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新的二芳基哌嗪基脒类化合物——化学合成和5-HT重摄取抑制活性 被引量：4

Synthesis and 5-HT reuptake inhibition activity of biarylbenzamidine derivatives
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摘要 为了寻找新的5-HT重摄取抑制活性的抗抑郁药,设计合成了31个哌嗪取代的二苯脒类化合物,通过1H NMR,HRMS对化合物结构进行了确证,并测定了化合物的体外5-HT重摄取抑制活性。结果表明所有化合物都有一定程度的5-HT重摄取抑制活性。其中化合物5 i、4a和5m具有较强的5-HT重摄取抑制活性,其活性与阳性对照品丙咪嗪相当或稍强,值得进一步研究。 A series of biarylbenzamidine analogs were synthesized and tested for their biological activities of inhibiting the reuptake of 5-HT. All of them were new compounds, and their structures were confirmed by 1^H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibition activity. Among the tested compounds, 5i, 4a and 5m exhibited potent inhibitory activity against 5-HT reuptake in vitro. It is a chance to find a better precursor of SSRIs （ selective serotonin reuptake inhibitors） for further optimization of compounds.
作者 秦芳 王娜沙 杨静 张建军 王亚芳 杨光中
机构地区 中国医学科学院北京协和医学院药物研究所
出处 《药学学报》 CAS CSCD 北大核心 2008年第6期619-625,共7页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目(30572233) 北京市自然科学基金资助项目(7062045).
关键词 合成 哌嗪取代的二苯脒类化合物 5-HT重摄取抑制活性 抗抑郁 synthesis biarylbenzamidine derivative 5-HT reuptake inhibition activity antidepression
分类号 R916.2 [医药卫生—药学]
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  • 1[1]C.J.L.Murray,A.D.Lopez (Eds.),The Global Burden of Disease:A comprehensive Assessment of Mortality an Disability from Diseases.Injuries and Risk Factors in 1990 and Projected to 2020,Harvard University,Cambridge,MA,1996. 被引量：1
  • 2[2]M.Vaswani,F.K.Linda,Ramesh,S.Prog.Neuro.Psycopha.27 (2003) 85. 被引量：1
  • 3[3]D.Spinks,G.Spinks,Curr.Med.Chem.9 (2002) 799. 被引量：1
  • 4[4]S.H.Preskom,R.Ross,C.Y.Stanga,in:S.H.Preskorn,J.P.Feighner,C.Y.Stanga (Fdls.),Antidepressants:Past,Present and Future,Springer,Berlin,2004,pp.241-262. 被引量：1
  • 5[5]S.I.Ankier,G.P.Ellis,Recent progress in the development of new antidepressant drugs,Prog.Med.Chem 23 (1986) 121. 被引量：1
  • 6[6]L.N.Nikolenko,S.I.Popov,J.Gen.Chem.USSR 32 (1962) 29. 被引量：1
  • 7[7]H.G.Vogel,W.H.Vogel,Drug Discovery and Evaluation-Pharmacological Assays (2nd ed.),pp.S390-S391. 被引量：1
  • 8[8](1) MS (ESI) m/z (%):280 (M + H,100),180(85); 1HNMR (CDCl3,δ (ppm)):2.48 (s,3H,-NCH3),2.67(br,4H,-CH2-(NMe)-CH2-),3.64 (br,4H,-CH2-N-CH2-),6.60(d,2H,J= 7.8 Hz,ArH),6.79(t,1H,ArH),7.01(t,2H,J= 7.8 Hz,ArH),7.12(m,2H,ArH),7.25(m,3H,ArH).(2)MS(ESI) m/z (%):298(M + H,100),198(50); 1HNMR (CDCl3,ppm):2.34(s,3H,-NCH3),2.46(br,4H,-CH2-(NMe)-CH2-),3.44(br,4H,-CH2-N-CH2-),6.46(m,2H,ArH),6.67(m,2H,ArH),7.07(m,2H,ArH),7.23(m,3H,ArH).(3) MS(ESI) m/z (%):314(M + H,100),214 (40);1HNMR (CDCl3,δ (ppm)):2.40(s,3H,-NCH3),2.54(br,4H,-CH2-(NMe)-CH2-),3.50(bt,4H,-CH2-N-CH2-),6.48(m,2H,ArH),6.95(m,2H,ArH),7.10(m,2H,ArH),7.24(m,3H,ArH).(4) MS(ESI) m/z (%):310(M+ H,100),210(35); 1HNMR (CDCl3,δ (ppm)):2.40 (s,3H,-NCH3),2.56(br,4H,-CH2-(NMe)-CH2-),3.56(br,4H,-CH2-N-CH2-),3.66(s,3H,-OCH3),6.55(m,4H,ArH),7.12(m,2H,ArH),7.25(m,3H,ArH).(5) MS(ESI) m/z (%):336(M + H,100); 1HNMR (CDCl3,δ (ppm)):1.18(s,9H,-C-(CH3)3),2.43(s,3H,-NCH3),2.63(br,4H,-CH2-(NMe)-CHz-),3.57(br,4H,-CH2-N-CH2-),6.55(m,2H,ArH),7.15(m,2H,ArH),7.19(m,2H,ArH),7.25(m,3H,ArH).(6) MS(ESI) m/z (%):360(100),358(M + H,100),260(40),258(40); 1HNMR (CDCl3,δ (ppm)):2.42(s,3H,-NCH3),2.63(br,4H,-CH2-(NMe)-CH2-),3.55(br,4H,-CH2-N-CH2-),6.42(m,1H,ArH),6.65(m,1H,ArH),6.90(m,2H,ArH),7.18(m,2H,ArH),7.23(m,2H,ArH),7.40(m,1H,ArH).(7) MS(ESI)m/z (%):310(M + H,100),210(18); 1HNMR (CDCl3,δ (ppm)):2.34(s,3H,-NCH3),2.47(br,4H,-CH2-(NMe)-CH2-),3.48(br,4H,-CH2-N-CH2-),3.66(s,3H,-OCH3),6.51(m,1H,ArH),6.61(m,2H,ArH),6.75(m,1H,ArH),7.15(m,4H,ArH),7.25 (m,1H,ArH).(8) MS(ESI) m/z (%):330(M + H,100),230(20); 1HNMR (CDCl3,δ (ppm):2.45(s,3H,-NCH3),2.61(br,4H,-CH2-(NMe)-CH2-),3.64(br,4H,-CH2-N-CH2-),6.33(m,1H,ArH),7.10(m,7H,ArH),7.42(m,2H,ArH),7.76(m,1H,ArH),8.19(m,1H,ArH).(9) MS(ESI) m/z (%):280 (M+H,100),180(40); 1HNMR (acetone-d6,δ (ppm)):0.96(d,3H,J= 6.0 Hz,Cz-CH3),2.43(q,1H,3Jaa = 10.5 Hz,2Jae = 12.9 Hz,C3-aH),2.85 (m,5H,C5-2H,C6-2H,C3-eH),3.76(br,1H,C2-H),6.45(m,2H,ArH),6.62(m,1H,ArH),6.89(m,2H,ArH),7.12(m,2H,ArH),7.22(m,3H,ArH).(10) MS(ESI) m/z (%):34(M + H,100),248(63); 1HNMR (CDCl3,δ (ppm)):1 被引量：1
  • 9Goodwin G M.How do antidepressants affect serotonin receptors? The role of serotonin receptors in the therapeutic and side effect profile of SSRIS.J Clin Psychiatry,1996,57(suppl.4):9. 被引量：1
  • 10Hans-J ü,rgen Mller M D,et al.Are all antidepressant s the same? J ClinPsychiatry,2000,61(suppl 6):24-28. 被引量：1

