CN1840531A - 用于肿瘤成像和光动力学疗法的卟啉基化合物 - Google Patents
用于肿瘤成像和光动力学疗法的卟啉基化合物 Download PDFInfo
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- CN1840531A CN1840531A CNA2006100549777A CN200610054977A CN1840531A CN 1840531 A CN1840531 A CN 1840531A CN A2006100549777 A CNA2006100549777 A CN A2006100549777A CN 200610054977 A CN200610054977 A CN 200610054977A CN 1840531 A CN1840531 A CN 1840531A
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Abstract
本发明描述了关于合成某些124I-标记的光敏剂的首次报道,所述光敏剂涉及氯和菌绿素,具有660~800nm的长波长吸收。在最初的研究中,这些化合物显示出通过正电子发射断层成像法(PET)检测肿瘤和通过光动力学疗法(PDT)治疗肿瘤的巨大潜力。肿瘤成像术的发展或改良的光动力学治疗剂本身代表重要的步骤,但是双官能试剂(PET成像和PDT)提供了诊断身体扫描随后靶向治疗的潜力。
Description
关于联邦政府赞助研究的声明
本发明是用来自国家卫生研究院基金号NIH(1R21 CA109914-01和CA 55792)的资金作出的。美国政府可具有本发明的某些权利。
发明背景
射电金属标记的络合物和生物分子如诊断剂的应用是药物化学相对新的领域。对99mTc放射性药物的研究是配位化学研究的开始,因为它涉及诊断成像。从那以后,用于早期诊断的新型放射性药物的开发一直是功能成像的一个活跃领域。近年来,广泛用于核医学的成像形式包括γ闪烁成像法和正电子发射断层成像法(PET)。γ闪烁成像法需要含放射γ射线的核素的放射性药物,而γ相机或SPECT(单光子发射断层成像术)相机能够对注射了放射γ射线的放射性药物的病人成像。γ光子的能量非常重要,因为大多数γ相机被设计在100~250KeV的范围内。以低于这一范围的γ能量衰减的放射性核素产生太多的散射,而γ能量大于250KeV又难以校准,在这两者的任一种情况下,图像都没有足够的质量。PET需要用发射正电子的放射性核素(β+)标记的放射性药物和用于对病人成像的PET相机。正电子衰减导致发射两个以180°分离的511KeV的光子。PET扫描器包含圆形排列的检测器,检测器具有被设计为专门检测以相反方向发射的511KeV光子的符合电路。射电金属试剂也被用来监测各种类型的癌症治疗。在设计射电金属基的放射性药物中,要考虑的重要因素包括射电金属的半衰期、衰减的模式和成本以及同位素的可获得性。对于诊断成像来说,放射性核素的半衰期必须足够长以进行期望的化学变化来合成放射性药物,并且该半衰期必须足够长以能够在病人体内的靶组织中积累,同时能够通过非靶器官清除。用于PET和γ闪烁成像法中放射性药物的射电金属半衰期为约10分钟(62Cu)至几天(67Ga)。期望的半衰期取决于放射性药物在靶组织中定位所需要的时间。例如,基于心脏或大脑灌注的放射性药物需要较短的半衰期,因为它们可快速到达靶,然而肿瘤靶标化合物经常需要更长的时间到达靶,以获得最佳的靶/本底比。
放射性药物试剂的设计需要优化发病位置(癌症肿瘤)的体内具体寻靶与相关放射性核素的放射性在非靶处的清除和其物理放射性衰减性质之间的平衡。在选择性放射标记的药物设计中遇到了多个难题。这些难题包括涉及以下方面的问题:有效的药物传送、放射性在靶位点停留时间的最大化、药物的体内分解代谢和新陈代谢,以及如果从非靶位点清除放射性标记的药物或代谢物,还包括相对速度的优化。由于必须考虑多个参数,开发用于成像和癌症治疗的有效放射性药物是复杂的问题,其不能简单地通过以任何方式将放射性核素依附到非辐射标记的寻靶载体上来完成。因此,标记方法中涉及到的化学是药物设计方法的整体和重要部分。例如,如果射电金属化的螯合物在某种程度上被附加到生物分子寻靶实体上,螯合物的结构和物理化学性质必须与放射性药物在发病位置的高特定吸收相容,甚至可能地帮助促进这种吸收。至少,这种射电金属螯合物应不影响药动力学、结合特异性或对癌细胞的亲和性。很清楚,如果要形成安全有效的成像/治疗剂,放射性核素的选择和用于分子放射标记的化学策略是关键的要素。
