)δ174.10,145.03,140.19,140.10,135.90,133.66,133.07,131.24,129.59,129.36,129.31,127.14,126.57,126.27,123.91.
HRMS(ESI):m/z理论值：C17H11N3O2[M+H]+290.0924,实测值：290.0922.
化合物25：
(E)-9-(羟基亚氨基)-3-(2,4,6-三甲基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.09(s,1H),8.35-8.26(m,2H),8.00-7.95(m,1H),7.73-7.65(m,1H),7.62-7.54(m,1H),7.03(s,2H),3.34(s,9H).
13C NMR(101MHz,DMSO-d6)δ174.25,144.93,140.19,139.83,138.97,135.02,133.96,133.14,132.50,130.95,129.58,129.12,127.34,126.10,124.05,21.06,17.48.
HRMS(ESI):m/z理论值：C20H17N3O2[M+H]+322.1394,实测值：322.1392.
化合物26：
(E)-9-(羟基亚氨基)-3-(2-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.09(s,1H),8.50(s,1H),8.32(dd,J＝8.0,1.2Hz,1H),8.01(dd,J＝8.0,1.4Hz,1H),7.75-7.65(m,2H),7.64-7.56(m,2H),7.51-7.44(m,1H),7.38(td,J＝8.0,1.2Hz,1H).
13C NMR(101MHz,DMSO-d6)δ174.23,158.18(155.70,J＝248.0Hz),145.23,139.94(139.68,J＝26.0Hz),133.93,133.26,131.86(131.78,J＝8.0Hz),130.84,129.64,129.18,127.94,127.80,126.10,125.33(125.29,J＝4.0Hz),124.21,124.10,116.75(116.55,J＝20.0Hz).
HRMS(ESI):m/z理论值：C17H10FN3O2[M+H]+308.0830,实测值：308.0831.
化合物27：
(E)-9-(羟基亚氨基)-3-(3-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.08(s,1H),8.49(s,1H),8.30(dd,J＝8.0,1.2Hz,1H),8.03(dd,J＝8.0,1.4Hz,1H),7.70(td,J＝8.0,1.4Hz,1H),7.62-7.54(m,3H),7.48-7.43(m,1H),7.42-7.35(m,1H).
13C NMR(101MHz,DMSO-d6)δ174.15,163.26(160.83,J＝243.0Hz),145.03,140.17(140.02,J＝15.0Hz),137.30,137.19,133.70,133.11,131.17,130.96(130.87,J＝9.0Hz),129.58,127.19,126.28,123.92,122.87(122.84,J＝3.0Hz),116.42(116.21,J＝21.0Hz),114.56(114.31,J＝25.0Hz).
HRMS(ESI):m/z理论值：C17H10FN3O2[M+H]+308.0830,实测值：308.0832.
化合物28：
(E)-9-(羟基亚氨基)-3-(4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.07(s,1H),8.45(s,1H),8.32-8.27(m,1H),8.02(dd,J＝8.0,1.4Hz,1H),7.72-7.62(m,3H),7.61-7.55(m,1H),7.41-7.35(m,2H).
13C NMR(101MHz,DMSO-d6)δ174.18,163.67(161.22,J＝245.0Hz),145.09,140.08,133.72,133.10,132.30(132.27,J＝3.0Hz),131.19,129.59,128.95(128.86,J＝9.0Hz),127.28,126.60,126.24,123.93,116.22(115.99,J＝23.0Hz).
HRMS(ESI):m/z理论值：C17H10FN3O2[M+H]+308.0830,实测值：308.0829.
化合物29：
(E)-9-(羟基亚氨基)-3-(4-甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.07(s,1H),8.40(s,1H),8.32-8.28(m,1H),8.02(dd,J＝8.0,1.4Hz,1H),7.70(td,J＝8.0,1.4Hz,1H),7.59(td,J＝8.0,1.2Hz,1H),7.51-7.47(m,2H),7.08-7.04(m,2H),3.82(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.10,159.95,159.53,145.06,140.16,133.63,133.05,131.28,129.59,128.73,127.82,127.23,126.25,123.90,114.40,56.00.
HRMS(ESI):m/z理论值：C18H13FN3O3[M+H]+320.1030,实测值：320.1026.
化合物30：
(E)-9-(羟基亚氨基)-3-(3-氯-4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.13(s,1H),8.52(s,1H),8.30(dd,J＝8.0,1.2Hz,1H),8.05-7.97(m,2H),7.72-7.64(m,2H),7.62-7.55(m,2H).
13C NMR(101MHz,DMSO-d6)δ174.25,158.99(156.52,J＝247.0Hz),145.02,139.91,133.71,133.19,132.90(132.87,J＝3.0Hz),131.06,129.61,129.20,127.83,127.75,127.28,126.26,123.95,120.02(119.83,J＝19.0Hz),117.46(117.24J＝22.0Hz).
HRMS(ESI):m/z理论值：C17H9ClFN3O2[M+H]+342.0440,实测值：342.0438.
化合物31：
(E)-9-(羟基亚氨基)-3-(3-溴-4-氟苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.06(s,1H),8.47(s,1H),8.30(dd,J＝8.0,1.2Hz,1H),8.10-8.00(m,2H),7.72–7.66(m,2H),7.61-7.53(m,2H).
13C NMR(101MHz,DMSO-d6)δ174.27,159.55,145.12,140.03(139.98,J＝5.0Hz),133.77,133.16,133.15,131.83,131.11,129.59,128.45,128.37,127.34,126.25,123.96,117.20(116.96,J＝24.0Hz),108.33(108.11,J＝22.0Hz).
HRMS(ESI):m/z理论值：C17H9BrFN3O2[M+H]+385.9935,实测值：385.9930.
化合物32：
(E)-9-(羟基亚氨基)-3-甲基-8-硝基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ14.67(s,1H),9.66(s,1H),8.37(d,J＝7.8Hz,1H),8.25(d,J＝7.9Hz,1H),8.09(t,J＝7.8Hz,1H),4.14(s,3H).
HRMS(ESI):m/z理论值：C17H9BrFN3O2[M+H]+273.0619,实测值：273.0620.
实施例4
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升乙酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘甲烷(0.2毫升)，反应2小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-甲基-1,4-萘醌咪唑(0.31克)。将2-甲基萘醌咪唑(0.2克)、羟胺盐酸盐(0.28克)、吡啶(0.7毫升)溶于乙醇(70毫升)，在105摄氏度下反应36小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.16克)。
将2,3,-二氨-1,4-萘醌(20克)溶于100毫升乙酸里面回流反应6小时，得到蒽醌咪唑，或者加入不同取代的卤代烃反应，用实施例4的方法可制得化合物33-41，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物33：
(E)-9-(羟基亚氨基)-2,3-二甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.26(d,J＝0.8Hz,2H),8.07(dd,J＝8.0,4.0Hz,1H),7.72-7.64(m,1H),7.61-7.52(m,1H),4.00(s,3H),2.81(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.27,145.22,140.18,139.62,133.71,133.06,131.04,129.58,127.17,126.12,123.92,34.14,20.1.
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+241.0851,实测值：241.0854.
化合物34：
(E)-3-丁基-9-(羟基亚氨基)-2-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.14(s,1H),8.27(d,J＝7.9Hz,1H),8.12(dd,J＝7.8,1.5Hz,1H),7.73–7.65(m,1H),7.65–7.57(m,1H),4.41(d,J＝15.1Hz,2H),1.73–1.65(m,2H),1.32(q,J＝7.4Hz,2H),0.90(t,J＝7.3Hz,3H).
化合物35：
(E)-11-(羟基亚氨基)-2,3-二甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.09(s,1H),8.77(d,J＝12.4Hz,2H),8.15(dd,J＝26.4,7.8Hz,2H),7.64(d,J＝20.0Hz,2H),4.03(s,3H),2.54(s,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+292.1081,实测值：292.1082.
化合物36：
(E)-3-乙基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮1HNMR(400MHz,DMSO-d6)δ13.87(s,1H),8.84(s,2H),8.21(dd,J＝22.4,8.2Hz,2H),7.82-7.64(m,2H),4.60(d,J＝7.8Hz,2H),2.79(s,3H),1.40(d,J＝8.0Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+306.1237,实测值：306.1240.
化合物37：
(E)-3-异丁基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.90(s,1H),8.84(s,2H),8.20(dd,J＝15.0,8.4Hz,2H),7.81-7.58(m,2H),4.41(d,J＝7.0Hz,2H),2.78(s,3H),2.22-2.14(m,1H),0.95(d,J＝6.8Hz,6H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+344.1550,实测值：344.1554.
化合物38：
(E)-11-(羟基亚氨基)-2-甲基-3-(3-甲基-2-烯-1-基)-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.44(s,1H),8.81(s,2H),8.24-8.13(m,2H),7.74-7.66(m,2H),5.30-5.22(m,2H),5.14-5.10(m,1H),2.65(s,3H),1.84(s,3H),1.70(s,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+346.1550,实测值：346.1555.
化合物39：
(E)-2-(4-(羟基亚氨基)-2-甲基-11-氧代-4,11-二氢-1H-蒽[2,3-d]咪唑-1-基)乙腈
1H NMR(400MHz,DMSO-d6)δ13.46(s,1H),8.69(s,2H),8.26(s,2H),7.76(d,J＝6.4Hz,2H),5.70(s,2H),2.59(s,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+317.1033,实测值：317.1035.
化合物40：
(E)-3-苄基-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.78(d,J＝33.2Hz,2H),8.15(dd,J＝16.8,7.8Hz,2H),7.65(d,J＝19.9Hz,2H),7.43-7.12(m,5H),5.83(s,2H),2.65(s,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+368.1394,实测值：368.1395.
化合物41：
(E)-3-(4-氟苄基)-11-(羟基亚氨基)-2-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.50(s,1H),8.81(d,J＝16.8Hz,2H),8.24–8.13(m,2H),7.75–7.60(m,2H),7.16(d,J＝8.8Hz,4H),5.86(s,2H),2.62(s,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+386.1300,实测值：386.1327.
实施例5
将2,3,-二氨-1,4-苯醌(4克)溶于13毫升二甲基亚砜里面，加入丁醛(2.12毫升)，80摄氏度下敞口反应13小时，冷却到室温后缓慢加入水，析出固体抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(0.15克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘丁烷(0.2毫升)，反应2小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-甲基-1,4-萘醌咪唑(0.31克)。将2-甲基萘醌咪唑(0.2克)、羟胺盐酸盐(0.11克)、吡啶(0.35毫升)溶于乙醇(35毫升)，在105摄氏度下反应36小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.15克)。
将2,3,-二氨-1,4-苯醌(4克)溶于13毫升二甲基亚砜里面与不同的醛反应；或者将2,3,-二氨-1,4-萘醌(20克)溶于二甲基亚砜与不同醛反应；或者加入不同取代的卤代烃反应，用实施例5的方法可制得化合物42-59，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物42：
(E)-3-丁基-9-(羟基亚氨基)-2-乙基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.26(s,1H),8.25(d,J＝7.9Hz,1H),8.10(d,J＝8.0Hz,1H),7.75–7.65(m,1H),7.60(t,J＝7.5Hz,1H),4.38(t,J＝7.5Hz,2H),2.86(q,J＝7.5Hz,2H),1.67(ddd,J＝12.6,10.2,6.5Hz,2H),1.31(td,J＝7.5,3.7Hz,5H),0.89(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+298.1550,实测值：298.1557.
化合物43：
(E)-3-丁基-9-(羟基亚氨基)-2-丙基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.95(s,1H),8.42(d,J＝7.8Hz,1H),8.28–8.21(m,1H),7.65(t,J＝7.3Hz,1H),7.59–7.55(m,1H),4.46(t,J＝7.6Hz,2H),2.80(t,J＝7.6Hz,2H),1.93(h,J＝7.7Hz,2H),1.79(q,J＝7.7Hz,2H),1.44(q,J＝7.6Hz,2H),1.08(t,J＝7.4Hz,3H),0.99(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+312.1707,实测值：312.1709.
化合物44：
(E)-2-(仲丁基)-3-丁基-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.32(s,1H),8.26(d,J＝8.0Hz,1H),8.13(d,J＝7.8Hz,1H),7.70(t,J＝7.7Hz,1H),7.62(t,J＝7.5Hz,1H),4.52-4.40(m,2H),3.08(q,J＝6.8Hz,1H),1.80(dt,J＝14.0,7.4Hz,1H),1.67(q,J＝7.3Hz,3H),1.39–1.32(m,2H),1.28(d,J＝6.8Hz,3H),0.90(t,J＝7.4Hz,3H),0.83(t,J＝7.2Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+326.1863,实测值：326.1865.
化合物45：
(E)-3-丁基-9-(羟基亚氨基)-2-异丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1HNMR(400MHz,Chloroform-d)δ13.91(s,1H),8.38(d,J＝7.8Hz,1H),8.21(d,J＝7.8Hz,1H),7.62(t,J＝7.6Hz,1H),7.54(t,J＝7.6Hz,1H),4.44(t,J＝7.8Hz,2H),2.68(d,J＝7.0Hz,2H),2.32(dp,J＝13.8,6.8Hz,1H),1.78(p,J＝7.6Hz,2H),1.44(p,J＝7.4Hz,2H),1.11–0.91(m,9H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+326.1863,实测值：326.1862.
化合物46：
(E)-3-丁基-9-(羟基亚氨基)-2-(戊烷-3-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ14.05(s,1H),8.44(dd,J＝8.0,1.2Hz,1H),8.29–8.20(m,1H),7.67(td,J＝7.6,1.6Hz,1H),7.59(td,J＝7.6,1.4Hz,1H),4.57–4.46(m,2H),2.79(tt,J＝8.4,5.6Hz,1H),1.92–1.80(m,6H),1.49(h,J＝7.4Hz,2H),1.02(t,J＝7.4Hz,3H),0.90(t,J＝7.4Hz,6H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+340.2020,实测值：340.2025.
