Identification of a crucial amino acid in the helix position 6.51 of human tachykinin neurokinin 1 and 3 receptors contributing to the insurmountable mode of antagonism by dual NK 1/NK 3 antagonists

Journal of Medicinal Chemistry

Volumn 55, Issue 11, 2012, Pages 5061-5076

  Bissantz, Caterina ^a   Bohnert, Claudia ^a   Hoffmann, Torsten ^a   Marcuz, Anne ^a   Schnider, Patrick ^a   Malherbe, Pari ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3,5 BIS TRIFLUOROMETHYLPHENYL) N [4 (4 FLUORO 2 METHYLPHENYL) 6 (4 METHANESULFONYL 3 METHYLPIPERAZIN 1 YL) PYRIDIN 3 YL] N METHYLISOBUTYRAMIDE; 2 (3,5 TRIFLUOROMETHYLPHENYL) N [4 (4 FLUORO 2 METHYLPHENYL) 6 (3 HYDROXY 2 HYDROXYMETHYLPYRROLIDIN 1 YL)PYRIDIN 3 YL] N METHYLISOBUTYRAMIDE; 2 BENZHYDRYL 3 (2 METHOXYBENZYLAMINO) 1 AZABICYCLO[2.2.2]OCTANE; APREPITANT; NEUROKININ 1 RECEPTOR; NEUROKININ 1 RECEPTOR ANTAGONIST; NEUROKININ 3 RECEPTOR; NEUROKININ 3 RECEPTOR ANTAGONIST; OSANETANT; PHENYLALANINE; RO 4583298; RO 4908594; TALNETANT; TYROSINE; UNCLASSIFIED DRUG;

AMINO ACID ANALYSIS; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG RECEPTOR BINDING; DRUG STRUCTURE; EMBRYO; HUMAN; HUMAN CELL; MOLECULAR MODEL; PROTEIN STRUCTURE; RECEPTOR AFFINITY; RECEPTOR BLOCKING; SEQUENCE HOMOLOGY; SITE DIRECTED MUTAGENESIS;

AMINO ACIDS; AMINOPYRIDINES; BENZENEACETAMIDES; HEK293 CELLS; HUMANS; INOSITOL PHOSPHATES; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; MUTATION; PROTEIN STRUCTURE, SECONDARY; RADIOLIGAND ASSAY; RECEPTORS, NEUROKININ-1; RECEPTORS, NEUROKININ-3; STEREOISOMERISM;

EID: 84862300097     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2017072     Document Type: Article

References (50)

