Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with 'inverted' binding mode

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 17, 2014, Pages 4867-4881

  Darras, Fouad H ^a   Wehle, Sarah ^b   Huang, Guozheng ^a,b   Sotriffer, Christoph A ^b   Decker, Michael ^a,b  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

Alzheimer's disease; Cholinesterase inhibitors; Computational study; Heterocycles; Quinazolinones

Indexed keywords

10 (3 BROMOPROPOXY) 5H ISOQUINOLINO[1,2 B]QUINAZOLIN 8(6H) ONE; 10 (BENZYLOXY) 5H ISOQUINOLINO[1,2 B]QUINAZOLIN 8(6H) ONE; 10 HYDROXY 5H ISOQUINOLINO[1,2 B]QUINAZOLIN 8(6H) ONE; 11 (3 BROMOPROPOXY) 6,7DIHYDROBENZO[3,4]AZEPINO[2,1 B]QUINAZOLIN 9(5H) ONE; 11 (BENZYLOXY) 6,7 DIHYDROBENZO[3,4]AZEPINO[2,1B]QUINAZOLIN 9(5H) ONE; 11 HYDROXY 6,7 DIHYDROBENZO[3,4]AZEPINO[2,1 B]QUINAZOLIN 9(5H) ONE; 2 (3 BROMOPROPOXY) 7,8,9,10 TETRAHYDROAZEPINO[2,1 B]QUINAZOLIN 12(6H) ONE; 2 (3 BROMOPROPOXY) 8,9 DIHYDRO 6H PYRIDO[2,1 B]QUINAZOLIN 11(7H) ONE; 2 (BENZYLOXY) 7,8,9,10 TETRAHYDROAZEPINO[2,1 B]QUINAZOLIN 12(6H) ONE; 2 (BENZYLOXY) 8,9 DIHYDRO 6H PYRIDO[2,1 B]QUINAZOLIN 11(7H) ONE; 2 HYDROXY 7,8,9,10 TETRAHYDROAZEPINO[2,1 B]QUINAZOLIN 12(6H) ONE; 2 HYDROXY 8,9 DIHYDRO 6H PYRIDO[2,1 B]QUINAZOLIN 11(7H) ONE; 7 (3 BROMOPROPOXY) 2,3 DIHYDROPYRROLO[2,1 B]QUINAZOLIN 9(1H) ONE; 7 (BENZYLOXY) 2,3 DIHYDROPYRROLO[2,1 B]QUINAZOLIN 9(1H) ONE; 7 HYDROXY 2,3 DIHYDROPYRROLO[2,1 B]QUINAZOLIN 9(1H) ONE; 8 (3 BROMOPROPOXY)ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 (BENZYLOXY)ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 HYDROXYISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (1H IMIDAZOL 1 YL)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (3,4 DIHYDROISOQUINOLIN 2(1H) YL)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (AZEPAN 1 YL)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (DIETHYLAMINO)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (PIPERIDIN 1 YL)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; 8 [3 (PYRROLIDIN 1 YL)PROPOXY]ISOINDOLO[1,2 B]QUINAZOLIN 10(12H) ONE; ACETYLCHOLINESTERASE; AMINE; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; QUINAZOLINONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG BINDING; DRUG MECHANISM; DRUG SYNTHESIS; ENZYME INHIBITION; INVERTED BINDING MODE; MOLECULAR DOCKING; NONHUMAN; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; HUMAN; METABOLISM; SYNTHESIS;

ACETYLCHOLINESTERASE; AMINES; BINDING SITES; BUTYRYLCHOLINESTERASE; CHOLINESTERASE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MOLECULAR STRUCTURE; QUINAZOLINONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84906935545     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.06.045     Document Type: Article

References (49)

