CN109369727A - 一种抗癌靶向配合物及其制备方法和应用 - Google Patents
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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Abstract
本发明涉及一种抗癌靶向配合物及其制备方法和应用。所述配合物以下述通式化合物所示:
Description
技术领域
本发明涉及药物靶向配合物领域,更具体的涉及一种抗癌靶向配合物及其制备方法和应用。
背景技术
顺铂作为广泛使用的抗肿瘤药物,对多种肿瘤,尤其是头颈部肿瘤及卵巢肿瘤具有独特疗效,但顺铂的毒副作用及其致癌性,在一定程度上限制了其在临床上的应用而成为备受关注的问题。顺铂的临床毒理已有大量研究,并证实有不少药物可拮抗顺铂的毒副作用。顺铂的细胞毒性和遗传毒性也不容忽视,以细菌为材料进行的Ames试验,以小鼠为对象及以鼠或人体细胞系为材料进行的微核或(和)染色体研究,证实顺铂具有杀伤细胞和诱发基因突变,微核形成,及染色体损伤等细胞毒和遗传毒作用。顺铂对人体细胞的毒性仍需进行广泛而深入的研究。
1978年美国FDA批准上市的顺铂是临床上用于治疗多种癌症的首选化疗药物,并且对骨肉瘤、子宫颈癌、乳腺癌等实体瘤有明显疗效。然而,由于顺铂的水溶性差、肿瘤选择性低等特点导致其在临床上的应用受到很大的限制包括具有严重的毒副作用及耐药性。因此研究开发具有肿瘤靶向性的高效低毒的新型铂类抗肿瘤药物至关重要,从而降低化疗药物的毒副作用,提高肿瘤选择性。将具有靶向性的功能性基团引入到铂配合物中是一种有效的研究策略。
发明内容
本发明的目的之一在于提供了一种抗癌靶向配合物。
本发明的另一目的在于提供含上述抗癌靶向配合物的药物组合物。
本发明的另一目的在于提供了所述抗癌靶向配合物的制备方法。
本发明还提供了上述抗癌靶向配合物制备抗癌药物的用途。
为解决上述问题,本发明提供了如下技术方案:
一种如式I所示的配合物,如下所示:
其中,选自
X和Y选自O或N,但是X和Y不同时为N;为多齿配体。
优选地,所述选自如下基团:
更优选地,选自下述配合物:
所述的配合物的制备方法,其包括下述步骤:
二氯双取代氨基铂与相应的配体化合物反应。
本发明还提供一种组合物,其包括权利要求1-3任一所述的如式I所示的配合物,和药学上可接受的助剂、载体或稀释剂。
所述的组合物,其剂型选自素片、薄膜包衣片、糖衣片、肠衣片、分散片、胶囊、颗粒剂、口服溶液或口服混悬液。
所述的如式I所示的配合物用于制备治疗肿瘤或癌症药物的用途,所述肿瘤或癌症为胃癌、宫颈腺癌、结肠癌、肺癌、肝癌、胶质瘤、食道癌、肠癌、鼻咽癌、乳腺癌、淋巴癌、肾癌、胰腺癌、膀胱癌、卵巢癌、子宫癌、骨癌、胆囊癌、唇癌、黑素瘤、舌癌、喉癌、血癌、前列腺癌、脑瘤、鳞癌、皮肤癌、血管瘤、脂肪瘤、宫颈癌和甲状腺癌。
优选地,所述肿瘤或癌症为结肠癌。
本发明也提供了治疗肿瘤或癌症的方法(或本发明的化合物或其立体异构体、互变异构体、药物上可接受的盐、溶剂化物或前药用于制备治疗这些疾病药物的用途),包括根据治疗需要,向寄主施予治疗有效量的至少一种本发明化合物,或其立体异构体、互变异构体、药物上可接受的盐、溶剂化物或其前药。
本发明也提供了治疗疾病的方法,包括根据治疗需要向患者施予治疗有效量的式I配合物,其中所述疾病是胃癌、宫颈腺癌、结肠癌、肺癌、肝癌、胶质瘤、食道癌、肠癌、鼻咽癌、乳腺癌、淋巴癌、肾癌、胰腺癌、膀胱癌、卵巢癌、子宫癌、骨癌、胆囊癌、唇癌、黑素瘤、舌癌、喉癌、血癌、前列腺癌、脑瘤、鳞癌、皮肤癌、血管瘤、脂肪瘤、宫颈癌和甲状腺癌。优选地为结肠癌。
本发明也提供了治疗疾病的方法,包括根据治疗需要向患者施予治疗有效量的式I配合物,与其它治疗试剂联合使用。
“药物上可接受的助剂、载体或稀释剂”一般指的是通常在该领域中接受的,可传递生物活性试剂至动物,尤其是哺乳动物。配制药物上可接受载体,根据本领域普通技术人员所熟知的许多因素。这些包括没有限制被配制的活性试剂的类型和特性;含试剂组合物施予的受体;组合物施予途径;和定向治疗指示。药物上可接受的载体包括水性和非水性液态媒介,以及多种固态和半固态剂型。这些载体包括许多不同组分和添加剂,除了活性试剂之外,这些额外组分由于多种原因包含于配方中,如活性试剂、粘合剂等的稳定性,这是本领域普通技术人员所熟知的。
