Design and synthesis of new tetrazolyl- and carboxy-biphenylylmethyl-quinazolin-4-one derivatives as angiotensin II AT1 receptor antagonists

Journal of Medicinal Chemistry
Mohamed A H IsmailMatthew H Todd

Abstract

A series of novel quinazolin-4-ones was designed and their molecular modeling simulation fitting to a new HipHop 3D pharmacophore model using CATALYST was examined. Several compounds showed significant high simulation fit values. The designed compounds were synthesized and eight of them were biologically evaluated in vitro using an AT1 receptor binding assay, where compound XX competed weakly against radiolabeled Sar1Ile8-angiotensin II (Ang II) binding, compounds XIV and XXII showed moderate competition, and compound XXV showed almost equal ability to displace radiolabeled Sar1Ile8-Ang II binding to AT1 receptors as losartan. In vivo biological evaluation study of compounds XIV, XXII, and XXV on both normotensive and hypertensive rats revealed that compound XXV demonstrated higher hypotensive and antihypertensive activity than the reference compound losartan. To obtain a highly active compound from a candidate set of only eight tested compounds illustrates the power and utility of our pharmacophore model.

References

Jul 21, 1992·European Journal of Pharmacology·J ZhangJ C Van Meel
Sep 1, 1991·Journal of Medicinal Chemistry·N B MantloC S Sweet
Oct 1, 1994·Journal of Computer-aided Molecular Design·K PrendergastD J Underwood
Apr 1, 1994·Journal of Medicinal Chemistry·W R SchoenR G Ball
Oct 15, 1993·Journal of Medicinal Chemistry·S E de LaszloS S Kivlighn
Feb 2, 1996·Journal of Medicinal Chemistry·R R WexlerP B Timmermans
Jun 20, 1996·The New England Journal of Medicine·T L GoodfriendK J Catt
Jun 20, 1996·European Journal of Pharmacology·A SachinidisH Vetter
Sep 1, 2000·Bioorganic & Medicinal Chemistry·J B BremnerB F Yates
Jul 27, 2001·Current Medicinal Chemistry·Y Kurogi, O F Güner
Jul 20, 2002·Bioorganic & Medicinal Chemistry Letters·Bertrand CottineauJacques Chenault
Nov 28, 2002·European Journal of Heart Failure·Emil PantevMalin Malmsjö
Feb 21, 2003·Journal of Medicinal Chemistry·Eva M Krovat, Thierry Langer
Jun 18, 2003·Clinical Therapeutics·Julie A Brousil, John M Burke
May 1, 1964·Journal of Medicinal Chemistry·R J STEDMANR J FERLAUTO
Dec 4, 2003·American Journal of Hypertension·Giuseppe ManciaGuido Grassi
Feb 3, 2004·The Journal of Biological Chemistry·Takanobu TakezakoSadashiva S Karnik

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Citations

Apr 25, 2013·Journal of Medicinal Chemistry·Moni SharmaPrem M S Chauhan
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunB Kalluraya
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Hoong-Kun FunBalakrishna Kalluraya
Jun 29, 2011·Future Medicinal Chemistry·Chenzhong LiaoMarc C Nicklaus
Mar 30, 2017·Bioorganic & Medicinal Chemistry Letters·Suresh PoudapallyVidya Katangoor
Aug 2, 2008·Bioorganic & Medicinal Chemistry·Osamu OhnoDaisuke Uemura
Oct 23, 2008·The Journal of Organic Chemistry·Lukas J Goossen, Thomas Knauber
Nov 13, 2010·Bioorganic & Medicinal Chemistry·Prashant NaikMange Ram Yadav

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