化合物47：
(E)-3-丁基-9-(羟基亚氨基)-2-叔丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1HNMR(400MHz,Chloroform-d)δ14.09(s,1H),8.40(d,J＝7.8Hz,1H),8.25(d,J＝7.8Hz,1H),7.64(t,J＝7.2Hz,1H),7.56(t,J＝7.8Hz,1H),4.62-4.49(m,2H),1.95-1.85(m,2H),1.60-1.53(m,11H),1.03(t,J＝7.2Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+326.1863,实测值：326.1864.
化合物48：
(E)-3-丁基-9-(羟基亚氨基)-2-(2-(5-甲基呋喃-2-基)乙基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.87(s,1H),8.42(d,J＝7.8Hz,1H),8.24(d,J＝7.8Hz,1H),7.67–7.62(m,1H),7.60–7.53(m,1H),5.91(d,J＝3.0Hz,1H),5.88–5.81(m,1H),4.38(t,J＝7.6Hz,2H),3.24–3.07(m,3H),2.25(s,3H),1.90-1.83(m,1H),1.78-1.67(m,2H),1.41(q,J＝7.6Hz,2H),0.97(t,J＝7.2Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+378.1812,实测值：378.1813.
化合物49：
(E)-3-丁基-9-(羟基亚氨基)-2-环丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1HNMR(400MHz,Chloroform-d)δ14.08(s,1H),8.42(d,J＝7.8Hz,1H),8.29–8.19(m,1H),7.65(td,J＝8.2,7.8,1.6Hz,1H),7.60–7.51(m,1H),4.44–4.28(m,2H),3.68(q,J＝8.5Hz,1H),2.62–2.52(m,2H),2.44(q,J＝8.9Hz,2H),2.17(q,J＝9.5Hz,1H),2.09-2.04(m,1H),1.76(p,J＝7.8Hz,2H),1.48-1.35(m,2H),0.98(t,J＝7.3Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+324.1707,实测值：324.1709.
化合物50：
(E)-3-丁基-9-(羟基亚氨基)-2-苯基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.92(s,1H),8.46(d,J＝7.8Hz,1H),8.29(d,J＝7.8Hz,1H),7.69(d,J＝7.4Hz,2H),7.63-7.58(m,5H),4.58(t,J＝7.8Hz,2H),1.86(q,J＝7.6Hz,2H),1.37–1.31(m,2H),0.89(t,J＝7.2Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+346.1550,实测值：346.1554.
化合物51：
(E)-3-丁基-9-(羟基亚氨基)-2-(4-异丙基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.96(s,1H),8.44(d,J＝7.8Hz,1H),8.28(dd,J＝78,1.6Hz,1H),7.93–7.54(m,4H),7.52–7.31(m,2H),4.57(t,J＝7.8Hz,2H),1.92-1.83(m,2H),1.42-1.25(m,8H),0.90(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+388.2020,实测值：388.2024.
化合物52：
(E)-3-丁基-9-(羟基亚氨基)-2-(3,4,5-三甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.85(s,1H),8.45(d,J＝7.8Hz,1H),8.29(d,J＝7.8Hz,1H),7.68(t,J＝8.0Hz,1H),7.60(t,J＝7.4Hz,1H),6.88(s,2H),4.63–4.52(m,2H),3.94(s,9H),1.92-1.86(m,2H),1.40-1.34(m,2H),0.93(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+436.1867,实测值：436.1868.
化合物53：
(E)-3-丁基-2-(3-氯-4-甲氧基苯基)-9-(羟基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.10(s,1H),8.30(d,J＝8.0Hz,1H),8.16(d,J＝7.6Hz,1H),7.81(s,1H),7.70(d,J＝8.4Hz,2H),7.64(d,J＝7.6Hz,1H),7.34(d,J＝8.5Hz,1H),4.48(t,J＝8.4Hz,2H),3.94(s,3H),1.72-1.67(m,2H),1.19-1.12(m,2H),0.76(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+410.1266,实测值：410.1266.
化合物54:
(E)-3-丁基-9-(羟基亚氨基)-2-萘基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.83(s,1H),8.50(dd,J＝7.8,1.2Hz,1H),8.34(dd,J＝7.8,1.6Hz,1H),8.12(dd,J＝7.2,2.2Hz,1H),8.01(dd,J＝8.0,1.8Hz,1H),7.78–7.51(m,7H),4.38(t,J＝7.4Hz,2H),1.67(p,J＝7.6Hz,2H),1.13(h,J＝7.4Hz,2H),0.69(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+396.1707,实测值：396.1709.
化合物55：
(E)-3-丁基-9-(羟基亚氨基)-2-(三氟甲基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ12.85(s,1H),8.41(dd,J＝8.0,1.2Hz,1H),8.24(dd,J＝7.8,1.6Hz,1H),7.69(td,J＝7.8,1.6Hz,1H),7.59(td,J＝7.6,1.2Hz,1H),4.72–4.54(m,2H),1.88(p,J＝8.0Hz,2H),1.50(h,J＝7.4Hz,2H),1.01(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+338.1111,实测值：338.1115.
化合物56：
(E)-3-丁基-9-(羟基亚氨基)-2-(呋喃-2-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.80(s,1H),8.43(d,J＝8.0Hz,1H),8.28(d,J＝7.8Hz,1H),7.66(d,J＝10.2Hz,2H),7.61–7.55(m,1H),7.24(d,J＝4.8Hz,1H),4.96–4.89(m,2H),1.89(q,J＝7.6Hz,2H),1.47(q,J＝7.6Hz,2H),0.99(t,J＝7.2Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+336.1343,实测值：336.1344.
化合物57：
(E)-3-丁基-9-(羟基亚氨基)-2-(噻吩-2-基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,Chloroform-d)δ13.78(s,1H),8.44(d,J＝8.0Hz,1H),8.34–8.13(m,1H),7.70–7.52(m,4H),7.24(s,1H),4.82–4.71(m,2H),1.95(p,J＝8.2Hz,2H),1.53–1.45(m,2H),1.01(t,J＝7.4Hz,3H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+352.1114,实测值：352.1116.
化合物58：
(E)-2-乙基-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮1HNMR(400MHz,DMSO-d6)δ13.71(s,1H),8.60(d,J＝5.6Hz,2H),8.21-8.15(m,2H),7.71-7.65(m,2H),2.76(q,J＝7.6Hz,2H),1.27(t,J＝7.6Hz,2H),4.09(s,1H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+306.1237,实测值：306.1236.
化合物59：
(E)-2-(呋喃-2-基)-11-(羟基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ13.85(s,1H),8.69(s,2H),8.27-8.22(m,2H),7.95(d,J＝1.2Hz,1H),7.76-7.70(m,2H),7.35(d,J＝3.4Hz,1H),6.75-6.70(m,1H),4.25(s,1H).
HRMS(ESI):m/z理论值：C12H9N3O2[M+H]+344.1030,实测值：344.1031.
实施例6
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升甲酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘甲烷(0.2毫升)，反应2小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-甲基-1,4-萘醌咪唑(0.31克)。将2-甲基萘醌咪唑(0.2克)、甲氧基胺盐酸盐(0.1克)、吡啶(0.08毫升)溶于乙醇(30毫升)，在125摄氏度下反应12小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(0.15克)。
将2,3,-二氨-1,4-萘醌(20克)溶于100毫升甲酸里面回流反应6小时得到蒽醌咪唑，使用不同取代的胺氧盐酸盐，用实施例6的方法可制得化合物60-77，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物60：
(E)和(Z)-9-(甲氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.99(dd,J＝8.0,1.2Hz,1H),8.31-8.20(m,4H),8.16-8.07(m,2H),7.82-7.60(m,5H),4.24(s,3H),4.20(s,4H),4.03(s,4H),3.99(s,3H).
13C NMR(101MHz,DMSO)δ175.40,174.52,145.91,145.85,145.58,140.34,139.95,139.03,133.69,133.20,133.12,132.39,131.62,131.20,131.09,129.94,128.10,128.03,127.04,126.43,126.16,124.33,64.73,64.47,34.20,33.92.
HRMS(ESI):m/z理论值：C13H11N3O2[M+H]+242.0924,实测值：242.0928.
化合物61：
(E)和(Z)-9-(乙氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮1HNMR(400MHz,DMSO-d6)δ9.04(dd,J＝8.0,1.2Hz,1H),8.30(dd,J＝8.0,1.2Hz,2H),8.26-8.20(m,3H),8.14-8.07(m,3H),7.79(td,J＝8.0,1.6Hz,1H),7.75-7.68(m,3H),7.63(td,J＝8.0,1.2Hz,2H),4.53-4.42(m,6H),4.04(s,6H),4.00(s,3H),1.46-1.32(m,9H).
13C NMR(101MHz,DMSO)δ175.42,174.53,146.10,145.90,145.64,140.16,139.75,139.33,133.66,133.50,133.04,132.38,131.51,131.07,129.79,128.08,128.04,127.00,126.37,126.10,124.33,124.09,72.72,72.20,34.16,33.90,15.29,15.04.
HRMS(ESI):m/z理论值：C14H13N3O2[M+H]+256.1081,实测值：256.1085.
化合物62：
(E)和(Z)-9-(苄氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.30-8.22(m,2H),8.11(dd,J＝8.0,1.2Hz,1H),7.71(td,J＝8.0,1.6Hz,1H),7.64(td,J＝8.0,1.2Hz,1H),7.55-7.49(m,2H),7.45-7.31(m,3H),5.50(s,2H),4.03(s,3H).
化合物63：
(E)和(Z)-9-(异丙氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.07(dd,J＝8.0,1.2Hz,1H),8.33(dd,J＝8.0,1.2Hz,1H),8.28-8.21(m,2H),8.16-8.10(m,2H),7.80(td,J＝8.0,1.6Hz,1H),7.72(td,J＝8.0,1.4Hz,2H),7.63(td,J＝8.0,1.2Hz,1H),4.72-4.60(m,2H),4.04(s,3H),4.00(s,3H),1.43(dd,J＝12.0,8.0Hz,12H).
13C NMR(101MHz,DMSO)δ175.44,174.53,146.27,145.91,145.69,139.80,139.47,139.28,133.77,133.66,133.03,132.39,131.42,131.07,130.99,129.68,128.14,128.00,127.00,126.32,126.07,124.33,79.35,78.63,34.16,33.91,22.10,21.97.
HRMS(ESI):m/z理论值：C15H15N3O2[M+H]+270.1237,实测值：270.1238.
化合物64：
(E)和(Z)-9-(丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.03(dd,J＝8.0,1.2Hz,2H),8.30(dd,J＝8.0,1.2Hz,1H),8.28-8.21(m,4H),8.14(s,3H),7.87-7.78(m,3H),7.76-7.69(m,3H),7.64(td,J＝8.0,1.2Hz,1H),4.48-4.38(m,7H),4.04(s,3H),4.00(s,7H),1.85-1.72(m,7H),1.53-1.39(m,7H),1.00-0.92(m,10H).
13C NMR(101MHz,DMSO)δ175.45,174.54,146.12,145.96,145.75,140.23,139.79,139.45,133.74,133.53,133.09,132.41,131.42,131.14,129.82,128.11,128.07,127.07,126.92,126.40,126.14,124.34,76.88,76.36,34.17,33.92,31.53,31.20,19.23,19.08,14.25,14.23.
HRMS(ESI):m/z理论值：C16H17N3O2[M+H]+284.1394,实测值：284.1398.
化合物65：
(E)和(Z)-9-(异丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.04(dd,J＝8.1,1.2Hz,1H),8.33-8.23(m,4H),8.15-8.09(m,3H),7.82(td,J＝8.0,1.6Hz,1H),7.75-7.69(m,2H),7.64(td,J＝8.0,1.2Hz,2H),4.25(d,J＝8.0Hz,2H),4.21(d,J＝8.0Hz,3H),4.04(s,5H),4.00(s,3H),2.20-2.09(m,3H),1.01(t,J＝6.0Hz,16H).
13C NMR(101MHz,DMSO)δ175.44,174.52,146.10,145.95,145.77,140.24,139.84,139.48,133.73,133.50,133.07,132.42,131.34,131.14,131.10,129.80,128.08,127.09,126.40,126.13,124.32,83.43,82.87,34.16,33.92,28.50,28.21,19.45,19.42.
HRMS(ESI):m/z理论值：C16H17N3O2[M+H]+284.1394,实测值：284.1397.
化合物66：
(E)和(Z)-9-(叔丁氧基亚氨基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.10(dd,J＝8.0,1.2Hz,1H),8.38(dd,J＝8.0,1.2Hz,1H),8.27-8.21(m,2H),8.15-8.10(m,2H),7.83-7.60(m,5H),4.05(s,3H),4.01(s,4H),1.50(s,12H),1.48(s,9H).
13C NMR(101MHz,DMSO)δ175.47,174.56,146.58,145.91,145.70,139.61,139.39,138.81,134.17,133.61,133.01,132.40,131.32,131.05,130.83,129.52,128.22,127.95,126.95,126.23,126.02,124.29,82.90,82.08,34.15,33.90,28.02,27.74.
HRMS(ESI):m/z理论值：C16H17N3O2[M+H]+284.1394,实测值：284.1393.
化合物67：
(E)和(Z)-9-((环丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.10(dd,J＝8.0,1.2Hz,1H),8.33-8.24(m,4H),8.16-8.09(m,3H),7.84-7.77(m,1H),7.75-7.70(m,2H),7.64(td,J＝8.0,1.2Hz,2H),4.32-4.24(m,5H),4.04(s,5H),4.00(s,3H),1.36-1.26(m,3H),0.65-0.55(m,6H),0.48-0.35(m,5H).
13C NMR(101MHz,DMSO)δ175.45,174.54,146.15,145.95,145.72,140.08,139.62,139.41,133.69,133.58,133.07,132.40,131.50,131.11,131.09,129.77,128.17,128.06,127.04,126.39,126.12,124.35,81.62,80.98,34.16,33.91,11.04,10.65,3.64,3.59.