最近几年来,卟啉基化合物已用于通过光动力学疗法(PDT)来治疗癌症。某些卟啉和相关四吡咯体系在恶性肿瘤中的浓度高于在大多数正常组织中的浓度,这已成为将这些分子用作光敏剂的主要原因。一些四吡咯基化合物已在各种恶性肿瘤上起作用,包括皮肤、肺、膀胱、头、颈和食道。PDT的精确机理还不知道,但是,动物的体内数据表明,直接杀死细胞和肿瘤微管功能的丧失起了重要作用。
光动力学疗法(PDT)利用由光动力学方法造成的局部氧化损害的生物结果。初始光动力方法的进行需要以下这些关键要素:光敏剂、光和氧气。表面的可见病变或那些可用内窥镜检查的病变,例如支气管内的或食管的肿瘤,是容易治疗的,但是大部分恶性病变太深,目前这一代光敏剂中引发单线态氧产物所需波长的光达不到。虽然早已开发了通过被终端散射器“盖上”的光纤将治疗光传送到深层病变的技术,但是深层病变无疑是从皮肤表面看不见的,因而深层肿瘤的PDT是非常不切实际的。
附图说明
图1示出了反应混合物在Maxsil C8柱上的HPLC色谱图。
图2示出了纯化的标记化合物的HPLC色谱图。
图3示出了本发明化合物的制备流程示意图(方案1)。
图4示出了在RIF肿瘤细胞中变化药物浓度和光剂量的条件下,对于用碘类似物在体外感光的比较,存活百分比对光剂量的示图。
图5示出了对于植入RIF肿瘤的C3H老鼠暴露在激光(665nm,135J/cm2,75mW/cm2)中30分钟,在24小时后注射(post injection)化合物2,用变化浓度的3-去乙烯基(devinyl)-3-(1’-碘苄氧基)乙基类似物“化合物2”在体内感光之后,尺寸小于400mm3的肿瘤百分数对时间天数的示图。其中未显示出任何肿瘤再生长的老鼠被认为是治愈的(肿瘤是平的)。
图6示出了具有RIF肿瘤的老鼠用I124类似物4(50μCi)在(A)24小时、(B)48小时和(C)72小时后注射下的PET肿瘤图像。
发明简述
根据本发明,我们已发现一系列化合物,其能够克服与在现有技术中深层肿瘤的辐射成像法相关的问题。具体地,这些化合物是氯、菌绿素、卟啉、焦脱镁叶绿酸(pyropheophorbide)、红紫素二酰亚胺(purpurinimide)或菌红紫素二酰亚胺(bacteriopurpurinimide)的124I-苯基衍生物。
更具体地,本发明的优选化合物包括下式的化合物:
或其药学可接受的衍生物,其中:
R1和R2各自独立地为取代或未取代的烷基、取代或未取代的烯基、-C(O)Ra或-COORa或-CH(CH3)(ORa)或-CH(CH3)(O(CH2)nXRa),其中Ra为氢、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基,或者取代或未取代的环烷基,其中R2可为CH=CH2,CH(OR20)CH3,C(O)Me,C(=NR20)CH3或CH(NHR20)CH3;
其中X为芳基或杂芳基;
n为0~6的整数;
其中R20为甲基、丁基、庚基、十二烷基或3,5-二(三氟甲基)-苄基;和
R1a和R2a各自独立地为氢或取代或未取代的烷基,或一起形成共价键;
R3和R4各自独立地为氢或取代或未取代的烷基;
R3a和R4a各自独立地为氢或取代的或未取代的烷基,或一起形成共价键;
R5为氢或取代的或未取代的烷基;
R6和R6a各自独立地为氢或取代的或未取代的烷基,或一起形成=O;
R7为共价键、亚烷基、氮杂烷基或氮杂芳烷基或=NR20,其中R20为-CH2X-R1或-YR1,其中Y为芳基或杂芳基;
R8和R8a各自独立地为氢或取代的或未取代的烷基,或一起形成=O;
R9和R10各自独立地为氢、或取代的或未取代的烷基,R9可为-CH2CH2COORa,其中Ra为烷基;