本发明式I配合物可以治疗症状的任何适合方式施予,取决于位点专一治疗或传递药物的量。局部投药通常优选皮肤相关疾病,癌性或癌性前症状的系统性治疗,但其它传递模式也是考虑的。例如口服施予化合物,如以片剂、胶囊、颗粒、粉末或包括糖浆剂的液体配方形式;局部如以溶液、悬浮液、凝胶或软膏;舌下给药;脸颊地;胃肠外给药如通过皮下、静脉注射、肌肉注射或胸骨内注射或灌注术(如无菌水或非水溶液或悬浮液);经鼻的如通过吸入喷雾;局部地如以乳液或软膏形式;经直肠地如以栓剂形式;或脂质体地。可施予含非毒性、药物上可接受赋形剂或稀释剂的剂量单位配方。可以立即释放或延缓释放的形式施予所述化合物。立即释放或延缓释放可以适合的药物组合物获得,在部分延缓释放的实例中,使用设备如皮下移植或渗透泵。
口服施予的示例性组合物包括悬浮液,其可含有如用于传输的微晶纤维素、作为悬浮剂的海藻酸或海藻酸钠、作为粘度增强剂的甲基纤维素和现有技术中已知的那些甜味剂或调味剂;立即释放的片剂可含有如微晶纤维素、磷酸二钙盐、淀粉、硬脂酸镁和/或乳糖和/或其它赋形剂、粘合剂、膨胀剂、崩解剂、稀释剂和润滑剂如现有技术中已知的那些。本发明化合物也可通过舌下和/或颊部施予进行口服传递,如压模、压缩或冻干片剂。示例性组合物可包括快速溶解的稀释剂如甘露醇、乳糖、蔗糖和/或环糊精类。包含在这些配方中也可以是高分子量赋形剂如纤维素或聚乙烯二醇(PEG);有助于粘膜附着的赋形剂如羟丙基纤维素(HPC)、羟丙甲基纤维素(HPMC)、羧甲基纤维素钠(SCMC)和/或马来酸酐共聚物(如);和控制释放的试剂如聚丙烯酸共聚物(如CARBOPOL)。也可加入润滑剂、助流剂、香料、着色剂和稳定剂有助于制备和使用。
喷雾法或吸入施予的示例性组合物包括溶液,所述溶液可含有苄基醇或其它适合防腐剂、提高吸收性和/或生物活性的吸收促进剂、和/或其它可溶性或分散性试剂如现有技术中已知的那些。
肠胃外施药的示例性组合物包括注射溶液或悬浮液,其可含有如适合的非毒性、肠胃可接受稀释剂或溶剂,如甘露醇、1,3-丁二醇、水、格林氏溶液、等渗氯化钠溶液,或其它适合的分散或润湿和悬浮试剂,包括合成的单或甘油二酯类,和脂肪酸包括油酸。
直肠给药的示例性组合物包括栓剂,其可含如适合的非刺激性赋形剂,如可可脂、合成甘油酯类或聚乙烯二醇类,在普通温度下为固体,但溶解和/或溶入肠胃内释放药物。
治疗有效量的本发明化合物可由本领域普通技术人员确定,并对哺乳动物而言包括示例性剂量约从0.05至1000mg/kg;1-1000mg/kg;1-50mg/kg;5-250mg/kg;250-1000mg/kg,按照每天每千克体重的活性化合物量,其可以单一剂量或以单独的分开剂量形式施予,如每天从1到4倍。可以理解的是,对于特别受体的特殊剂量水平和药剂频率可改变病取决于多种因素,包括使用的特殊化合物活性、所述化合物代谢稳定性和作用长度、种族、年龄、体重、一般健康状况、受体性别和饮食、施予模式和时间、排泄速率、药物组合和特殊疾病的严重程度。用于治疗的优选受体包括动物,最优选哺乳种族如人类和家禽动物如狗、猫、马及其类似物。
实施例
下面通过实施例对本发明作进一步说明。应该理解的是,本发明实施例所述方法仅仅是用于说明本发明,而不是对本发明的限制,在本发明的构思前提下对本发明制备方法的简单改进都属于本发明要求保护的范围。如无特别说明,实施例中用到的所有原料和溶剂均购自Aldrich公司。
制备实施例1:
氮气保护下,在反应容器中加入100mmol顺铂,200毫升无水DMF,50mmol的乙酰丙酮,保持反应温度在60~70℃之间,TLC跟踪反应至反应结束。除去反应体系中的DMF,水洗,过滤,固体用V水∶V石油醚=10∶1的混合溶剂重结晶,得到淡黄色固体的下述化合物(收率51%)。
m/z:399.00;
元素分析:C5H13Cl2N2O2Pt;C:15.05%,H:3.29%,Cl:17.76%,N:7.02%,O:8.02%,Pt:48.86%。
1H NMR(300MHz,DMSO,ppm):δ:4.46(s,1H,CH);1.5(s,6H,NH3);1.02(s,3H,CH3);0.99(s,3H,CH3).
