CN111825685B - 一类血卟啉单氟代烷基双醚与氟代苯基烷基双醚衍生物及其在医药领域的应用 - Google Patents

一类血卟啉单氟代烷基双醚与氟代苯基烷基双醚衍生物及其在医药领域的应用 Download PDF

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CN111825685B
CN111825685B CN202010726290.3A CN202010726290A CN111825685B CN 111825685 B CN111825685 B CN 111825685B CN 202010726290 A CN202010726290 A CN 202010726290A CN 111825685 B CN111825685 B CN 111825685B
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ethyl
bis
porphyrin
difluorophenyl
deuteroporphyrin
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CN111825685A (zh
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陈志龙
李慢一
严懿嘉
张嘉辉
朱雪雪
高迎华
山妮妮
坎敏敏
王来兴
韩一平
江颖
马大福
奧多纳
邱彦
金辉
吴晓锋
阮继武
陈婷
刘世芳
张洪涛
糜乐
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SHANGHAI XIANHUI MEDICAL TECHNOLOGY CO LTD
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
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    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P17/00—Drugs for dermatological disorders
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract

本发明涉及一类血卟啉单氟代烷基双醚(I)与氟代苯基烷基双醚衍生物(II)及其在医药领域的应用，该类化合物具有下述结构：

Description

一类血卟啉单氟代烷基双醚与氟代苯基烷基双醚衍生物及其在医药领域的应用
技术领域
本发明涉及到光敏药物与光动力疗法，具体涉及一类血卟啉单氟代烷基双醚与氟代苯基烷基双醚衍生物及其在医药领域的应用。
背景技术
光动力疗法(photodynamic therapy，PDT)作为治疗肿瘤、视网膜黄斑变性、光化性角化病、鲜红斑痣、尖锐湿疣等疾病的新方法(Chem.Rev.2019,119,797-828)，已经在临床治疗中取得了令人瞩目的成就，其机理是光敏剂进入机体后，随血液循环选择性地聚集于靶组织，然后用一定波长的激光照射到靶组织，产生活性氧(如单线态氧)作用于靶细胞，引起细胞代谢紊乱，从而杀伤靶细胞。
在光动力治疗中，光敏药物(也称光敏剂或光动力药物)作为能量的载体、反应的桥梁起着决定性的作用。目前最常用的光敏剂是1993年在加拿大批准治疗膀胱癌的光敏素II(Photofrin II)，该药物是由多个化合物组成的混合物，制备过程中各成分的含量较难控制，有些成分在皮肤中滞留时间长，需避光4周以上，病人难以耐受(国外医药-合成药、生化药、制剂分册,1998,19(1)：32-34；世界临床药物,2018,39(4)：285-288)，因此限制了光动力技术在医学上的应用。为了克服光敏素II组成成分复杂、有较强皮肤光毒作用的缺点，本团队许德余、张浩等早期研发了血卟啉单甲醚(中国医药工业杂志,1989,20(2)：60-63)，也称海姆泊芬(HMME，Hemoporfin)，它具有化合物成分明确、给药后避光期短等明显优点，成为全国首个治疗鲜红斑痣的光敏药物(中国激光医学杂志,2018,27(1)：01-05)，但血卟啉单甲醚仍存在组成成分为一对异构体、结构不是很稳定的缺点。
氟的范德华半径接近氢离子，可完美代替氢；此外，氟还可以增加药物疏水性，使之更亲脂，提高生物利用度。由于氟电负性大，吸引电子能力强，可增强药物和靶点作用力；且相对于其他卤素原子，氟与碳原子结合更牢固，键能更高，可提高药物的代谢稳定性。随着第一个含氟药物(5-氟尿嘧啶)成功开发，氟取代策略逐渐成为了药物研发的重要策略之一。
福田容三、大谷卓三等人在专利(JP19860088799)中报道了血卟啉多氟取代或者全氟取代烷基醚衍生物，但该专利并没有报道这些化合物的药理活性。我们制备了该专利中的代表性化合物3,8-二(1-(2,2-二氟乙氧基)乙基)次卟啉(式1)和3,8-二(1-(3,3,3-三氟丙氧基)乙基)次卟啉(式2)，并对其结构进行改造，制备了3,8-二(1-(2-氟乙氧基)乙基)次卟啉(I1)与3,8-二(1-(3-氟丙氧基)乙基)次卟啉(I2)，药理活性实验结果表明，血卟啉单氟取代烷基双醚衍生物比相同烷基长度的血卟啉多氟取代或者全氟取代烷基双醚衍生物的光动力抗肿瘤效果好。据此，我们设计并制备了一类新的结构稳定、皮肤光毒副作用弱、工艺简单易行的血卟啉单氟代烷基双醚衍生物。
另外，在本团队研发的血卟啉单甲醚以及娄达军与许德余等研发血卟啉醚类衍生物(专利CN 1113914A)的基础上，我们在血卟啉烷基醚衍生物的烷基末端引入了氟代苯基，设计并制备了一类结构新颖、制备工艺简单的血卟啉氟代苯基烷基双醚衍生物。药理活性实验结果表明，血卟啉氟代苯基烷基双醚衍生物的光动力抗肿瘤效果比本团队早期研发的血卟啉醚类衍生物好。
Figure GDA0004104654720000021
发明内容
为了克服光敏素II或血卟啉单甲醚等现有光敏药物存在的某些缺点，如组分复杂、稳定性较差、皮肤光毒时间较长等，本发明设计合成了新的血卟啉单氟代烷基双醚衍生物、血卟啉单氟或双氟代苯基烷基双醚衍生物。研究表明氟原子的引入提高了化合物的单线态氧产率，改善了血卟啉醚类衍生物在肿瘤组织中的吸收、分布与代谢，光动力治疗效果得以加强；新化合物结构稳定、皮肤光毒副作用弱、制备工艺简单易行。在付出大量创造性劳动后合成了新的血卟啉单氟代烷基双醚衍生物与氟代苯基烷基双醚醚衍生物，完成了本发明。
本发明涉及一类血卟啉单氟代烷基双醚与血卟啉氟代苯基烷基双醚衍生物及其应用。
本发明概述如下：
一类血卟啉单氟代烷基双醚衍生物具有下述结构(I)：
Figure GDA0004104654720000022
其中，R为H或M，M主要是锂、钠、钾离子，且优先选择钠和钾离子；n1为1-8的整数。
一类血卟啉单氟或双氟代苯基烷基双醚衍生物具有下述结构(II)：
Figure GDA0004104654720000031
其中，R为H或M，M主要是锂、钠、钾离子，且优先选择钠和钾离子；R1、R2、R3、R4、R5各自独立的选自为氢、氟，n2为0-4的整数；
当苯环上只有一个氟原子取代：R1为F时，R2、R3、R4、R5为H；R2为F时，R1、R3、R4、R5为H；R3为F时，R1、R2、R4、R5为H；
当苯环上有两个氟原子取代：R1、R2为F时，R3、R4、R5为H；R1、R3为F时，R2、R4、R5为H；R1、R4为F时，R2、R3、R5为H；R1、R5为F时，R2、R3、R4为H；R2、R3为F时，R1、R4、R5为H；R2、R4为F时，R1、R3、R5为H。
本发明所述的血卟啉单氟代烷基双醚衍生物(式I)，该类化合物包括：
3,8-二(1-(2-氟乙氧基)乙基)次卟啉(I1)；
3,8-二(1-(3-氟丙氧基)乙基)次卟啉(I2)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉(I3)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉(I4)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉(I5)；
3,8-二(1-(7-氟庚氧基)乙基)次卟啉(I6)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钠盐(I7)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钾盐(I8)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钠盐(I9)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钾盐(I10)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钠盐(I11)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钾盐(I12)。
本发明所述的血卟啉单氟或双氟代苯基烷基双醚衍生物(式II)，该类化合物包括：
3,8-二(1-(2-氟苯基甲氧基)乙基)次卟啉(II1)；
3,8-二(1-(3-氟苯基甲氧基)乙基)次卟啉(II2)；
3,8-二(1-(4-氟苯基甲氧基)乙基)次卟啉(II3)；
3,8-二[1-(2-(2-氟苯基)乙氧基)乙基]次卟啉(II4)；
3,8-二[1-(2-(3-氟苯基)乙氧基)乙基]次卟啉(II5)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉(II6)；
3,8-二[1-(3-(2-氟苯基)丙氧基)乙基]次卟啉(II7)；
3,8-二[1-(3-(3-氟苯基)丙氧基)乙基]次卟啉(II8)；
3,8-二[1-(3-(4-氟苯基)丙氧基)乙基]次卟啉(II9)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉(II10)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉(II11)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉(II12)；