当被取代时,Ra~R10的每个被一个或多个取代基取代,取代基各自独立地选自Q,其中Q为烷基、卤代烷基、卤素、拟卤素或-COORb,其中Rb为氢、烷基、烯基、炔基、环烷基、芳基、杂芳基、芳烷基或ORc,其中Rc为氢、烷基、烯基、炔基、环烷基或芳基或CONRdRe,其中Rd和Re各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或NRfRg,其中Rf和Rg各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或=NRh,其中Rh为氢、烷基、烯基、炔基、环烷基或芳基,或者为氨基酸残基;
每个Q独立地为未取代或被一个或多个取代基取代,取代基各自独立地选自Q1,其中Q1为烷基、卤代烷基、卤素、拟卤素或-COORb,其中Rb为氢、烷基、烯基、炔基、环烷基、芳基、杂芳基、芳烷基或ORc,其中Rc为氢、烷基、烯基、炔基、环烷基或芳基或CONRdRe,其中Rd和Re各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或NRfRg,其中Rf和Rg各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或=NRh,其中Rh为氢、烷基、烯基、炔基、环烷基或芳基,或者为氨基酸残基;
条件是化合物包含至少一个含124I-苯基的Q。
这些化合物具有高的肿瘤吸收性和合适的用于肿瘤成像的放射学寿命。
本发明也提供将这些化合物用于成像的方法,同时允许核成像,引导使得能够用PDT治疗的光纤在深层肿瘤中植入。
发明详述
在焦脱镁叶绿酸-a的一系列烷基醚类似物的研究基础上,发明人开发了吸收相对长波长的光敏剂,焦脱镁叶绿酸-a 1的3-(1-己氧基)乙基-衍生物(HPPH)。这种化合物是亲肿瘤的(tumor-avid),目前在Roswell Park Cancer Institute处于人体临床试验阶段I/II。发明人研究了这种化合物与单-或双-二氨基乙硫醇(N2S2配合基)结合用作“媒介物”的用途。从体内生物分布试验获得的结果表明,药物的肿瘤/非肿瘤吸收率取决于时间和肿瘤尺寸。在时间上发现HPPH基化合物从肿瘤的清除比从大多数非肿瘤组织的清除要慢。但是,发现99mTc短短6小时的半衰期与24小时的成像时间不匹配,这表明使用更长存活期的同位素可提供有用的扫描剂。开发改良的肿瘤成像剂的另一方法可以是用那些表现明显更高的肿瘤与非肿瘤比率的化合物代替HPPH。有关的长存活期放射性核素的合成可产生改良的成像和治疗(PDT)剂。
有效用作成像剂和光敏剂的化合物创造了肿瘤诊断和治疗的全新范例。在外周静脉注射该化合物之后,可用扫描器对病人扫描。从而可确定肿瘤点的位置,当病人保持在扫描器中时,参与的核专家可经皮插入超细针头,该针头可用作将光传输纤维插入到病变组织的插入器。因为每个纤维直径小于400微米,插入器针头将产生可忽略的组织损伤。光源可被连接到纤维上,可开始对病变的PDT扫描,而不对其它器官产生任何明显的伤害。因为相同分子代表反差媒质和治疗媒质,所以在放置针头/纤维过程中,可连续对病变成像,而就分离的诊断/治疗成像的定位或“图像重合”而言没有任何模糊。该范例将使PDT的低毒和高效适用于从头颅基到骨盆底的任何实际位置。
正电子发射断层成像法(PET)是允许非侵入性使用正电子标记的分子成像探针的技术,以成像和测定活体中细胞功能的生物化学过程。相比于单光子发射计算机断层显像术(SPECT),为了产生断层图像,PET敏感度增加至少十倍。最通常使用的正电子发射核素短的半衰期不适于具有以天计的生物半衰期的药物。但是,碘-124是具有4.2天半衰期的正电子发射剂,适于具有几天生物半衰期的标记探针。因为有限的可获得性和包括多种高能γ射线的复杂衰减机理,这种同位素还未广泛使用。Pentlow等首次指出,用124I定量成像是可能的。