制备实施例2:
以类似于实施例1的反应步骤和条件,将顺铂替换为相应的顺式-二氯(乙二胺)-合铂,制备下述化合物,收率65%。
m/z:424.02;
元素分析:C7H15Cl2N2O2Pt;C:19.75%,H:3.57%,Cl:16.69%,N:6.59%,O:7.54%,Pt:45.88%。
1H NMR(300MHz,DMSO,ppm):δ:4.46(s,1H,CH);2.91(s,4H,CH2);1.5(s,4H,NH2);1.02(s,3H,CH3);0.99(s,3H,CH3).
制备实施例3:
(1)氮气保护下,在反应容器中加入50mmol的1,2-环己二胺,60ml的乙醇,缓慢滴加K2PtCl4水溶液(20mmol的K2PtCl4,30ml去离子水),75~80℃下搅拌过夜,水洗,干燥,得粗品化合物。
(2)氮气保护下,在反应容器中加入100mmol步骤(1)产物,200毫升无水DMF,50mmol的乙酰丙酮,保持反应温度在70~80℃之间,TLC跟踪反应至反应结束。除去反应体系中的DMF,水洗,过滤,固体用V水∶V石油醚=10∶1的混合溶剂重结晶,得到淡黄色固体的下述化合物(收率60%)。
m/z:479.06;
元素分析:C11H21Cl2N2O2Pt;C:27.57%,H:4.41%,Cl:14.79%,N:5.84%,O:6.68%,Pt:40.71%。
1H NMR(300MHz,DMSO,ppm):δ:4.46(s,1H,CH);2.52(s,2H,CH);1.49~1.74(m,4H,CH2);1.5(s,4H,NH2);1.11~1.21(m,4H,CH2);1.02(s,3H,CH3);0.99(s,3H,CH3).
制备实施例4:
以类似于实施例3的反应步骤和条件,将1,2-环己二胺替换为相应的环己胺,制备下述化合物,收率66%。
m/z:562.13;
元素分析:C17H33Cl2N2O2Pt;C:36.24%,H:5.90%,Cl:12.58%,N:4.97%,O:5.68%,Pt:34.62%。
1H NMR(300MHz,DMSO,ppm):δ:4.46(s,1H,CH);2.57(m,2H,CH);1.49~1.74(m,8H,CH2);1.5(s,4H,NH2);1.44~1.46(m,4H,CH2);1.11~1.21(m,8H,CH2);1.02(s,3H,CH3);0.99(s,3H,CH3).
制备实施例5:
以类似于实施例3的反应步骤和条件,将1,2-环己二胺替换为相应的联吡啶,制备下述化合物,收率70%。
m/z:520.01;
元素分析:C15H15Cl2N2O2Pt;C:34.57%,H:2.89%,Cl:13.60%,N:5.36%,O:6.14%,Pt:37.43%。
1H NMR(300MHz,DMSO,ppm):δ:8.78(d,2H,CH);8.59(d,2H,CH);7.57(d,2H,CH);7.09(d,2H,CH);4.46(s,1H,CH);1.02(s,3H,CH3);0.99(s,3H,CH3).