3,8-二(1-(2,3-二氟苯基甲氧基)乙基)次卟啉(II13)；
3,8-二(1-(2,4-二氟苯基甲氧基)乙基)次卟啉(II14)；
3,8-二(1-(2,5-二氟苯基甲氧基)乙基)次卟啉(II15)；
3,8-二(1-(2,6-二氟苯基甲氧基)乙基)次卟啉(II16)；
3,8-二(1-(3,4-二氟苯基甲氧基)乙基)次卟啉(II17)；
3,8-二(1-(3,5-二氟苯基甲氧基)乙基)次卟啉(II18)；
3,8-二[1-(2-(2,3-二氟苯基)乙氧基)乙基]次卟啉(II19)；
3,8-二[1-(2-(2,4-二氟苯基)乙氧基)乙基]次卟啉(II20)；
3,8-二[1-(2-(2,5-二氟苯基)乙氧基)乙基]次卟啉(II21)；
3,8-二[1-(2-(2,6-二氟苯基)乙氧基)乙基]次卟啉(II22)；
3,8-二[1-(2-(3,4-二氟苯基)乙氧基)乙基]次卟啉(II23)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉(II24)；
3,8-二[1-(3-(2,3-二氟苯基)丙氧基)乙基]次卟啉(II25)；
3,8-二[1-(3-(2,4-二氟苯基)丙氧基)乙基]次卟啉(II26)；
3,8-二[1-(3-(2,5-二氟苯基)丙氧基)乙基]次卟啉(II27)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉(II28)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉(II29)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉(II30)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉(II31)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉(II32)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉(II33)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钠盐(II34)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钾盐(II35)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉二钠盐(II36)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉二钾盐(II37)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉二钠盐(II38)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉二钾盐(II39)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉二钠盐(II40)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉二钾盐(II41)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钠盐(II42)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钾盐(II43)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II44)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II45)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II46)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II47)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II48)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II49)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II50)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II51)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II52)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II53)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II54)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II55)。
本发明首次制备了所述的新的血卟啉单氟代烷基双醚衍生物(式I)和血卟啉氟代苯基烷基双醚衍生物(式II)，具备新颖性。
与福田容三、大谷卓三等人在专利(JP19860088799)中报道的血卟啉多氟取代或者全氟取代烷基双醚衍生物相比，本发明所述的血卟啉氟代烷基双醚衍生物(I)具有更高的光动力抗肿瘤活性；本发明所述的血卟啉氟代苯基烷基双醚衍生物(II)的抗肿瘤效果较本团队娄达军、许德余等研发的血卟啉醚类衍生物好；因此本发明所述的新化合物具有实质性的进步。
本发明所述的血卟啉单氟代烷基双醚衍生物(I)与血卟啉氟代苯基烷基双醚衍生物(II)具有显著的光动力活性，可作为肿瘤、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治疗药物，具有实用性。
具体实施方式
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。
[实施例1]
3,8-二(1-(2-氟乙氧基)乙基)次卟啉(I1)的制备：
Figure GDA0004104654720000061
在圆底烧瓶中加入原卟啉二甲酯(614mg，1.041mmol)，再加入含量约为30％的溴化氢/醋酸溶液(7mL)，室温搅拌约36h，TLC监测反应完全后，减压蒸馏除去溶剂；向残留固体中加入2-氟乙醇(3mL)使之溶解，室温搅拌4h，反应结束后，加入乙酸乙酯(EA)稀释，用水洗涤四次，减压蒸馏除去溶剂；用四氢呋喃(THF，8mL)溶解残留物，加入NaOH溶液(2M，3mL)后室温搅拌2h，加水(50mL)稀释，并加入稀盐酸溶液(2M，3mL)调节pH至弱酸性，用乙酸乙酯(50mL×3)萃取，饱和氯化钠溶液洗涤(50mL×3)，无水硫酸钠干燥后，对所得残留物柱层析分离纯化得到暗红色粉末I1(371mg，51.53％)。1H NMR(400MHz,Pyr-d5)δppm：11.01(s,1H),10.96(s,1H),10.89(s,1H,),10.40(s,1H),6.36(d,J＝7.0Hz,2H),4.87(m,4H),4.70(s,4H),4.08(d,J＝30.5Hz,4H),3.75–3.67(m,12H),3.65(s,4H),2.36(d,J＝12.7Hz,6H),-3.02(s,2H).13C NMR(101MHz,Pyr-d5)δppm:176.90,165.51,165.39,164.01,163.89,163.05,162.94,161.54,148.32,145.90,133.42,132.11,124.09,123.91,122.28,112.96,112.74,105.64,105.39,105.13,100.61,100.22,99.69,99.37,99.27,99.12,74.80,66.06,39.22,26.81,23.81,14.09,14.04,12.92,12.83.19F NMR(377MHz,Pyr-d5)δppm:17.20-16.94(m).MS(MALDI TOF)(DART Positive):m/z calcd for C38H44F2N4O6[M+H]+,690.3；found,690.7.
[实施例2]
3,8-二(1-(3-氟丙氧基)乙基)次卟啉(I2)的制备：
Figure GDA0004104654720000062
采用化合物I1的合成方法制备了化合物I2。1H NMR(400MHz,Pyr-d5)δppm：10.96(s,1H),10.89(d,J＝10.0Hz,2H,),10.39(s,1H,),6.29(s,2H,),4.69(s,4H,),3.94(s,4H,),3.69(s,12H,),3.65(s,4H,),2.36(s,6H,),1.36-1.19(m,8H,),-3.03(s,2H,).13CNMR(101MHz,Pyr-d5)δppm：176.92,174.67,151.66,151.01,150.60,137.31,136.91,136.67,136.28,125.28,124.93,124.69,124.25,100.65,100.40,100.10,99.33,99.03,83.90,82.28,75.19,66.64,39.23,33.41,33.09,32.90,31.27,30.89,26.86,24.23,23.82,22.69,15.57,14.12,14.07,12.94,12.91,12.81,12.76.19F NMR(377MHz,DMSO-d6)δppm：17.66(s).MS(MALDI TOF)(DART Positive):m/z calcd for C40H48F2N4O6[M+H]+,719.6；found,719.6.