1. Tamminga, C. A.; Holcomb, H. H. Phenotype of schizophrenia: a review and formulation Mol. Psychiatry. 2005, 10, 27-39
2. Leucht, S.; Wahlbeck, K.; Hamann, J.; Kissling, W. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis Lancet 2003, 361, 1581-1589
3. Emonds-Alt, X.; Bichon, D.; Ducoux, J. P.; Heaulme, M.; Miloux, B.; Poncelet, M.; Proietto, V.; Van Broeck, D.; Vilain, P.; Neliat, G. SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor Life Sci. 1995, 56, PL27-PL32
4. Nguyen-Le, X. K.; Nguyen, Q. T.; Gobeil, F.; Pheng, L. H.; Emonds-Alt, X.; Breliere, J. C.; Regoli, D. Pharmacological characterization of SR 142801: a new non-peptide antagonist of the neurokinin NK-3 receptor Pharmacology 1996, 52, 283-291
5. Giardina, G. A.; Raveglia, L. F.; Grugni, M.; Sarau, H. M.; Farina, C.; Medhurst, A. D.; Graziani, D.; Schmidt, D. B.; Rigolio, R.; Luttmann, M.; Cavagnera, S.; Foley, J. J.; Vecchietti, V.; Hay, D. W. Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)- N -(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4- carboxamide (SB 223412) J. Med. Chem. 1999, 42, 1053-1065
6. Sarau, H. M.; Griswold, D. E.; Potts, W.; Foley, J. J.; Schmidt, D. B.; Webb, E. F.; Martin, L. D.; Brawner, M. E.; Elshourbagy, N. A.; Medhurst, A. D.; Giardina, G. A.; Hay, D. W. Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist J. Pharmacol. Exp. Ther. 1997, 281, 1303-1311
7. Meltzer, H.; Prus, A. NK3 receptor antagonists for the treatment of schizophrenia Drug Discovery Today: Ther. Strategies 2006, 3, 555-560
8. Meltzer, H. Y.; Arvanitis, L.; Bauer, D.; Rein, W. Placebo-controlled evaluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder Am. J. Psychiatry 2004, 161, 975-984
9. Spooren, W.; Riemer, C.; Meltzer, H. Opinion: NK3 receptor antagonists: the next generation of antipsychotics? Nat. Rev. Drug Discovery 2005, 4, 967-975
10. Dawson, L. A.; Smith, P. W. Therapeutic utility of NK3 receptor antagonists for the treatment of schizophrenia Curr. Pharm. Des. 2010, 16, 344-357
11. Alexander, S. P.; Mathie, A.; Peters, J. A. Guide to receptors and channels (GRAC), 5th edition Br. J. Pharmacol. 2011, 164 (Suppl. 1) S1-S324
12. Almeida, T. A.; Rojo, J.; Nieto, P. M.; Pinto, F. M.; Hernandez, M.; Martin, J. D.; Candenas, M. L. Tachykinins and tachykinin receptors: structure and activity relationships Curr. Med. Chem. 2004, 11, 2045-2081
13. Severini, C.; Improta, G.; Falconieri-Erspamer, G.; Salvadori, S.; Erspamer, V. The tachykinin peptide family Pharmacol. Rev. 2002, 54, 285-322
14. Marco, N.; Thirion, A.; Mons, G.; Bougault, I.; Le Fur, G.; Soubrie, P.; Steinberg, R. Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea pig Neuropeptides 1998, 32, 481-488
15. Dawson, L. A.; Cato, K. J.; Scott, C.; Watson, J. M.; Wood, M. D.; Foxton, R.; de la Flor, R.; Jones, G. A.; Kew, J. N.; Cluderay, J. E.; Southam, E.; Murkitt, G. S.; Gartlon, J.; Pemberton, D. J.; Jones, D. N.; Davies, C. H.; Hagan, J. In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia Neuropsychopharmacology 2008, 33, 1642-1652
16. Ebner, K.; Muigg, P.; Singewald, G.; Singewald, N. Substance P in stress and anxiety: NK-1 receptor antagonism interacts with key brain areas of the stress circuitry Ann. N.Y. Acad. Sci. 2008, 1144, 61-73
17. Blier, P.; Gobbi, G.; Haddjeri, N.; Santarelli, L.; Mathew, G.; Hen, R. Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response J. Psychiatry Neurosci. 2004, 29, 208-218
18. Santarelli, L.; Gobbi, G.; Debs, P. C.; Sibille, E. T.; Blier, P.; Hen, R.; Heath, M. J. Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 1912-1917