HRMS(ESI):m/z理论值：C16H15N3O2[M+H]+282.1237,实测值：282.1238.
化合物68：
(E)和(Z)-9-((烯丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.03(dd,J＝8.0,1.2Hz,1H),8.30-8.21(m,6H),8.15-8.08(m,4H),7.80(td,J＝8.0,1.6Hz,1H),7.77-7.65(m,4H),7.64(td,J＝8.0,1.2Hz,3H),6.22-6.08(m,4H),5.55-5.40(m,4H),5.36-5.27(m,4H),5.00-4.92(m,7H),4.04(s,8H),3.99(s,3H).
13C NMR(101MHz,DMSO)δ175.43,174.51,145.94,145.72,140.65,140.24,139.31,135.14,134.58,134.13,133.71,133.34,133.09,132.42,131.59,131.22,131.12,129.93,128.15,128.05,127.08,126.48,126.15,124.37,119.04,118.54,77.72,77.22,34.16,33.92.
HRMS(ESI):m/z理论值：C15H13N3O2[M+H]+268.1081,实测值：268.1083.
化合物69：
(E)和(Z)-3-甲基-9-(((4-甲氧基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.05-8.98(m,1H),8.34-8.27(m,3H),8.27-8.20(m,4H),8.15-8.09(m,4H),7.76-7.61(m,8H),7.49-7.43(m,8H),6.99-6.93(m,8H),5.44(s,2H),5.41(s,6H),4.03(s,9H),3.99(s,3H),3.76(s,3H),3.75(s,9H).
13C NMR(101MHz,DMSO)δ175.43,174.52,159.81,159.60,145.98,145.75,140.52,140.16,139.34,133.72,133.41,133.13,132.42,131.50,131.19,131.13,130.65,130.54,129.93,129.82,129.17,128.15,128.09,127.08,126.48,126.16,124.38,114.40,114.24,78.57,78.04,55.58,55.55,34.16,33.92.
HRMS(ESI):m/z理论值：C20H17N3O3[M+H]+348.1343,实测值：348.1339.
化合物70：
(E)和(Z)-3-甲基-9-(((4-氯苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.03(dd,J＝8.0,1.2Hz,1H),8.28-8.22(m,5H),8.14-8.08(m,3H),7.82-7.60(m,7H),7.57-7.43(m,13H),5.51(s,2H),5.49(s,4H),4.03(s,6H),3.99(s,3H).
13C NMR(101MHz,DMSO)δ175.42,174.50,145.97,145.80,140.99,140.68,139.26,137.10,136.54,133.77,133.30,133.21,133.16,132.98,132.47,131.63,131.33,131.31,131.16,130.52,130.32,130.06,129.03,128.87,128.27,128.03,127.13,126.55,126.20,124.40,77.67,77.17,34.17,33.92.
HRMS(ESI):m/z理论值：C19H14ClN3O2[M+H]+352.0847,实测值：352.0843.
化合物71：
(E)和(Z)-3-甲基-9-(((4-三氟甲基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
yellow solid,100mg,％yield,m.p.136-138℃.
1H NMR(400MHz,DMSO-d6)δ9.07(dd,J＝8.0,1.2Hz,1H),8.28-8.21(m,4H),8.14-8.07(m,3H),7.82-7.60(m,17H),5.63(s,2H),5.60(s,3H),4.04(s,5H),3.99(s,3H).
13C NMR(101MHz,DMSO)δ175.40,174.48,145.95,145.80,145.73,142.98,142.48,141.24,140.95,139.23,133.78,133.15,133.11,132.48,131.70,131.35,131.16,130.09,128.94,128.74,128.62,128.31,128.00,127.13,126.57,126.19,126.07,125.95,125.91,125.87,125.83,125.79,125.76,125.72,125.68,124.39,123.37,77.49,77.04,34.17,33.90.
HRMS(ESI):m/z理论值：C20H14F3N3O2[M+H]+386.1111,实测值：386.1107.
化合物72：
(E)和(Z)-3-甲基-9-(((4-氟苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.03(dd,J＝8.0,1.4Hz,1H),8.33-8.20(m,5H),8.18-8.09(m,3H),7.79-7.53(m,12H),7.30-7.17(m,7H),5.50(s,2H),5.48(s,3H),4.03(s,5H),3.99(s,3H).
13C NMR(101MHz,DMSO)δ175.43,174.51,163.71,163.54,161.12,145.98,145.88,145.79,140.85,140.53,139.28,134.26,134.23,133.76,133.72,133.69,133.27,133.16,132.46,131.59,131.28,131.16,131.06,130.98,130.84,130.76,130.03,129.51,128.24,128.04,127.12,126.54,126.19,124.40,115.96,115.79,115.75,115.57,77.83,77.35,34.17,33.92.
HRMS(ESI):m/z理论值：C19H14FN3O2[M+H]+336.1143,实测值：336.1140.
化合物73：
(E)和(Z)-3-甲基-9-(((全氟苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
yellow solid,100mg,％yield,m.p.224-226℃.
1H NMR(400MHz,DMSO-d6)δ8.92(dd,J＝8.0,1.2Hz,1H),8.26-8.07(m,7H),7.83-7.71(m,4H),7.65(td,J＝8.0,1.2Hz,2H),5.61(s,2H),5.53(s,3H),4.02(s,5H),3.98(s,3H).
13C NMR(101MHz,DMSO)δ175.39,174.49,146.06,145.82,145.43,144.63,141.75,141.24,138.94,133.86,133.81,133.32,132.90,132.55,131.67,131.67,131.59,131.23,130.34,130.11,128.49,128.46,127.93,127.87,127.20,126.26,124.69,124.25,65.48,64.75,34.17,33.93.
HRMS(ESI):m/z理论值：C19H10F5N3O2[M+H]+408.0766,实测值：408.0767.
化合物74：
(E)和(Z)-3-甲基-9-(((4-硝基苄基)氧基)亚胺基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.09(dd,J＝8.0,1.2Hz,1H),8.31-8.17(m,14H),8.13-8.09(m,3H),7.84-7.62(m,15H),5.67(s,2H),5.65(s,5H),4.08-4.02(m,8H),3.99-3.97(m,3H).
13C NMR(101MHz,DMSO)δ175.42,174.50,147.64,147.47,146.09,145.97,145.85,145.66,145.55,141.45,141.20,139.20,133.85,133.21,133.02,132.51,131.79,131.46,131.18,130.20,129.18,128.95,128.37,127.98,127.19,126.62,126.24,124.43,124.15,124.03,77.09,76.65,34.20,33.93.
HRMS(ESI):m/z理论值：C19H14N4O4[M+H]+363.1088,实测值：363.1084.
化合物75：
(E)和(Z)-11-(苄氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.67(s,1H),8.79(d,J＝6.8Hz,2H),8.73(s,1H),8.27(s,1H),8.23–8.08(m,6H),8.00–7.95(m,1H),7.73–7.55(m,11H),7.46–7.33(m,8H),5.57(s,2H),5.53(s,3H),4.06(s,5H),4.01(s,3H).
HRMS(ESI):m/z理论值：C19H14N4O4[M+H]+368.1394,实测值：368.1397.
化合物76：
(E)和(Z)-11-(丁氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),8.75(d,J＝2.1Hz,2H),8.69(s,1H),8.24(s,1H),8.21–8.09(m,5H),8.02–7.98(m,1H),7.73–7.59(m,5H),4.45(dt,J＝20.6,6.6Hz,5H),4.05(s,3H),4.01(s,4H),1.90-1.75(m,5H),1.57-1.45(m,5H),1.05-0.96(m,7H).
HRMS(ESI):m/z理论值：C19H14N4O4[M+H]+334.2210,实测值：334.2214.
化合物77：
(E)和(Z)-11-(叔丁氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.70(s,1H),8.87(s,1H),8.81(s,1H),8.74(s,1H),8.28–8.13(m,5H),8.07–8.02(m,1H),7.75–7.60(m,4H),4.08(s,3H),4.04(s,3H),1.55(s,9H),1.52(s,9H).
HRMS(ESI):m/z理论值：C19H14N4O4[M+H]+334.2210,实测值：334.2213.
实施例7
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升甲酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘甲烷(0.2毫升)，反应2小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-甲基-1,4-萘醌咪唑(0.31克)。将2-甲基萘醌咪唑(0.2克)、羟胺盐酸盐(0.3克)、吡啶(0.7毫升)溶于乙醇(70毫升)，在105摄氏度下反应36小时，反应结束溶液中析出固体，直接抽滤，真空烘干得到淡黄色固体(E)-9-(羟基亚氨基)-3-甲基-3,6,7,9-四氢-4H-萘酚[2,3-d]咪唑-4-酮(0.15克)。将106毫克的肟化产物加入到2毫升二甲基亚砜溶液中，再依次加入56微升溴甲基乙基醚和104毫克氢氧化钾，室温下反应两小时。反应完全加水淬灭，二氯甲烷萃取，饱和食盐水洗涤有机相，无水硫酸镁干燥，浓缩之后硅胶色谱柱分离。
将肟化产物和不同取代的卤代烃反应，用实施例7的方法可制得化合物78-82，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物78：
(E)-9-((2-甲氧基乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.34-8.24(m,2H),8.16-8.09(m,1H),7.76-7.70(m,1H),7.65(td,J＝8.0,1.2Hz,1H),4.53(t,J＝4.0Hz,2H),4.04(s,3H),3.76(t,J＝4.0Hz,2H),3.32(s,3H).
13C NMR(101MHz,DMSO)δ175.46,145.74,140.04,139.32,133.40,133.14,131.13,129.95,128.15,126.17,124.43,76.07,70.75,58.76,34.18.
HRMS(ESI):m/z理论值：C15H15N3O3[M+H]+286.1186,实测值：286.1188.
化合物79：
(E)和(Z)-9-((2-(苄氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.30-8.25(m,2H),8.15-8.10(m,1H),7.75-7.61(m,2H),7.38-7.31(m,2H),7.30-7.21(m,3H),4.63-4.54(m,4H),4.04(s,3H),3.89-3.82(m,2H).
13C NMR(101MHz,DMSO-d6)δ175.45,145.72,140.12,139.36,138.95,133.39,133.08,131.13,129.92,128.60,128.15,127.86,127.74,126.14,124.43,76.28,72.40,68.47,34.18.
HRMS(ESI):m/z理论值：C21H19N3O3[M+H]+362.1499,实测值：362.1495.
化合物80：
(E)-9-((2-(2-甲氧基乙氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.31(dd,J＝8.0,1.2Hz,1H),8.24(s,1H),8.13(dd,J＝8.0,1.6Hz,1H),7.72(td,J＝8.0,1.6Hz,1H),7.65(td,J＝8.0,1.4Hz,1H),4.55-4.49(m,2H),4.04(s,3H),3.86-3.80(m,2H),3.64-3.59(m,2H),3.46-3.42(m,2H),3.22(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.45,145.72,140.07,139.31,133.40,133.13,131.13,129.95,128.15,126.16,124.45,76.25,71.78,70.26,69.26,58.52,34.18.
HRMS(ESI):m/z理论值：C17H19N3O4[M+H]+330.1448,实测值：330.1447.
化合物81：
(E)和(Z)-9-((2-(2-(2-甲氧基乙氧基)乙氧基)乙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.30(dd,J＝8.0,1.2Hz,1H),8.23(s,1H),8.14-8.10(m,1H),7.74-7.69(m,1H),7.65(td,J＝8.0,1.2Hz,1H),4.55-4.51(m,2H),4.04(s,3H),3.87-3.82(m,2H),3.65-3.59(m,2H),3.54-3.47(m,4H),3.39-3.35(m,2H),3.19(s,3H).
13C NMR(101MHz,DMSO-d6)δ175.44,145.70,140.04,139.29,133.39,133.11,131.10,129.93,128.12,126.14,124.43,76.23,71.70,70.48,70.24,70.03,69.26,58.46,34.16.
HRMS(ESI):m/z理论值：C19H23N3O5[M+H]+374.1710,实测值：374.1709.
化合物82：
(E)-9-((3-氨基丙氧基)亚胺基)-3-甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.30-8.25(m,2H),8.15-8.10(m,1H),7.75-7.61(m,2H),4.04(s,3H)，3.51(t,J＝8.0Hz,2H),2.68(t,J＝8.0Hz,2H),1.79-1.70(m,2H)。
HRMS(ESI):m/z理论值：C19H23N3O5[M+H]+285.1346,实测值：285.1347.
实施例8
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升甲酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘丁烷(0.18毫升)，反应5小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-丁基-1,4-萘醌咪唑(0.31克)。将2-丁基萘醌咪唑(0.21克)、甲氧基胺盐酸盐(0.3克)、吡啶(0.7毫升)溶于乙醇(70毫升)，在105摄氏度下反应36小时，反应结束后浓缩，硅胶色谱柱分离得到淡黄色产物(0.18克)。
将2,3,-二氨-1,4-萘醌(20克)溶于100毫升甲酸里面回流反应6小时得到蒽醌咪唑，使用不同取代的卤代烃，或者使用不同取代的胺氧盐酸盐，用实施例8的方法可制得化合物83-86，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物83：
(E)和(Z)-3-丁基-9-(甲氧基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.00(dd,J＝8.0,1.2Hz,1H),8.34-8.21(m,4H),8.13(dd,J＝8.0,1.4Hz,1H),7.82-7.62(m,4H),4.46(t,J＝7.2Hz,2H),4.40(t,J＝7.0Hz,2H),4.24(s,3H),4.21(s,3H),1.84-1.72(m,4H),1.37-1.18(m,4H),0.91(t,J＝8.0Hz,6H).
13C NMR(101MHz,DMSO)δ175.14,174.26,146.33,145.50,145.23,140.43,140.02,139.65,133.69,133.17,133.10,132.43,131.59,131.20,131.15,129.93,127.94,127.51,127.14,126.25,125.85,124.31,64.75,64.49,46.53,46.39,32.75,19.52,19.50,13.88.
