期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

2-吲哚啉酮类化合物的合成及其体外活性研究 被引量：1

Synthesis and biological evaluation of 2-indolinone derivatives as dopamine D4 receptor ligands
下载PDF
导出
摘要 为开发新型多巴胺D4受体配基,以2-吲哚啉酮和1,4-二溴丁烷为原料,制得目标化合物1-(4-(4-(4-苯甲基)-1-哌嗪基)丁基)-2-吲哚啉酮、1-(4-(4-(4-氯苯甲基)-1-哌嗪基)丁基)-2-吲哚啉酮、1-(4-(4-(4-甲基苯甲基)-1-哌嗪基)丁基)-2-吲哚啉酮。通过体外受体结合分析,测定了这3个目标化合物对多巴胺D2、D3、D4.2受体的亲和性。实验结果表明:化合物1-(4-(4-(4-氯苯甲基)-1-哌嗪基)丁基)-2-吲哚啉酮对D4受体亲和选择性较大,其亲和常数(Ki)为0.5 nmol/L。 To develop novel dopamine D4 receptor ligands,1-（4-（4-（4-benzyl）-1-piperazinyl）butyl）indolin-2-one,1-（4-（4-（4-chlorobenzyl）-1-piperazinyl）butyl）indolin-2-one and 1-（4-（4-（4-methylbenzyl）-1-piperazinyl）butyl）indolin-2-one were synthesized from 2-indolinone and 1,4-dibromobutane.Through invitro receptor binding studies,the affinities of the three compounds at D2,D3,D4 receptor subtypes were determined.The experimental results showed that 1-（4-（4-（4-chlorobenzyl）-1-piperazinyl）butyl）-2-indolinone exhibited a remarkable affinity to D4 receptor with Ki value of 0.5 nmol/L.
作者 李谷才 张儒 蒋开军
机构地区 湖南工程学院化学化工学院
出处 《化学试剂》 CAS CSCD 北大核心 2012年第7期593-596,600,共5页 Chemical Reagents
基金 湖南省自然科学基金资助项目(07JJ6014)
关键词 2-吲哚啉酮 配体 多巴胺D4受体 生物学评价 2-indolinone ligand dopamine D4 receptor biological evaluation
分类号 O626 [理学—有机化学]
  • 相关文献

参考文献20

  • 1EHLICHT K, GOTZ A, BOLLINGER S, et al. Dopamine D2,D3 and D4 selective phenylpiperazines as molecular probes to explore the origins of subtype specific receptor binding[ J ]. J. Med. Chem. ,2009,52 ( 15 ) :4 923-4 935.
  • 2HOBNER H, HAUBMANN C, UTZ W, et al. Conjugatedenynes as nonaromatie catechol bioisosteres: synthesis, binding experiments, and computational studies of novel dopamine receptor agonists recognizing preferentially the D3 subtype [ J ]. J. Med. Chem. ,2000,43 ( 4 ) :756-762.
  • 3李凡,舒斯云,包新民.多巴胺受体的结构和功能[J].中国神经科学杂志,2003,19(6):405-410. 被引量：71
  • 4冯雪,徐平,李生斌.成瘾行为与多巴胺D_4受体的研究进展[J].陕西医学杂志,2005,34(1):89-91. 被引量：1
  • 5金国章.遐思:精神分裂症病因和药物治疗[J].中国处方药,2005(8):7-11. 被引量：5
  • 6LAUZON N M, LAVIOLETTE S R. Dopamine D4-recep- tor modulation of cortical neuronal network activity and e- motional processing:implications for neuropsychiatric dis- orders [J].Behav. Brain Res. , 2010,208 ( 1 ) : 12-22.
  • 7STEFAN L, HARALD H, PETER G. Synthesis and bio- logical investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype [ J ]. Bioorg. Med. Chem. Lett. ,2006,16(11) :2 955-2 959.
  • 8IRIS R, GOTTFR1ED S. Dopamine D4 receptor exon m polymorphism,adverse life events and personality traits in a nonclinical German adult sample[ J]. Neuropsycholoiol- ogy ,2011,63 ( 1 ) :52-58.
  • 9LINZ S, MI-LLER J, HOBNER H, et al. Design, synthesis and dopamine D4 receptor binding activities of new N-het- eroaromatic 5/6-ring Mannich bases [ J ]. Bioorg. Med. Chem. , 2009,17 ( 13 ) :4 448-4 458.
  • 10PRANTE O,TIETZE R, HOCKE C, et al. Synthesis, ra- diofluorination, and in vitro evaluation of pyrazolo [ 1 , 5- a] pyridine-based dopamine D4 receptor ligands: discov- ery of an inverse agonist radioligand for PET [ J 3. J. Med. Chem. ,2008,51(fi) :1 800-1 810.