19. Hale, J. J.; Mills, S. G.; MacCoss, M.; Finke, P. E.; Cascieri, M. A.; Sadowski, S.; Ber, E.; Chicchi, G. G.; Kurtz, M.; Metzger, J.; Eiermann, G.; Tsou, N. N.; Tattersall, F. D.; Rupniak, N. M.; Williams, A. R.; Rycroft, W.; Hargreaves, R.; MacIntyre, D. E. Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3- oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist J. Med. Chem. 1998, 41, 4607-4614
20. Kramer, M. S.; Winokur, A.; Kelsey, J.; Preskorn, S. H.; Rothschild, A. J.; Snavely, D.; Ghosh, K.; Ball, W. A.; Reines, S. A.; Munjack, D.; Apter, J. T.; Cunningham, L.; Kling, M.; Bari, M.; Getson, A.; Lee, Y. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression Neuropsychopharmacology 2004, 29, 385-392
21. McLean, S.; Ganong, A.; Seymour, P. A.; Bryce, D. K.; Crawford, R. T.; Morrone, J.; Reynolds, L. S.; Schmidt, A. W.; Zorn, S.; Watson, J.; Fossa, A.; DePasquale, M.; Rosen, T.; Nagahisa, A.; Tsuchiya, M.; Heym, J. Characterization of CP-122,721; a nonpeptide antagonist of the neurokinin NK1 receptor J. Pharmacol. Exp. Ther. 1996, 277, 900-908
22. Ebner, K.; Sartori, S. B.; Singewald, N. Tachykinin receptors as therapeutic targets in stress-related disorders Curr. Pharm. Des. 2009, 15, 1647-1674
23. Minthorn, E.; Mencken, T.; King, A. G.; Shu, A.; Rominger, D.; Gontarek, R. R.; Han, C.; Bambal, R.; Davis, C. B. Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret Drug Metab. Dispos. 2008, 36, 1846-1852
24. Ratti, E.; Bellew, K.; Bettica, P.; Bryson, H.; Zamuner, S.; Archer, G.; Squassante, L.; Bye, A.; Trist, D.; Krishnan, K. R.; Fernandes, S. Results from 2 randomized, double-blind, placebo-controlled studies of the novel NK1 receptor antagonist casopitant in patients with major depressive disorder J. Clin. Psychopharmacol. 2011, 31, 727-733
25. Hoffmann, T.; Koblet, A.; Peters, J.-U.; Schnider, P.; Sleight, A.; Stadler, H. Dual NK1/NK3 Antagonists for Treating Schizophrenia. WO 2005/002577, 2005.
26. Vauquelin, G.; Van Liefde, I.; Birzbier, B. B.; Vanderheyden, P. M. New insights in insurmountable antagonism Fundam. Clin. Pharmacol. 2002, 16, 263-272
27. Malherbe, P.; Knoflach, F.; Hernandez, M. C.; Hoffmann, T.; Schnider, P.; Porter, R. H.; Wettstein, J. G.; Ballard, T. M.; Spooren, W.; Steward, L. Characterization of RO4583298 as a novel potent, dual antagonist with in vivo activity at tachykinin NK1 and NK3 receptors Br. J. Pharmacol. 2011, 162, 929-946
28. Bromidge, S. M.; Catalani, M. P.; Heer, J. P.; Smethurst, C. A. P.; Tommasi, S. Novel Lactam Compounds. PCT Int. Appl. WO 2011054773, 2011.
29. Catalani, M. P.; Alvaro, G.; Bernasconi, G.; Bettini, E.; Bromidge, S. M.; Heer, J.; Tedesco, G.; Tommasi, S. Identification of novel NK1/NK3 dual antagonists for the potential treatment of schizophrenia Bioorg. Med. Chem. Lett. 2011, 21, 6899-6904
30. Lowe, J. A., 3rd; Drozda, S. E.; Snider, R. M.; Longo, K. P.; Zorn, S. H.; Morrone, J.; Jackson, E. R.; McLean, S.; Bryce, D. K.; Bordner, J. The discovery of (2 S,3 S)- cis -2-(diphenylmethyl)- N -[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst J. Med. Chem. 1992, 35, 2591-2600
31. Malherbe, P.; Bissantz, C.; Marcuz, A.; Kratzeisen, C.; Zenner, M. T.; Wettstein, J. G.; Ratni, H.; Riemer, C.; Spooren, W. Me-talnetant and osanetant interact within overlapping but not identical binding pockets in the human tachykinin neurokinin 3 receptor transmembrane domains Mol. Pharmacol. 2008, 73, 1736-1750
32. Palczewski, K.; Kumasaka, T.; Hori, T.; Behnke, C. A.; Motoshima, H.; Fox, B. A.; Le Trong, I.; Teller, D. C.; Okada, T.; Stenkamp, R. E.; Yamamoto, M.; Miyano, M. Crystal structure of rhodopsin: a G protein-coupled receptor Science 2000, 289, 739-745
33. Cherezov, V.; Rosenbaum, D. M.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Kuhn, P.; Weis, W. I.; Kobilka, B. K.; Stevens, R. C. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor Science 2007, 318, 1258-1265