共引文献9

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  • 1Jing Yang Xiaofang Wang Hui Wen Fang Qin Guang Zhong Yang.Design, synthesis and in vitro evaluation of phenylbenzamidine derivatives as SSRIs[J].Chinese Chemical Letters,2007,18(7):814-816. 被引量：4
  • 2Phillips MR, Yang G, Li S, et al. Suicide and the unique prevalence pattern of schizophrenia in China's Mainland: a retrospective observational study [J]. Lancet, 2004, 364: 1062-1068. 被引量：1
  • 3Meltzer HY, Li Z, Kaneda Y, et al. Serotonin receptors: their key role in drugs to treat schizophrenia [J]. Prog Neuropsychopharmacol Biol Psychiatry, 2003, 27:1159-1172. 被引量：1
  • 4De Vry J, Schreiber R, Melon C, et al. 5-HT1A receptors are differentially involved in the anxiolytic- and antidepressantlike effects of 8-OH-DPAT and fluoxetine in the rat [J]. Eur Neuropsychopharmacol, 2004, 14: 487-495. 被引量：1
  • 5Leucht S, Pitschel-Walz G, Abraham D, et al. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials [J]. Schizophr Res, 1999, 35:51-68. 被引量：1
  • 6Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials [J]. Schizophr Res, 2003, 61: 123- 136. 被引量：1
  • 7Miyamoto S, Duncan GE, Marx CE, et al. Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs [J]. Mol Psychiatry, 2005, 10: 79-104. 被引量：1
  • 8Garzya V, Forbes IT, Gribble AD, et al. Studies towards the identification of a new generation of atypical antipsychotic agents [J]. Bioorg Med Chem Lett, 2007, 17: 400-405. 被引量：1
  • 9Ravina E, Ramos RG, Masaguer CF, et al. Synthesis of N-(2-guanidinoethyl) tetrahydrothieno [3,2-c]azepine, N-(2- guanidinoethyl)tetrahydro-2-benzazepine and N-(2-guanidinoethyl) tetrahydro-1-benzazepine as analogous to antihypertensive agent guanetidine [J]. Synth Commun, 1994, 24: 321-326. 被引量：1
  • 10Braje W, Haupt A, Lubisch W, et al. Tetrahydrobenzazepines as dopamine D3 receptor modulators, their preparation, pharmaceutical compositions and use in the treatment of CNS disorders and renal function disorders: PCT, 2005058328 [P]. 2005-3-31. 被引量：1

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药学学报
2008年 第6期

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