[实施例3]
3,8-二(1-(4-氟丁氧基)乙基)次卟啉(I3)的制备：
Figure GDA0004104654720000071
采用化合物I1的合成方法制备了化合物I3。1H NMR(400MHz,Pyr-d5)δppm：11.00(s,1H,),10.94(s,1H,),10.89(s,1H,),10.40(s,1H,),6.27(s,2H,),4.69(s,4H,),4.51(s,2H,),4.39(s,2H,),3.83(s,2H,),3.78–3.69(m,12H,),3.67(s,2H,),3.64(s,4H,),2.37(s,6H,),1.95(s,4H,),-3.02(s,2H,).13CNMR(101MHz,Pyr-d5)δppm：175.39,150.17,149.08,139.72,135.78,135.38,135.14,134.76,123.76,123.64,123.41,123.17,122.73,99.04,98.71,97.49,96.25,84.75,83.12,73.50,68.79,37.70,27.87,27.68,26.22,25.41,22.30,11.45,11.40,11.34,11.26.19FNMR(377MHz,Pyr-d5)δppm：-216.99(d,J＝24.5Hz),-217.08(s),-217.12--217.34(m).MS(MALDI TOF)(DART Positive):m/z calcdfor C42H52F2N4O6[M+H]+,746.8；found,746.8.
[实施例4]
3,8-二(1-(5-氟戊氧基)乙基)次卟啉(I4)的制备：
Figure GDA0004104654720000072
采用化合物I1的合成方法制备了化合物I4。1H NMR(600MHz,DMSO-d6)δppm:7.09(s,1H),6.86(d,J＝7.2Hz,2H),6.60(s,1H),5.14(s,1H),4.30(d,J＝1.8Hz,3H),3.36(d,J＝13.6Hz,4H),2.89(s,1H),2.48(s,2H),2.42(s,1H),2.11(d,J＝12.0Hz,12H),1.57(d,J＝16.6Hz,5H),1.51(d,J＝1.8Hz,4H),1.29(s,4H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,124.43,99.30,96.93,95.92,93.26,82.86,70.63,70.09,69.11,37.88,30.18,26.33,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,Pyr-d5)δppm:-218.20(s).MS(MALDI TOF)(DART Positive):m/zcalcd for C44H56F2N4O6[M+H]+,774.4；found,774.5.
[实施例5]
3,8-二(1-(6-氟己氧基)乙基)次卟啉(I5)的制备：
Figure GDA0004104654720000081
采用化合物I1的合成方法制备了化合物I5。1H NMR(600MHz,DMSO-d6)δppm:7.12(s,8H),7.08(s,8H),6.99(s,8H),6.69(s,8H),5.19(s,8H),4.36(s,17H),4.30(s,18H),3.36(d,J＝15.0Hz,30H),2.85(s,8H),2.48(d,J＝4.1Hz,42H),2.11(d,J＝12.0Hz,96H),1.59(s,3H),1.53(dd,J＝38.5,8.4Hz,66H),1.43(s,35H),1.29(s,31H),1.09(s,25H).13CNMR(150MHz,DMSO-d6)δppm:175.89,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96),136.32,136.18,135.34,133.23,131.95,124.43,99.30,96.93,95.92,93.26,82.86,70.63,70.09,69.11,37.88,30.18,28.99,26.58,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-218.20(s).MS(MALDITOF)(DART Positive):m/z calcd for C46H60F2N4O6[M+H]+,802.4；found,802.5.
[实施例6]
3,8-二(1-(7-氟庚氧基)乙基)次卟啉(I6)的制备：
Figure GDA0004104654720000082
采用化合物I1的合成方法制备了化合物I6。1H NMR(600MHz,DMSO-d6)δppm:7.22(s,3H),7.12(s,3H),6.88(s,3H),6.53(s,3H),5.21(s,3H),4.27(d,J＝34.5Hz,15H),4.23–3.99(m,5H),3.36(d,J＝10.7Hz,10H),2.85(s,3H),2.48(d,J＝3.8Hz,15H),2.11(d,J＝12.0Hz,35H),1.58(s,11H),1.53(t,J＝5.2Hz,12H),1.43(s,11H),1.27(d,J＝18.0Hz,22H),1.09(s,9H).13CNMR(150MHz,DMSO-d6)δppm:175.89,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,124.43,99.30,96.93,95.92,93.26,82.86,70.63,70.09,69.11,37.88,30.18,29.02,26.58,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-218.20(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H64F2N4O6[M+H]+,830.5；found,830.6.
[实施例7]
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钠盐(I7)的制备：
Figure GDA0004104654720000091
将3,8-二(1-(4-氟丁氧基)乙基)次卟啉10g(14.48mmol)加到烧瓶中，加入60mL乙醇，搅拌使固体溶解。缓慢加入2mol/L的氢氧化钠水溶液14.48mL(28.96mmol)，继续搅拌30分钟。减压除去溶剂，真空干燥，得到3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钠盐(I7)10.64g，收率约100％。MS(ESI)m/z：744.1[M-2Na+1]+,767.9[M-Na]+,790.5[M]+。UV-vis(H2O)λmax/nm(logε)401(15.63),502(1.50),533(0.98),563(0.69),624(0.45)。焰色反应呈黄色。
[实施例8]
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钾盐(I8)的制备：
Figure GDA0004104654720000092
将3,8-二(1-(4-氟丁氧基)乙基)次卟啉10g(14.48mmol)加到100mL的烧瓶中，加入60mL乙醇，搅拌使固体溶解。缓慢加入2mol/L的氢氧化钾水溶液14.48mL(28.96mmol)，继续搅拌30分钟。减压除去溶剂，真空干燥，得到3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钾盐(I8)10.64g，收率约100％。MS(ESI)m/z：744.6[M-2K+1]+,767.0[M-K]+,790.1[M]+。UV-vis(H2O)λmax/nm(logε)402(15.87),502(1.34),533(0.96),566(0.73),623(0.44)。焰色反应呈浅紫色。
[实施例9]
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钠盐(I9)的制备：
Figure GDA0004104654720000101
采用化合物I7的合成方法制备了化合物I9。MS(ESI)m/z：771.1[M-2Na+1]+,795.5[M-Na]+,818.6[M]+。UV-vis(H2O)λmax/nm(logε)402(16.53),500(1.44),534(0.95),569(0.71),623(0.42)。焰色反应呈黄色。
[实施例10]
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钾盐(I10)的制备：
Figure GDA0004104654720000102
采用化合物I8的合成方法制备了化合物I10。MS(ESI)m/z：771.1[M-2K+1]+,795.5[M-K]+,818.6[M]+。UV-vis(H2O)λmax/nm(logε)402(15.53),501(1.38),535(0.99),567(0.74),621(0.43)。焰色反应呈浅紫色。
[实施例11]
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钠盐(I11)的制备：
Figure GDA0004104654720000103
采用化合物I7的合成方法制备了化合物I11。MS(ESI)m/z：800.1[M-2Na+1]+,823.4[M-Na]+,845.9[M]+。UV-vis(H2O)λmax/nm(logε)402(15.49),501(1.36),533(0.97),569(0.69),625(0.45)。焰色反应呈黄色。
[实施例12]
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钾盐(I12)的制备：
Figure GDA0004104654720000111
采用化合物I8的合成方法制备了化合物I12。MS(ESI)m/z：800.7[M-2Na+1]+,823.3[M-Na]+,818.6[M]+。UV-vis(H2O)λmax/nm(logε)402(16.48),501(1.56),535(0.87),568(0.73),622(0.39)。焰色反应呈浅紫色。
[实施例13]
3,8-二(1-(2-氟苯基甲氧基)乙基)次卟啉(II1)的制备：
Figure GDA0004104654720000112
采用化合物I1的合成方法制备了化合物II1。1H NMR(600MHz,DMSO-d6)δppm:7.63(s,3H),7.28–7.18(m,9H),7.08(d,J＝5.5Hz,4H),6.95(s,2H),6.87(s,2H),5.30(s,2H),4.82(s,4H),4.60(d,J＝61.9Hz,6H),2.87(s,2H),2.49(d,J＝8.1Hz,11H),2.11(d,J＝12.0Hz,24H),1.59(s,6H),1.09(s,6H).13C NMR(150MHz,DMSO-d6)δppm:175.89,160.34,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,130.52,129.83,129.05,124.47,115.21,99.30,96.93,95.92,93.26,69.12,68.41,66.85,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19FNMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd forC48H48F2N4O6[M+H]+,814.4；found,814.2.
