CN118267472A - 一类萘并卟吩阳离子衍生物及在其生物医药与材料领域应用 - Google Patents
一类萘并卟吩阳离子衍生物及在其生物医药与材料领域应用 Download PDFInfo
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Abstract
本发明涉及一类萘并卟吩阳离子衍生物及其在生物医药与材料领域的应用,该化合物具有下述结构(I)和(II):
Description
技术领域
本发明属光敏药物与光动力疗法领域,具体涉及一类萘并卟吩阳离子衍生物及其在医药与材料等领域的应用。
背景技术
光动力疗法是一种较为新颖的治疗肿瘤、微生物感染性疾病、鲜红斑痣等疾病的治疗方法,包括光动力抗微生物疗法(PACT)和光动力抗肿瘤疗法(PDT)等。与传统抗肿瘤治疗方法(如手术、免疫治疗、放疗或化疗)相比,光动力抗肿瘤疗法以其创口小、侵袭性小、可控性高、全身毒副作用低等优点备受关注。另一方面,多年来抗生素的滥用导致了耐多重抗生素的病原微生物的出现,为人类健康埋下了重大隐患。光动力抗微生物疗法因其独特的氧化损伤机制,在理论上具备广谱抗菌性以及不易产生耐药性的特性。
光动力疗法由三个核心元素组成:光敏剂、特定波长的光和氧源。根据光物理化学途径,PDT通常分为两种类型,I型和II型。在激光照射下,处于基态的光敏剂可以激发到单线态,然后经系间穿越达到三重态,经I型机制进行抽氢或电子转移产生的自由基,会立即与周围的H2O或O2反应生成H2O2、•OH或O2 •-等活性氧物质;经II型机制,处于三重态的光敏剂直接将能量转移到附近的3O2而产生细胞毒单线态氧(1O2)。目前关于PDT研究的报道主要以II型机制为主(Coord. Chem. Rev. 2019, 395, 46-62)。
迄今为止,尚未有适用于光动力抗微生物的光敏药物(光敏剂)被批准用于临床。该领域的光敏剂仍处于研发阶段。其中有关亚甲基蓝(Methylene Blue,1)应用于抗微生物的研究报道较多。2007年Labriola等报道亚甲基蓝有一定的抗乳腺癌作用(BMC Cancer2017, 17, 194);2012年Mousa等报道了亚基蓝有一定的体外抗丙肝病毒活性(Intervirology 2012, 5, 61-70)。2021年Sellera等报道了亚甲基蓝具有光动力抗菌作用(Photodiagnosis Photodyn. Ther. 2021, 31, 102274)。但由于亚甲基蓝吸收强度弱、摩尔消光系数低等原因,其应用受到很大局限。
卟啉类化合物(porphyrin)因其高光转化效率及易被化学修饰,近年来逐渐受到了科学家的青睐。此类分子紫外-可见光吸收波长在400-700nm之间,主要应用于光动力抗肿瘤的研究,应用于抗微生物的研究相对较少。2005年Okamoto等合成四苯基卟啉季铵盐(2)(J. Phys. Chem. B 2005, 109, 19839–19844),该文仅对化合物 2 进行了简单的光谱性质表征,并未对其抗菌活性进行进一步研究。2013年Orlandi团队报道5,15-二芳基卟啉阳离子衍生物(3)展现出一定的体外抗菌活性(J. Photoch. Photobio 2013, 127,123–132)。
由于长期感染某些病原微生物容易引起组织癌变,如幽门螺旋杆菌易诱导胃癌、高危型HPV病毒感染易导致宫颈癌等,因此肿瘤相关的微生物对肿瘤的发生、进展及治疗有较严重的影响。考虑到目前市场上还没有存在同时满足抗肿瘤和抗微生物感染的光敏剂药物,因此研发出兼具PDT和PACT两种功能的光敏剂具有重要的科学意义与应用价值。
为研发出兼具PDT和PACT两种功能的高效光敏剂,我们设计制备了一类中介位苯基取代的萘并卟吩阳离子衍生物(TNP,化合物I、II)。药理实验表明,该类化合物具有抗肿瘤与抗微生物双重作用,可发展为治疗肿瘤、微生物感染等疾病的双功能光动力药物;此外该类化合物的高效光动力作用在视网膜黄斑变性、光化性角化病、鲜红斑痣、尖锐湿疣等疾病的治疗也有优良的应用前景。
发明内容
为开发具有抗肿瘤与抗微生物双重作用的高效光敏药物,我们设计制备了一类新型中介位苯基取代的萘并卟吩阳离子衍生物。药理实验表明,该类化合物具有显著的光动力抗肿瘤活性,活性高于对照药物海姆泊芬;该类化合物具有显著的抗菌活性,活性高于对照化合物亚甲基蓝(
1)、四苯基卟啉季铵盐(2)及5,15-二芳基卟啉衍生物(3)。由于该类化合物具有抗肿瘤与抗微生物双重作用,可发展为治疗肿瘤、微生物感染等疾病的双重光动力药物;此外该类化合物的高效光动力作用在视网膜黄斑变性、光化性角化病、鲜红斑痣、尖锐湿疣等疾病的治疗也有优良的应用前景,还可作为光学染料与试剂应用于近红外荧光成像、荧光标记或光电材料领域。
本发明概述如下:
本专利涉及一类萘并卟吩阳离子衍生物及其在医药与材料领域的应用,其特征是具有下述结构(I)和(II):
其中A为烷基、含N或O或S原子的烷基、含羰基烷基、酰胺键的烷基、同时含烷烃基、羧(酯)基、羟基或氨基侧链的各类烷基;
R1 = ,,,,,
其中X=Cl, Br, I;
R2 = -H, -F, -Cl, -Br, -I, -OH, -O(CH2)mCH3, -(CH2)mCH3, -(CH2)mO(CH2)nC(CH3)3, -(CH2)mO(CH2)nCH(CH3)2, -(CH2)mCOOH, -(CH2)mCH(CH3)COOH, -(CH2)mC(CH3)2COOH, -(CH2)mOH, -(CH2)mC6H4OH, -(CH2)mCO(CH2)nOH, -(CH2)mO(CH2)nOH, -(CH2)m(OCH2CH2)pOH, -(CH2)mR1, -(CH2)mC(CH3)2R1, -(CH2)mCH(CH3)R1, -(CH2)mO(CH2)nR1, -(CH2)mS(CH2)nR1, -(CH2)mO(CH2)mC(CH3)2R1, -(CH2)mO(CH2)mCH(CH3)R1, -(CH2)mS(CH2)mC(CH3)2R1, -(CH2)mS(CH2)mCH(CH3)R1, -(CH2)m(OCH2CH2)pR1, -(CH2)mCO(CH2)mC(CH3)2R1, -(CH2)mCO(CH2)mCH(CH3)R1, -(CH2)mCONH(CH2)nR1, -(CH2)mCONH(CH2)nC(CH3)2R1, -(CH2)mCONH(CH2)nCH(CH3)R1或氨基酸衍生物, m=0-7, n=1-7, p=1-5。
根据权利要求1的式(I)和(Ⅱ),其中
A为-(CH2) N- , -(CH2)mC(CH3)2-, -(CH2)mCH(CH3)-, -(CH2)mO(CH2) N- , -(CH2)mS(CH2) N- , -(CH2)mO(CH2)mC(CH3)2-, -(CH2)mO(CH2)mCH(CH3)-, -(CH2)mS(CH2)mC(CH3)2-, -(CH2)mS(CH2)mCH(CH3)-, -(CH2)m(OCH2CH2)p-, -(CH2)mCO(CH2)mC(CH3)2-, -(CH2)mCO(CH2)mCH(CH3)-, -(CH2)mCONH(CH2) N- , -(CH2)mCONH(CH2)nC(CH3)2-, -(CH2)mCONH(CH2)nCH(CH3)-, -R3(CH2)mC(CH3)2-, -R3(CH2)mCH(CH3)-, -R3O(CH2) N- , -R3O(CH2)mC(CH3)2-, -R3O(CH2)mCH(CH3)-, -R3(OCH2CH2)p-, -R3CO(CH2)mCH(CH3)-, -R3CO(CH2)mC(CH3)2-, m=0-7, n=1-7, p=1-5; 其中R3为-CH[(CH2)mCH3], -CH[(CH2)nOCH3], -CH[(CH2)nOH], -CH[(CH2)mCOOH], -CH[(CH2)mO(CH2)nC(CH3)3], -CH[(CH2)mCOO(CH2)mCH3], -CH[(CH2)m(OCH2CH2)nCH3)], -CH[(CH2)mCO(CH2)nC(CH3)3], -CH[(CH2)mCO(CH2)nCH(CH3)2], -CH[(CH2)mCONH(CH2)nC(CH3)3], -CH((CH2)mCONH[CH2)nCH(CH3)2], m=0-7, n=1-7。
根据权利要求1中提及的氨基酸衍生物,其中氨基酸衍生物为:
-(CH2)mCONH(CH2)nCOOH, -(CH2)mCONHCH(CH3)COOH, -(CH2)mCONH(CH2)nCO(CH2)pCOOH, -(CH2)mCONHCH[CH(CH3)2]COOH, -(CH2)mCONHCH[CH2CH(CH3)2]COOH, -(CH2)mCONHCH[CH(CH3)CH2CH3]COOH, -(CH2)mCONHCH(CH2C6H5)COOH, -(CH2)mCON[(CH2)nCOOH]2, -(CH2)mCONHCH(COOH)CH2COOH, m=0-7, n=1-7, p=1-5。
根据权利要求1所述的一类萘并卟吩阳离子衍生物(I),其特征在于该类化合物中包括如下化合物:
5,10,15,20-四[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(I1);
5,10,15,20-四[4-(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(I2);
5,10,15,20-四[4-(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(I3);
5,10,15,20-四[4-(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(I4);
5,10,15,20-四[4-(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(I5);
5,10,15,20-四[4-(7-(吡啶基)庚氧基)苯基]萘并卟吩四溴化物(I6);
5,10,15,20-四[4-(2-(N,N,N-三甲基)乙氧基)苯基]萘并卟吩四溴化物(I7);
5,10,15,20-四[4-(3-(N,N,N-三甲基)丙氧基)苯基]萘并卟吩四溴化物(I8);
5,10,15,20-四[4-(4-(N,N,N-三甲基)丁氧基)苯基]萘并卟吩四溴化物(I9);
5,10,15,20-四[4-(5-(N,N,N-三甲基)戊氧基)苯基]萘并卟吩四溴化物(I10);
