Design, synthesis, and biological evaluation of 3,4-dihydroquinolin-2(1 H)-one and 1,2,3,4-tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors

Journal of Medicinal Chemistry

Volumn 54, Issue 15, 2011, Pages 5562-5575

  Ramnauth, Jailall ^a   Speed, Joanne ^a   Maddaford, Shawn P ^a   Dove, Peter ^a   Annedi, Subhash C ^a   Renton, Paul ^a   Rakhit, Suman ^a   Andrews, John ^a   Silverman, Sarah ^a   Mladenova, Gabriela ^a   Zinghini, Salvatore ^a   Nair, Sheela ^b   Catalano, Concettina ^b   Lee, David K H ^b   De Felice, Milena ^c   Porreca, Frank ^c  

^a NeurAxon Inc   (Canada)

^b NoAb BioDiscoveries Inc   (Canada)

^c UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4 TETRAHYDROQUINOLINE DERIVATIVE; 3,4 DIHYDROQUINOLIN 2(1H)ONE; N [1 (1 METHYLPYRROLIDIN 3 YL) 1,2,3,4 TETRAHYDROQUINOLIN 6 YL)THIOPHENE 2 CARBOXIMIDAMIDE; N [1 (PIPERIDIN 4 YL) 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [1 METHYLPIPERIDIN 4 YL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (1 METHYLPYRROLIDIN 2 YL)ETHYL] 2 OXO 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIETHYLAMINO)ETHYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIETHYLAMINO)ETHYL] 2 OXO 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIMETHYLAMINO)ETHYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL)THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIMETHYLAMINO)ETHYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIMETHYLAMINO)ETHYL] 2 OXO 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIMETHYLAMINO)ETHYL] 8 FLUORO 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [2 (DIMETHYLAMINO)ETHYL] 8 FLUORO 2 OXO 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [3 (DIMETHYLAMINO)PROPYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [1 [3 (PYRROLIDIN 1 YL)PROPYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; N [2 OXO 1 2 (PIPERIDIN 1 YL)ETHYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL)THIOPHENE 2 CARBOXIMIDAMIDE; N [2 OXO 1 [2 (PYRROLIDIN 1 YL)ETHYL] 1,2,3,4 TETRAHYDROQUINOLIN 6 YL]THIOPHENE 2 CARBOXIMIDAMIDE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; OXYGENASE INHIBITOR; UNCLASSIFIED DRUG;

ALLODYNIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HYPERALGESIA; MIGRAINE; NEUROPATHIC PAIN; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; HUMANS; HYPERALGESIA; MALE; MIGRAINE DISORDERS; NEURALGIA; NITRIC OXIDE SYNTHASE TYPE I; QUINOLINES; RATS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79961228804     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm200648s     Document Type: Article

References (32)