HRMS(ESI):m/z理论值：C16H17N3O2[M+H]+284.1394,实测值：284.1394.
化合物84：
(E)和(Z)-3-丁基-9-(乙氧基亚氨基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.06(d,J＝8.0Hz,1H),8.37-8.19(m,6H),8.14(d,J＝8.0Hz,2H),7.83-7.61(m,6H),4.55-4.36(m,11H),1.82-1.72(m,6H),1.46-1.38(m,9H),1.35-1.20(m,7H),0.91(t,J＝8.0Hz,9H).
13C NMR(101MHz,DMSO)δ175.16,174.27,146.52,145.50,145.27,140.23,139.77,133.69,133.43,133.07,132.42,131.50,131.13,129.82,128.00,127.43,127.13,126.21,125.79,124.31,72.74,72.25,46.52,46.38,32.78,19.52,19.50,15.29,15.06,13.89.
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+298.1550,实测值：298.1549.
化合物85：
(E)和(Z)-9-((苄氧基)亚胺基)-3-丁基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.06(dd,J＝8.0,1.2Hz,1H),8.36-8.24(m,6H),8.22(s,1H),8.13(dd,J＝8.0,1.6Hz,2H),7.81-7.69(m,4H),7.65(dd,J＝8.0,1.4Hz,2H),7.63-7.59(m,1H),7.56-7.49(m,6H),7.45-7.31(m,16H),5.53(s,2H),5.50(s,5H),4.45(t,J＝7.2Hz,5H),4.39(t,J＝7.1Hz,2H),1.82-1.72(m,7H),1.34-1.22(m,7H),0.90(td,J＝8.0,1.0Hz,11H).
化合物86：
(E)和(Z)-11-((甲氧基)亚胺基)-3-(2-(2-甲氧基乙氧基)乙基)-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.55(s,2H),8.74(d,J＝9.3Hz,3H),8.69(s,1H),8.63(s,1H),8.59(s,1H),8.25–8.04(m,12H),7.75–7.63(m,7H),4.58(dq,J＝16.0,5.2Hz,7H),4.25(s,5H),4.18(s,3H),3.83-3.75(m,7H),3.55-3.10(m,7H),3.14–3.12(m,8H).
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+380.1605,实测值：380.1609.
实施例9
将2,3,-二氨-1,4-苯醌(20克)溶于100毫升乙酸里面，回流反应6小时，冷却到室温后倒入到冰水混合物中，加氨水调节pH到9-10，抽滤，真空干燥后得到黄色固体1,4-萘醌咪唑(22克)。在二甲基亚砜溶液(3毫升)依次加入1,4萘醌咪唑(0.3克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘丁烷(0.18毫升)，反应5小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体2-丁基-1,4-萘醌咪唑(0.31克)。将2-丁基萘醌咪唑(0.21克)、甲氧基胺盐酸盐(0.3克)、吡啶(0.7毫升)溶于乙醇(70毫升)，在105摄氏度下反应36小时，反应结束后浓缩，硅胶色谱柱分离得到淡黄色产物(0.16克)。
将2,3,-二氨-1,4-萘醌(20克)溶于100毫升甲酸里面回流反应6小时得到蒽醌咪唑，用实施例9的方法可制得化合物87-88，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物87：
(E)和(Z)-9-((苄氧基)亚胺基)-2,3-二甲基-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.99(dd,J＝8.0,1.4Hz,1H),8.22-8.16(m,4H),8.05(dd,J＝7.8,1.6Hz,3H),7.73–7.68(m,1H),7.66–7.62(m,3H),7.58(td,J＝7.6,1.4Hz,3H),7.51–7.45(m,7H),7.39–7.31(m,8H),7.31–7.26(m,3H),5.48(s,2H),5.46(s,5H),3.93(s,8H),3.87(s,3H),2.45(s,8H),2.40(s,3H).
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+332.1394,实测值：332.1398.
化合物88：
(E)和(Z)-11-((苄氧基)亚胺基)-2,3-二甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.69(d,J＝10.2Hz,2H),8.13(d,J＝8.2Hz,1H),8.05(d,J＝8.0Hz,1H),7.69–7.52(m,2H),7.39–7.31(m,3H),5.59(s,2H),4.03(s,3H),2.72(s,3H).
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+382.1550,实测值：382.1558.
实施例10
将2,3,-二氨-1,4-苯醌(4克)溶于13毫升二甲基亚砜里面，加入3,4,5-三甲氧基苯甲醛(2.5毫升)，80摄氏度下敞口反应13小时，冷却到室温后缓慢加入水，析出固体抽滤，真空干燥后得到黄色固体2-(3,4,5-三甲氧基苯基)-1,4-萘醌咪唑(0.15克)。在二甲基亚砜溶液(3毫升)依次加入萘醌咪唑(0.4克)、氢氧化钾(0.15克)，混合物在50摄氏度下搅拌30分钟，加入碘丁烷(0.17毫升)，反应5小时后加水析出固体，抽滤水洗，真空干燥得到黄色固体1-丁基-2-(3,4,5-三甲氧基苯基)-1,4-萘醌咪唑(0.35克)。将萘醌咪唑(0.42克)、苄氧基胺盐酸盐(0.64克)、吡啶(0.7毫升)溶于乙醇(70毫升)，在105摄氏度下反应36小时，反应结束后浓缩，硅胶色谱柱分离得到淡黄色产物(0.36克)。
将2,3,-二氨-1,4-萘醌(4克)溶于13毫升二甲基亚砜里面，与不同的醛反应，或者使用不同取代的胺氧盐酸盐，用实施例10的方法可制得化合物89-90，其他化合物用料和反应条件均不变，原料均可市场购得：
化合:89：
(E)和(Z)-9-((苄氧基)亚胺基)-3-丁基-2-(3,4,5-三甲氧基苯基)-3,9-二氢-4H-萘酚[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ9.04(d,J＝8.0Hz,1H),8.27(t,J＝7.0Hz,2H),8.13(dd,J＝7.8,1.6Hz,2H),7.72(dt,J＝15.2,7.4Hz,3H),7.63(t,J＝7.6Hz,2H),7.57–7.50(m,3H),7.47(d,J＝7.4Hz,2H),7.40-7.18(m,14H),6.98(s,3H),6.95(s,2H),5.52(s,2H),5.48(s,3H),4.53(s,3H),4.47(t,J＝7.4Hz,3H),4.41(t,J＝7.6Hz,2H),3.82(s,4H),3.80(s,7H),3.72(d,J＝1.2Hz,5H),1.70-1.65(m,5H),1.21–1.15(m,5H),0.85-0.70(m,7H).
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+526.2337,实测值：526.2337.
化合物90：
(E)和(Z)-2-环丙基-11-(甲氧基亚氨基)-3-甲基-3,11-二氢-4H-蒽醌[2,3-d]咪唑-4-酮
1H NMR(400MHz,DMSO-d6)δ8.55(s,2H),8.18-8.12(m,2H),7.73-7.60(m,2H),2.15-2.01(m,1H),1.12-0.97(m,4H),4.05(s,3H),3.84(s,3H).
HRMS(ESI):m/z理论值：C17H19N3O2[M+H]+332.1394,实测值：332.1395.
实施例11
化合物1(0.05毫摩尔)在3毫升乙腈中加入31微升碘甲烷在120摄氏度下反应24小时。反应完全之后去除溶剂得到黄色固体，打浆半小时之后抽滤得到最终产物。
使用上述不同的合成中间体化合物，用实施例11的方法可制得化合物91-118，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物91：
(E)-1-甲基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.50(s,1H),9.57(s,1H),9.25(dd,J＝10.0,0.5Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),8.01-7.93(m,1H),7.85(td,J＝5.0,1.5Hz,1H),4.19(s,3H),4.10(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.28,143.85,138.38,135.34,135.31,131.90,131.49,130.83,127.34,127.16,125.39,38.98,36.41.
HRMS(ESI-TOF)m/z理论值：C13H12N3O2[M-I]+,242.0924,实测值：242.0928.
化合物92：
(E)-1-乙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.49(s,1H),9.67(s,1H),9.26(dd,J＝10.0,1.0Hz,1H),8.34(dd,J＝10.0,1.0Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.85(td,J＝10.0,1.0Hz,1H),4.63(q,J＝7.5Hz,2H),4.11(s,3H),1.53(t,J＝5.0Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.01,143.12,138.52,135.86,135.28,131.83,131.37,130.85,127.39,127.03,124.77,44.93,39.09,15.42.
HRMS(ESI-TOF)m/z理论值：C14H14N3O2[M-I]+,256.1081,实测值：256.1078.
化合物93：
(E)-4-(羟基亚氨基)-3-甲基-9-氧代-1-丙基-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.51(s,1H),9.67(s,1H),9.25(dd,J＝10.0,1.0Hz,1H),8.34(dd,J＝10.0,1.5Hz,1H),8.00-7.93(m,1H),7.85(td,J＝10.0,1.0Hz,1H),4.57(t,J＝7.0Hz,2H),4.11(s,3H),1.96-1.85(m,2H),0.96(t,J＝7.5Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.09,143.40,138.51,135.95,135.29,131.88,131.43,130.91,127.42,127.08,124.84,50.68,39.17,23.13,10.92.
HRMS(ESI-TOF)m/z理论值：C15H16N3O2[M-I]+,270.1237,实测值：270.1244.
化合物94：
(E)-1-丁基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.50(s,1H),9.67(s,1H),9.25(dd,J＝10.0,0.5Hz,1H),8.34(dd,J＝10.0,1.5Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.85(td,J＝10.0,1.5Hz,1H),4.60(t,J＝7.0Hz,2H),4.10(s,3H),1.91-1.85(m,2H),1.44-1.33(m,2H),0.95(t,J＝7.5Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.06,143.37,138.52,135.93,135.28,131.85,131.40,130.89,127.42,127.06,124.80,49.00,39.16,31.69,19.28,13.86.
HRMS(ESI-TOF)m/z理论值：C16H18N3O2[M-I]+,284.1394,实测值：284.1393.:
化合物95：
(E)-4-(羟基亚氨基)-1-异丙基-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.50(s,1H),9.81(s,1H),9.24(dd,J＝8.0,1.2Hz,1H),8.35(dd,J＝8.0,1.6Hz,1H),8.04-7.90(m,1H),7.85(td,J＝8.0,1.2Hz,1H),5.49-5.40(m,1H),4.11(s,3H),1.61(d,J＝8.0Hz,6H).
13C NMR(101MHz,DMSO-d6)δ174.04,141.76,138.52,135.96,135.23,131.88,131.36,131.04,127.51,126.85,124.69,52.90,39.23,22.54.
HRMS(ESI-TOF)m/z理论值：C15H16N3O2[M-I]+,270.12374,实测值：270.1237.:
化合物96：
(E)-4-(羟基亚氨基)-1-异丁基-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.51(s,1H),9.68(s,1H),9.25(dd,J＝10.0,0.5Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),7.99-7.93(m,1H),7.85(td,J＝10.0,1.0Hz,1H),4.44(d,J＝10.0Hz,2H),4.12(s,3H),2.27-2.10(m,1H),0.98(d,J＝5.0Hz,6H).
13C NMR(126MHz,DMSO-d6)δ174.14,143.52,138.52,136.06,135.31,131.87,131.41,130.92,127.42,127.08,124.84,55.59,39.26,29.14,19.66.
HRMS(ESI-TOF)m/z理论值：C16H18N3O2[M-I]+,284.1394,实测值：284.1387.:
化合物97：
(E)-4-(羟基亚氨基)-3-甲基-1-(2-甲基丁基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.50(s,1H),9.69(s,1H),9.25(dd,J＝8.0,0.8Hz,1H),8.33(dd,J＝8.0,1.4Hz,1H),8.01-7.91(m,1H),7.84(td,J＝8.0,1.2Hz,1H),4.56(dd,J＝12.0,4.0Hz,1H),4.42-4.35(m,1H),4.12(s,3H),2.07-1.90(m,1H),1.53-1.40(m,1H),1.33-1.19(m,1H),1.00-0.87(m,6H).
13C NMR(101MHz,DMSO-d6)δ174.12,143.58,138.52,136.06,135.29,131.86,131.40,130.91,127.43,127.07,124.87,54.38,39.27,35.19,26.25,16.46,11.30.
HRMS(ESI-TOF)m/z理论值：C17H20N3O2[M-I]+,298.1550,实测值：298.1551.
化合物98：
(E)-1-(叔丁基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.50(s,1H),9.67(s,1H),9.19(dd,J＝8.0,1.2Hz,1H),8.38(dd,J＝8.0,1.4Hz,1H),7.98-7.91(m,1H),7.89-7.79(m,1H),4.11(s,3H),1.81(s,9H).
13C NMR(101MHz,DMSO-d6)δ173.08,142.92,138.84,138.42,134.98,131.90,131.45,130.93,1210.06,126.24,126.02,63.89,36.40,28.72.
HRMS(ESI-TOF)m/z理论值：C16H18N3O2[M-I]+,284.1394,实测值：284.1395.
化合物99：
(E)-1-环丙基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.48(s,1H),9.73(s,1H),9.31-9.16(m,1H),8.35(dd,J＝10.0,1.5Hz,1H),7.96(td,J＝10.0,1.0Hz,1H),7.86(td,J＝10.0,1.0Hz,1H),4.16-4.05(m,1H),4.06(s,3H),1.31-1.18(m,4H).
13C NMR(126MHz,DMSO-d6)δ173.42,143.46,138.43,135.56,135.19,131.93,131.43,131.00,127.40,126.93,126.42,39.02,31.83,7.48.
HRMS(ESI-TOF)m/z理论值：C15H14N3O2[M-I]+,268.1081,实测值：268.1081.