在我们尝试开发有效的双官能诊断/治疗剂的过程中,我们最初合成和评价了某些焦脱镁叶绿酸类似物(由叶绿素-a衍生)-N2S2-99mTc结合物(23)。体内的生物分布结果表明,99mTc短短6h的半衰期与24小时的成像时间(药物的最大吸收和治疗时间)不匹配,这表明使用更长存活期的同位素可提供有用的扫描剂。因此,我们的目的是,将124I正电子发射剂引入某些亲肿瘤的卟啉基光敏剂,该光敏剂含碘苄基官能团,并研究它们在肿瘤成像和光动力学疗法中的用途。
有几种用碘同位素标记化合物的方法。冷碘-至放射性碘-的转变是可能的,但是所得产物的比活度低。已经表明,通常脂肪链上取代的碘比芳香结构中存在的碘更不稳定。因此,我们制备了一系列芳香烷基醚,并评价了它们在体外(RIF细胞)和体内的效果(RIF细胞)。在一系列具有变化的含碘苯基的碳单元的烷基醚类似物中,最初筛选时发现3-去乙烯基-3-(1’-3”-碘苄氧基)乙基焦脱镁叶绿酸-a(方案1)与HPPH一样有效,HPPH是我们实验室开发的光敏剂,且其正处于人体临床试验的阶段II。
本发明化合物的例子是:
焦脱镁叶绿酸-a 红紫素二酰亚胺 菌红紫素二酰亚胺
红紫素二酰亚胺类 和 菌红紫素二酰亚胺类
其中R为-COOH、-CO2R3、-CONHR4、单糖、二糖、多糖、叶酸残基或整合素拮抗剂;当存在R1时,其为C1-C12烷基,R3为C1-C12烷基,R4为氨基酸残基。
甲基-3-去乙烯基-3-{1’-(3-碘苄氧基)乙基}焦脱镁叶绿酸-a:如图3所示,通过文献过程从叶绿素-a获得焦脱镁叶绿酸-a1。它与HBr/乙酸反应,中间体不稳定的溴衍生物立即与3-碘苄基乙醇在氮气气氛和室温下反应45分钟。标准的处理之后,用柱色谱(氧化铝Gr.III,用二氯甲烷洗提)提纯反应混合物,期望的碘衍生物2以70%的产率被分离。UV-vis(CH2Cl2):662(4.75×104),536(1.08×104),505(1.18×104),410(1.45×105)。1H-NMR(CDCl3;400MHz):δ9.76,9.55和8.56(全部s,1H,meso-H);7.76(s,1H,ArH);7.64(d,J=6.8,1H,ArH);7.30(d,J=8.0,1H,ArH);7.05(t,J=8.2,1H,ArH);6.00(q,J=6.9,1H,31-H);5.20(dd(ABX模式),J=19.6,60.0,2H,132-CH2);4.70(d,J=12.0,1H,OCH2Ar);4.56(dd,J=3.2,11.6,1H,OCH2Ar);4.48-4.53(m,1H,18-H);4.30-4.33(m,1H,17-H);3.72(q,J=8.0,2H,8-CH2CH3);3.69,3.61,3.38和3.21(全部s,全部3H,对于173-CO2CH3和3×环CH3);2.66-2.74,2.52-2.61和2.23-2.37(m,4H,171和172-H);2.18(dd,J=2.8,6.4,3H,32-CH3);1.83(d,J=8.0,3H,18-CH3);1.72(t,J=7.6,3H,8-CH2CH3);0.41(brs,1H,NH);-1.71(brs,1H,NH)。质量:对于C41H43N4O4I计算:782.测量:805(M++Na)。
甲基-3-去乙烯基-3-{1’-(3-叔丁基锡苄氧基)乙基}焦脱镁叶绿酸-a:
1H-NMR(CDCl3;600MHz):δ9.76,9.54和8.55(全部s,1H,meso-H);7.43(m,2H,ArH);7.36(m,2H,ArH);6.01(q,J=6.7,1H,31-H);5.20,dd(ABX模式),J=19.1,87.9,2H,132-CH2);4.78(dd,J=5.4,11.9,1H,OCH2Ar);4.61(dd,J=1.7,12.0,1H,OCH2Ar),4.50(q,J=7.4,1H,18-H);4.32(d,J=8.8,1H,17-H);3.72(q,J=7.8,2H,8-CH2CH3);3.69,3.61,3.37和3.18(全部s,全部3H,对于173-CO2CH3和3×环CH3);2.66-2.75,2.52-2.61和2.23-2.37(m,4H,171和172-H);2.16(m,3H,32-CH3);1.83(d,J=7.2,3H,18-CH3);1.72(t,J=7.6,3H,8-CH2CH3);0.45(brs,1H,NH);0.19(s,9H,叔丁基锡);-0.59(brs,1H,NH)。质量:对于C45H52N4O4Sn计算:831。测量:854(M++Na)。