34. Rosenbaum, D. M.; Cherezov, V.; Hanson, M. A.; Rasmussen, S. G.; Thian, F. S.; Kobilka, T. S.; Choi, H. J.; Yao, X. J.; Weis, W. I.; Stevens, R. C.; Kobilka, B. K. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function Science 2007, 318, 1266-1273
35. Kenakin, T.; Jenkinson, S.; Watson, C. Determining the potency and molecular mechanism of action of insurmountable antagonists J. Pharmacol. Exp. Ther. 2006, 319, 710-723
36. Malherbe, P.; Kratzeisen, C.; Marcuz, A.; Zenner, M. T.; Nettekoven, M. H.; Ratni, H.; Wettstein, J. G.; Bissantz, C. Identification of a critical residue in the transmembrane domain 2 of tachykinin neurokinin 3 receptor affecting the dissociation kinetics and antagonism mode of osanetant (SR 142801) and piperidine-based structures J. Med. Chem. 2009, 52, 7103-7112
37. Jaakola, V. P.; Griffith, M. T.; Hanson, M. A.; Cherezov, V.; Chien, E. Y.; Lane, J. R.; Ijzerman, A. P.; Stevens, R. C. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist Science 2008, 322, 1211-1217
38. Chien, E. Y.; Liu, W.; Zhao, Q.; Katritch, V.; Han, G. W.; Hanson, M. A.; Shi, L.; Newman, A. H.; Javitch, J. A.; Cherezov, V.; Stevens, R. C. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist Science 2010, 330, 1091-1095
39. Lindstrom, E.; von Mentzer, B.; Pahlman, I.; Ahlstedt, I.; Uvebrant, A.; Kristensson, E.; Martinsson, R.; Noven, A.; de Verdier, J.; Vauquelin, G. Neurokinin 1 receptor antagonists: correlation between in vitro receptor interaction and in vivo efficacy J. Pharmacol. Exp. Ther. 2007, 322, 1286-1293
40. Topaloglu, A. K.; Reimann, F.; Guclu, M.; Yalin, A. S.; Kotan, L. D.; Porter, K. M.; Serin, A.; Mungan, N. O.; Cook, J. R.; Ozbek, M. N.; Imamoglu, S.; Akalin, N. S.; Yuksel, B.; O'Rahilly, S.; Semple, R. K. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction Nat. Genet. 2009, 41, 354-358
41. Silveira, L. G.; Tusset, C.; Latronico, A. C. Impact of mutations in kisspeptin and neurokinin B signaling pathways on human reproduction Brain Res. 2010, 1364, 72-80
42. Cassel, J. A.; Daubert, J. D.; DeHaven, R. N. [(3)H]Alvimopan binding to the micro opioid receptor: comparative binding kinetics of opioid antagonists Eur. J. Pharmacol. 2005, 520, 29-36
43. Copeland, R. A.; Pompliano, D. L.; Meek, T. D. Drug-target residence time and its implications for lead optimization Nat. Rev. Drug Discovery 2006, 5, 730-739
44. Lacourciere, Y.; Asmar, R. A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Candesartan/losartan study investigators Am. J. Hypertens. 1999, 12, 1181-1187
45. Swinney, D. C. Biochemical mechanisms of drug action: what does it take for success? Nat. Rev. Drug Discovery 2004, 3, 801-808
46. Swinney, D. C. The role of binding kinetics in therapeutically useful drug action Curr. Opin. Drug Discovery Dev. 2009, 12, 31-39
47. Ballesteros, J. A.; Weinstein, H. Integrated methods for construction three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors Methods Neurosci. 1995, 25, 366-428
48. Henikoff, S.; Henikoff, J. G. Amino acid substitution matrices from protein blocks Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 10915-10919
49. Wu, L. H.; Vartanian, M. A.; Oxender, D. L.; Chung, F. Z. Identification of methionine134 and alanine146 in the second transmembrane segment of the human tachykinin NK3 receptor as reduces involved in species-selective binding to SR 48968 Biochem. Biophys. Res. Commun. 1994, 198, 961-966
50. Harrison, T.; Korsgaard, M. P.; Swain, C. J.; Cascieri, M. A.; Sadowski, S.; Seabrook, G. R. High affinity, selective neurokinin 2 and neurokinin 3 receptor antagonists from a common structural template Bioorg. Med. Chem. Lett. 1998, 8, 1343-1348