1. Mustafa, A. K.; Gadalla, M. M.; Synder, S. H. Signaling by gasotransmitter Sci. Signaling 2009, 2, 1-8
2. Murad, F. Shattuck Lecture. Nitric oxide and cyclic GMP in cell signaling and drug development N. Engl. J. Med. 2006, 355, 2003-2011 (Pubitemid 44708019)
3. Moncada, S.; Palmer, R. M.; Higgs, E. A. Nitric oxide: physiology, pathophysiology, and pharmacology Pharmacol. Rev. 1991, 43, 109-142
4. Stuehr, D. J. Structure-function aspects in the nitric oxide synthases Annu. Rev. Pharmacol. Toxicol. 1997, 37, 339-359 (Pubitemid 27238880)
5. Bredt, D. S.; Hwang, P. M.; Glatt, C. E.; Lowenstein, C; Reed, R. R.; Snyder, S. H. Cloned and expressed nitric oxide structurally resembles cytochrome P-450 reductase Nature 1991, 351, 714-718 (Pubitemid 21896670)
6. Abu-Soud, H. M.; Stuehr, D. J. Nitric oxide synthases reveal a role for calmodulin in controlling electron transfer Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10769-10772 (Pubitemid 23347124)
7. Vallance, P.; Leiper, J. Blocking NO synthesis: how, where and why? Nature Rev. Drug Discovery 2002, 1, 939-950 (Pubitemid 37361600)
8. Miclescu, A.; Gordh, T. Nitric oxide and pain: "Something old, something new" Acta Anaesthesiol. Scand. 2009, 53, 1107-1120
9. Calabrese, V.; Mancuso, C.; Calvani, M.; Rizzarelli, E.; Butterfield, A. D.; Stella, A. M. G. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity Nature Rev. Neurosci. 2007, 8, 766-775 (Pubitemid 47462116)
10. Gruber, H-J; Bernecker, C.; Lechner, A.; Weiss, S.; Wallner-Blazek, M.; Meinitzer, A.; Hobarth, G.; Renner, W.; Fauler, G.; Horejsi, R.; Fazekas, F.; Truschnig-Wilders, M. Increased nitric oxide stress is associated with migraine Cephalalgia 2009, 30, 486-492
11. Tanabe, M.; Nagatani, Y.; Saitoh, K.; Takasu, K.; Ono, H. Pharmacological assessments of nitric oxide synthase isoforms and downstream diversity of NO signaling in the maintenance of thermal and mechanical hypersensitivity after peripheral nerve injury in mice Neuropharmacology 2009, 56, 702-708
12. Huang, P. L.; Huang, Z.; Mashimo, H.; Bloch, K. D.; Moskowitz, M, A.; Bevan, J. A.; Fishman, M. C. Hypertension in mice lacking the gene for endothelial nitric oxide synthase Nature 1995, 377, 239-242
13. Lassen, H. L.; Iversen, H. K.; Olesen, J. A dose-response study of nitric oxide synhtase inhibition in different vascular beds in man Eur. J. Clin. Pharmacol. 2003, 59, 499-505 (Pubitemid 37363561)
14. Erdal, E. P.; Litzinger, E. A.; Seo, J.; Zhu, Y.; Ji, H.; Silverman, R. B. Selective neuronal nitric oxide synthase inhibitors Curr. Top. Med. Chem. 2005, 5, 603-624 (Pubitemid 41179723)
15. Silverman, R. B. Design of selective neuronal nitric oxide synthase inhibitors for the prevention and treatment of neurodegenerative diseases Acc. Chem. Res. 2009, 42, 439-451
16. Maddaford, S.; Annedi, S. C.; Ramnauth, J.; Rakhit, S. Advancements in the development of nitric oxide synthase inhibitors Annu. Rep. Med. Chem. 2009, 44, 27-50
17. Patman, J.; Bhardwaj, N.; Ramnauth, J.; Annedi, S. C.; Renton, P.; Maddaford, S. P.; Rakhit, S.; Andrews, J. S. Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors Bioorg. Med. Chem. Lett. 2007, 17, 2540-2544 (Pubitemid 46509840)
18. Vernier, J.-M.; El-Abdellaoui, H.; Holsenback, H.; Cosford, N. D. P.; Bleicher, L.; Barker, G.; Bontempi, B.; Chavez-Noriega, L.; Menzaghi, F.; Rao, T. S.; Reid, R.; Sacaan, A. I.; Suto, C.; Washburn, M.; Lloyd, G. K.; McDonald, I. 4-[[2-(1-Methyl-2-pyrrolidinyl)ethyl]thio]-phenol hydrochloride (SIB-1553A): a novel cognitive enhancer with selectivity for neuronal nicotinic acetylcholine receptors J. Med. Chem. 1999, 42, 1684-1686 (Pubitemid 29244961)
19. Huang, X.; Buchwald, S. L. New ammonia equivalents for the Pd-catalyzed amination of aryl halides Org. Lett. 2001, 3, 3417-3419 (Pubitemid 33625374)
20. Singer, J. M.; Barr, B. M.; Coughenour, L. L.; Gregory, T. F.; Walters, M. A. 8-Substituted 3,4-dihydroquinolinones as a novel scaffold for atypical antipsychotic activity Bioorg. Med. Chem. Lett. 2005, 15, 4560-4563 (Pubitemid 41253895)
21. Chen, M.-H.; Fitzgerald, P.; Singh, S. B.; O'Neill, E. A.; Schwartz, C. D.; Thompson, C. M.; O'Keefe, S. J.; Zaller, D. M.; Doherty, J. B. Synthesis and biological activity of quinolinone and dihydroquinolinone p38 MAP kinase inhibitors Bioorg. Med. Chem. Lett. 2008, 18, 2222-2226 (Pubitemid 351380846)
22. Zhang, Z. G.; Reif, D.; MacDonald, J.; Tang, W. X.; Kamp, D. K.; Gentile, R. J.; Shakespeare, W. C.; Murray, R. J.; Chopp, M. ARL 17477, a potent and selective neuronal NOS inhibitor decreases infarct volume after transient middle cerebral artery occlusion in rats J. Cereb. Blood Flow Metab. 1996, 16, 599-604 (Pubitemid 26227068)
23. Stuehr, D. J. Structure-function aspects in the nitric oxide synthases Annu. Rev. Pharmacol. Toxicol. 1997, 37, 339-359 (Pubitemid 27238880)
24. Murad, F. Nitric oxide signaling: would you believe that a simple free radical could be a second messenger, autacoids, paracrine substance, neurotransmitter, and hormone? Recent Prog. Horm. Res. 1998, 53, 43-59 (Pubitemid 128472735)
25. Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors J. Am. Chem. Soc. 2008, 130, 3900-3914 (Pubitemid 351429856)
26. Lipinski, C. A. Drug-like properties and the causes of poor solubility and poor permeability J. Pharmacol. Toxicol. Methods 2000, 44, 235-249 (Pubitemid 32239479)
27. Wenlock, M. C.; Austin, R. P.; Barton, P.; Davis, A. M.; Leeson, P. D. A comparison of physicochemical property profiles of development and marketed oral drugs J. Med. Chem. 2003, 46, 1250-1256 (Pubitemid 36428230)
28. Kelder, J.; Grootenhuis, P. D.; Bayada, D. M.; Delbressine, L. P.; Ploemen, J. P. Polar molecular surface as a dominating determinant for oral adsorption and brain penetration of drugs Pharm. Res. 1999, 16, 1514-1519 (Pubitemid 29510546)
29. Veber, D. F.; Johnson, S. R.; Cheng, H. Y.; Smith, B. R.; Ward, K. W.; Kopple, K. D. Molecular properties that influence the oral bioavailability of drug candidates J. Med. Chem. 2002, 45, 2615-2623 (Pubitemid 34595232)
30. Zhang, W.; Ramanmoorthy, Y.; Kilicarslan, T.; Nolte, H.; Tyndale, R. F.; Sellers, E. M. Inhibition of cytochromes P450 by antifungal imidazole derivatives Drug Metab. Dispos. 2001, 30, 314-318 (Pubitemid 34175023)
31. Kim, S. H.; Chung, J. M. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat Pain 1992, 50, 355-363
32. Edelmayer, R. M.; Vanderah, T. W.; Majuta, L.; Zhang, E.-T.; Fioravanti, B.; De Felice, M.; Chichorro, J. G.; Ossipov, M. H.; King, T.; Lai, J.; Kori, S. H.; Nelsen, A. C.; Cannon, K. E.; Heinricher, M. M.; Porreca, F. Medullary pain facilitating neurons mediate allodynia in headache-related pain Ann. Neurol. 2009, 65, 184-193