[实施例14]
3,8-二(1-(3-氟苯基甲氧基)乙基)次卟啉(II2)的制备：
Figure GDA0004104654720000121
采用化合物I1的合成方法制备了化合物II2。1H NMR(600MHz,DMSO-d6)δppm:7.34(d,J＝9.9Hz,1H),7.31(s,4H),7.39–7.10(m,16H),7.02(s,2H),6.47(s,2H),6.15(s,2H),5.25(s,2H),4.71(s,4H),4.60(s,4H),4.39(s,2H),2.97(s,2H),2.54(s,2H),2.46(s,5H),2.10(d,J＝11.9Hz,23H),1.58(s,6H),1.08(s,6H).13C NMR(150MHz,DMSO-d6)δppm:175.89,162.92,147.86,145.38,144.33,142.54,141.65,140.96,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,128.79,124.40,115.96,114.68,99.30,96.93,95.92,93.26,71.55,69.12,68.41,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-113.10(s).MS(MALDI TOF)(DART Positive):m/zcalcd for C48H48F2N4O6[M+H]+,814.4；found,814.6.
[实施例15]
3,8-二(1-(4-氟苯基甲氧基)乙基)次卟啉(II3)的制备：
Figure GDA0004104654720000122
采用化合物I1的合成方法制备了化合物II3。1H NMR(600MHz,DMSO-d6)δppm:7.25(s,3H),7.19(d,J＝8.4Hz,5H),6.91(s,1H),6.61(s,1H),6.12(s,1H),5.29(s,1H),4.64(s,2H),4.52(s,2H),4.43(s,1H),2.99(s,1H),2.56(s,1H),2.48(s,3H),2.11(d,J＝12.0Hz,12H),1.58(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,163.53,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.66,133.23,131.95,131.76,124.43,115.77,99.30,96.93,95.92,93.26,71.12,69.12,68.41,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-115.50(s).MS(MALDI TOF)(DART Positive):m/z calcd forC48H48F2N4O6[M+H]+,814.4；found,814.9.
[实施例16]
3,8-二[1-(2-(2-氟苯基)乙氧基)乙基]次卟啉(II4)的制备：
Figure GDA0004104654720000131
采用化合物I1的合成方法制备了化合物II4。1H NMR(600MHz,DMSO-d6)δppm:7.60(s,1H),7.17(d,J＝12.0Hz,3H),7.06(s,2H),6.84(s,1H),6.69(s,1H),6.47(s,1H),6.19(s,1H),5.21(s,1H),4.13(s,1H),3.76(d,J＝5.9Hz,4H),2.91(s,1H),2.75(d,J＝1.4Hz,4H),2.55(s,1H),2.48(s,2H),2.11(d,J＝12.0Hz,12H),1.58(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,162.40,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,131.71,127.98,127.76,125.51,124.43,116.97,99.30,96.93,95.92,93.26,70.63,70.09,68.94,37.88,33.60,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C50H52F2N4O6[M+H]+,842.4；found,841.8.
[实施17]
3,8-二[1-(2-(3-氟苯基)乙氧基)乙基]次卟啉(II5)的制备：
Figure GDA0004104654720000132
采用化合物I1的合成方法制备了化合物II5。1H NMR(400MHz,Pyr-d5)δppm：10.91(s,1H),10.88(d,J＝3.9Hz,2H),10.39(s,1H),7.09(s,6H),6.94(s,2H),6.32(d,J＝6.7Hz,2H),4.70(s,4H),4.10(d,J＝4.4Hz,4H),3.70(d,J＝3.2Hz,12H),3.66(s,4H),3.18(s,4H),2.36(d,J＝6.5Hz,6H),-3.03(s,2H).13C NMR(101MHz,Pyr-d5)δppm：181.90,175.38,164.14,161.72,150.16,149.16,149.08,149.02,142.56,135.77,135.61,135.37,135.12,134.74,129.91,124.99,123.75,122.72,116.05,115.84,113.03,112.82,98.96,98.58,97.79,97.48,73.63,69.78,64.51,37.70,36.53,34.51,31.47,28.97,25.35,22.61,22.30,14.20,14.00,11.46,11.39,11.31,11.24,0.61.19F NMR(377MHz,Pyr-d5)δppm：-111.88--112.52(m).MS(MALDI TOF)(DART Positive):m/z calcd for C50H52F2N4O6[M+H]+,842.6；found,842.6.
[实施例18]
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉(II6)的制备：
Figure GDA0004104654720000141
采用化合物I1的合成方法制备了化合物II6。1H NMR(400MHz,Pyr-d5)δppm：10.89(s,3H),10.39(s,1H),7.23(s,4H),6.95(s,4H),6.32(s,2H),4.69(s,4H),4.06(s,4H),3.68(d,J＝15.5Hz,18H),3.15(s,4H),2.36(s,4H),-3.03(s,2H).13C NMR(101MHz,Pyr-d5)δppm:176.84,175.39,162.75,160.34,150.16,149.08,135.77,135.37,135.13,134.74,130.75,130.68,123.76,123.41,123.15,122.89,122.72,115.09,114.88,98.99,98.62,97.79,97.48,80.54,73.59,70.16,56.95,37.70,36.02,31.59,29.68,29.54,27.31,25.99,25.38,25.32,23.80,22.30,21.15,19.27,16.77,11.45,11.39,11.28,11.23,-14.90.19F NMR(377MHz,Pyr-d5)δppm：-114.93--116.04(m).MS(MALDI TOF)(DARTPositive):m/z calcd for C50H52F2N4O6[M+H]+,842.6；found,842.3.