5,10,15,20-四[4-(6-(N,N,N-三甲基)己氧基)苯基]萘并卟吩四溴化物(I11);
5,10,15,20-四[4-(7-(N,N,N-三甲基)庚氧基)苯基]萘并卟吩四溴化物(I12);
5,10,15,20-四[4-(2-(N,N-二乙基-N-甲基)乙氧基)苯基]萘并卟吩四溴化物(I13);
5,10,15,20-四[4-(3-(N,N-二乙基-N-甲基)丙氧基)苯基]萘并卟吩四溴化物(I14);
5,10,15,20-四[4-(4-(N,N-二乙基-N-甲基)丁氧基)苯基]萘并卟吩四溴化物(I15);
5,10,15,20-四[4-(5-(N,N-二乙基-N-甲基)戊氧基)苯基]萘并卟吩四溴化物(I16);
5,10,15,20-四[4-(6-(N,N-二乙基-N-甲基)己氧基)苯基]萘并卟吩四溴化物(I17);
5,10,15,20-四[4-(7-(N,N-二乙基-N-甲基)庚氧基)苯基]萘并卟吩四溴化物(I18);
5,10,15,20-四[4-(2-(N,N,N-三乙基)乙氧基)苯基]萘并卟吩四溴化物(I19);
5,10,15,20-四[4-(3-(N,N,N-三乙基)丙氧基)苯基]萘并卟吩四溴化物(I20);
5,10,15,20-四[4-(4-(N,N,N-三乙基)丁氧基)苯基]萘并卟吩四溴化物(I21);
5,10,15,20-四[4-(5-(N,N,N-三乙基)戊氧基)苯基]萘并卟吩四溴化物(I22);
5,10,15,20-四[4-(6-(N,N,N-三乙基)己氧基)苯基]萘并卟吩四溴化物(I23);
5,10,15,20-四[4-(7-(N,N,N-三乙基)庚氧基)苯基]萘并卟吩四溴化物(I24);
5,10,15,20-四[4-(2-(三苯基鏻)乙氧基)苯基]萘并卟吩四溴化物(I25);
5,10,15,20-四[4-(3-(三苯基鏻)丙氧基)苯基]萘并卟吩四溴化物(I26);
5,10,15,20-四[4-(4-(三苯基鏻)丁氧基)苯基]萘并卟吩四溴化物(I27);
5,10,15,20-四[4-(5-(三苯基鏻)戊氧基)苯基]萘并卟吩四溴化物(I28);
5,10,15,20-四[4-(6-(三苯基鏻)己氧基)苯基]萘并卟吩四溴化物(I29);
5,10,15,20-四[4-(7-(三苯基鏻)庚氧基)苯基]萘并卟吩四溴化物(I30);
5,10,15,20-四[4-(2-(喹啉基)乙氧基)苯基]萘并卟吩四溴化物(I31);
5,10,15,20-四[4-(3-(喹啉基)丙氧基)苯基]萘并卟吩四溴化物(I32);
5,10,15,20-四[4-(4-(喹啉基)丁氧基)苯基]萘并卟吩四溴化物(I33);
5,10,15,20-四[4-(5-(喹啉基)戊氧基)苯基]萘并卟吩四溴化物(I34);
5,10,15,20-四[4-(6-(喹啉基)己氧基)苯基]萘并卟吩四溴化物(I35);
5,10,15,20-四[4-(7-(喹啉基)庚氧基)苯基]萘并卟吩四溴化物(I36)。
根据权利要求1所述的一类萘并卟吩阳离子衍生物(Ⅱ),其特征在于该类化合物中包括如下化合物:
5,15,-二[3,5-二(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ1);
5,15,-二[3,5-二(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ2);
5,15,-二[3,5-二(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ3);
5,15,-二[3,5-二(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ4);
5,15,-二[3,5-二(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ5);
5,15,-二[3,5-二(7-(吡啶基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ6);
5,15,-二[3,5-二(2-(N,N,N-三甲基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ7);
5,15,-二[3,5-二(3-(N,N,N-三甲基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ8);
5,15,-二[3,5-二(4-(N,N,N-三甲基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ9);
5,15,-二[3,5-二(5-(N,N,N-三甲基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ10);
5,15,-二[3,5-二(6-(N,N,N-三甲基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ11);
5,15,-二[3,5-二(7-(N,N,N-三甲基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ12);
5,15,-二[3,5-二(2-(N,N-二乙基-N-甲基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ13);
5,15,-二[3,5-二(3-(N,N-二乙基-N-甲基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ14);
5,15,-二[3,5-二(4-(N,N-二乙基-N-甲基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ15);
5,15,-二[3,5-二(5-(N,N-二乙基-N-甲基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ16);
5,15,-二[3,5-二(6-(N,N-二乙基-N-甲基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ17);
5,15,-二[3,5-二(7-(N,N-二乙基-N-甲基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ18);
5,15,-二[3,5-二(2-(N,N,N-三乙基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ19);
5,15,-二[3,5-二(3-(N,N,N-三乙基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ20);
5,15,-二[3,5-二(4-(N,N,N-三乙基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ21);
5,15,-二[3,5-二(5-(N,N,N-三乙基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ22);
5,15,-二[3,5-二(6-(N,N,N-三乙基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ23);
5,15,-二[3,5-二(7-(N,N,N-三乙基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ24);
5,15,-二[3,5-二(2-(三苯基鏻)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ25);
5,15,-二[3,5-二(3-(三苯基鏻)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ26);
5,15,-二[3,5-二(4-(三苯基鏻)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ27);
5,15,-二[3,5-二(5-(三苯基鏻)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ28);
5,15,-二[3,5-二(6-(三苯基鏻)己氧基)苯基]萘并卟吩四溴化物(Ⅱ29);
5,15,-二[3,5-二(7-(三苯基鏻)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ30);
5,15,-二[3,5-二(2-(喹啉基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ31);
5,15,-二[3,5-二(3-(喹啉基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ32);
5,15,-二[3,5-二(4-(喹啉基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ33);
5,15,-二[3,5-二(5-(喹啉基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ34);
5,15,-二[3,5-二(6-(喹啉基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ35);
5,15,-二[3,5-二(7-(喹啉基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ36)。
所述的萘并卟吩阳离子衍生物(I)和(II)可用于诊断和治疗微生物感染性疾病、肿瘤、视网膜黄斑变性、光化性角化病、鲜红斑痣、尖锐湿疣等疾病的光动力药物领域,还可作为光学染料与试剂应用于荧光成像、荧光标记或光电材料领域。
具体制备方案
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解,在阅读了本发明讲授的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
一般方案1:
R4为含Cl,Br,I的R1。
步骤(i)中,将取代苯甲醛、与4,9-二氢-2H-苯并[f]异吲哚溶于二氯甲烷,氮气保护下加入催化量的三氟化硼乙醚,室温搅拌反应,薄层层析色谱(TLC)监测原料消失产物生成,加入二氯二氰基苯醌(DDQ),继续搅拌反应,TLC监测氧化完全。减压蒸除溶剂,所得残留物柱层析分离纯化得到墨绿色粉末(Ⅳ)。