124I-标记的光敏剂的制备:
通过在1,4-二烷中使2与六甲基二锡烷和二-(三苯基磷化氢)钯(II)二氯化物反应(见图3)得到的三甲基锡类似物3(50μg)溶于100μl 10%乙酸的甲醇溶液中。加入0.1N NaOH中的Na124I。混合溶液,加入IODOGEN珠粒。反应混合物在室温下培养30分钟,使用HPLC(图1)提纯反应产物。收集标记的产物。提纯产物的HPLC色谱如图2所示。
为了评价3-碘苄氧基乙基-焦脱镁叶绿酸-a2的体外光敏效果,RIF肿瘤细胞在α-DMEM与10%胎牛血清、青霉素和链霉素中生长。细胞保持在5%CO2、95%空气和100%湿度中。为了确定PDT效果,这些细胞被置于96孔板中,且在整体媒质(complete media)中密度为1×104细胞孔。过夜培养以使细胞附着之后,以变化的浓度单独加入HPPH和相关的冷碘衍生物2。在黑暗中37℃下培养3小时之后,用PBS洗涤细胞一次,用光照射。光处理之后,洗涤细胞一次,并将细胞置于整体媒质中,培养48小时。然后向每个孔中加入10μl MTT的4-mg/ml溶液。37℃下培养4小时之后,除去MTT+介质,加入100μl DMSO以使福尔马肼晶体溶解。在微滴定板读取器上560nm的吸收度下读取96孔板。在1.0μM浓度下获得最优的细胞杀死效果。对于每个测试的化合物,结果以相应的黑暗(有药物,没有光)对比试验的存活百分比作图(图4)。每个数据点代表3个单独试验的平均值,误差线为标准偏差。每个试验用了5个重复孔。
甲基3-碘-苄氧基-乙基-焦脱镁叶绿酸-a:HPPH和如图3中所示的碘-苄氧基乙基-焦脱镁叶绿酸-a2的体外光敏效果,在变化的试验条件下比较,结果概括于图4中。可看出,两种光敏剂在0.6μM药物浓度下产生类似的效果。但是,在较低浓度0.3μM下,发现碘-类似物2效果稍微更好。
体内光敏效果:
在带有RIF肿瘤的C3H老鼠中(5只老鼠/组)确定体内效果。肿瘤暴露于665nm(体内吸收)的光中30分钟,使用激光(135J/cm2)。每天测量肿瘤再生长(细节见所述项目的‘方法’部分)。从图5可看出,3-去乙烯基-3-(1’-碘苄氧基)乙基类似物在1.0和1.5μmol/kg剂量下非常有效。在较低剂量(0.25和0.50μmol/kg)下,在10和15天后注射下观察到肿瘤再生长。进一步研究以在变化的注量和注量速度以及时间间隔下优化治疗条件,目前在进展中。
体内肿瘤成像:
在最初试验中,分别在3组C3H老鼠(3只老鼠/组,在前肢上带有RIF肿瘤)中注射不同放射性剂量(35、50和100μCi)的I-124标记的光敏剂2,用小动物PET扫描器在24、48和72h时间间隔时成像(图6的图像A、B和C)。在所有的放射性剂量中,在药物的48小时后注射时获得最好的图像。但是,如所预期的,化合物在某些其它器官中特别是在肝中存在是明显的。
生物分布研究:
48小时后注射时PET成像之后,杀死一组老鼠(3只老鼠/组),确定I-124PET试剂在选择器官/g中的生物分布。结果概括于表1中。
→部分 | 血液 | 肌肉 | 脾脏 | 肾脏 | 肺 | 心脏 | 肝脏 | 肠 | 胃 | 肿瘤 |
老鼠1 | 1.47 | 0.18 | 2.04 | 1.09 | 0.99 | 0.79 | 3.46 | 3.6 | 1.3 | 2.4 |
老鼠2 | 1.33 | 0.49 | 2.23 | 1.21 | 1.29 | 1.21 | 3.22 | 2.22 | 0.66 | 2.15 |
老鼠3 | 0.57 | 0.37 | 2.05 | 0.99 | 1.00 | 0.98 | 3.26 | 1.69 | 1.10 | 2.10 |
平均值 | 1.12 | 0.35 | 2.11 | 1.10 | 1.09 | 0.99 | 3.31 | 2.47 | 1.02 | 2.22 |