[实施例19]
3,8-二[1-(3-(2-氟苯基)丙氧基)乙基]次卟啉(II7)的制备：
Figure GDA0004104654720000142
采用化合物I1的合成方法制备了化合物II7。1H NMR(600MHz,DMSO-d6)δppm:7.60(s,3H),7.29(s,2H),7.24(s,2H),7.17(d,J＝12.0Hz,6H),7.06(s,3H),6.65(s,2H),6.37(s,2H),5.22(s,2H),4.22(s,2H),3.37(d,J＝7.8Hz,6H),2.90(s,2H),2.62(d,J＝6.4Hz,9H),2.48(s,6H),2.11(d,J＝12.0Hz,23H),1.88(d,J＝12.4Hz,5H),1.58(s,6H),1.09(s,6H).13C NMR(150MHz,DMSO-d6)δppm:175.89,162.22,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,131.09,129.53,127.49,125.10,124.43,116.40,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,31.25,30.71,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C52H56F2N4O6[M+H]+,870.4；found,870.0.
[实施例20]
3,8-二[1-(3-(3-氟苯基)丙氧基)乙基]次卟啉(II8)的制备：
Figure GDA0004104654720000151
采用化合物I1的合成方法制备了化合物II8。1H NMR(600MHz,DMSO-d6)δppm:7.33(s,8H),7.28–6.96(m,40H),7.00(s,19H),7.00(s,13H),6.59(s,5H),5.95(s,5H),4.79(s,5H),4.11(s,5H),3.34(d,J＝14.7Hz,16H),2.81(s,6H),2.77(s,11H),2.47(d,J＝10.9Hz,28H),2.11(d,J＝12.0Hz,59H),1.96(s,6H),1.88(s,9H),1.58(s,15H),1.09(s,15H).13CNMR(150MHz,DMSO-d6)δppm:175.89,164.01,147.86),145.38,144.33,143.34,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,128.73,125.72,124.43,115.60,112.51,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,34.78,30.67,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-113.10(s).MS(MALDI TOF)(DART Positive):m/z calcd for C52H56F2N4O6[M+H]+,870.4；found,870.5.
[实施例21]
3,8-二[1-(3-(4-氟苯基)丙氧基)乙基]次卟啉(II9)的制备：
Figure GDA0004104654720000152
采用化合物I1的合成方法制备了化合物II9。1H NMR(600MHz,DMSO-d6)δppm:7.41(s,2H),7.34(s,2H),7.17(d,J＝12.0Hz,16H),6.19(s,2H),6.05(s,2H),5.27(s,2H),4.47(s,2H),3.38(d,J＝2.7Hz,6H),2.77(s,4H),2.72(s,3H),2.60(s,2H),2.48(s,5H),2.11(d,J＝12.0Hz,24H),1.91(d,J＝17.7Hz,6H),1.58(s,6H),1.09(s,6H).13C NMR(150MHz,DMSO-d6)δppm:175.89,162.39,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,138.38,136.32,136.18,135.34,133.23,131.95,130.13,124.43,116.27,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,34.34,30.67,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-115.50(s).MS(MALDITOF)(DART Positive):m/z calcd for C52H56F2N4O6[M+H]+,870.4；found,870.1.
[实施例22]
3,8-二(1-(2,3-二氟苯基甲氧基)乙基)次卟啉(II13)的制备：
Figure GDA0004104654720000161
采用化合物I1的合成方法制备了化合物II13。1H NMR(600MHz,DMSO-d6)δppm:7.13(d,J＝6.0Hz,9H),7.06–7.01(m,11H),6.96(s,3H),6.48(s,3H),5.33(s,3H),4.81(s,6H),4.73(s,6H),4.49(s,3H),2.95(s,3H),2.48(s,7H),2.30(s,5H),2.11(d,J＝12.0Hz,35H),1.58(s,9H),1.09(s,9H).13C NMR(150MHz,DMSO-d6)δppm:175.89,152.46,151.71,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,132.82,131.95,125.57,125.32,124.43,117.81,99.30,96.93,95.92,93.26,69.12,68.41,66.40,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-138.10(s),-140.70(s).MS(MALDI TOF)(DART Positive):m/zcalcd for C48H46F4N4O6[M+H]+,850.3；found,850.6.
[实施例23]
3,8-二(1-(2,4-二氟苯基甲氧基)乙基)次卟啉(II14)的制备：
Figure GDA0004104654720000162
采用化合物I1的合成方法制备了化合物II14。1H NMR(600MHz,DMSO-d6)δppm:7.24(s,4H),7.21(s,4H),7.14(s,3H),6.96(s,4H),6.91(d,J＝17.6Hz,10H),6.70(s,3H),5.24(s,3H),4.81(s,6H),4.68(s,6H),4.51(s,3H),2.87(s,3H),2.49(d,J＝10.4Hz,16H),2.11(d,J＝12.0Hz,35H),1.58(s,9H),1.09(s,9H).13C NMR(150MHz,DMSO-d6)δppm:175.89,163.76,163.18–159.75,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,131.42,124.63,111.79,103.68,99.30,96.93,95.92,93.26,69.12,68.41,66.85,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-109.90(s),-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H46F4N4O6[M+H]+,850.3；found,850.5.
[实施例24]
3,8-二(1-(2,5-二氟苯基甲氧基)乙基)次卟啉(II15)的制备：
Figure GDA0004104654720000171
采用化合物I1的合成方法制备了化合物II15。1H NMR(600MHz,DMSO-d6)δppm:7.19(d,J＝4.0Hz,11H),7.15(s,8H),7.10(s,5H),7.01(s,4H),6.67(s,4H),5.93(s,4H),5.28(s,4H),4.72(d,J＝6.5Hz,16H),4.50(s,4H),2.74(s,5H),2.68(s,6H),2.48(s,10H),2.11(d,J＝12.0Hz,48H),1.58(s,12H),1.09(s,12H).13C NMR(150MHz,DMSO-d6)δppm:175.89,157.80,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,129.12,124.43,116.48,115.70,99.30,96.93,95.92,93.26,69.12,68.41,66.56,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19FNMR(566MHz,DMSO-d6)δppm:-113.10(s),-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H46F4N4O6[M+H]+,850.3；found,850.8.
[实施例25]
3,8-二(1-(2,6-二氟苯基甲氧基)乙基)次卟啉(II16)的制备：
Figure GDA0004104654720000172
采用化合物I1的合成方法制备了化合物II16。1H NMR(600MHz,DMSO-d6)δppm:7.74(s,1H),7.40(s,4H),7.32(s,1H),7.10(s,1H),6.95(s,1H),6.64(s,1H),5.18(s,1H),4.92-4.53(m,5H),2.79(s,1H),2.57(s,1H),2.48(s,2H),2.11(d,J＝12.0Hz,12H),1.59(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,160.58,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,131.45,124.43,121.09,111.87,99.30,96.93,95.92,93.26,69.12,68.41,64.92,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H46F4N4O6[M+H]+,850.3；found,850.7.
[实施例26]
3,8-二(1-(3,4-二氟苯基甲氧基)乙基)次卟啉(II17)的制备方法：
Figure GDA0004104654720000181
采用化合物I1的合成方法制备了化合物II17。1H NMR(600MHz,DMSO-d6)δppm:7.31(s,1H),7.20(s,1H),7.11(s,1H),7.03(s,1H),6.96(s,1H),6.61(s,1H),6.26(s,1H),5.30(s,1H),4.67(s,2H),4.57(s,2H),4.45(s,1H),3.00(s,1H),2.56(s,1H),2.48(s,3H),2.11(d,J＝12.0Hz,12H),1.58(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,151.45,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.13,135.34,133.23,131.95,126.73,124.43,118.60,117.45,99.30,96.93,95.92,93.26,71.55,69.12,68.41,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19FNMR(566MHz,DMSO-d6)δppm:-136.00(s),-138.10(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H46F4N4O6[M+H]+,850.3；found,850.2.