化合物100：
(E)-4-(羟基亚氨基)-1-(2-甲氧基乙基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.51(s,1H),9.65(s,1H),9.25(d,J＝10.0,1H),8.33(dd,J＝10.0,1.5Hz,1H),7.97(td,J＝10.0,1.5Hz,1H),7.85(td,J＝10.0,1.0Hz,1H),4.81(t,J＝5.0Hz,2H),4.14(s,3H),3.81(t,J＝5.0Hz,2H),3.30(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.24,143.67,138.44,135.78,135.33,131.86,131.44,130.88,127.41,127.09,124.77,69.37,58.66,48.91,39.15.
HRMS(ESI-TOF)m/z理论值：C15H16N3O3[M-I]+,286.1186,实测值：286.1187.:
化合物101：
(E)-4-(羟基亚氨基)-3-甲基-1-(3-甲基-2-烯-1-基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.50(s,1H),9.62(s,1H),9.25(dd,J＝10.0,1.0Hz,1H),8.34(dd,J＝10.0,1.5Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.85(td,J＝10.0,1.0Hz,1H),5.55-5.45(m,1H),5.22(d,J＝5.0Hz,2H),4.11(s,3H),1.84(s,3H),1.80(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.14,142.89,141.39,138.44,135.86,135.31,131.89,131.45,130.86,127.42,127.07,124.81,116.94,47.08,39.11,26.02,18.66.
HRMS(ESI-TOF)m/z理论值：C17H18N3O2[M-I]+,296.1394,实测值：296.1390.
化合物102:
(E)-1-苄基-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.53(s,1H),9.76(s,1H),9.24(d,J＝10.0Hz,1H),8.30(dd,J＝10.0,1.5Hz,1H),7.95(td,J＝10.0,1.5Hz,1H),7.83(td,J＝10.0,1.0Hz,1H),7.51-7.45(m,2H),7.45-7.36(m,3H),5.88(s,2H),4.13(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.00,143.75,138.46,136.14,135.37,134.74,131.87,131.44,130.76,129.34,129.11,128.56,127.39,127.12,124.57,51.80,39.35.
HRMS(ESI-TOF)m/z理论值：C19H16N3O2[M-I]+,318.1237,实测值：318.1233.
化合物103：
(E)-1-(2-乙氧基-2-氧乙基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.62(s,1H),9.61(s,1H),9.27(d,J＝10.0Hz,1H),8.30(dd,J＝10.0,1.5Hz,1H),7.99(td,J＝10.0,1.5Hz,1H),7.88-7.82(m,1H),5.58(s,2H),4.26(q,J＝7.0Hz,2H),4.19(s,3H),1.27(t,J＝7.0Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.04,166.57,144.24,138.22,135.63,135.54,131.97,131.59,130.42,127.36,127.23,124.83,62.54,49.97,39.38,14.51.
HRMS(ESI-TOF)m/z理论值：C16H16N3O4[M-I]+,314.1135,实测值：314.1138.:
化合物104：
(E)-4-(羟基亚氨基)-3-甲基-9-氧代-1-苯基-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.60(s,1H),10.00(s,1H),9.28(d,J＝5.0,Hz,1H),8.23(dd,J＝10.0,1.5Hz,1H),8.01-7.95(m,1H),7.84(td,J＝10.0,1.0Hz,1H),7.77-7.74(m,2H),7.71-7.67(m,3H),4.19(s,3H).
13C NMR(126MHz,DMSO-d6)δ172.91,144.41,138.47,135.61,135.26,133.99,131.95,131.41,131.18,131.04,129.83,127.44,126.91,126.62,125.20,39.40.
HRMS(ESI-TOF)m/z理论值：C18H14N3O2[M-I]+,304.1081,实测值：304.1085.
化合物105：
(E)-4-(羟基亚氨基)-1-均三甲基-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.58(s,1H),9.81(s,1H),9.29(dd,J＝10.0,0.5Hz,1H),8.18(dd,J＝10.0,1.0Hz,1H),8.03-7.93(m,1H),7.82(td,J＝10.0,1.0Hz,1H),7.16(s,2H),4.20(s,3H),2.38(s,3H),2.04(s,6H).
13C NMR(126MHz,DMSO-d6)δ173.08,144.26,140.75,138.74,136.36,135.27,135.12,131.82,131.44,130.87,130.41,129.56,127.35,127.27,124.97,39.78,21.15,17.54.
HRMS(ESI-TOF)m/z理论值：C21H20N3O2[M-I]+,346.1550,实测值：346.1555.
化合物106：
(E)-4-(羟基亚氨基)-3-甲基-9-氧代-1-(噻吩-2-基甲基)-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ13.01(s,1H),8.49(s,1H),8.27(d,J＝7.8Hz,1H),8.12(dd,J＝8.0,1.6Hz,1H),7.69(t,J＝7.6Hz,1H),7.60(t,J＝7.1Hz,1H),7.43(d,J＝5.9Hz,1H),7.19(d,J＝3.0Hz,1H),6.95(dd,J＝5.1,3.5Hz,1H),5.88(s,2H)，4.28(s,3H).
HRMS(ESI-TOF)m/z理论值：C17H14N3O2S[M-I]+,324.0801,实测值：324.0802.
化合物107：
(E)-1-((1,3-二氧杂环-2-基)甲基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.53(s,1H),9.64(s,1H),9.25(dd,J＝10.0,0.5Hz,1H),8.33(dd,J＝10.0,1.5Hz,1H),8.01-7.93(m,1H),7.85(td,J＝10.0,1.0Hz,1H),5.34(t,J＝3.5Hz,1H),4.91(d,J＝5.0Hz,2H),4.16(s,3H),3.86(s,4H).
13C NMR(126MHz,DMSO-d6)δ174.18,144.11,138.36,135.52,135.39,131.89,131.45,130.83,127.43,127.06,125.01,99.99,65.37,49.50,39.28.
HRMS(ESI-TOF)m/z理论值：C16H15N3O4[M-I]+,314.1135,实测值：314.1136.
化合物108：
(E)-1-(4-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.54(s,1H),9.71(s,1H),9.24(dd,J＝10.0,0.5Hz,1H),8.31(dd,J＝10.0,1.5Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.83(td,J＝10.0,1.0Hz,1H),7.57(dd,J＝10.0,5.0Hz,2H),7.28(t,J＝10.0Hz,2H),5.85(s,2H),4.12(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.02,163.66(161.71,J＝243.8Hz),143.70,138.45,136.13,135.39,131.89,131.45,131.20(131.14,J＝7.5Hz),130.89(130.87,J＝2.5Hz),130.76,127.40,127.12,124.57,116.29(116.12,J＝21.3Hz),51.15,39.33.
HRMS(ESI-TOF)m/z理论值：C19H15FN3O2[M-I]+,336.1143,实测值：336.1138.
化合物109：
(E)-1-(2-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.68(s,1H),10.08(s,1H),9.29(dd,J＝10.0,1.0Hz,1H),8.24(dd,J＝10.0,1.5Hz,1H),8.03-7.95(m,1H),7.89-7.77(m,3H),7.68-7.61(m,1H),7.54(td,J＝10.0,1.0Hz,1H),4.21(s,3H).
13C NMR(126MHz,DMSO)δ172.95,157.58(155.57,J＝251.3Hz),145.03,138.34,135.74,135.52,133.83(133.77,J＝7.5Hz),132.01,131.52,130.65,128.91,127.34,127.06,125.88(125.85,J＝3.8Hz),125.17,121.97(121.87,J＝12.5Hz),117.28(117.13,J＝18.8Hz),39.62.
HRMS(ESI-TOF)m/z理论值：C18H13FN3O2[M-I]+,322.0986,实测值：322.0986.
化合物110：
(E)-1-(3-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.64(s,1H),10.04(d,J＝0.4Hz,1H),9.28(dd,J＝8.0,0.8Hz,1H),8.25(dd,J＝8.0,1.2Hz,1H),8.03-7.95(m,1H),7.85(td,J＝8.0,1.2Hz,1H),7.80-7.71(m,2H),7.66-7.54(m,2H),4.20(s,3H).
13C NMR(101MHz,DMSO)δ172.90,163.16(160.72,J＝244.0Hz),144.62,138.38,135.43,135.33,135.07(134.96,J＝11.0Hz),131.98,131.76(131.67,J＝9.0Hz),131.41,130.99,127.49,126.87,125.21,123.05(123.02,J＝3.0Hz),118.47(118.26,J＝21.0Hz),114.78(114.53,J＝25.0Hz),39.45.
HRMS(ESI-TOF)m/z理论值：C18H13FN3O2[M-I]+,322.0986,实测值：322.0982.:
化合物111：
(E)-1-(4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.60(s,1H),9.96(s,1H),9.26(d,J＝8.0Hz,1H),8.22(d,J＝8.0Hz,1H),7.95(t,J＝8.0Hz,1H),7.86-7.72(m,3H),7.54(t,J＝8.0Hz,2H),4.17(s,3H).
13C NMR(126MHz,DMSO)δ172.97,164.38(162.40,J＝1910.0Hz),144.56,138.40,135.41(135.31,J＝10.0Hz),131.97,131.44,130.99,130.26,130.24,129.22(129.14,J＝10.0Hz),127.44,126.91,125.32,116.93(116.74,J＝19.0Hz),39.39.
HRMS(ESI-TOF)m/z理论值：C18H13FN3O2[M-I]+,322.0986,实测值：322.0991.
化合物112：
(E)-1-(2-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.55(s,1H),9.71(s,1H),9.25(dd,J＝10.0,1.0Hz,1H),8.29(dd,J＝10.0,1.5Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.83(td,J＝10.0,1.0Hz,1H),7.52-7.43(m,2H),7.37-7.30(m,1H),7.24(td,J＝10.0,1.0Hz,1H),5.94(s,2H),4.14(s,3H).
13C NMR(126MHz,DMSO-d6)δ173.93,161.62(159.66,J＝245.0Hz),144.04,138.44,136.14,135.42,131.90,131.61(131.55,J＝7.5Hz),131.46,130.70,130.67,127.40,127.13,125.35(125.32,J＝3.8Hz),124.67,121.80(121.69,J＝13.8Hz),116.23(116.07,J＝20.0Hz),46.44(46.41,J＝3.8Hz),39.32.
HRMS(ESI-TOF)m/z理论值：C19H15FN3O2[M-I]+,336.1143,实测值：336.1145.
化合物113：
(E)-1-(3-氟苄基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.55(s,1H),9.74(s,1H),9.25(dd,J＝10.0,1.0Hz,1H),8.30(dd,J＝10.0,2.0Hz,1H),7.96(td,J＝10.0,1.5Hz,1H),7.83(td,J＝10.0,1.0Hz,1H),7.50-7.45(m,1H),7.36-7.29(m,2H),7.26-7.18(m,1H),5.89(s,2H),4.13(s,3H).
13C NMR(126MHz,DMSO-d6)δ173.96,163.70(161.76,J＝242.5Hz),143.95,138.48,137.47(137.41,J＝7.5Hz),136.15,135.39,131.88,131.45,131.39(131.32,J＝8.8Hz),130.75,127.40,127.15,124.61,124.59,115.98(115.82,J＝20.0Hz),115.41(115.23,J＝22.5Hz),51.21,39.38.
HRMS(ESI-TOF)m/z理论值：C19H15FN3O2[M-I]+,336.1143,实测值：336.1146.
化合物114：
(E)-4-(羟基亚氨基)-1-(4-甲氧基苯基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.58(s,1H),9.92(s,1H),9.27(dd,J＝10.0,1.0Hz,1H),8.24(dd,J＝10.0,1.5Hz,1H),8.01-7.93(m,1H),7.84(td,J＝10.0,1.5Hz,1H),7.66(d,J＝10.0Hz,2H),7.21(d,J＝10.0Hz,2H),4.17(s,3H),3.89(s,3H).
13C NMR(126MHz,DMSO-d6)δ172.93,161.12,144.32,138.47,135.44,135.22,131.94,131.40,131.08,127.96,127.42,126.91,126.64,125.31,114.85,56.23,39.30.
HRMS(ESI-TOF)m/z理论值：C19H16N3O3[M-I]+,334.1186,实测值：334.1184.
化合物115：
(E)-4-(羟基亚氨基)-1-(4-甲氧基苄基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.51(s,1H),9.68(s,1H),9.23(dd,J＝10.0,1.0Hz,1H),8.32(dd,J＝10.0,1.0Hz,1H),7.99-7.91(m,1H),7.83(td,J＝10.0,1.0Hz,1H),7.52-7.45(m,2H),7.04-6.96(m,2H),5.79(s,2H),4.10(s,3H),3.76(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.06,160.08,143.40,138.44,136.09,135.36,131.88,131.43,130.78,130.66,127.41,127.09,126.36,124.56,114.74,55.72,51.49,39.29.
HRMS(ESI-TOF)m/z理论值：C20H18N3O3[M-I]+,348.1343,实测值：348.1347.
化合物116：
(E)-1-(3-氯-4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ14.66(s,1H),10.02(s,1H),9.28(dd,J＝10.0,1.0Hz,1H),8.26(dd,J＝10.0,1.5Hz,1H),8.17(dd,J＝10.0,2.5Hz,1H),7.99(td,J＝5.0,1.5Hz,1H),7.88-7.77(m,3H),4.20(s,3H).
13C NMR(126MHz,DMSO-d6)δ173.01,159.77(157.78,J＝250.0Hz),144.77,138.33,135.39,135.23,132.01,131.44,130.92,130.75(130.72,J＝3.8Hz),129.46,128.10(1210.03,J＝8.8Hz),127.49,126.88,125.30,120.56(120.40,J＝20.0Hz),118.20(118.02,J＝22.5Hz),39.46.
HRMS(ESI-TOF)m/z理论值：C18H12ClFN3O2[M-I]+,356.0597,实测值：356.0593.
化合物117：
(E)-1-(3-溴-4-氟苯基)-4-(羟基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.65(s,1H),10.02(s,1H),9.28(dd,J＝8.0,1.2Hz,1H),8.33-8.20(m,2H),8.02-7.95(m,1H),7.90-7.80(m,2H),7.75(t,J＝8.0Hz,1H),4.19(s,3H).