步骤(ⅱ)中,将化合物(Ⅳ)溶于N,N-二甲基甲酰胺和四氢呋喃混合溶液中,再加入相应的含氮或含磷化合物。反应物在氮气下70 ℃搅拌10 h。减压蒸除有机溶剂后,甲醇/乙醚重结晶,真空干燥得到墨绿色固体(I)。
一般方案2:
R4为含Cl,Br,I的R1。
步骤(i)中,将取代苯甲醛与二(4,9-二氢-2H-苯并[f]异吲哚-1-基)甲烷溶于二氯甲烷,氮气保护下加入催化量的三氟乙酸,室温搅拌反应,薄层层析色谱(TLC)监测原料消失产物生成,加入二氯二氰基苯醌(DDQ),继续搅拌反应,TLC监测氧化完全。减压蒸除溶剂,所得残留物柱层析分离纯化得到墨绿色粉末(Ⅴ)。
步骤(ⅱ)中,将化合物(Ⅴ)溶于N,N-二甲基甲酰胺和四氢呋喃混合溶液中,加入相应的含氮或含磷化合物,反应物在氮气下70 ℃搅拌反应10 h。减压蒸除有机溶剂后,MeOH/Et2O重结晶,真空干燥得到墨绿色固体(Ⅱ)。
[实施例1]
5,10,15,20-四[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(I1)的制备
4-(2-溴乙氧基)苯甲醛(Ⅲ1, 1.76 g, 7.68 mmol)和4,9-二氢-2H-苯并[f]异吲哚(1.3 g, 7.68 mmol)溶于二氯甲烷(200mL),氮气保护下逐滴滴加三氟化硼乙醚(0.22g, 1.64mmol),室温搅拌反应2 h。加入二氯二氰基苯醌DDQ(3.57 g, 15.6 mmol),继续搅拌反应8 h。减压蒸除溶剂,所得残留物柱层析分离(洗脱剂为二氯甲烷)纯化得到1.17 g墨绿色粉末Ⅳ1,收率40.4%。1H NMR (600 MHz, Chloroform-d, +TFA) δ 8.61 – 8.52 (m,2.4 Hz, 8H), 8.05 (s, 8H), 7.80 (dd, J = 6.4, 3.3 Hz, 8H), 7.56 – 7.46 (m,16H), 4.71 – 4.62 (m, 8H), 3.94 (t, J = 6.1 Hz, 8H). 13C NMR (151 MHz,Chloroform-d, +TFA) δ 160.06, 141.37, 137.10, 133.39, 132.77, 129.75, 129.39,127.12, 124.75, 116.04, 111.73, 68.36, 29.08. HRMS (MALDI-TOF): (m/z) calcedfor C84H58Br4N4O4 1502.1192; found, 1502.1208。
向50 mL反应瓶中加入Ⅳ1(0.1 g, 0.07 mmol)、THF(5 mL)、N,N-二甲基甲酰胺(5mL)和吡啶(1.1 mL, 13.3 mmol),反应混合物在氮气气氛下70 ℃搅拌10 h,减压蒸除有机溶剂,MeOH/Et2O重结晶,真空干燥滤饼得到114 mg墨绿色固体I1,收率92.4%。1H NMR (600MHz, DMSO-d 6, +TFA) δ 9.48 (d, J = 6.0 Hz, 8H), 8.84 (t, J = 7.9 Hz, 4H),8.53 (s, 8H), 8.42 (t, J = 7.0 Hz, 8H), 7.82 (s, 8H), 7.74 – 7.64 (m, 8H),7.61 (d, J = 8.2 Hz, 16H), 5.38 (t, J = 5.2 Hz, 8H), 5.01 (t, J = 5.2 Hz,8H). 13C NMR (150 MHz, DMSO-d 6) δ 159.76, 146.36, 145.80, 137.08, 132.65,131.90, 129.73, 129.68, 128.96, 128.16, 127.61, 123.34, 116.15, 111.40,67.10, 60.17. HRMS (MALDI-TOF): (m/z) calced for C104H78Br4N8O4 375.9040 [(M-4Br)/4]; found, 375.9052。
[实施例2]
5,10,15,20-四[4-(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(I2)的制备
参照化合物I1的合成方法制备了化合物I2。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 9.46 (d, J = 6.0 Hz, 8H), 8.79 –8.66 (m, 12H), 8.29 (t, J = 7.0 Hz, 8H), 8.02 (s, 8H), 7.89 – 7.85 (m, 8H),7.69 – 7.63 (m, 8H), 7.50 (d, J = 8.0 Hz, 8H), 5.12 (d, J = 7.7 Hz, 8H), 4.57(d, J = 36.0 Hz, 8H), 2.75 (p, J = 8.6, 7.4 Hz, 8H). 13C NMR (150 MHz, DMSO-d 6, +TFA) δ 160.68, 146.26, 145.78, 141.56, 137.56, 132.52, 129.91, 129.43,128.54, 128.18, 123.87, 116.29, 111.78, 66.08, 59.43. HRMS (MALDI-TOF): (m/z)calced for C108H86Br4N8O4 389.9196 [(M-4Br)/4]; found, 389.9203。
[实施例3]
5,10,15,20-四[4-(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(I3)的制备
参照化合物I1的合成方法制备了化合物I3。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 9.33 (d, J = 6.0 Hz, 8H), 8.71 (t, J= 7.9 Hz, 4H), 8.65 (d, J = 7.9 Hz, 8H), 8.29 (t, J = 6.9 Hz, 8H), 7.98 (s,8H), 7.80 (d, J = 7.3 Hz, 8H), 7.61 (d, J = 7.8 Hz, 16H), 4.91 (t, J = 7.3Hz, 8H), 4.47 (s, 8H), 2.35 (t, J = 7.8 Hz, 8H), 2.05 (t, J = 7.5 Hz, 8H). 13CNMR (150 MHz, DMSO-d 6, +TFA) δ 161.23, 146.14, 145.42, 141.62, 137.58,132.46, 132.37, 129.99, 129.41, 128.71, 128.12, 123.81, 116.40, 111.91,68.12, 61.08, 28.36, 25.99. HRMS (MALDI-TOF): (m/z) calced forC112H94Br4N8O4403.9353 [(M-4Br)/4]+; found, 403.9369。
[实施例4]
5,10,15,20-四[4-(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(I4)的制备
参照化合物I1的合成方法制备了化合物I4。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 9.27 (d, J = 6.0 Hz, 8H), 8.68 (dt,J = 13.2, 7.5 Hz, 12H), 8.26 (t, J = 7.0 Hz, 8H), 8.00 (s, 8H), 7.84 – 7.78(m, 8H), 7.61 (d, J = 7.8 Hz, 16H), 4.81 (t, J = 7.5 Hz, 8H), 4.49 – 4.35 (m,8H), 2.24 – 2.15 (m, 8H), 2.10 – 2.05 (m, 8H), 1.73 – 1.64 (m, 8H). 13C NMR(150 MHz, DMSO-d 6, +TFA) δ 160.72, 145.55, 144.83, 137.01, 131.90, 131.77,129.53, 128.87, 128.13, 127.55, 123.24, 115.89, 111.45, 67.86, 60.61, 39.80,30.65, 28.13, 22.16. HRMS (MALDI-TOF): (m/z) calced for C116H102Br4N8O4 417.9509[(M-4Br)/4]; found, 417.9526。
[实施例5]
5,10,15,20-四[4-(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(I5)的制备
参照化合物I1的合成方法制备了化合物I5。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 9.23 (d, J = 6.0 Hz, 8H), 8.71 (d, J= 8.0 Hz, 8H), 8.66 (t, J = 7.8 Hz, 4H), 8.23 (t, J = 7.0 Hz, 8H), 8.04 (s,8H), 7.85 – 7.78 (m, 8H), 7.61 (d, J = 7.9 Hz, 15H), 4.75 (t, J = 7.5 Hz,8H), 4.42 (t, J = 7.5 Hz, 8H), 2.14 – 2.08 m, 9H), 2.05 – 1.97 (m, 8H), 1.75– 1.65 (m, 8H), 1.58 – 1.50 (m, 8H). 13C NMR (150 MHz, DMSO-d 6, +TFA) δ161.03, 145.61, 144.94, 141.29, 137.28, 132.16, 131.80, 129.42, 129.02,128.23, 127.78, 123.47, 116.06, 111.44, 68.20, 60.86, 30.90, 28.66, 25.51,25.21. HRMS (MALDI-TOF): (m/z) calced for C120H110N8O4Br4 431.9666 [(M-4Br)/4];found, 431.9652。
[实施例6]
5,10,15,20-四[4-(3-(N,N,N-三甲铵基)丙氧基)苯基]萘并卟吩四溴化物(I8)的制备