生物活性实施例:
毒性实验:
选用健康昆明种小鼠,由广东药科大学实验中心提供。小鼠饲养于无毒塑料盒内,每盒5只,雌、雄分笼,每天换1次垫料,自由摄食和饮水,室温保持18-20℃,自然光照。药物以0.9%氯化钠水溶液溶解,受试物剂量以mg/kg表示。按以下剂量腹腔注射给药,给药容积为0.1mL/10g,按照如下剂量给药:50、100、150、200、300mg/kg。给药后每天观察记录动物的外观、精神、饮食、睡眠、活动情况以及逐日死亡分布,连续观察10天,按Bliss法计算LD50。高浓度组给药后,小鼠精神萎靡,死前粪便不成形,消瘦,竖毛,抱团萎缩不动。
由上表可以看出,本发明的式I配合物具有较低毒性。
式I配合物对肿瘤细胞的抑制作用:
取对数生长期细胞,消化、计数,接种于96孔培养板中,每孔100μL。培养24h后,以不同浓度复合物处理肿瘤细胞。药物作用72h后,去上清,每孔加入100μL MTT(1mg/mL),继续培养4h,弃上清,每孔加入100μL DMSO,振荡混匀,用酶标仪在570nm处测定吸光度值。计算抑制率。计算公式:抑制率(%)=(对照组吸光度值-给药组吸光度值)/(对照组吸光度值-空白组吸光度值)×100%。采用IC50计算软件(中国药科大学)求出半数抑制浓度(IC50)。表中数据的单位是μmol/L。
实验肿瘤株包括人胃癌细胞BGC、人宫颈腺癌细胞HeLa、人结肠癌细胞HCT116。细胞购自广东省微生物菌种保藏中心细胞库。实验结果如下表所示。
Claims (7)
1.一种如式I所示的配合物,其特征在于如下所示:
其中,选自
X和Y选自O或N,但是X和Y不同时为N;为多齿配体。
2.根据权利要求1所述的配合物,其特征在于:所述选自如下基团:
3.根据权利要求1或2所述的配合物,其特征在于选自下述配合物:
4.权利要求1-3任一所述的配合物的制备方法,其特征在于包括下述步骤:
二氯双取代氨基铂与相应的配体化合物反应。
5.一种组合物,其特征在于包括权利要求1-3任一所述的如式I所示的配合物,和药学上可接受的助剂、载体或稀释剂。
6.根据权利要求5所述的组合物,其特征在于:其剂型选自素片、薄膜包衣片、糖衣片、肠衣片、分散片、胶囊、颗粒剂、口服溶液或口服混悬液。
7.1-3任一所述的如式I所示的配合物用于制备治疗肿瘤或癌症药物的用途,所述肿瘤或癌症为胃癌、宫颈腺癌、结肠癌、肺癌、肝癌、胶质瘤、食道癌、肠癌、鼻咽癌、乳腺癌、淋巴癌、肾癌、胰腺癌、膀胱癌、卵巢癌、子宫癌、骨癌、胆囊癌、唇癌、黑素瘤、舌癌、喉癌、血癌、前列腺癌、脑瘤、鳞癌、皮肤癌、血管瘤、脂肪瘤、宫颈癌和甲状腺癌;优选结肠癌。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4658048A (en) * | 1984-06-20 | 1987-04-14 | Shionogi & Co., Ltd. | Platinum complexes |
CN101891769A (zh) * | 2010-06-18 | 2010-11-24 | 河北大学 | 抗肿瘤药物铂配合物 |
-
2018
- 2018-11-20 CN CN201811390122.0A patent/CN109369727B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4658048A (en) * | 1984-06-20 | 1987-04-14 | Shionogi & Co., Ltd. | Platinum complexes |
CN101891769A (zh) * | 2010-06-18 | 2010-11-24 | 河北大学 | 抗肿瘤药物铂配合物 |
Non-Patent Citations (3)
Title |
---|
MASSIMO LA DEDA等: "Cyclometalated Pt trans-diiodo adducts: experimental and computational studies within an homologous series of compounds", 《DALTON TRANS.》 * |
ZOUFENG XU等: "Halogenated Pt Complexes from N-Halosuccinimide Oxidation of Pt Antitumor Drugs: Synthesis, Mechanistic Investigation, and Cytotoxicity", 《EUR. J. INORG. CHEM.》 * |
张海燕: "基于反式1,2-环己二胺抗肿瘤位阻铂(Ⅱ)配合物的研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112500437A (zh) * | 2020-12-18 | 2021-03-16 | 河北医科大学 | 环氧铂配合物及其制备方法和用途 |
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