13C NMR(101MHz,DMSO)δ173.01,161.09(158.62,J＝247.0Hz),144.79,138.33,135.38,135.20,132.12(131.99,J＝13.0Hz),131.44,130.97,130.93,130.92,128.70(128.61,J＝9.0Hz),127.48,126.88,125.32,117.93(117.69,J＝24.0Hz),108.84(108.62,J＝22.0Hz),39.44.
HRMS(ESI-TOF)m/z理论值：C18H12BrFN3O2[M-I]+,400.0091,实测值：400.0088.
化合物118：
(E)-4-(羟基亚氨基)-1,3-二甲基-5-硝基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ14.67(s,1H),9.67(s,1H),8.41(d,J＝7.8Hz,1H),8.30(d,J＝7.9Hz,1H),8.19(t,J＝7.8Hz,1H),4.14(d,J＝21.7Hz,6H).
HRMS(ESI-TOF)m/z理论值：C18H12BrFN3O2[M-I]+,287.0775,实测值：287.0778.
实施例12
化合物1(0.05毫摩尔)在3毫升乙腈中加入310微升碘甲烷在70摄氏度下反应48小时。反应完全之后去除溶剂得到黄色固体，打浆半小时之后抽滤得到最终产物。
使用上述不同的合成中间体化合物，用实施例12的方法可制得化合物119-126，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物119：
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(E)和(Z)-1-丁基-4-(甲氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ9.65(s,1H),9.02(dd,J＝5.0,0.5Hz,1H),8.35(dd,J＝10.0,1.0Hz,1H),7.99-7.92(m,1H),7.88(td,J＝5.0,1.0Hz,1H),4.60(t,J＝7.0Hz,2H),4.41(s,3H),4.13(s,3H),1.93-1.81(m,2H),1.43-1.35(m,2H),0.95(t,J＝5.0Hz,3H).
13C NMR(126MHz,DMSO-d6)δ173.98,143.58,138.41,135.35,134.86,132.54,131.66,131.22,127.73,126.70,125.33,66.37,49.06,39.25,31.67,19.28,13.86.
HRMS(ESI-TOF)m/z理论值：C17H20N3O2[M-I]+,298.1550,实测值：298.1555.
化合物120：
(E)和(Z)-1-丁基-4-(乙氧基亚氨基)-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：134-136℃.
1H NMR(500MHz,DMSO-d6)δ9.67(s,1H),9.05(d,J＝10.0Hz,1H),8.34(dd,J＝10.0,1.5Hz,1H),7.98(td,J＝10.0 1.5Hz,1H),7.88(td,J＝10.0,1.0Hz,1H),4.67(q,J＝7.0Hz,2H),4.60(t,J＝7.0Hz,2H),4.13(s,3H),1.94-1.82(m,2H),1.50(t,J＝7.0Hz,3H),1.42-1.33(m,2H),0.95(t,J＝7.5Hz,3H).
13C NMR(126MHz,DMSO-d6)δ173.97,143.54,138.27,135.36,135.06,132.45,131.55,131.19,127.70,126.73,125.24,74.48,49.06,39.33,31.67,19.28,15.04,13.87.
HRMS(ESI-TOF)m/z理论值：C18H22N3O2[M-I]+,312.1707,实测值：312.1707.
化合物121：
(E)和(Z)-4-((苄氧基)亚胺基)-1-丁基-3-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：122-124℃.
1H NMR(500MHz,DMSO-d6)δ9.62(s,1H),9.09(d,J＝10.0Hz,1H),8.34(dd,J＝10.0,1.0Hz,1H),8.01-7.94(m,1H),7.88(td,J＝10.0,1.0Hz,1H),7.61-7.54(m,2H),7.48-7.37(m,3H),5.68(s,2H),4.57(t,J＝7.0Hz,2H),4.03(s,3H),1.90-1.77(m,2H),1.41-1.32(m,2H),0.97-0.90(m,3H).
13C NMR(126MHz,DMSO)δ173.94,143.58,138.73,136.71,135.39,134.89,132.57,131.60,131.25,129.47,129.21,129.18,127.76,126.70,125.35,80.08,49.03,39.33,31.66,19.24,13.85.
HRMS(ESI-TOF)m/z理论值：C23H23N3O2[M-I]+,374.1863,实测值：374.1863.
化合物122：
(E)和(Z)-1-丁基-3-乙基-4-(甲氧基亚氨基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：135-137℃.
1H NMR(500MHz,DMSO-d6)δ9.71(s,1H),9.02(d,J＝10.0Hz,1H),8.34(d,J＝10.0,1H),7.97(td,J＝10.0,1.5Hz,1H),7.88(t,J＝10.0,1H),4.65-4.55(m,5H),4.41(s,3H),1.92-1.83(m,3H),1.54(t,J＝7.0Hz,3H),1.47-1.35(m,3H),0.95(t,J＝7.0Hz,4H).
13C NMR(126MHz,DMSO-d6)δ174.09,142.86,138.14,135.34,134.19,132.51,131.70,131.11,127.70,126.81,125.71,66.27,49.20,47.07,31.65,19.35,14.86,13.89.
HRMS(ESI-TOF)m/z理论值：C18H22N3O2[M-I]+,312.1707,实测值：312.1708.
化合物123：
(E)和(Z)-4-(甲氧基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：167-169℃.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.01(d,J＝8.0,1H),8.33(dd,J＝4.0,1.2Hz,1H),7.97(td,J＝8.0,1.6Hz,1H),7.88(td,J＝8.0,1.2Hz,1H),4.41(s,3H),4.18(s,3H),4.13(s,3H).
13C NMR(101MHz,DMSO)δ174.16,144.05,138.25,135.38,134.26,132.56,131.72,131.10,127.63,126.76,125.85,66.37,39.08,36.44.
HRMS(ESI-TOF)m/z理论值：C14H14N3O2[M-I]+,256.1081,实测值：256.1085.
化合物124：
(E)和(Z)-4-(乙氧基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：165-167℃.
1H NMR(500MHz,DMSO-d6)δ9.57(s,1H),9.06(dd,J＝10.0,1.0Hz,1H),8.34(dd,J＝10.0,1.0Hz,1H),7.98(td,J＝10.0,1.5Hz,1H),7.88(td,J＝5.0,1.0Hz,1H),4.67(q,J＝7.0Hz,2H),4.18(s,3H),4.13(s,3H),1.50(t,J＝7.0Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.18,144.02,138.15,135.39,134.49,132.49,131.62,131.11,127.63,126.81,125.80,74.48,39.12,36.43,15.02.
HRMS(ESI-TOF)m/z理论值：C15H15N3O2[M-I]+,270.1243,实测值：270.1244.
化合物125：
(E)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：177-179℃.
1H NMR(500MHz,DMSO-d6)δ9.53(s,1H),9.08(dd,J＝10.0,1.0Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),8.01-7.93(m,1H),7.88(td,J＝10.0,1.0Hz,1H),7.60-7.55(m,2H),7.49-7.38(m,3H),5.68(s,2H),4.16(s,3H),4.03(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.15,144.04,138.61,136.66,135.42,134.32,132.61,131.66,131.16,129.49,129.23,129.19,127.67,126.77,125.90,80.09,39.13,36.39.
(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),8.22(d,J＝8.1Hz,1H),8.15(d,J＝7.8Hz,1H),7.86(t,J＝7.7Hz,1H),7.75(t,J＝7.6Hz,1H),7.54(d,J＝7.1Hz,2H),7.41(d,J＝8.2Hz,3H),5.57(s,2H),4.13(s,3H),4.00(s,3H).
(E)和(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.55(s,3H),9.50(s,1H),9.04(d,J＝8.0Hz,1H),8.29(dd,J＝8.0,1.6Hz,1H),8.20(dd,J＝8.0,1.2Hz,3H),8.13(dd,J＝7.8,1.4Hz,3H),7.97–7.90(m,1H),7.84(td,J＝7.6,1.6Hz,4H),7.73(td,J＝7.6,1.2Hz,3H),7.59–7.48(m,8H),7.47–7.33(m,12H),5.64(s,2H),5.55(s,6H),4.11(s,3H),4.11(s,6H),3.99(s,3H),3.98(s,6H).
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,332.1394,实测值：332.1402.
化合物126：
(E)和(Z)-3-乙基-4-(甲氧基亚氨基)-1-甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：162-164℃.
1H NMR(500MHz,DMSO-d6)δ9.57(s,1H),9.06(d,J＝10.0Hz,1H),8.34(dd,J＝10.0,2.0Hz,1H),7.98(td,J＝10.0,2.0Hz,1H),7.88(td,J＝10.0,1.5Hz,1H),4.67(q,J＝7.0Hz,2H),4.18(s,3H),4.13(s,3H),1.50(t,J＝7.0Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.18,144.02,138.15,135.39,134.49,132.49,131.62,131.11,127.63,126.81,125.80,74.48,39.12,36.43,15.02.
HRMS(ESI-TOF)m/z理论值：C15H16N3O2[M-I]+,270.1237,实测值：270.1241.
实施例13
化合物1(0.05毫摩尔)在3毫升乙腈中加入150微升碘甲烷在100摄氏度下反应8小时。反应完全之后去除溶剂得到黄色固体，打浆半小时之后抽滤得到最终产物。
使用上述不同的合成中间体化合物，用实施例13的方法可制得化合物127-151，其他化合物用料和反应条件均不变，原料均可市场购得：
化合物127：
(E)和(Z)-4-(异丙氧基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：187-189℃.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.07(dd,J＝8.0,0.4Hz,1H),8.34(dd,J＝8.0,1.2Hz,1H),8.03-7.95(m,1H),7.88(td,J＝8.0,1.2Hz,1H),4.92-4.82(m,1H),4.18(s,3H),4.14(s,3H),1.51(d,J＝8.0Hz,6H).
13C NMR(101MHz,DMSO-d6)δ174.16,143.98,137.79,135.40,134.67,132.39,131.52,131.09,127.60,126.84,125.73,81.42,39.23,36.45,21.77.
HRMS(ESI-TOF)m/z理论值：C16H18N3O2[M-I]+,284.1394,实测值：284.1399.
化合物128：
(E)和(Z)-4-(丁氧基亚胺)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：201-203℃.
1H NMR(500MHz,DMSO-d6)δ9.59(s,1H),9.03(dd,J＝8.0,1.0Hz,1H),8.34(dd,J＝8.0,1.5Hz,1H),8.02–7.93(m,1H),7.90–7.85(m,1H),4.64(t,J＝6.5Hz,2H),4.18(s,3H),4.12(s,3H),1.95–1.77(m,2H),1.53–1.42(m,2H),0.98(t,J＝7.5Hz,3H).
13C NMR(126MHz,DMSO-d6)δ174.16,144.02,138.15,135.43,134.46,132.49,131.48,131.10,127.64,126.80,125.78,78.53,39.11,36.43,31.07,19.09,14.20.
HRMS(ESI-TOF)m/z理论值：C17H20N3O2[M-I]+,298.1550,实测值：298.1551.
化合物129：
(E)和(Z)-4-(异丁氧基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：139-141℃.
1H NMR(500MHz,DMSO-d6)δ9.57(s,1H),9.03(J＝10.0Hz,1H),8.35(dd,J＝10.0,1.5Hz,1H),8.05-7.98(m,1H),7.89(t,J＝7.5Hz,1H),4.44(d,J＝6.5Hz,2H),4.18(s,3H),4.12(s,3H),2.30-2.15(m,1H),1.05(d,J＝5.0Hz,6H).
13C NMR(126MHz,DMSO-d6)δ174.16,144.03,138.16,135.45,134.47,132.51,131.41,131.13,127.69,126.82,125.81,84.91,39.11,36.43,28.32,19.37.
HRMS(ESI-TOF)m/z理论值：C17H20N3O2[M-I]+,298.1550,实测值：298.1551.
化合物130：
(E)和(Z)-4-(叔丁氧基亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：221-223℃.
1H NMR(500MHz,DMSO-d6)δ9.59(s,1H),9.10(dd,J＝10.0Hz,1H),8.35(dd,J＝5.0,1.5Hz,1H),8.02-7.95(m,1H),7.91-7.85(m,1H),4.19(s,3H),4.15(s,3H),1.56(s,9H).
13C NMR(126MHz,DMSO-d6)δ174.19,143.95,137.64,135.39,134.97,132.32,131.49,131.12,127.59,126.94,125.70,85.60,39.44,36.44,27.70,27.65.
HRMS(ESI-TOF)m/z理论值：C17H20N3O2[M-I]+,298.1550,实测值：298.1551.
化合物131：
(E)和(Z)-4-((环丙基甲氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：170-172℃.
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.09(dd,J＝8.0,0.4Hz,1H),8.34(dd,J＝8.0,1.6Hz,1H),8.03-7.95(m,1H),7.88(td,J＝8.0,1.2Hz,1H),4.47(d,J＝8.0Hz,2H),4.18(s,4H),4.13(s,3H),1.47-1.35(m,1H),0.70-0.62(m,2H),0.51-0.42(m,2H).
13C NMR(101MHz,DMSO-d6)δ174.17,144.01,1310.08,135.38,134.48,132.46,131.56,131.11,127.62,126.88,125.79,83.19,39.14,36.44,10.70,3.76.
HRMS(ESI-TOF)m/z理论值：C17H18N3O2[M-I]+,296.1394,实测值：296.1397.
化合物132：
(E)和(Z)-4-((烯丙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体，熔点：139-141℃.
1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),9.04(dd,J＝8.0,1.2Hz,1H),8.34(dd,J＝8.0,1.2Hz,1H),7.99(td,J＝8.0,1.2Hz,1H),7.89(td,J＝8.0,1.2Hz,1H),6.28-6.15(m,1H),5.58-5.50(m,1H),5.46-5.39(m,1H),5.12(d,J＝8.0Hz,2H),4.18(s,3H),4.10(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.16,144.07,138.48,135.41,134.38,133.51,132.59,131.66,131.13,127.67,126.74,125.88,120.67,79.10,39.17,36.44.