参照化合物I1的合成方法制备了化合物I8。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.83 – 8.59 (m, 8H), 8.01 (s, 8H),7.83 (s, 8H), 7.65 (d, J = 8.0 Hz, 8H), 7.62 (d, J = 7.5 Hz, 8H), 4.53 (s,8H), 3.89 – 3.74 (m, 8H), 3.30 (s, 36H). 13C NMR (150 MHz, DMSO-d 6, +TFA) δ160.81, 137.50, 132.87, 132.36, 130.55, 129.45, 128.01, 123.77, 116.45,112.24 65.99, 63.55, 52.95, 23.31. HRMS (MALDI-TOF): (m/z) calced forC100H102N8O4Br4 369.9509 [(M-4Br)/4]; found, 369.9514。
[实施例7]
5,10,15,20-四[4-(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(I9)的制备
参照化合物I1的合成方法制备了化合物I9。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.62 (s, 8H), 7.97 (s, 8H), 7.80 (s,8H), 7.65 (d, J = 8.1 Hz, 8H), 7.62 (s, 8H), 4.50 (s, 8H), 3.60 (t, J = 8.2Hz, 8H), 3.23 (s, 36H), 2.14 – 2.03 (m, 16H). 13C NMR (150 MHz, DMSO-d 6, +TFA)δ 160.63, 137.02, 131.90, 129.55, 128.89, 127.55, 123.25, 115.91, 111.45,67.47, 65.04, 52.22, 25.75, 19.25. HRMS (MALDI-TOF): (m/z) calced forC104H110N8O4Br4 383.9666 [(M-4Br)/4]; found, 383.9681。
[实施例8]
5,10,15,20-四[4-(5-(N,N,N-三甲铵基)戊氧基)苯基]萘并卟吩四溴化物(I10)的制备
参照化合物I1的合成方法制备了化合物I10。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.56 (s, 8H), 7.94 (s, 8H), 7.78 (s,8H), 7.62 (t, J = 9.4 Hz, 16H), 4.46 (s, 8H), 3.54 – 3.43 (m, 8H), 3.17 (s,36H), 2.15 – 2.03 (m, 8H), 2.01 – 1.90 (m, 8H), 1.74 – 1.62 (m, 8H). 13C NMR(150 MHz, DMSO-d 6, +TFA) δ 161.06, 141.32, 137.31, 132.21, 131.86, 129.42,129.06, 127.81, 123.51, 116.06, 111.45, 68.02, 65.38, 52.34, 28.45, 22.71,22.18. HRMS (MALDI-TOF): (m/z)calced for C108H118N8O44Br4 397.9822 [(M-4Br)/4];found, 397.9819。
[实施例9]
5,10,15,20-四[4-(6-(N,N,N-三甲铵基)己氧基)苯基]萘并卟吩四溴化物(I11)的制备
参照化合物I1的合成方法制备了化合物I11。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.40 (d, J = 127.2 Hz, 8H), 7.90 (s,8H), 7.75 (s, 8H), 7.61 (d, J = 7.9 Hz, 16H), 4.46 (s, 8H), 3.38 (t, J = 7.0Hz, 8H), 3.15 (s, 36H), 2.14 – 1.99 (m, 8H), 1.893 – 1.81 (m, 8H), 1.79 –1.69 (m, 8H), 1.61 – 1.47 (m, 8H). 13C NMR (150 MHz, DMSO-d 6, +TFA) δ 161.31,137.53, 132.43, 130.29, 129.44, 128.09, 123.80, 116.47, 112.17, 68.66, 65.80,52.72, 29.11, 26.27, 25.76, 22.65. HRMS (MALDI-TOF): (m/z) calced forC112H126N8O44Br4 411.9979 [(M-4Br)/4]; found, 411.9995。
[实施例10]
5,10,15,20-四[4-(3-(N,N-二乙基-N-甲基铵基)丙氧基)苯基]萘并卟吩四溴化物(I14)的制备
参照化合物I1的合成方法制备了化合物I14。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.55 (s, 8H), 7.91 (s, 8H), 7.77 (s,8H), 7.68 – 7.53 (m, 16H), 4.54 (s, 8H), 3.68 (t, J = 8.0 Hz, 12H), 3.52 (q,J = 7.2 Hz, 16H), 3.15 (s, 24H), 2.47 – 2.41 (m, 8H), 1.39 (t, J = 7.2 Hz,24H). 13C NMR (150 MHz, DMSO-d 6, +TFA) δ 160.98, 141.68, 137.73, 132.64,132.55, 130.03, 129.51, 128.20, 123.91, 116.51, 111.91, 65.92, 57.45, 56.39,47.36, 22.58, 8.19. HRMS (MALDI-TOF): (m/z)calced for C106H114N8O4 390.9744 [(M-4Br)/4]; found, 390.9755。
[实施例11]
5,10,15,20-四[4-(5-(N,N-二乙基-N-甲基铵基)戊氧基)苯基]萘并卟吩四溴化物(I16)的制备
参照化合物I1的合成方法制备了化合物I16。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.57 (s, 8H), 7.93 (s, 8H), 7.78 (s,8H), 7.62 (dd, J = 20.8, 7.6 Hz, 16H), 4.49 (s, 8H), 3.53 – 3.40 (m, 25H),3.08 (s, 12H), 2.06 (d, J = 14.1 Hz, 16H), 1.34 (t, J = 7.2 Hz, 24H). 13C NMR(150 MHz, DMSO-d 6, +TFA) δ 161.14, 141.87, 137.56, 132.44, 130.16, 129.43,128.08, 123.80, 116.44, 112.01, 67.92, 59.56, 56.21, 47.15, 26.17, 18.98,8.08. HRMS (MALDI-TOF): (m/z)calced for C116H134N8O44Br4 426.0135 [(M-4Br)/4];found, 426.0138。
[实施例12]
5,10,15,20-四[4-(4-(N,N,N-三乙基铵基)丁氧基)苯基]萘并卟吩四溴化物(I21)的制备
参照化合物I1的合成方法制备了化合物I21。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.62 (s, 8H), 7.97 (s, 8H), 7.80 (s,8H), 7.65 (d, J = 8.1 Hz, 8H), 7.62 (s, 8H), 4.50 (s, 8H), 3.60 (t, J = 8.2Hz, 8H), 3.23 (s, 36H), 2.14 – 2.03 (m, 16H). 13C NMR (150 MHz, DMSO-d 6, +TFA)δ 160.63, 137.02, 131.90, 129.55, 128.89, 127.55, 123.25, 115.91, 111.45,67.47, 65.04, 52.22, 25.75, 19.25. HRMS (MALDI-TOF): (m/z) calced forC116H134N8O4Br4 426.0135 [(M-4Br)/4]; found, 426.0149。
[实施例13]
5,10,15,20-四[4-(4-(三苯基鏻)丁氧基)苯基]萘并卟吩四溴化物(I27)的制备
参照化合物I1的合成方法制备了化合物I27。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 8.82 (d, J = 2.6 Hz, 4H), 7.78 –7.71 (m, 24H), 7.71 – 7.61 (m, 40H), 7.42 – 7.36 (m, 4H), 7.26 – 7.21 (m,4H), 7.08 – 7.02 (m, 4H), 7.06 – 6.97 (m, 4H), 3.99 (t, J = 5.3 Hz, 8H), 3.86(t, J = 5.3 Hz, 8H), 1.99 – 1.94 (m, 8H), 1.77 – 1.71 (m, 8H). 13C NMR (150MHz, DMSO-d 6, +TFA) δ 160.83, 159.92, 138.23, 135.22, 133.80, 131.58, 130.87,130.82, 130.68, 130.55, 125.54, 125.48, 120.84, 116.87, 116.84, 116.74,116.69, 67.87, 27.32, 23.83, 21.81. HRMS (MALDI-TOF): (m/z) calced forC132H118N4O4P4Br4 486.9529 [(M-4Br)/4]; found, 486.9546。
[实施例14]