标准偏差 | 0.48 | 0.16 | 0.11 | 0.11 | 0.17 | 0.21 | 0.13 | 1.03 | 0.33 | 0.16 |
表1:I-124标记的光敏剂4在48小时后注射的老鼠(3只老鼠/组)的一些选择器官中的生物分布结果
与癌症相关的具体分子靶的成像应该能够更早诊断和更好地治疗肿瘤患者。正电子发射断层成像法(PET)是高度灵敏的非侵入性技术,相对于解剖治疗方法,其理想地适合于癌症生物学的临床前和临床成像。通过使用放射标记的示踪剂,其以非药理学剂量注射,电脑可重建三维图像,以显示有关示踪剂的浓度和位置。与其它正电子发射剂相比,I-124由于其更长的半衰期(4.2天)而具有优势。我们的发明报道了关于制备I-124标记的光敏剂的首次实例,该光敏剂与氯和菌绿素有关,具有660~800nm的长波长吸收。我们也已示出了这些亲肿瘤性化合物在肿瘤检测和治疗中的应用。我们的方法也提供了通过寻靶已知在肿瘤中具有过量表现的特定受体,开发目标专一的双官能试剂的方法,这些研究目前在进展中。
Claims (3)
1.一种氯、菌绿素、卟啉、焦脱镁叶绿酸、红紫素二酰亚胺或菌红紫素二酰亚胺的124I-苯基衍生物。
2.一种下式的化合物:
或其药学可接受的衍生物,其中:
R1和R2各自独立地为取代或未取代的烷基、取代或未取代的烯基、-C(O)Ra或-COORa或-CH(CH3)(ORa)或-CH(CH3)(O(CH2)nXRa),其中Ra为氢、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基,或者取代或未取代的环烷基,其中R2可为CH=CH2,CH(OR20)CH3,C(O)Me,C(=NR21)CH3或CH(NHR21)CH3;
其中X为芳基或杂芳基;
n为0~6的整数;
其中R20为甲基、丁基、庚基、十二烷基或3,5-二(三氟甲基)-苄基;和
R1a和R2a各自独立地为氢或取代或未取代的烷基,或一起形成共价键;
R3和R4各自独立地为氢或取代或未取代的烷基;
R3a和R4a各自独立地为氢或取代或未取代的烷基,或一起形成共价键;
R5为氢或取代或未取代的烷基;
R6和R6a各自独立地为氢或取代或未取代的烷基,或一起形成=O;
R7为共价键、亚烷基、氮杂烷基或氮杂芳烷基或=NR20,其中R20为-CH2X-R1或-YR1,其中Y为芳基或杂芳基;
R8和R8a各自独立地为氢或取代或未取代的烷基,或一起形成=O;
R9和R10各自独立地为氢或取代或未取代的烷基,R9可为-CH2CH2COORa,其中Ra为烷基;
当被取代时,各个Ra~R10被一个或多个取代基取代,取代基各自独立地选自Q,其中Q为烷基、卤代烷基、卤素、拟卤素或-COORb,其中Rb为氢、烷基、烯基、炔基、环烷基、芳基、杂芳基、芳烷基或ORc,其中Rc为氢、烷基、烯基、炔基、环烷基或芳基或CONRdRe,其中Rd和Re各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或NRfRg,其中Rf和Rg各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或=NRh,其中Rh为氢、烷基、烯基、炔基、环烷基或芳基,或者为氨基酸残基;
各个Q独立地为未取代或被一个或多个取代基取代,取代基各自独立地选自Q1,其中Q1为烷基、卤代烷基、卤素、拟卤素或-COORb,其中Rb为氢、烷基、烯基、炔基、环烷基、芳基、杂芳基、芳烷基或ORc,其中Rc为氢、烷基、烯基、炔基、环烷基或芳基或CONRdRe,其中Rd和Re各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或NRfRg,其中Rf和Rg各自独立地为氢、烷基、烯基、炔基、环烷基或芳基或=NRh,其中Rh为氢、烷基、烯基、炔基、环烷基或芳基,或者为氨基酸残基;
条件是化合物包含至少一个含124I-苯基的Q。
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