HRMS(ESI-TOF)m/z理论值：C16H16N3O2[M-I]+,282.1237,实测值：282.1239.
化合物133：
(E)和(Z)-4-(((4-甲氧基苄基)氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.54(s,1H),9.05(dd,J＝10.0,0.8Hz,1H),8.32(dd,J＝8.0,1.2Hz,1H),8.02-7.92(m,1H),7.86(td,J＝8.0,1.2Hz,1H),7.56-7.49(m,2H),7.03-6.95(m,2H),5.60(s,2H),4..16(s,3H),4.06(s,3H),3.77(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.13,160.14,144.02,138.38,135.38,134.37,132.53,131.58,131.44,131.11,128.50,127.63,126.79,125.83,114.51,79.91,55.65,39.22,36.41.
HRMS(ESI-TOF)m/z理论值：C21H20N3O3[M-I]+,363.11499实测值：363.1499.
化合物134：
(E)和(Z)-4-(((4-氯苄基)氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.54(s,1H),9.07(dd,J＝8.0,0.8Hz,1H),8.33(dd,J＝8.0,1.6Hz,1H),8.01-.95(m,1H),7.88(td,J＝8.0,1.2Hz,1H),7.65-7.58(m,2H),7.55-7.48(m,2H),5.67(s,2H),4.16(s,3H),4.02(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.14,144.05,138.81,135.74,135.43,134.25,133.88,132.66,131.75,131.41,131.16,129.19,127.68,126.73,125.93,78.99,39.17,36.41.
HRMS(ESI-TOF)m/z理论值：C20H17ClN3O2[M-I]+,366.1004,实测值：366.1006.
化合物135：
(E)和(Z)-1,3-二甲基-9-氧代-4-(((4-(三氟甲基)苄基)氧基)亚胺基)-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体,熔点：158-160℃.
1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),9.11(dd,J＝8.0,0.8Hz,1H),8.34(dd,J＝8.0,0.8Hz,1H),7.99(td,J＝8.0,1.6Hz,1H),7.89(td,J＝8.0,1.2Hz,1H),7.86-7.76(m,4H),5.78(s,2H),4.16(s,3H),4.00(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.14,144.07,141.53,139.03,135.46,134.20,132.73,131.84,131.19,129.63,129.32,127.71,126.72,126.11(126.08,126.04,126.00,J＝4.0Hz),123.26,78.84,39.12,36.41.
HRMS(ESI-TOF)m/z理论值：C21H17F3N3O2[M-I]+,400.1267,实测值：400.1268.
化合物136：
(E)和(Z)-4-(((4-氟苄基)氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
黄色固体,熔点：175-177℃。
1H NMR(400MHz,DMSO-d6)δ9.54(s,1H),9.07(d,J＝8.0Hz,1H),8.32(dd,J＝8.0,1.2Hz,1H),7.97(td,J＝8.0,1.6Hz,1H),7.88(td,J＝8.0,1.2Hz,1H),7.69-7.56(m,2H),7.35-7.24(m,2H),5.66(s,2H),4.16(s,3H),4.03(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.14,163.99(161.55,J＝244.0Hz),144.04,138.68,135.40,134.29,133.02(132.99,J＝3.0Hz),132.62,131.98(131.89,J＝9.0Hz),131.70,131.15,127.66,126.75,125.91,116.14(115.93,J＝21.0Hz),79.14,39.18,36.41.
HRMS(ESI-TOF)m/z理论值：C20H17FN3O2[M-I]+,350.1299,实测值：350.1302.
化合物137：
(E)和(Z)-1,3-二甲基-9-氧代-4-(((全氟苯基)甲氧基)亚胺基)-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.54(s,1H),8.94(d,J＝8.0Hz,1H),8.30(d,J＝8.0Hz,1H),8.02-7.92(m,1H),7.87(t,J＝8.0Hz,1H),5.78(s,2H),4.14(s,3H),4.03(s,3H).
13C NMR(126MHz,DMSO-d6)δ175.44,174.10,144.09,139.74,135.84,135.44,133.92,132.92,132.27,131.84,131.26,127.79,127.39,126.66,126.23,66.49,38.71,36.47.
HRMS(ESI-TOF)m/z理论值：C20H13F5N3O2[M-I]+,422.0922,实测值：422.0920.
化合物138：
(E)和(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-溴化物
1H NMR(500MHz,DMSO-d6)δ9.53(s,1H),9.08(dd,J＝10.0,1.0Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),8.01-7.93(m,1H),7.88(td,J＝10.0,1.0Hz,1H),7.60-7.55(m,2H),7.49-7.38(m,3H),5.68(s,2H),4.16(s,3H),4.03(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.15,144.04,138.61,136.66,135.42,134.32,132.61,131.66,131.16,129.49,129.23,129.19,127.67,126.77,125.90,80.09,39.13,36.39.
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,322.1394,实测值：322.1393.
化合物139：
(E)和(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-对甲苯磺酰化物
1H NMR(500MHz,DMSO-d6)δ9.53(s,1H),9.08(dd,J＝10.0,1.0Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),8.01-7.93(m,1H),7.88(td,J＝10.0,1.0Hz,1H),7.60-7.55(m,2H),7.49-7.38(m,3H),5.68(s,2H),4.16(s,3H),4.03(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.15,144.04,138.61,136.66,135.42,134.32,132.61,131.66,131.16,129.49,129.23,129.19,127.67,126.77,125.90,80.09,39.13,36.39.
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,322.1394,实测值：322.1393.
化合物140：
(E)和(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-硫酸二甲酯化物
1H NMR(500MHz,DMSO-d6)δ9.53(s,1H),9.08(dd,J＝10.0,1.0Hz,1H),8.33(dd,J＝10.0,1.0Hz,1H),8.01-7.93(m,1H),7.88(td,J＝10.0,1.0Hz,1H),7.60-7.55(m,2H),7.49-7.38(m,3H),5.68(s,2H),4.16(s,3H),4.03(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.15,144.04,138.61,136.66,135.42,134.32,132.61,131.66,131.16,129.49,129.23,129.19,127.67,126.77,125.90,80.09,39.13,36.39.
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,322.1394,实测值：322.1395.
化合物141：
(E)和(Z)-1,3-二甲基-4-(((4-硝基苄基)氧基)亚胺基)-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(500MHz,DMSO-d6)δ9.54(s,1H),9.11(d,J＝10.0Hz,1H),8.35-8.28(m,3H),8.00(td,J＝10.0,1.5Hz,1H),7.90(td,J＝10.0,1.0Hz,1H),7.84(d,J＝10.0Hz,2H),5.83(s,2H),4.16(s,3H),3.98(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.14,147.97,144.44,144.09,139.22,135.47,134.14,132.79,131.92,131.21,130.21,127.74,126.70,126.04,124.28,78.38,39.14,36.44.
HRMS(ESI-TOF)m/z理论值：C20H17N4O4[M-I]+,377.1244,实测值：377.1247.
化合物142：
(E)和(Z)-4-((苯氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.62(s,3H),9.56(s,1H),9.07(d,J＝8.0Hz,1H),8.35(dd,J＝8.0,1.6Hz,1H),8.29(dd,J＝8.0,1.2Hz,3H),8.18(dd,J＝7.8,1.4Hz,3H),8.03–7.95(m,1H),7.89(td,J＝7.6,1.6Hz,4H),7.79(td,J＝7.6,1.2Hz,3H),7.69–7.58(m,8H),7.49–7.36(m,12H),4.14(s,3H),4.13(s,6H),4.02(s,3H),4.00(s,6H).
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,318.1237,实测值：318.1238.
化合物143：
(E)-4-(((1,3-二氧杂环-2-基)甲氧基)亚氨基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.56(s,1H),9.03(d,J＝8.0Hz,1H),8.35(d,J＝8.0Hz,1H),7.98(t,J＝8.0Hz,1H),7.87(t,J＝8.0Hz,1H),5.46(t,J＝4.0Hz,2H),4.18(s,3H),4.06(s,3H),4.01(t,J＝4.0Hz,2H),3.98(s,J＝4.0Hz,2H).
HRMS(ESI-TOF)m/z理论值：C20H18N3O2[M-I]+,328.1292,实测值：328.1297.
化合物144：
(E)-4-((2-甲氧基乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.55(s,1H),9.02(d,J＝8.0Hz,1H),8.32(d,J＝8.0Hz,1H),7.96(t,J＝8.0Hz,1H),7.86(t,J＝8.0Hz,1H),4.73(t,J＝4.0Hz,2H),4.16(s,3H),4.11(s,3H),3.81(t,J＝4.0Hz,2H),3.32(s,3H).
13C NMR(126MHz,DMSO-d6)δ174.17,144.02,138.40,135.39,134.38,132.57,131.62,131.14,127.65,126.78,125.88,77.73,70.56,58.77,39.12,36.45.
HRMS(ESI-TOF)m/z理论值：C16H18N3O3[M-I]+,300.1343,实测值：300.1347.
化合物145：
(E)-4-((2-(苄氧基)乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),9.04(d,J＝8.0Hz,1H),8.32(d,J＝8.0Hz,1H),7.94(t,J＝8.0Hz,1H),7.87(t,J＝8.0Hz,1H),7.34-7.19(m,4H),4.76(t,J＝4.0Hz,2H),4.56(s,2H),4.16(s,3H),4.03(s,3H),3.90(t,J＝4.0Hz,2H).
13C NMR(126MHz,DMSO-d6)δ174.17,144.00,138.69,138.43,135.32,134.33,132.59,131.65,131.15,128.71,1210.04,127.98,127.65,126.79,125.87,77.75,72.48,68.19,39.03,36.46.
HRMS(ESI-TOF)m/z理论值：C22H22N3O3[M-I]+,376.1656,实测值：376.1656.
化合物146：
(E)-4-((2-(2-甲氧基乙氧基)乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.58(s,1H),9.07(dd,J＝8.0,0.8Hz,1H),8.34(dd,J＝8.0,1.2Hz,1H),8.00-7.93(m,1H),7.89(td,J＝8.0,1.2Hz,1H),4.82-4.69(m,2H),4.18(s,3H),4.13(s,3H),3.95-3.86(m,2H),3.68-3.59(m,2H),3.53-3.44(m,2H),3.23(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.17,144.01,138.40,135.34,134.37,132.57,131.68,131.13,127.62,126.77,125.86,77.83,71.77,70.18,69.12,58.57,39.08,36.43.
HRMS(ESI-TOF)m/z理论值：C18H22N3O4[M-I]+,344.1605,实测值：344.1609.
化合物147：
(E)和(Z)-4-((2-(2-(2-甲氧基乙氧基)乙氧基)乙氧基)亚胺基)-1,3-二甲基-9-氧代-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.63(s,1H),9.56(s,1H),9.02(d,J＝8.0Hz,1H),8.34-8.09(m,3H),8.01-7.70(m,4H),4.78-4.58(m,4H),4.21-4.01(m,11H),3.90-3.80(m,4H),3.63-3.42(m,10H),3.40-3.30(m,5H),3.16(d,J＝12.0Hz,5H).
13C NMR(101MHz,DMSO)δ175.23,174.18,144.73,144.01,138.39,137.03,135.84,135.36,134.81,133.19,132.56,131.67,131.13,131.03,130.53,129.74,128.12,127.62,127.38,126.61,125.85,125.38,77.84,76.78,71.73,70.42,70.26,70.22,70.10,70.05,70.01,69.12,68.72,58.54,58.50,41.50,39.09,36.70,36.62,36.42.
HRMS(ESI-TOF)m/z理论值：C20H26N3O5[M-I]+,388.1867,实测值：388.1866.
化合物148：
(E)和(Z)-4-((苄氧基)亚胺基)-1-丁基-3-甲基-9-氧代-2-(3,4,5-三甲氧基苯基)-4,9-二氢-1H-萘酚[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.01(d,J＝8.1Hz,1H),8.27(dd,J＝7.8,1.6Hz,1H),8.17–8.08(m,5H),7.93–7.89(m,1H),7.85–7.79(m,3H),7.72(t,J＝7.4Hz,3H),7.54–7.47(m,7H),7.45-7.30(m,9H),5.64(s,2H),5.54(s,2H),5.53(s,3H),4.10(d,J＝3.4Hz,8H),4.02(s,2H),3.95(s,3H),3.84(s,6H),2.76(s,3H),2.75(s,5H),2.67(s,3H).
HRMS(ESI-TOF)m/z理论值：C20H26N3O5[M-I]+,540.2493,实测值：540.2495.
化合物149：
(E)和(Z)-4-((苄氧基)亚胺基)-1,3-二甲基-11-氧代-4,11-二氢-1H-蒽[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.67(s,1H),9.60(s,1H),9.54(s,1H),8.88(s,1H),8.82(s,1H),8.74(s,1H),8.31–8.13(m,4H),7.84–7.68(m,4H),7.68-7.55(m,4H),7.51–7.38(m,6H),5.71(s,2H),5.61(s,2H),4.17(m,6H),4.02(s,3H),4.00(s,3H).
13C NMR(101MHz,DMSO-d6)δ174.07,144.77,144.17,138.54,137.03,136.19,135.13,135.08,133.61,132.73,130.69,130.54,130.41,130.37,130.17,130.10,129.85,129.75,129.40,129.26,129.23,129.17,129.13,129.04,128.92,128.47,126.26,125.23,122.71,79.71,78.95.
HRMS(ESI-TOF)m/z理论值：C20H26N3O5[M-I]+,382.1550,实测值：382.1555.
化合物150：
(E)和(Z)-4-((烯丙氧基)亚胺基)-1,3-二甲基-11-氧代-4,11-二氢-1H-蒽[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.67(s,2H),9.58(s,2H),8.98(s,2H),8.87(s,1H),8.75(s,1H),8.38–8.34(m,2H),8.23(dd,J＝6.4,2.8Hz,3H),7.87–7.79(m,5H),6.32–6.17(m,5H),5.18(dt,J＝5.8,1.2Hz,3H),5.07(d,J＝6.0Hz,2H),4.23–4.20(m,5H),4.20(s,3H),4.11(d,J＝1.6Hz,8H).