5,10,15,20-四[4-(4-(喹啉基)丁氧基)苯基]萘并卟吩四溴化物(I33)的制备
参照化合物I1的合成方法制备了化合物I33。
1H NMR (600 MHz, DMSO-d 6, +TFA) δ 9.48 (dd, J = 6.0, 1.3 Hz, 4H), 9.15(dt, J = 8.2, 1.4 Hz, 4H), 8.68 (s, 8H), 8.54 – 8.46 (m, 4H), 8.42 (dd, J =8.8, 0.9 Hz, 4H), 8.20 – 8.12 (m, 4H), 8.09 (dd, J = 8.2, 6.0 Hz, 4H), 8.02(s, 8H), 7.98 – 7.91 (m, 4H), 7.82 (s, 8H), 7.65 (s, 8H), 7.63 (s, 8H), 4.47(s, 8H), 3.04 (s, 8H), 2.17 – 2.02 (m, 8H), 1.96 –1.83 (m, 8H). 13C NMR (150MHz, DMSO-d 6, +TFA) δ 161.21, 160.83, 160.61, 159.92, 148.79, 142.30, 141.37,138.23, 138.16, 138.13, 131.58, 131.50, 130.87, 130.82, 130.68, 130.55,130.52, 130.15, 128.65, 128.25, 126.95, 126.66, 125.54, 125.48, 120.51,120.12, 116.87, 116.84, 116.74, 116.69, 68.03, 59.23, 26.99, 26.42. HRMS(MALDI-TOF): (m/z) calced for C96H86N8O44Br4 353.9196 [(M-4Br)/4]; found,353.9208。
[实施例15]
5,15,-二[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ1)的制备
3,5-二(2-溴乙氧基)苯甲醛(Ⅴ1, 1.31 g, 3.71 mmol)和二(4,9-二氢-2H-苯并[f]吲哚-1-基)甲烷(1.3 g, 3.71 mmol)溶于二氯甲烷(200 mL),氮气保护下加入三氟乙酸(84.6 mg, 0.742 mmol),室温搅拌反应2 h。加入二氯二氰基苯醌DDQ(2.95 g, 13.0mmol),继续搅拌反应8 h。减压蒸除溶剂,所得残留物柱层析分离(洗脱剂为二氯甲烷)纯化得到1.07 g墨绿色粉末Ⅵ1,收率42.6%。1H NMR (600 MHz, Chloroform-d, +TFA) δ 10.81(s, 2H), 9.81 (s, 4H), 8.53 (d, J = 8.2 Hz, 4H), 8.35 (s, 4H), 8.12 (d, J =8.3 Hz, 4H), 7.87 (t, J = 7.3 Hz, 4H), 7.79 (t, J = 7.4 Hz, 4H), 7.75 (d, J =2.2 Hz, 4H), 7.41 – 7.38 (m, 2H), 4.51 (t, J = 6.0 Hz, 8H), 3.70 (t, J = 6.0Hz, 8H), 1.51 (s, 4H). HRMS (MALDI-TOF): (m/z) calced for C72H50Br4N4O41350.0520 [M]+; found, 1354.0519。
向50 mL反应瓶中加入Ⅳ1(0.15 g, 0.11 mmol)、THF(5 mL)、N,N-二甲基甲酰胺(5 mL)和吡啶(1.78 mL, 22.1 mmol),反应混合物在氮气气氛下70 ℃搅拌10 h,减压蒸除有机溶剂,MeOH/Et2O重结晶,真空干燥滤饼得到179.1 mg墨绿色固体I1,收率96.7%。1H NMR(600 MHz, DMSO-d 6) δ 11.49 (s, 1H), 10.88 (s, 2H), 9.25 (d, J = 6.1 Hz, 4H),8.75 (d, J = 8.0 Hz, 2H), 8.56 (t, J = 7.8 Hz, 2H), 8.12 (t, J = 6.9 Hz, 4H),7.97 (s, 4H), 7.89 (q, J = 7.5, 6.6 Hz, 4H), 7.66 (s, 2H), 7.58 (s, 1H), 5.17(t, J = 5.2 Hz, 4H), 4.83 (t, J = 4.9 Hz, 4H), -0.40 (s, 2H). 13C NMR (150MHz, DMSO-d 6) δ 160.50, 151.84, 147.10, 145.32, 141.94, 140.71, 135.40,134.97, 132.80, 129.56, 128.26, 127.54, 123.65, 122.76, 120.03, 119.97,117.62, 104.90, 97.06, 95.78, 68.92, 61.51. HRMS (MALDI-TOF): (m/z)calced forC92H70N8O4Br4 337.6375 [(M-4Br)/4]+; found, 337.6384。
[实施例16]
5,15,-二[3,5-二(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ2)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ2。
1H NMR (600 MHz, DMSO-d 6) δ 11.52 (s, 2H), 10.89 (s, 4H), 9.17 (d, J =6.0 Hz, 8H), 8.77 (s, 4H), 8.46 (t, J = 7.8 Hz, 4H), 8.09 (s, 8H), 7.98 (t, J= 7.0 Hz, 12H), 7.91 (s, 4H), 7.56 (s, 4H), 7.42 (s, 2H), 4.88 (t, J = 6.9Hz, 8H), 4.38 (t, J = 6.1 Hz, 8H), 2.58 – 2.53 (m, 8H), -0.39 (s, 2H). 13C NMR(151 MHz, DMSO-d 6) δ 161.11, 145.49, 144.73, 142.28, 140.67, 138.99, 136.43,133.62, 131.82, 129.41, 128.80, 128.03, 126.50, 126.47, 123.73, 120.70,114.51, 111.49, 102.78, 91.96, 67.83, 60.27, 40.04, 27.69, 25.34. HRMS(MALDI-TOF): (m/z) calced for C96H78Br4N8O4 351.9048 [(M-4Br)/4]+; found,351.9043。
[实施例17]
5,15,-二[3,5-二(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ3)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ3。
1H NMR (600 MHz, DMSO-d 6) δ 11.49 (s, 2H), 10.84 (s, 4H), 9.07 (d, J =6.0 Hz, 9H), 8.74 (d, J = 8.0 Hz, 4H), 8.53 (t, J = 7.7 Hz, 4H), 8.16 (s,4H), 8.07 (t, J = 6.8 Hz, 13H), 7.95 (t, J = 7.2 Hz, 4H), 7.86 (t, J = 7.3Hz, 4H), 7.62 (d, J = 2.2 Hz, 4H), 7.53 (d, J = 2.5 Hz, 2H), 4.67 (t, J = 7.5Hz, 9H), 4.32 (t, J = 6.6 Hz, 9H), 2.12 (q, J = 7.6 Hz, 8H), 1.86 (p, J = 6.7Hz, 9H), -0.41 (s, 2H). 13C NMR (150 MHz, DMSO-d 6) δ 161.61, 145.99, 145.23,142.78, 141.16, 139.49, 136.92, 134.12, 132.32, 129.91, 129.30, 128.53,126.99, 126.97, 124.23, 121.20, 115.01, 111.98, 103.28, 92.46, 68.33, 60.77,28.19, 25.83. HRMS (MALDI-TOF): (m/z) calced for C100H86N8O4Br4 365.9196 [(M-4Br)/4]+; found, 365.9204。
[实施例18]
5,15,-二[3,5-二(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ4)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ4。
1H NMR (600 MHz, Chloroform-d) δ 11.49 (s, 2H), 10.83 (s, 4H), 9.01(d, J = 6.0 Hz, 8H), 8.72 (d, J = 8.1 Hz, 4H), 8.51 (t, J = 7.7 Hz, 4H), 8.16(s, 4H), 8.05 (t, J = 7.0 Hz, 12H), 7.97 – 7.91 (m, 4H), 7.85 (t, J = 7.2 Hz,4H), 7.59 (d, J = 2.3 Hz, 4H), 7.49 (d, J = 2.4 Hz, 2H), 4.55 (t, J = 7.5 Hz,8H), 4.28 (t, J = 6.6 Hz, 8H), 1.89 – 1.81 (m, 16H), 1.45 (p, J = 7.6 Hz,8H), -0.42 (s, 2H). 13C NMR (150 MHz, DMSO-d 6) δ 160.67, 151.84, 150.70,145.62, 141.94, 140.39, 135.43, 134.97, 132.80, 128.93, 127.08, 126.47,123.65, 122.71, 121.65, 120.03, 119.97, 117.98, 105.07, 97.06, 68.38, 62.18,30.72, 29.24, 23.30. HRMS (MALDI-TOF): (m/z) calced for C104H94N8O4Br4 379.9353[(M-4Br)/4]+; found, 379.9369。