二级参考文献72

  • 1[1]Gingrich JA, Caron MG. Rcecnt advances in the molecular biology of dopamine receptor [J]. Annu Rev Neurosci, 1993, 16: 299-321.
  • 2[2]Ng GY, Moillac B, George SR, et al. Desensitization phosphorylation and palmitoylation of the human dopamine D1 receptor [J].Eur J Pharmacol, 1994, 267( 1 ): 7-19.
  • 3[3]Jackson DM, Westlind-Danielsson A. Dopamine receptors: molecular biology, biochemistry and behavioural aspects [J]. Pharmacol Ther, 1994, 64(2): 291-370.
  • 4[4]Valdenaire O, Vernier P, Maus M, et al. Transcription of the rat dopamine-D2-receptor gene from two promoters [ J ]. Eur J Biochem, 1994, 220(2): 577-584.
  • 5[5]Civelli O, Bunzow JR, Grandy DK, etal. Molecular biology of the dopamine receptors [J]. Eur J Pharmacol, 1991,207(4): 277-286.
  • 6[6]Smiley JF, AI Levey, BJ Ciliax, et al. D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines [J]. Proc Natl Acad Sci USA, 1994, 91(12): 5720-5724.
  • 7[7]Levey AI, Hersch SM, Rye DB, et al. Localization of D1 and spiperone and in GH3 cells that express a D2-like receptor with an unusual low affinity for haloperidol in response to NGF. D2 dopamine receptors in brain with subtype-specific antibodies [J]. Proc Natl Acad Sci USA, 1993, 90(19): 8861-8865.
  • 8[8]Mrzlak L, Bergon C, Pappy M,et al. Localization of dopamine D4 receptors in G A B Aergic neurons of the primate brain [J]. Nsture, 1996, 381(6579): 245-248.
  • 9[9]Xu M, Mratalla R, GoldLH, et al. Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopsmine-mediated behavioral responses [J]. Cell, 1994, 79 (4):729-742.
  • 10[10]Baik JH, Picetti R, Saiardi A, et al. Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors [ J ]. Nature,1995, 377 ( 6548 ): 424-428.

共引文献108

同被引文献11

  • 1Pawel Z,Krzysztof M,Andrzej M,et al.Quinoline-and Isoquinoline-sulfonamide Derivatives of LCAP as Potent CNS Multi-receptor-5-HTjJ5-HT2a/5-HT7 and D2/D3/D:Agents:the Synthesis and Pharmacological Evaluation [J].Bioorg Med Chem,2012,20:1545-1556.
  • 2Takami G,Ota M,Nakashima A,et al.Effects of Atypical Antipsychotics and Haloperidol on PC12 Cells:Only Aripiprazole Phosphorylates AMP-activated Protein Kinase [J].J Neural Transm,2010,117(10):1139-1153.
  • 3Rostom S A.Novel Fused Pyrrole Heterocyclie Ring Systems as Structure Analogs of LE 300:Synthesis and Pharmacological Evaluation as Serotonin 5-HT2A,Dopamine and Histamine Ⅲ Receptor Ligands [J].Arch Pharm,2010,343(2):73-80.
  • 4Lauzon N M,Laviolette S R.Dopamine D4-receptor Modulation of Cortical Neuronal Network Activity and Emotional Processing:Implications for Neuropsychiatric Disorders[J].Behav Brain Res,2010,205(1):12-22.
  • 5Stefan L,Harald H,Peter G.Synthesis and Biological Investigations of Dopaminergic Partial Agonists Preferentially Recognizing the D4 Receptor Subtype [J].Bioorg Med Chem Lett,2006,16(11):2955-2959.
  • 6Iris R,Gottfried S.Dopamine D4 Receptor Exon Ill Polymorphism,Adverse Life Events and Personality Traits in a Nonclinical German Adult Sample[J].Neuropsycholoiology,2011,63(1):52-58.
  • 7Linz S,Mller J,H bner H,et al.Design,Synthesis and Dopamine D4 Receptor Binding Activities of New N-Heteroaromatic 5/6-ring Mannich Bases [J].Bioorg Med Chem,2009,17(13):4448-4458.
  • 8Lacivita E,De Giorgio P,Lee IT,et al.Design,Synthesis,Radiolabehng,and in vivo Evaluation of Carbon-11 Labeled N-[ 2-[ 4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide,a Potential Positron Emission Tomography Tracer for the Dopamine D(4)Receptors [J].J Med Chem,2010,53(20):7344-7355.
  • 9Olaf P,Rainer T,Jcarsten H,et al.Synthesis,Radiofluorination,and in Vitro Evaluation of Pyrazolo [ 1,5-ct]pyridine-based Dopamine D4 Receptor Ligands:Discovery of an Inverse Agonist Radioligand for PET [ 33.J Med Chem,2008,51:1800-1810.
  • 10季卫东,周家秀,杨闯,黄晓琪,姚静,郭田友,郭兰婷,刘协和.抽动秽语综合征汉族患者的执行功能及与多巴胺D4受体第3外显子48bp可重复序列多态性[J].中国心理卫生杂志,2010,24(8):568-573. 被引量：7

引证文献1

二级引证文献1

化学试剂
2012年 第7期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部