注册 English

Synthesis and biological evaluation of novel phenothiazine derivatives as non-peptide arginine vasopressin V2 receptor antagonists

Shuang Zhi ,  Shuai Mu ,  Ying Liu ,  Min Gong ,  Ping-Bao Wang ,  Deng-Ke Liu

downloadPDF
Citation:  Shuang Zhi, Shuai Mu, Ying Liu, Min Gong, Ping-Bao Wang, Deng-Ke Liu. Synthesis and biological evaluation of novel phenothiazine derivatives as non-peptide arginine vasopressin V2 receptor antagonists[J]. Chinese Chemical Letters, 2015, 26(5): 627-630. doi: 10.1016/j.cclet.2015.01.022 shu

Synthesis and biological evaluation of novel phenothiazine derivatives as non-peptide arginine vasopressin V2 receptor antagonists

    • 通讯作者: Deng-Ke Liu,
摘要: A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by 1HNMR, 13CNMRandHRMS, and biological activitywas evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, 1t and 1v exhibited excellent diuretic activity, especially 1r and 1v. Therefore, 1r and 1v are potent novelAVP V2receptor antagonist candidates.

English

  • 

    1. [1] G. Decaux, A. Soupart, G. Vassart, Non-peptide arginine-vasopressin antagonists: the vaptans, Lancet 371 (2008) 1624-1632.[1] G. Decaux, A. Soupart, G. Vassart, Non-peptide arginine-vasopressin antagonists: the vaptans, Lancet 371 (2008) 1624-1632.

    2. [2] A. Dietrich, S. Mathia, H. Kaminski, et al., Chronic activation of vasopressin V2 receptor signalling lowers renal medullary oxygen levels in rats, Acta Physiol. 207 (2013) 721-731.[2] A. Dietrich, S. Mathia, H. Kaminski, et al., Chronic activation of vasopressin V2 receptor signalling lowers renal medullary oxygen levels in rats, Acta Physiol. 207 (2013) 721-731.

    3. [3] C. Vaidya, W. Ho, B.J. Freda, Management of hyponatremia: providing treatment and avoiding harm, Clevel. Clin. J. Med. 77 (2010) 715-726.[3] C. Vaidya, W. Ho, B.J. Freda, Management of hyponatremia: providing treatment and avoiding harm, Clevel. Clin. J. Med. 77 (2010) 715-726.

    4. [4] A.A. Rabinstein, N. Bruder, Management of hyponatremia and volume contraction, Neurocrit. Care 15 (2011) 354-360.[4] A.A. Rabinstein, N. Bruder, Management of hyponatremia and volume contraction, Neurocrit. Care 15 (2011) 354-360.

    5. [5] S.K. Kumar, P.J. Mather, AVP receptor antagonists in patients with CHF, Heart Fail. Rev. 14 (2009) 83-86.[5] S.K. Kumar, P.J. Mather, AVP receptor antagonists in patients with CHF, Heart Fail. Rev. 14 (2009) 83-86.

    6. [6] B. Bishara, H. Shiekh, T. Karram, et al., Effects of novel vasopressin receptor antagonists on renal function and cardiac hypertrophy in rats with experimental congestive heart failure, J. Pharmacol. Exp. Ther. 326 (2008) 414-422.[6] B. Bishara, H. Shiekh, T. Karram, et al., Effects of novel vasopressin receptor antagonists on renal function and cardiac hypertrophy in rats with experimental congestive heart failure, J. Pharmacol. Exp. Ther. 326 (2008) 414-422.

    7. [7] E. Higashihara, V.E. Torres, A.B. Chapman, et al., Tolvaptan in autosomal dominant polycystic kidney disease: three years’ experience, Clin. J. Am. Soc. Nephrol. 6 (2011) 2499-2507.[7] E. Higashihara, V.E. Torres, A.B. Chapman, et al., Tolvaptan in autosomal dominant polycystic kidney disease: three years’ experience, Clin. J. Am. Soc. Nephrol. 6 (2011) 2499-2507.

    8. [8] A. Soupart,M. Coffernils, B. Couturier, F. Gankam-Kengne, G. Decaux, Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH, Clin. J. Am. Soc. Nephrol. 7 (2012) 742-747.[8] A. Soupart,M. Coffernils, B. Couturier, F. Gankam-Kengne, G. Decaux, Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH, Clin. J. Am. Soc. Nephrol. 7 (2012) 742-747.

    9. [9] F. Ali, M.A. Raufi, B. Washington, J.K. Ghali, Conivaptan: a dual receptor vasopressin V-1a/V-2 antagonist, Cardiovasc. Drug Rev. 25 (2007) 261-279.[9] F. Ali, M.A. Raufi, B. Washington, J.K. Ghali, Conivaptan: a dual receptor vasopressin V-1a/V-2 antagonist, Cardiovasc. Drug Rev. 25 (2007) 261-279.

    10. [10] R.W. Schrier, P. Gross, M. Gheorghiade, et al., a selective oral vasopressin V-2-receptor antagonist, for hyponatremia, N. Engl. J. Med. 355 (2006) 2099- 2112.[10] R.W. Schrier, P. Gross, M. Gheorghiade, et al., a selective oral vasopressin V-2-receptor antagonist, for hyponatremia, N. Engl. J. Med. 355 (2006) 2099- 2112.

    11. [11] B.T. Bowman, M.H. Rosner, Lixivaptan-an evidence-based review of its clinical potential in the treatment of hyponatremia, Core Evid. 8 (2013) 47-56.[11] B.T. Bowman, M.H. Rosner, Lixivaptan-an evidence-based review of its clinical potential in the treatment of hyponatremia, Core Evid. 8 (2013) 47-56.