[实施例19]
5,15,-二[3,5-二(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ5)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ5。
1H NMR (600 MHz, DMSO-d 6) δ 11.48 (s, 2H), 10.82 (s, 4H), 9.02 (d, J =5.9 Hz, 8H), 8.72 (s, 4H), 8.54 (t, J = 7.8 Hz, 4H), 8.17 (s, 4H), 8.08 (t, J= 6.9 Hz, 8H), 8.05 (s, 4H), 7.94 (s, 4H), 7.85 (s, 4H), 7.58 (s, 4H), 7.48(s, 2H), 4.51 (t, J = 7.6 Hz, 8H), 4.27 (t, J = 6.7 Hz, 8H), 1.83-1.76 (m,16H), 1.47 (p, J = 7.6 Hz, 8H), 1.27 (p, J = 7.8 Hz, 8H), -0.42 (s, 2H). 13CNMR (150 MHz, DMSO-d 6) δ 160.67, 151.84, 149.70, 145.32, 143.13, 141.94,140.65, 135.40, 134.97, 133.47, 131.57, 130.90, 128.93, 127.57, 126.83,123.65, 121.79, 120.03, 119.97, 117.98, 105.07, 95.78, 68.37, 56.81, 29.87,29.27, 28.85, 25.92. HRMS (MALDI-TOF): (m/z) calced for C108H102N8O4Br4 393.9509[(M-4Br)/4]+; found, 393.9513。
[实施例20]
5,15,-二[3,5-二(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ9)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ9。
1H NMR (600 MHz, DMSO-d 6) δ 11.50 (s, 2H), 10.84 (s, 4H), 8.74 (d, J =8.1 Hz, 4H), 8.19 (s, 4H), 8.11 (d, J = 8.2 Hz, 4H), 7.97 (t, J = 7.2 Hz,4H), 7.89 (t, J = 7.2 Hz, 4H), 7.65 (d, J = 2.1 Hz, 4H), 7.57 (d, J = 10.2Hz, 2H), 4.33 (d, J = 5.8 Hz, 8H), 3.32 (d, J = 7.1 Hz, 8H), 2.96 (s, 36H),1.86 (d, J = 7.2 Hz, 16H), -0.39 (s, 2H). 13C NMR (150 MHz, DMSO-d 6) δ 160.67,129.35, 128.26,127.57, 127.08, 127.04, 126.47, 122.76, 122.71, 121.79,121.65, 120.86, 120.03, 119.97, 105.21, 105.07, 104.16, 96.67, 67.73, 45.60,29.71, 24.19, 23.84. HRMS (MALDI-TOF): (m/z) calced for C92H102N8O4Br4 345.7001[(M-4Br)/4]+; found, 345.7010。
[实施例21]
5,15,-二[3,5-二(4-(N,N-二乙基-N-甲基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ15)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ15。
1H NMR (600 MHz, DMSO-d 6) δ 11.51 (s, 2H), 10.86 (s, 4H), 8.75 (d, J =8.1 Hz, 4H), 8.19 (s, 4H), 8.11 (d, J = 8.2 Hz, 4H), 7.97 (t, J = 7.3 Hz,4H), 7.89 (t, J = 7.3 Hz, 4H), 7.65 (d, J = 2.1 Hz, 4H), 7.58 (d, J = 2.3 Hz,2H), 4.35 (t, J = 6.4 Hz, 8H), 3.18 (m, 24H), 2.80 (s, 12H), 1.89 – 1.82 (m,8H), 1.80 (q, J = 8.4, 7.7 Hz, 8H), 1.06 (t, J = 7.2 Hz, 24H), -0.40 (s, 2H).13C NMR (150 MHz, DMSO-d 6) δ 160.67, 151.84, 149.70, 145.32, 141.94, 140.65,135.43, 134.63, 132.80, 129.56, 126.07, 123.65, 122.71, 120.03, 117.98,105.07, 104.16, 97.06, 95.78, 67.73, 47.06, 40.31, 29.67, 27.85, 21.19,11.91. HRMS (MALDI-TOF): (m/z)calced for C100H118N8O4Br4 373.9822 [(M-4Br)/4]+;found, 373.9820。
[实施例22]
5,15,-二[3,5-二(4-(N,N,N-三乙基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ21)的制备
参照化合物Ⅱ1的合成方法制备了化合物Ⅱ21。
1H NMR (600 MHz, DMSO-d 6) δ 11.51 (s, 2H), 10.86 (s, 4H), 8.75 (d, J =8.2 Hz, 4H), 8.19 (s, 4H), 8.09 (d, J = 8.2 Hz, 4H), 7.97 (t, J = 7.3 Hz,4H), 7.89 (t, J = 7.3 Hz, 4H), 7.62 (d, J = 2.2 Hz, 4H), 7.53 (d, J = 2.4 Hz,2H), 4.31 (t, J = 6.5 Hz, 8H), 3.14 (q, J = 7.2 Hz, 24H), 3.11 – 3.06 (m,8H), 2.78 (s, 12H), 1.64 – 1.56 (m, 8H), 1.46 (p, J = 7.6 Hz, 8H), 1.06 (t, J= 7.2 Hz, 36H), -0.41 (s, 2H). 13C NMR (150 MHz, DMSO-d 6) δ 159.91, 150.74,140.60, 135.09, 133.19, 132.82, 132.39, 131.96, 129.38, 128.96, 128.25,127.08, 126.47, 124.71, 122.34, 120.38, 119.87, 116.68, 67.43, 60.75, 52.26,25.45, 20.92, 8.58. HRMS (MALDI-TOF): (m/z) calced for C104H126N8O4Br4 387.9979[(M-4Br)/4]+; found, 387.9971。
[实施例23]
MTT法测定光敏剂抗肿瘤增殖实验
受试细胞:
人食管癌细胞KYSE-150。
光源:
MDL-III-730型激光器;SD2490型激光功率测量仪。
受试化合物:
5,10,15,20-四[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(I1);5,10,15,20-四[4-(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(I2);5,10,15,20-四[4-(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(I3);5,10,15,20-四[4-(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(I4);5,10,15,20-四[4-(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(I5);5,10,15,20-四[4-(3-(N,N,N-三甲铵基)丙氧基)苯基]萘并卟吩四溴化物(I8);5,10,15,20-四[4-(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(I9);5,10,15,20-四[4-(5-(N,N,N-三甲铵基)戊氧基)苯基]萘并卟吩四溴化物(I10);5,10,15,20-四[4-(6-(N, N,N-三甲铵基)己氧基)苯基]萘并卟吩四溴化物(I11);5,15,-二[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ1);5,15,-二[3,5-二(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ2);5,15,-二[3,5-二(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ3);5,15,-二[3,5-二(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ4);5,15,-二[3,5-二(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ5);5,15,-二[3,5-二(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ9);5,15,-二[3,5-二(4-(N,N-二乙基-N-甲基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ15);5,15,-二[3,5-二(4-(N,N,N-三乙基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ21),对照化合物:
药物海姆泊芬;
四苯基卟吩季铵盐(化合物2);
5,15-二芳基卟吩衍生物(化合物3)
光动力抗肿瘤细胞增殖作用实验:
收集处于对数生长期的细胞,用完全培养基重悬成细胞悬液,接种于96孔板,每孔100 μL,置于37 ℃ 5% CO2培养箱培养,24 h后加入受试化合物;继续培养24 h后进行光照处理(波长730 nm,光剂量8 J/cm2)并加入培养基继续培养;24 h后进行MTT检测。检测前4h每孔加入20 μL 5 mg/mL的MTT,4 h后去除培养液后每孔加入150 μL DMSO,于酶标仪检测OD570 。实验重复三次。实验结果见表1,结果发现受试萘并卟吩阳离子衍生物中,部分受试化合物有非常显著的抗人食管癌细胞增殖活性,部分受试化合物活性较弱甚至微乎其微(如化合物I10,I11),其中化合物I3,I4,I8- I9,II1-II5,II9,II15和II21的光动力抗肿瘤活性均显著优于对照物海姆泊芬、化合物2和3。系列二中的受试化合物光动力抗肿瘤增殖活性更为优异,即在更小的药物剂量条件下,表现出更高的肿瘤抑制能力。
表1 新化合物对Eca-109人食管癌细胞增殖抑制作用
与对照药海姆泊芬相比,*P<0.05,**P<0.01,***P<0.001;
与对照化合物3相比,# P <0.05,## P <0.01,### P <0.001。
[实施例24]
光动力抗菌活性研究
受试菌株:
大肠杆菌(E.coli),金黄色葡萄球菌(S.aureus)。
光源:
MDL-III-730型激光器;SD2490型激光功率测量仪。
受试化合物:
5,10,15,20-四[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(I1);5,10,15,20-四[4-(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(I2);5,10,15,20-四[4-(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(I3);5,10,15,20-四[4-(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(I4);5,10,15,20-四[4-(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(I5);5,10,15,20-四[4-(3-(N,N,N-三甲铵基)丙氧基)苯基]萘并卟吩四溴化物(I8);5,10,15,20-四[4-(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(I9);5,10,15,20-四[4-(5-(N,N,N-三甲铵基)戊氧基)苯基]萘并卟吩四溴化物(I10);5,10,15,20-四[4-(6-(N, N,N-三甲铵基)己氧基)苯基]萘并卟吩四溴化物(I11);5,15,-二[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ1);5,15,-二[3,5-二(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ2);5,15,-二[3,5-二(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ3);5,15,-二[3,5-二(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ4);5,15,-二[3,5-二(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ5);5,15,-二[3,5-二(4-(N,N,N-三甲铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ9);5,15,-二[3,5-二(4-(N,N-二乙基-N-甲基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ15);5,15,-二[3,5-二(4-(N,N,N-三乙基铵基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ21);对照药物:
亚甲基蓝(MB);
四苯基卟吩季铵盐(化合物2);
5,15-二芳基卟吩衍生物(化合物3)。
光动力抗菌实验:
受试化合物用LB液体培养基以二倍梯度稀释法稀释至浓度为128~0.25 μM的溶液。将培养至对数生长期的细菌悬液用LB液体培养基稀释成106 CFU/mL,取50 μL细菌悬液于96孔板中与50 μL不同浓度的化合物于37 ℃培养箱共同孵育30 min,而后进行光照处理(波长730 nm,光剂量10 J/cm2),置于37 ℃培养箱培养。18 h后观察96孔板中个孔的澄清程度,将澄清孔所对应的最小化合物终浓度即完全抑制细菌生长的最低化合物浓度视为该化合物的最小抑菌浓度(MIC, μM),实验重复3次,实验结果见表2。结果发现受试萘并卟吩化合物对两种细菌有一定的抑菌效果,系列I中的受试化合物的光动力抗菌效果弱于对照化合物亚甲基蓝,强于对照化合物2;系列II中的受试化合物的抑菌效果优于系列I中的化合物,且光动力抗菌活性均明显优于亚甲基蓝、化合物2和化合物3。
表2. 新化合物MIC值(单位:μM)
Claims (6)
1.一类萘并卟吩阳离子衍生物及其在生物医药与材料领域的应用,其特征是具有下述结构(I)和(II):
:
其中A为烷基、含N或O或S原子的烷基、含羰基烷基、酰胺键的烷基、同时含烷烃基、羧(酯)基、羟基或氨基侧链的各类烷基;
R1 = ,,,,,:
其中X=Cl, Br, I;
R2 = -H, -F, -Cl, -Br, -I, -OH, -O(CH2)mCH3, -(CH2)mCH3, -(CH2)mO(CH2)nC(CH3)3, -(CH2)mO(CH2)nCH(CH3)2, -(CH2)mCOOH, -(CH2)mCH(CH3)COOH, -(CH2)mC(CH3)2COOH, -(CH2)mOH, -(CH2)mC6H4OH, -(CH2)mCO(CH2)nOH, -(CH2)mO(CH2)nOH, -(CH2)m(OCH2CH2)pOH, -(CH2)mR1, -(CH2)mC(CH3)2R1, -(CH2)mCH(CH3)R1, -(CH2)mO(CH2)nR1, -(CH2)mS(CH2)nR1, -(CH2)mO(CH2)mC(CH3)2R1, -(CH2)mO(CH2)mCH(CH3)R1, -(CH2)mS(CH2)mC(CH3)2R1, -(CH2)mS(CH2)mCH(CH3)R1, -(CH2)m(OCH2CH2)pR1, -(CH2)mCO(CH2)mC(CH3)2R1, -(CH2)mCO(CH2)mCH(CH3)R1, -(CH2)mCONH(CH2)nR1, -(CH2)mCONH(CH2)nC(CH3)2R1, -(CH2)mCONH(CH2)nCH(CH3)R1或氨基酸衍生物, m=0-7, n=1-7, p=1-5。
2.根据权利要求1的式(I)和(Ⅱ),其中
A为-(CH2) N- , -(CH2)mC(CH3)2-, -(CH2)mCH(CH3)-, -(CH2)mO(CH2) N- , -(CH2)mS(CH2) N- ,-(CH2)mO(CH2)mC(CH3)2-, -(CH2)mO(CH2)mCH(CH3)-, -(CH2)mS(CH2)mC(CH3)2-, -(CH2)mS(CH2)mCH(CH3)-, -(CH2)m(OCH2CH2)p-, -(CH2)mCO(CH2)mC(CH3)2-, -(CH2)mCO(CH2)mCH(CH3)-, -(CH2)mCONH(CH2) N- , -(CH2)mCONH(CH2)nC(CH3)2-, -(CH2)mCONH(CH2)nCH(CH3)-, -R3(CH2)mC(CH3)2-, -R3(CH2)mCH(CH3)-, -R3O(CH2) N- , -R3O(CH2)mC(CH3)2-, -R3O(CH2)mCH(CH3)-, -R3(OCH2CH2)p-, -R3CO(CH2)mCH(CH3)-, -R3CO(CH2)mC(CH3)2-, m=0-7, n=1-7, p=1-5; 其中R3为-CH[(CH2)mCH3], -CH[(CH2)nOCH3], -CH[(CH2)nOH], -CH[(CH2)mCOOH], -CH[(CH2)mO(CH2)nC(CH3)3], -CH[(CH2)mCOO(CH2)mCH3], -CH[(CH2)m(OCH2CH2)nCH3)], -CH[(CH2)mCO(CH2)nC(CH3)3], -CH[(CH2)mCO(CH2)nCH(CH3)2], -CH[(CH2)mCONH(CH2)nC(CH3)3],-CH((CH2)mCONH[CH2)nCH(CH3)2], m=0-7, n=1-7。
3.根据权利要求1中提及的氨基酸衍生物,其中氨基酸衍生物为:
-(CH2)mCONH(CH2)nCOOH, -(CH2)mCONHCH(CH3)COOH, -(CH2)mCONH(CH2)nCO(CH2)pCOOH,-(CH2)mCONHCH[CH(CH3)2]COOH, -(CH2)mCONHCH[CH2CH(CH3)2]COOH, -(CH2)mCONHCH[CH(CH3)CH2CH3]COOH, -(CH2)mCONHCH(CH2C6H5)COOH, -(CH2)mCON[(CH2)nCOOH]2, -(CH2)mCONHCH(COOH)CH2COOH, m=0-7, n=1-7, p=1-5。
4.根据权利要求1所述的一类萘并卟吩阳离子衍生物(I),其特征在于该类化合物中包括如下化合物:
5,10,15,20-四[4-(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(I1);
5,10,15,20-四[4-(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(I2);
5,10,15,20-四[4-(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(I3);