1. C. Reitz, C. Brayne, and R. Mayeux Nat. Rev. Neurol. 7 2011 137
2. M. Goedert, and M.G. Spillantini Science 314 2006 777
3. M.P. Murphy, and I.H. LeVine J. Alzheimers Dis. 19 2010 311
4. M. Kolarova, F. García-Sierra, A. Bartos, J. Ricny, and D. Ripova Int. J. Alzheimers Dis. 2012 2012 1
5. M. Pohanka Curr. Med. Chem. 21 2013 356
6. A. Contestabile Behav. Brain Res. 221 2011 334
7. L. Fang, D. Appenroth, M. Decker, M. Kiehntopf, A. Lupp, S. Peng, C. Fleck, Y. Zhang, and J. Lehmann J. Med. Chem. 51 2008 7666
8. X. Chen, K. Zenger, A. Lupp, B. Kling, J. Heilmann, C. Fleck, B. Kraus, and M. Decker J. Med. Chem. 55 2012 5231
9. L. Fang, B. Kraus, J. Lehmann, J. Heilmann, Y. Zhang, and M. Decker Bioorg. Med. Chem. Lett. 18 2008 2905
10. V. Tumiatti, A. Minarini, M.L. Bolognesi, A. Milelli, M. Rosini, and C. Melchiorre Curr. Med. Chem. 17 2010 1825
11. A. Takeda, E. Loveman, A. Clegg, J. Kirby, J. Picot, E. Payne, and C. Green Int. J. Geriatr. Psychiatry 21 2006 17
12. M. Singh, M. Kaur, H. Kukreja, R. Chugh, O. Silakari, and D. Singh Eur. J. Med. Chem. 70 2013 165
13. B.R. Pinho, F. Ferreres, P. Valentão, and P.B. Andrade J. Pharm. Pharmacol. 65 2013 1681
14. E.L. Konrath, C. dos Santos Passos, L.C. Klein-Júnior, and A.T. Henriques J. Pharm. Pharmacol. 65 2013 1701
15. A.P. Macabeo, W.S. Vidar, X. Chen, M. Decker, J. Heilmann, B. Wan, S.G. Franzblau, E.V. Galvez, M.A. Aguinaldo, and G.A. Cordell Eur. J. Med. Chem. 46 2011 3118
16. D.J. Connolly, D. Cusack, T.P. O'Sullivan, and P.J. Guiry Tetrahedron 61 2005 10153
17. I. Khan, A. Ibrar, N. Abbas, and A. Saeed Eur. J. Med. Chem. 76 2014 193
18. P.C. Sharma, G. Kaur, R. Pahwa, A. Sharma, and H. Rajak Curr. Med. Chem. 18 2011 4786
19. R. Rajput, and A. Mishra Int. J. Pharm. Pharm. Sci. 4 2012 66
20. D.A. Horton, G.T. Bourne, and M.L. Smythe Chem. Rev. 103 2003 893
21. F. Hassanzadeh, E. Jafari, G.H. Hakimelahi, M.R. Khajouei, M. Jalali, and G.A. Khodarahmi Res. Pharm. Sci. 7 2012 87
22. S. Vanparia, T. Patel, R. Dixit, and B. Dixit Med. Chem. Res. 22 2013 5184
23. S.E. Abbas, F.M. Awadallah, N.A. Ibrahin, E.G. Said, and G.M. Kamel Eur. J. Med. Chem. 53 2012 141
24. A. El-Azab, S. Abdel-Hamide, M. Sayed-Ahmed, G. Hassan, T. El-Hadiyah, O. Al-Shabanah, O. Al-Deeb, and H. El-Subbagh Med. Chem. Res. 22 2013 2815
25. A. Testard, L. Picot, O. Lozach, M. Blairvacq, L. Meijer, L. Murillo, J.-M. Piot, V. Thiéry, and T.J. Besson Enzyme Inhib. Med. Chem. 20 2005 557
26. M.-J. Hour, L.-J. Huang, S.-C. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel, and K.-H. Lee J. Med. Chem. 43 2000 4479
27. M. Decker Eur. J. Med. Chem. 40 2005 305
28. G. Huang, B. Kling, F.H. Darras, J. Heilmann, and M. Decker Eur. J. Med. Chem. 81 2014 15
29. M. Decker, F. Krauth, and J. Lehmann Bioorg. Med. Chem. 14 2006 1966
30. F.H. Darras, S. Pockes, G. Huang, S. Wehle, A. Strasser, H.-J. Wittmann, M. Nimczick, C.A. Sotriffer, and M. Decker ACS Chem. Neurosci. 5 2014 225
31. M. Berlin, and C.W. Boyce Expert Opin. Ther. Pat. 17 2007 675
32. M. Tozer, and B. Kalindjian Expert Opin. Ther. Pat. 10 2000 1045
33. M. AbdulHameed, J. Liu, Y. Pan, L. Fang, C. Silva-Rivera, and C.-G. Zhan Theor. Chem. Acc. 130 2011 69
34. G.H.P. Roos, and K.A. Drastlik Heterocycles 60 2003 2023
35. D. Silva, M. Chioua, A. Samadi, P. Agostinho, P. Garcao, R. Lajarin-Cuesta, C. de Los Rios, I. Iriepa, I. Moraleda, L. Gonzalez-Lafuente, E. Mendes, C. Perez, M.I. Rodriguez-Franco, J. Marco-Contelles, and M. Carmo Carreiras ACS Chem. Neurosci. 4 2013 547
36. R.A.N. de Aquino, L.V. Modolo, R.B. Alves, and A. de Fatima Org. Biomol. Chem. 11 2013 8395
37. S.D. Bembenek, J.M. Keith, M.A. Letavic, R. Apodaca, A.J. Barbier, L. Dvorak, L. Aluisio, K.L. Miller, T.W. Lovenberg, and N.I. Carruthers Bioorg. Med. Chem. 16 2008 2968
38. The PyMOL Molecular Graphics System, Version 1.6.0.0 Schrödinger LLC.
39. F. Milletti, L. Storchi, G. Sforna, and G. Cruciani J. Chem. Inf. Model. 47 2007 2172
40. C.D. Andersson, N. Forsgren, C. Akfur, A. Allgardsson, L. Berg, C. Engdahl, W. Qian, F. Ekström, and A. Linusson J. Med. Chem. 56 2013 7615
41. O. Korb, T. Stutzle, and T.E. Exner J. Chem. Inf. Model. 49 2009 84
42. W.T. Mooij, and M.L. Verdonk Proteins 61 2005 272
43. M.D. Eldridge, C.W. Murray, T.R. Auton, G.V. Paolini, and R.P. Mee J. Comput. Aided Mol. Des. 11 1997 425
44. C.A. Baxter, C.W. Murray, D.E. Clark, D.R. Westhead, and M.D. Eldridge Proteins 33 1998 367
45. G. Jones, P. Willett, and R.C. Glen J. Mol. Biol. 245 1995 43
46. G. Jones, P. Willett, R.C. Glen, A.R. Leach, and R. Taylor J. Mol. Biol. 267 1997 727
47. C. Bissantz, B. Kuhn, and M. Stahl J. Med. Chem. 53 2010 5061
48. GOLDSUITE 5.1, GOLDSUITE 5.2, CCDC Software, http://www.ccdc.cam.ac.uk.
49. Molecular Operating Environment (MOE), 2012.10 and 2013.08; Chemical Computing Group, 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2011.