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

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

1.
a School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;
2.
b Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China

Corresponding author: Deng-Ke Liu,
Received Date: 27 January 2014
Available Online: 23 December 2014
Fund Project:

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.
- Arginine vasopressin V2 receptor,
- antagonist,
- Phenothiazine derivatives,
- Synthesis,
- Biological activities
1. [1]
  [1] G. Decaux, A. Soupart, G. Vassart, Non-peptide arginine-vasopressin antagonists: the vaptans, Lancet 371 (2008) 1624-1632.
2. [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.
3. [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.
4. [4]
  [4] A.A. Rabinstein, N. Bruder, Management of hyponatremia and volume contraction, Neurocrit. Care 15 (2011) 354-360.
5. [5]
  [5] S.K. Kumar, P.J. Mather, AVP receptor antagonists in patients with CHF, Heart Fail. Rev. 14 (2009) 83-86.
6. [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.
7. [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.
8. [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.
9. [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.
10. [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.
11. [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.
12. [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.
13. [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.
14. [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.
15. [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.
16. [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.
17. [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.
18. [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.
19. [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.
20. [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.
21. [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.
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