5,10,15,20-四[4-(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(I4);
5,10,15,20-四[4-(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(I5);
5,10,15,20-四[4-(7-(吡啶基)庚氧基)苯基]萘并卟吩四溴化物(I6);
5,10,15,20-四[4-(2-(N,N,N-三甲基)乙氧基)苯基]萘并卟吩四溴化物(I7);
5,10,15,20-四[4-(3-(N,N,N-三甲基)丙氧基)苯基]萘并卟吩四溴化物(I8);
5,10,15,20-四[4-(4-(N,N,N-三甲基)丁氧基)苯基]萘并卟吩四溴化物(I9);
5,10,15,20-四[4-(5-(N,N,N-三甲基)戊氧基)苯基]萘并卟吩四溴化物(I10);
5,10,15,20-四[4-(6-(N,N,N-三甲基)己氧基)苯基]萘并卟吩四溴化物(I11);
5,10,15,20-四[4-(7-(N,N,N-三甲基)庚氧基)苯基]萘并卟吩四溴化物(I12);
5,10,15,20-四[4-(2-(N,N-二乙基-N-甲基)乙氧基)苯基]萘并卟吩四溴化物(I13);
5,10,15,20-四[4-(3-(N,N-二乙基-N-甲基)丙氧基)苯基]萘并卟吩四溴化物(I14);
5,10,15,20-四[4-(4-(N,N-二乙基-N-甲基)丁氧基)苯基]萘并卟吩四溴化物(I15);
5,10,15,20-四[4-(5-(N,N-二乙基-N-甲基)戊氧基)苯基]萘并卟吩四溴化物(I16);
5,10,15,20-四[4-(6-(N,N-二乙基-N-甲基)己氧基)苯基]萘并卟吩四溴化物(I17);
5,10,15,20-四[4-(7-(N,N-二乙基-N-甲基)庚氧基)苯基]萘并卟吩四溴化物(I18);
5,10,15,20-四[4-(2-(N,N,N-三乙基)乙氧基)苯基]萘并卟吩四溴化物(I19);
5,10,15,20-四[4-(3-(N,N,N-三乙基)丙氧基)苯基]萘并卟吩四溴化物(I20);
5,10,15,20-四[4-(4-(N,N,N-三乙基)丁氧基)苯基]萘并卟吩四溴化物(I21);
5,10,15,20-四[4-(5-(N,N,N-三乙基)戊氧基)苯基]萘并卟吩四溴化物(I22);
5,10,15,20-四[4-(6-(N,N,N-三乙基)己氧基)苯基]萘并卟吩四溴化物(I23);
5,10,15,20-四[4-(7-(N,N,N-三乙基)庚氧基)苯基]萘并卟吩四溴化物(I24);
5,10,15,20-四[4-(2-(三苯基鏻)乙氧基)苯基]萘并卟吩四溴化物(I25);
5,10,15,20-四[4-(3-(三苯基鏻)丙氧基)苯基]萘并卟吩四溴化物(I26);
5,10,15,20-四[4-(4-(三苯基鏻)丁氧基)苯基]萘并卟吩四溴化物(I27);
5,10,15,20-四[4-(5-(三苯基鏻)戊氧基)苯基]萘并卟吩四溴化物(I28);
5,10,15,20-四[4-(6-(三苯基鏻)己氧基)苯基]萘并卟吩四溴化物(I29);
5,10,15,20-四[4-(7-(三苯基鏻)庚氧基)苯基]萘并卟吩四溴化物(I30);
5,10,15,20-四[4-(2-(喹啉基)乙氧基)苯基]萘并卟吩四溴化物(I31);
5,10,15,20-四[4-(3-(喹啉基)丙氧基)苯基]萘并卟吩四溴化物(I32);
5,10,15,20-四[4-(4-(喹啉基)丁氧基)苯基]萘并卟吩四溴化物(I33);
5,10,15,20-四[4-(5-(喹啉基)戊氧基)苯基]萘并卟吩四溴化物(I34);
5,10,15,20-四[4-(6-(喹啉基)己氧基)苯基]萘并卟吩四溴化物(I35);
5,10,15,20-四[4-(7-(喹啉基)庚氧基)苯基]萘并卟吩四溴化物(I36)。
5.根据权利要求1所述的一类萘并卟吩阳离子衍生物(Ⅱ),其特征在于该类化合物中包括如下化合物:
5,15,-二[3,5-二(2-(吡啶基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ1);
5,15,-二[3,5-二(3-(吡啶基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ2);
5,15,-二[3,5-二(4-(吡啶基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ3);
5,15,-二[3,5-二(5-(吡啶基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ4);
5,15,-二[3,5-二(6-(吡啶基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ5);
5,15,-二[3,5-二(7-(吡啶基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ6);
5,15,-二[3,5-二(2-(N,N,N-三甲基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ7);
5,15,-二[3,5-二(3-(N,N,N-三甲基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ8);
5,15,-二[3,5-二(4-(N,N,N-三甲基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ9);
5,15,-二[3,5-二(5-(N,N,N-三甲基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ10);
5,15,-二[3,5-二(6-(N,N,N-三甲基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ11);
5,15,-二[3,5-二(7-(N,N,N-三甲基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ12);
5,15,-二[3,5-二(2-(N,N-二乙基-N-甲基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ13);
5,15,-二[3,5-二(3-(N,N-二乙基-N-甲基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ14);
5,15,-二[3,5-二(4-(N,N-二乙基-N-甲基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ15);
5,15,-二[3,5-二(5-(N,N-二乙基-N-甲基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ16);
5,15,-二[3,5-二(6-(N,N-二乙基-N-甲基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ17);
5,15,-二[3,5-二(7-(N,N-二乙基-N-甲基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ18);
5,15,-二[3,5-二(2-(N,N,N-三乙基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ19);
5,15,-二[3,5-二(3-(N,N,N-三乙基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ20);
5,15,-二[3,5-二(4-(N,N,N-三乙基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ21);
5,15,-二[3,5-二(5-(N,N,N-三乙基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ22);
5,15,-二[3,5-二(6-(N,N,N-三乙基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ23);
5,15,-二[3,5-二(7-(N,N,N-三乙基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ24);
5,15,-二[3,5-二(2-(三苯基鏻)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ25);
5,15,-二[3,5-二(3-(三苯基鏻)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ26);
5,15,-二[3,5-二(4-(三苯基鏻)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ27);
5,15,-二[3,5-二(5-(三苯基鏻)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ28);
5,15,-二[3,5-二(6-(三苯基鏻)己氧基)苯基]萘并卟吩四溴化物(Ⅱ29);
5,15,-二[3,5-二(7-(三苯基鏻)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ30);
5,15,-二[3,5-二(2-(喹啉基)乙氧基)苯基]萘并卟吩四溴化物(Ⅱ31);
5,15,-二[3,5-二(3-(喹啉基)丙氧基)苯基]萘并卟吩四溴化物(Ⅱ32);
5,15,-二[3,5-二(4-(喹啉基)丁氧基)苯基]萘并卟吩四溴化物(Ⅱ33);
5,15,-二[3,5-二(5-(喹啉基)戊氧基)苯基]萘并卟吩四溴化物(Ⅱ34);
5,15,-二[3,5-二(6-(喹啉基)己氧基)苯基]萘并卟吩四溴化物(Ⅱ35);
5,15,-二[3,5-二(7-(喹啉基)庚氧基)苯基]萘并卟吩四溴化物(Ⅱ36)。
6.权利要求1所述的一类萘并卟吩阳离子衍生物(I)和(II)可用于诊断和治疗微生物感染性疾病、肿瘤、视网膜黄斑变性、光化性角化病、鲜红斑痣、尖锐湿疣等疾病的光动力药物领域,还可作为光学染料与试剂应用于荧光成像、荧光标记或光电材料领域。
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