[实施例27]
3,8-二(1-(3,5-二氟苯基甲氧基)乙基)次卟啉(II18)的制备：
Figure GDA0004104654720000182
采用化合物I1的合成方法制备了化合物II18。1H NMR(600MHz,DMSO-d6)δppm:7.14-7.09(m,6H),6.92(s,9H),6.83(s,2H),6.67(s,2H),5.30(s,2H),4.77(s,4H),4.64(s,4H),4.49(s,2H),2.87(s,2H),2.49(d,J＝11.3Hz,11H),2.11(d,J＝12.0Hz,24H),1.59(s,6H),1.09(s,6H).13C NMR(150MHz,DMSO-d6)δppm:175.89,164.10,147.86,145.38,144.33,142.54,141.65,141.00,140.81,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,124.43,110.73,103.71,99.30,96.93,95.92,93.26,71.57,69.12,68.41,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-47.80(s).MS(MALDI TOF)(DART Positive):m/z calcd for C48H46F4N4O6[M+H]+,850.3；found,850.6.
[实施例28]
3,8-二[1-(2-(2,4-二氟苯基)乙氧基)乙基]次卟啉(II20)的制备：
Figure GDA0004104654720000191
采用化合物I1的合成方法制备了化合物II20。1H NMR(600MHz,DMSO-d6)δppm:7.16(s,1H),6.93(s,2H),6.89(s,2H),6.72(s,1H),6.59(d,J＝14.7Hz,2H),6.10(s,1H),5.23(s,1H),4.27(s,1H),3.77(s,2H),3.73(s,2H),2.77–2.70(m,6H),2.48(s,3H),2.31(s,1H),2.11(d,J＝12.0Hz,12H),1.57(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,162.19,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.94,125.47,124.43,112.03,104.37,99.30,96.93,95.92,93.26,70.63,70.09,68.94,37.88,33.60,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-109.90(s),-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C50H50F4N4O6[M+H]+,878.4；found,878.7.
[实施例29]
3,8-二[1-(2-(2,6-二氟苯基)乙氧基)乙基]次卟啉(II22)的制备：
Figure GDA0004104654720000192
采用化合物I1的合成方法制备了化合物II22。1H NMR(600MHz,DMSO-d6)δppm:7.67(s,1H),7.37(s,4H),7.09(s,1H),6.91(d,J＝12.9Hz,2H),6.79(s,1H),5.19(s,1H),4.54(s,1H),3.76(d,J＝13.5Hz,4H),2.87(s,1H),2.77(d,J＝6.4Hz,4H),2.54(s,1H),2.48(s,2H),2.11(d,J＝12.0Hz,12H),1.57(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,164.30,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,130.61,124.43,116.95,113.99,99.30,96.93,95.92,93.26,70.63,70.09,69.20,37.88,32.06,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DARTPositive):m/z calcd for C50H50F4N4O6[M+H]+,878.4；found,877.7.
[实施例30]
3,8-二[1-(2-(3,5-二氟苯基)乙氧基)乙基]次卟啉(II24)的制备：
Figure GDA0004104654720000201
采用化合物I1的合成方法制备了化合物II24。1H NMR(600MHz,DMSO-d6)δppm:7.39(s,5H),7.05(d,J＝1.8Hz,10H),6.88(s,18H),6.80(s,6H),5.98(s,5H),5.21(s,5H),4.43(s,5H),3.76(s,5H),3.71(s,9H),2.80(d,J＝10.6Hz,17H),2.73(s,5H),2.62(s,8H),2.48(s,13H),2.11(d,J＝12.0Hz,59H),1.59(s,15H),1.09(s,15H).13C NMR(150MHz,DMSO-d6)δppm:175.89,165.11,147.86,145.38,144.33,142.54,141.65,141.27,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,124.43,113.95,101.50,99.30,96.93,95.92,93.26,70.63,70.09,68.84,38.11,37.88,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-47.80(s).MS(MALDI TOF)(DARTPositive):m/z calcd for C50H50F4N4O6[M+H]+,878.4；found,878.3.
[实施例31]
3,8-二[1-(3-(2,4-二氟苯基)丙氧基)乙基]次卟啉(II26)的制备：
Figure GDA0004104654720000202
采用化合物I1的合成方法制备了化合物II26。1H NMR(600MHz,DMSO-d6)δppm:7.23(s,5H),7.20(s,6H),7.16(s,7H),6.93(s,2H),6.93–6.83(m,21H),6.59(s,5H),5.29(s,5H),4.27(s,5H),3.38(d,J＝12.6Hz,17H),2.86(s,5H),2.63(s,10H),2.49(d,J＝6.6Hz,27H),2.11(d,J＝12.0Hz,59H),1.87(d,J＝10.9Hz,13H),1.59(s,15H),1.09(s,15H).13CNMR(150MHz,DMSO-d6)δppm:175.89,163.14,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,130.41,128.07,124.43,111.75,103.98,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,31.25,30.71,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-109.90(s),-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C52H54F4N4O6[M+H]+,906.4；found,906.7.
[实施例32]
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉(II28)的制备：
Figure GDA0004104654720000211
采用化合物I1的合成方法制备了化合物II28。1H NMR(600MHz,DMSO-d6)δppm:7.67(s,5H),7.37(s,16H),7.26(s,4H),6.98(s,4H),6.61(s,4H),6.52(s,4H),5.19(s,4H),4.17(s,4H),3.38(d,J＝13.9Hz,14H),2.96(s,4H),2.63(s,9H),2.54(s,7H),2.48(s,11H),2.11(d,J＝12.0Hz,50H),1.90(s,7H),1.87(s,7H),1.60(s,13H),1.09(s,13H).13CNMR(150MHz,DMSO-d6)δppm:175.89,162.91,147.86,145.38,144.33,142.54,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,129.78,124.43,121.20,112.64,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,31.24,30.08,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-116.50(s).MS(MALDI TOF)(DART Positive):m/z calcd for C52H54F4N4O6[M+H]+,906.4；found,906.1.
[实施例33]
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉(II30)的制备：
Figure GDA0004104654720000212
采用化合物I1的合成方法制备了化合物II30。1H NMR(600MHz,DMSO-d6)δppm:7.17(s,1H),6.84(d,J＝8.8Hz,4H),6.77(s,1H),6.39(s,1H),6.02(s,1H),5.21(s,1H),4.01(s,1H),3.35(d,J＝16.3Hz,3H),2.76(d,J＝2.0Hz,4H),2.67(s,1H),2.47(s,2H),2.10(d,J＝12.0Hz,11H),1.91(s,1H),1.85(s,1H),1.58(s,3H),1.09(s,3H).13C NMR(150MHz,DMSO-d6)δppm:175.89,165.49,147.86,145.38,144.33,142.54,142.24,141.65,141.00,140.02,139.19,138.96,136.32,136.18,135.34,133.23,131.95,124.43,112.18,99.64,99.30,96.93,95.92,93.26,70.63,70.09,69.65,37.88,35.17,30.67,23.32,22.58,21.53,21.05,12.32,11.42,10.86.19F NMR(566MHz,DMSO-d6)δppm:-47.80(s).MS(MALDITOF)(DART Positive):m/z calcd for C52H54F4N4O6[M+H]+,906.4；found,906.6.