    12. [12] A.L. Crombie, T.M. Antrilli, B.A. Campbell, et al., Synthesis and evaluation of azabicyclo 3.2.1 octane derivatives as potent mixed vasopressin antagonists, Bioorg. Med. Chem. Lett. 20 (2010) 3742-3745.[12] A.L. Crombie, T.M. Antrilli, B.A. Campbell, et al., Synthesis and evaluation of azabicyclo 3.2.1 octane derivatives as potent mixed vasopressin antagonists, Bioorg. Med. Chem. Lett. 20 (2010) 3742-3745.

    13. [13] I. Tsukamoto, H. Koshio, T. Kuramochi, et al., Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin- 5-ylidene)acetic acid as selective arginine vasopressin V-2 receptor agonists, Bioorg. Med. Chem. 17 (2009) 3130-3141.[13] I. Tsukamoto, H. Koshio, T. Kuramochi, et al., Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin- 5-ylidene)acetic acid as selective arginine vasopressin V-2 receptor agonists, Bioorg. Med. Chem. 17 (2009) 3130-3141.

    14. [14] A.A. Failli, J.S. Shumsky, R.J. Steffan, et al., Pyridobenzodiazepines: a novel class of orally active, vasopressin V-2 receptor selective agonists, Bioorg. Med. Chem. Lett. 16 (2006) 954-959.[14] A.A. Failli, J.S. Shumsky, R.J. Steffan, et al., Pyridobenzodiazepines: a novel class of orally active, vasopressin V-2 receptor selective agonists, Bioorg. Med. Chem. Lett. 16 (2006) 954-959.

    15. [15] A.M. Venkatesan, G.T. Grosu, A.A. Failli, et al., (4-Substituted-phenyl)-(5H- 10,11-dihydro-pyrrolo 2,1-c 1,4 benzodiazepin-1'-yl)-methanone derivatives as vasopressin receptor modulators, Bioorg. Med. Chem. Lett. 15 (2005) 5003- 5006.[15] A.M. Venkatesan, G.T. Grosu, A.A. Failli, et al., (4-Substituted-phenyl)-(5H- 10,11-dihydro-pyrrolo 2,1-c 1,4 benzodiazepin-1'-yl)-methanone derivatives as vasopressin receptor modulators, Bioorg. Med. Chem. Lett. 15 (2005) 5003- 5006.

    16. [16] M.J. Urbanski, R.H. Chen, K.T. Demarest, et al., 2,5-disubstituted 3,4-dihydro-2Hbenzo b 1,4 thiazepines as potent and selective V-2 arginine vasopressin receptor antagonists, Bioorg. Med. Chem. Lett. 13 (2003) 4031-4034.[16] M.J. Urbanski, R.H. Chen, K.T. Demarest, et al., 2,5-disubstituted 3,4-dihydro-2Hbenzo b 1,4 thiazepines as potent and selective V-2 arginine vasopressin receptor antagonists, Bioorg. Med. Chem. Lett. 13 (2003) 4031-4034.

    17. [17] S. Luk, R.S. Atayee, J.D. Ma, B.M. Best, Urinary diazepam metabolite distribution in a chronic pain population, J. Anal. Toxicol. 38 (2014) 135-142.[17] S. Luk, R.S. Atayee, J.D. Ma, B.M. Best, Urinary diazepam metabolite distribution in a chronic pain population, J. Anal. Toxicol. 38 (2014) 135-142.

    18. [18] M. Burnier, A.F. Fricker, D. Hayoz, J. Nussberger, H.R. Brunner, Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects, Eur. J. Clin. Pharmacol. 55 (1999) 633- 637.[18] M. Burnier, A.F. Fricker, D. Hayoz, J. Nussberger, H.R. Brunner, Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects, Eur. J. Clin. Pharmacol. 55 (1999) 633- 637.

    19. [19] S. Nodari, G.T. Jao, J.R. Chiong, Clinical utility of tolvaptan in the management of hyponatremia in heart failure patients, Int. J. Nephrol. Renovasc. Dis. 3 (2010) 51- 60.[19] S. Nodari, G.T. Jao, J.R. Chiong, Clinical utility of tolvaptan in the management of hyponatremia in heart failure patients, Int. J. Nephrol. Renovasc. Dis. 3 (2010) 51- 60.

    20. [20] S. Mu, Y. Liu, M. Gong, D.K. Liu, C.X. Liu, Synthesis and biological evaluation of substituted desloratadines as potent arginine vasopressin V2 receptor antagonists, Molecules 19 (2014) 2694-2706.[20] S. Mu, Y. Liu, M. Gong, D.K. Liu, C.X. Liu, Synthesis and biological evaluation of substituted desloratadines as potent arginine vasopressin V2 receptor antagonists, Molecules 19 (2014) 2694-2706.

    21. [21] S. Mu, X. S. Xie, D. Niu, et al., Synthesis and biological evaluation of novel derivatives of desloratadine, Chin. Chem. Lett. 24 (2013) 531-534.[21] S. Mu, X. S. Xie, D. Niu, et al., Synthesis and biological evaluation of novel derivatives of desloratadine, Chin. Chem. Lett. 24 (2013) 531-534.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  829
  • HTML全文浏览量:  6
文章相关
  • 发布日期:  2015-01-28
  • 收稿日期:  2014-01-27
  • 网络出版日期:  2014-12-23
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net