HRMS(ESI-TOF)m/z理论值：C20H26N3O5[M-I]+,332.1334,实测值：332.1335.
化合物151：
(E)和(Z)-1,3-二甲基-4-(((4-硝基苄基)氧基)亚胺基)-11-氧代-4,11-二氢-1H-蒽[2,3-d]咪唑-3-碘化物
1H NMR(400MHz,DMSO-d6)δ9.74(s,1H),9.53(s,1H),8.94(s,1H),8.34–8.24(m,5H),7.86–7.79(m,3H),5.86(s,2H),4.18(s,3H),3.97(s,3H).
HRMS(ESI-TOF)m/z理论值：C20H26N3O5[M-I]+,427.1401,实测值：427.1405.
用实施例1-10所述的方法得到的化合物都可以用实施例11-13获得最终的咪唑鎓生物。另外，其他类似的醌肟咪唑鎓衍生物及其合成中间体易用与上述实施例或制备方法中记载的方法制得，或用本领域技术人员显然易知的一些变化方法来制得。
本发明化合物的效果在下面的试验中得到确认。
试验例1、体外癌细胞增殖抑制试验
试验方法：胰腺癌细胞CFPAC-1在加入10％FBS和5％双抗的Dalbeco改进的Eagle培养基中进行培养。将CFPAC-1癌细胞接种在96孔板中孵化24小时；次日，每孔中添加各种浓度(100、20、10、1、0.1、0.01、0、001μM)的测试化合物和阳性对照药物，空白对照添加相应体积的新鲜培养基。添加24小时或48小时后，通过MTT甲臜的显色反应来评价细胞增殖。
试验结果：本发明的化合物良好地抑制了癌细胞的增殖，其半数致死浓度IC50值在1μM以下，最佳化合物能达到10nM以下。
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另外，本发明化合物(I)、(II)、(Ⅲ)和(Ⅳ)对其他癌细胞具有抑制增殖的良好活性，包括非小细胞肺癌细胞(H460，H1299)、肝癌细胞(HepG2)、直肠癌细胞(HT29)、白血病细胞(CCRF-CEM)、前列腺癌细胞(PC-3)、卵巢癌细胞(SKOV-3)、黑色素瘤细胞(A375)、骨髓瘤细胞(RPMI-8226)、食管癌细胞(TE-1)、胰腺癌细胞(CFPAC-1，PANC-1，SW1990，ASPC-1，BXPC-3)、膀胱癌细胞(5637)、胃癌细胞(KATO-III)。结果如下：
试验例2、体内癌细胞增殖抑制试验
试验方法：将3×107个CFPAC-1胰腺癌细胞移植到Balb/c裸鼠腋下皮下，从肿瘤体积分别长到50-100立方毫米、100-200立方毫米和大于200立方毫米时起开始给药，每三天给药一次，共给药7次，每次7mg/kg。对照组注射生理盐水。每次给药前用测径器测量肿瘤长短直径和称量老鼠体重，直至最终给药的次日。用下面公式计算出肿瘤体积。
肿瘤体积(mm3)＝1/2×[短径(mm)]2×长径(mm)
试验结果：在本试验中，本发明化合物(Ⅲ)和(Ⅳ)良好地抑制了癌细胞增殖，例如实施例123、124、125和128在给药7毫克/公斤的剂量下显示出与阳性对照组相比有100％的增殖抑制活性；化合物121、132、137、138、139、140、143、144、145、146、147抑制率高达80％以上，且有明显的剂量依赖性。
本发明化合物在移植了其它癌细胞(非小细胞肺癌A549)的动物模型中同样显示有良好地抑制癌细胞增殖的作用。
试验例3、化合物毒性试验
试验方法：将本发明实施例化合物121、123、124、125、128、132、137、138、139、140、143、144、145、146、147按5毫克/公斤剂量尾静脉注射每天给药，连续7天，监测balb/c小鼠体重变化。
试验结果：老鼠体重没有明显降低现象，状态良好，但阳性对照组吉西他滨老鼠体重明显下降，状态萎靡。
试验例4、抗病毒活性
实验方法：称取4.59mg化合物125于15ml离心管内，加入10ml灭菌水，旋涡震荡溶解，直至无明显黄色颗粒。分装-20℃保存，每支200μl，浓度为1mM.称取2.79mg西多福韦(分子量279)于15ml离心管内，加入10ml灭菌水溶解分装-20℃保存，每支200μl，浓度为1mM.
蚀斑实验：
1、用293A细胞铺24孔板，每孔15万细胞，37℃培养12-24h，待细胞长至90％时用于实验。
2、2％的低熔点agarose gel(琼脂糖胶)融化后放入56℃水浴锅备用。
3、将滴度为109TCID50/mL的腺病毒稀释105倍，将24孔板中的培养基弃去，每孔加入200μl病毒稀释液，37℃5％CO2培养箱中进行孵育，每30min晃一次，共孵育1h。
4、用2x MEM将待测药物化合物125和西多福韦进行二倍倍比稀释(将16μl化合物125加入8ml 2x MEM,震荡混匀，取4ml混合液加入新的4ml 2X MEM中混匀，依次类推，做5个稀释度分别为2μM、1μM、500nM、250nM、125nM；化合物125最高浓度1μM；同理，将400μl西多福韦加入7.6ml 2x MEM，震荡混匀，取4ml混合液加入新的4ml 2x MEM中混匀，依次类推，做5个稀释度分别为50μM、25μM、12.5μM、6.25μM、3.125μM)，将其置于37℃备用。
4、将病毒液弃去，将56℃预热的琼脂糖胶等体积的加入到2xMEM中，混匀，每孔加2ml，在室温中孵育中30min(凝胶)
5、37℃培养箱孵育，期间用荧光显微镜观察病毒复制情况。
实验结果：西多福韦组4天后能观察到许多非CPE形成的空白斑，5天后化合物127低浓度组也出现非CPE空白斑。化合物125对病毒的复制有抑制作用，且有很明显的剂量依赖性抑制作用。
以上对本发明的具体实施例进行了描述。需要理解的是，本发明并不局限于上述特定实施方式，本领域技术人员可以在权利要求的范围内做出各种变形或修改，这并不影响本发明的实质内容。
Claims (10)
1.一种稠合的醌肟咪唑鎓衍生物，其结构由下述通式(I)或(II)表示：
其中，
A环：选自无或有一个或多个取代基的芳环，或无或有一个或多个取代基的杂芳环；
R1、R2、R3和R4：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；
且，A环和R1、R2、R3和R4中的取代基选自B组的基团；
B组：-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-ORa、-SRa、-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-NRaRb、-O-低级亚烷基-O-低级亚烷基-NRaRb、-O-低级亚烷基-NRc-低级亚烷基-NRaRb、-O-CO-NRaRb、-SORa、-SO2Ra、-SO2NRaRb、-NRa-SO2Rb、-NRaRb、-NRc-低级亚烷基-NRaRb、-N(-低级亚烷基-NRaRb)2、-NO2、-CN、-卤素、-CO2Ra、-COO-、-CONRaRb、-CONRa-O-Rb、-NRa-CORb、-NRa-CO-NRbRc、-OCORa和-CORa；
Ra、Rb和Rc：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-低级亚烷基-(无或一个或多个取代基的5到7元饱和杂环)、-低级亚烷基-(无或一个或多个取代基的环烷基)、-低级亚烷基-(无或一个或多个取代基的芳基)、-低级亚烷基-(无或一个或多个取代基的杂芳基)；其中，取代基指低级烷基或杂烷基；
X-：抗衡阴离子，包括卤素离子、磺酸根离子、乙酸根离子、三氟乙酸根离子、碳酸根离子、硫酸根离子等；当取代基上阴离子与咪唑鎓阳离子形成内盐时，X-不存在。
2.根据权利要求1所述的稠合的醌肟咪唑鎓衍生物，其特征在于，所述结构式中，
A环：选自苯环、萘环或NO2取代的苯环；
R1：选自-氢原子、-低级烷基，-低级炔基，-低级烯基、-低级链烷基-O-低级链烷基、-低级链烷基-O-芳基、-低级链烷基-O-低级链烷基-O-低级链烷基、-低级链烷基-O-低级链烷基-O-低级链烷基-O-低级链烷基、-芳基、-5到7元饱和杂环、-杂芳基；
R2：选自低级链烷基；
R3：选自-氢原子、-低级链烷基、-3到7元饱和环烷基、-杂环基、-芳基、-低级链烷基取代的芳基、-卤素取代的芳基、-杂芳基、-低级链烷基取代的杂芳基、-O-低级链烷基、-S-低级链烷基、-酰基、-低级烷基取代的酰基；
R4：选自-氢原子、-低级链烷基、-低级链烯基、-低级炔基、-芳基、-CN、-3到7元饱和环烷基、-卤素取代的芳基、-低级烷基取代的芳基、-杂芳基、-CO2Ra、-饱和杂环基、-低级链烷基-ORa、-低级链烷基-O-低级链烷基、-低级链烷基-S-低级链烷基、-低级链烷基-O-低级链烷基-ORa；Ra为-低级链烷基。
3.一种稠合的醌肟咪唑衍生物及其盐酸盐，其结构由下述通式(Ⅲ)和(Ⅳ)表示：
其中，
A环：选自无或有一个或多个取代基的芳环，或无或有一个或多个取代基的杂芳环；
R1、R3和R4：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；
且，A环和R1、R2、R3和R4中的取代基可以选自B组的基团；
B组：-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基、-ORa、-SRa、-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-O-低级亚烷基-O-低级亚烷基-ORa、-O-低级亚烷基-NRaRb、-O-低级亚烷基-O-低级亚烷基-NRaRb、-O-低级亚烷基-NRc-低级亚烷基-NRaRb、-O-CO-NRaRb、-SORa、-SO2Ra、-SO2NRaRb、-NRa-SO2Rb、-NRaRb、-NRc-低级亚烷基-NRaRb、-N(-低级亚烷基-NRaRb)2、-NO2、-CN、-卤素、-CO2Ra、-COO-、-CONRaRb、-CONRa-O-Rb、-NRa-CORb、-NRa-CO-NRbRc、-OCORa和-CORa；
Ra、Rb和Rc：相同或不同，各自表示-氢原子、-无或一个或多个取代基的低级链烷基、-无或一个或多个取代基的低级链烯基、-无或一个或多个取代基的低级炔基、-无或一个或多个取代基的饱和杂环基、-无或一个或多个取代基的环烷基、-无或一个或多个取代基的环烯基、-无或一个或多个取代基的芳基、-无或一个或多个取代基的杂芳基；其中，取代基指低级烷基或杂烷基。
4.根据权利要求3所述的稠合的醌肟咪唑衍生物及其盐酸盐，其特征在于，所述结构式中，
A环：选自-苯环、-萘环或NO2取代的苯环；
R1：选自-氢原子、-低级烷基，-低级炔基，-低级烯基、-低级链烷基-O-低级链烷基、-低级链烷基-O-芳基、-低级链烷基-O-低级链烷基-O-低级链烷基、-低级链烷基-O-低级链烷基-O-低级链烷基-O-低级链烷基、-芳基、-5到7元饱和杂环、-杂芳基；
R3：选自-氢原子、-低级链烷基、-3到7元饱和环烷基、-杂环基、-芳基、-低级链烷基取代的芳基、-卤素取代的芳基、-杂芳基、-低级链烷基取代的杂芳基、-O-低级链烷基、-S-低级链烷基、-酰基、-低级烷基取代的酰基；
R4：选自-氢原子、-低级链烷基、-低级链烯基、-低级炔基、-芳基、-CN、-3到7元饱和环烷基、-卤素取代的芳基、-低级烷基取代的芳基、-杂芳基、-CO2Ra、-饱和杂环基、-低级链烷基-ORa、-低级链烷基-O-低级链烷基、-低级链烷基-S-低级链烷基、-低级链烷基-O-低级链烷基-ORa；Ra为低级链烷基。
5.一种药物组合物，包括权利要求1或2所述的一种或多种醌肟咪唑鎓衍生物和制药学上所容许的载体。
6.一种药物组合物，包括权利要求3或4所述的一种或多种稠合的醌肟咪唑衍生物或其盐酸盐，和制药学上所容许的载体。
7.一种根据权利要求5或6所述的药物组合物在制备抗癌、抗菌或抗病毒药物中的用途。
8.一种根据权利要求1或2所述的稠合的醌肟咪唑鎓衍生物和权利要求3或4所述的稠合的醌肟咪唑衍生物的制备方法，其特征在于，所述方法包括如下步骤：
A、以质子溶剂为溶剂，取代的醌咪唑衍生物和R1ONH2·HCl在弱碱的催化作用下或和相应的R1ONH2在弱碱盐酸盐的作用下发生肟化反应，得到醌肟咪唑衍生物/>
B、醌肟咪唑衍生物(III)或(IV)在有机溶剂中与相应的卤代物试剂R2X发生N-烷基化反应，得到醌肟咪唑鎓衍生物(Ⅰ)或(Ⅱ)。
9.如权利要求8所述的制备方法，其特征在于，步骤A中，所述的醌咪唑衍生物R1ONH2·HCl和弱碱的摩尔比为1：1.2～5：0.001～0.01,质子溶剂选自甲醇、乙醇、异丙醇，弱碱选自吡啶、三乙胺、碳酸钾，反应温度为90～125℃，反应时间为12～48小时。
10.如权利要求8所述的制备方法，其特征在于，步骤B中，所述醌肟咪唑衍生物(III)或(IV)和卤代物试剂R2X的摩尔比为1:1～1:100，溶剂选自乙腈、乙酸乙酯、四氢呋喃，反应温度50～120℃，反应时间为8～48小时。
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