[实施例34]
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钠盐(II34)的制备：
Figure GDA0004104654720000221
采用化合物I7的合成方法制备了化合物II34。MS(ESI)m/z：823.1[M-2Na+1]+,849.4[M-Na]+,872.2[M]+。UV-vis(H2O)λmax/nm(logε)402(17.72),499(1.46),533(0.90),568(0.68),622(0.39)。焰色反应呈黄色。
[实施例35]
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钾盐(II35)的制备：
Figure GDA0004104654720000222
采用化合物I8的合成方法制备了化合物II35。MS(ESI)m/z：771.5[M-2K+1]+,795.3[M-K]+,818.7[M]+。UV-vis(H2O)λmax/nm(logε)402(16.67),499(1.49),533(0.93),568(0.71),622(0.42)。焰色反应呈浅紫色。
[实施例36]
3,8-二[1-(2-(3,5-二氟苯基)乙氧基)乙基]次卟啉二钠盐(II42)的制备：
Figure GDA0004104654720000231
采用化合物I7的合成方法制备了化合物II42。MS(ESI)m/z：819.1[M-2Na+1]+,841.4[M-Na]+,864.8[M]+。UV-vis(H2O)λmax/nm(logε)401(18.81),499(1.58),533(0.95),568(0.72),621(0.39)。焰色反应呈黄色。
[实施例37]
3,8-二[1-(2-(3,5-二氟苯基)乙氧基)乙基]次卟啉二钾盐(II43)的制备：
Figure GDA0004104654720000232
采用化合物I8的合成方法制备了化合物II43。MS(ESI)m/z：819.3[M-2K+1]+,841.2[M-K]+,864.9[M]+。UV-vis(H2O)λmax/nm(logε)401(17.05),499(1.38),532(0.83),568(0.64),621(0.36)。焰色反应呈浅紫色。
[实施例38]
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II44)的制备：
Figure GDA0004104654720000233
采用化合物I7的合成方法制备了化合物II44。MS(ESI)m/z：904.5,[M-2Na+1]+,927.3[M-Na]+,950.8[M]+。UV-vis(H2O)λmax/nm(logε)401(18.89),499(1.54),533(0.85),568(0.79),621(0.49)。焰色反应呈黄色。
[实施例39]
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II45)的制备：
Figure GDA0004104654720000241
采用化合物I8的合成方法制备了化合物II45。MS(ESI)m/z：904.8[M-2K+1]+,927.4[M-K]+,983.2[M]+。UV-vis(H2O)λmax/nm(logε)401(17.05),499(1.38),532(0.83),568(0.64),621(0.36)。焰色反应呈浅紫色。
[实施例40]
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II48)的制备：
Figure GDA0004104654720000242
采用化合物I7的合成方法制备了化合物II48。MS(ESI)m/z：904.3[M-2Na+1]+,927.2[M-Na]+,950.7[M]+。UV-vis(H2O)λmax/nm(logε)401(19.41),497(1.68),536(0.99),567(0.81),622(0.43)。焰色反应呈黄色。
[实施例41]
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II49)的制备：
Figure GDA0004104654720000251
采用化合物I8的合成方法制备了化合物II49。MS(ESI)m/z：904.8[M-2K+1]+,927.4[M-K]+,983.4[M]+。UV-vis(H2O)λmax/nm(logε)401(18.05),499(1.36),532(0.85),567(0.65),621(0.37)。焰色反应呈浅紫色。
[实施例42]
光敏剂对人食管癌Eca-109细胞的光动力抗增殖实验
受试细胞：人食管癌细胞Eca-109。
激光器：XD-635AB型激光器。
受试化合物：
3,8-二(1-(2-氟乙氧基)乙基)次卟啉(化合物I1)；3,8-二(1-(3-氟丙氧基)乙基)次卟啉(化合物I2)；3,8-二(1-(4-氟丁氧基)乙基)次卟啉(化合物I3)；3,8-二(1-(5-氟戊氧基)乙基)次卟啉(化合物I4)；3,8-二(1-(6-氟己氧基)乙基)次卟啉(I5)；3,8-二(1-(7-氟庚氧基)乙基)次卟啉(I6)；3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钠盐(I7)；3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钾盐(I8)；3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钠盐(I9)；3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钾盐(I10)；3,8-二(1-(6-氟己氧基)乙基)次卟啉二钠盐(I11)；3,8-二(1-(6-氟己氧基)乙基)次卟啉二钾盐(I12)；3,8-二(1-(2-氟苯基甲氧基)乙基)次卟啉(II1)；3,8-二(1-(3-氟苯基甲氧基)乙基)次卟啉(II2)；3,8-二(1-(4-氟苯基甲氧基)乙基)次卟啉(II3)；3,8-二[1-(2-(2-氟苯基)乙氧基)乙基]次卟啉(II4)；3,8-二[1-(3-(2-氟苯基)丙氧基)乙基]次卟啉(II7)；3,8-二[1-(3-(4-氟苯基)丙氧基)乙基]次卟啉(II9)；3,8-二(1-(2,3-二氟苯基甲氧基)乙基)次卟啉(II13)；3,8-二(1-(2,4-二氟苯基甲氧基)乙基)次卟啉(II14)；3,8-二(1-(2,5-二氟苯基甲氧基)乙基)次卟啉(II15)；3,8-二(1-(2,6-二氟苯基甲氧基)乙基)次卟啉(II16)；3,8-二(1-(3,4-二氟苯基甲氧基)乙基)次卟啉(II17)；3,8-二(1-(3,5-二氟苯基甲氧基)乙基)次卟啉(II18)；3,8-二[1-(2-(2,4-二氟苯基)乙氧基)乙基]次卟啉(II20)；3,8-二[1-(2-(2,6-二氟苯基)乙氧基)乙基]次卟啉(II22)；3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉(II24)；3,8-二[1-(3-(2,4-二氟苯基)丙氧基)乙基]次卟啉(II26)；3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉(II28)；3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉(II30)；3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钠盐(II34)；3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钾盐(II35)；3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钠盐(II42)；3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钾盐(II43)；3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II44)；3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II45)；3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II48)；3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II49)；3,8-二(1-(2,2-二氟乙氧基)乙基)次卟啉(对照化合物1)；3,8-二(1-(3,3,3-三氟丙氧基)乙基)次卟啉(对照化合物2)；对照药物血卟啉单甲醚(也称海姆泊芬)。
实验方法：
将细胞培养瓶中处于对数生长期的Eca-109细胞用胰酶消化并离心后，用完全培养基重悬成一定量的细胞悬液，随之将其接种于96孔板，每孔100μL，置于37℃5％ CO2培养箱培养；24h后吸去旧培养基，每孔加入200μL光敏剂，继续孵育；24h后弃掉旧培养基进行光照(功率18mW/cm2，波长635nm，光剂量4J/cm2)，光照结束后加入新鲜培养基继续培养；24h后吸去培养液，每孔加入20μL 5mg/mLMTT，培养箱中孵育4h后每孔加入150μLDMSO溶解甲瓒，酶标仪570nm处检测OD值。实验重复三次。
数据处理：
所有实验数据以均数±标准差(Mean±SD)表示，通过Excel软件T-Test进行P值检验，P<0.05时表示两组数据间有显著性差异，P<0.01时表示两组数据间有十分显著性差异，P<0.001时表示两组数据间有极显著性差异。
实验结果：
如表1所示，结果发现血卟啉单氟代烷基双醚衍生物I1-I12和血卟啉单氟或双氟代芳香基烷基双醚衍生物II1-II4、II7、II9、II13-II18、II20、II22、II24、II26、II28、II30、II34、II35、II42、II43、II44、II45、II48、II49对人食管癌细胞均有抑制作用，随着碳链的增长对细胞的抑制作用愈加明显，且从表中可以看出化合物光动力抗肿瘤活性均优于对照化合物1、对照化合物2和对照药海姆泊芬。
表1新化合物对Eca-109人食管癌细胞增殖抑制作用
Figure GDA0004104654720000261
Figure GDA0004104654720000271
与对照化合物1相比，ΔP<0.05，ΔΔP<0.01，ΔΔΔP<0.001；
与对照化合物2相比，□P<0.05，□□P<0.01，□□□P<0.001；与对照药海姆泊芬相比，*P<0.05，**P<0.01，***P<0.001。

Claims (5)

1.一类血卟啉单氟代烷基双醚衍生物(式I)，其特征是具有下述结构：
Figure FDA0004126447960000011
其中，R为H或M，M是锂、钠、钾离子；n1为1-8的整数。
2.一类血卟啉氟代苯基烷基双醚衍生物(式II)，其特征是具有下述结构：
Figure FDA0004126447960000012
其中，R为H或M，M是锂、钠、钾离子；R1、R2、R3、R4、R5各自独立的选自为氢、氟，n2为0-4的整数；
当苯环上只有一个氟原子取代：R1为F时，R2、R3、R4、R5为H；R2为F时，R1、R3、R4、R5为H；R3为F时，R1、R2、R4、R5为H；
当苯环上有两个氟原子取代：R1、R2为F时，R3、R4、R5为H；R1、R3为F时，R2、R4、R5为H；R1、R4为F时，R2、R3、R5为H；R1、R5为F时，R2、R3、R4为H；R2、R3为F时，R1、R4、R5为H；R2、R4为F时，R1、R3、R5为H。
3.根据权利要求1所述的血卟啉单氟代烷基双醚衍生物，该类化合物为：
3,8-二(1-(2-氟乙氧基)乙基)次卟啉(I1)；
3,8-二(1-(3-氟丙氧基)乙基)次卟啉(I2)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉(I3)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉(I4)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉(I5)；
3,8-二(1-(7-氟庚氧基)乙基)次卟啉(I6)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钠盐(I7)；
3,8-二(1-(4-氟丁氧基)乙基)次卟啉二钾盐(I8)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钠盐(I9)；
3,8-二(1-(5-氟戊氧基)乙基)次卟啉二钾盐(I10)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钠盐(I11)；
3,8-二(1-(6-氟己氧基)乙基)次卟啉二钾盐(I12)。
4.根据权利要求2所述的血卟啉氟代苯基烷基双醚衍生物，该类化合物为：3,8-二(1-(2-氟苯基甲氧基)乙基)次卟啉(II1)；
3,8-二(1-(3-氟苯基甲氧基)乙基)次卟啉(II2)；
3,8-二(1-(4-氟苯基甲氧基)乙基)次卟啉(II3)；
3,8-二[1-(2-(2-氟苯基)乙氧基)乙基]次卟啉(II4)；
3,8-二[1-(2-(3-氟苯基)乙氧基)乙基]次卟啉(II5)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉(II6)；
3,8-二[1-(3-(2-氟苯基)丙氧基)乙基]次卟啉(II7)；
3,8-二[1-(3-(3-氟苯基)丙氧基)乙基]次卟啉(II8)；
3,8-二[1-(3-(4-氟苯基)丙氧基)乙基]次卟啉(II9)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉(II10)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉(II11)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉(II12)；
3,8-二(1-(2,3-二氟苯基甲氧基)乙基)次卟啉(II13)；
3,8-二(1-(2,4-二氟苯基甲氧基)乙基)次卟啉(II14)；
3,8-二(1-(2,5-二氟苯基甲氧基)乙基)次卟啉(II15)；
3,8-二(1-(2,6-二氟苯基甲氧基)乙基)次卟啉(II16)；
3,8-二(1-(3,4-二氟苯基甲氧基)乙基)次卟啉(II17)；
3,8-二(1-(3,5-二氟苯基甲氧基)乙基)次卟啉(II18)；
3,8-二[1-(2-(2,3-二氟苯基)乙氧基)乙基]次卟啉(II19)；
3,8-二[1-(2-(2,4-二氟苯基)乙氧基)乙基]次卟啉(II20)；
3,8-二[1-(2-(2,5-二氟苯基)乙氧基)乙基]次卟啉(II21)；
3,8-二[1-(2-(2,6-二氟苯基)乙氧基)乙基]次卟啉(II22)；
3,8-二[1-(2-(3,4-二氟苯基)乙氧基)乙基]次卟啉(II23)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉(II24)；
3,8-二[1-(3-(2,3-二氟苯基)丙氧基)乙基]次卟啉(II25)；
3,8-二[1-(3-(2,4-二氟苯基)丙氧基)乙基]次卟啉(II26)；
3,8-二[1-(3-(2,5-二氟苯基)丙氧基)乙基]次卟啉(II27)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉(II28)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉(II29)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉(II30)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉(II31)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉(II32)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉(II33)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钠盐(II34)；
3,8-二[1-(2-(4-氟苯基)乙氧基)乙基]次卟啉二钾盐(II35)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉二钠盐(II36)；
3,8-二[1-(4-(2-氟苯基)丁氧基)乙基]次卟啉二钾盐(II37)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉二钠盐(II38)；
3,8-二[1-(4-(3-氟苯基)丁氧基)乙基]次卟啉二钾盐(II39)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉二钠盐(II40)；
3,8-二[1-(4-(4-氟苯基)丁氧基)乙基]次卟啉二钾盐(II41)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钠盐(II42)；
3,8-二[1-(2-(3,5二氟苯基)乙氧基)乙基]次卟啉二钾盐(II43)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II44)；
3,8-二[1-(3-(2,6-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II45)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II46)；
3,8-二[1-(3-(3,4-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II47)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钠盐(II48)；
3,8-二[1-(3-(3,5-二氟苯基)丙氧基)乙基]次卟啉二钾盐(II49)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II50)；
3,8-二[1-(3-(2,6-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II51)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II52)；
3,8-二[1-(3-(3,4-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II53)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉二钠盐(II54)；
3,8-二[1-(3-(3,5-二氟苯基)丁氧基)乙基]次卟啉二钾盐(II55)。
5.权利要求1-4中任一项所述的化合物在制备诊断和治疗肿瘤、光化性角化病、视网膜黄斑变性、尖锐湿疣、鲜红斑痣疾病的光动力药物中的应用。
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