Discovery of a new series of potent and selective linear tachykinin NK 2 receptor antagonists

Journal of Medicinal Chemistry

Volumn 50, Issue 20, 2007, Pages 4793-4807

  Fedi, Valentina ^a   Altamura, Maria ^a   Catalioto, Rose Marie ^a   Giannotti, Danilo ^a   Giolitti, Alessandro ^a   Giuliani, Sandro ^a   Guidi, Antonio ^a   Harmat, Nicholas J S ^a   Lecci, Alessandro ^a   Meini, Stefania ^a   Nannicini, Rossano ^a   Pasqui, Franco ^a   Tramontana, Manuela ^a   Triolo, Antonio ^a   Maggi, Carlo Alberto ^a  

^a Menarini Ricerche SpA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALIPHATIC AMINE; AMINO ACID DERIVATIVE; AROMATIC COMPOUND; BENZO[B]THIOPHENE 2 CARBOXYLIC ACID [1 [1 (3 MORPHOLIN 4 YLPROPYLCARBAMOYL) 2 PHENYLETHYLCARBAMOYL]CYCLOPENTYL]AMIDE; BENZOTHIOPHENE DERIVATIVE; LIGAND; MEN 14268; MEN 15596; NEUROKININ 2 RECEPTOR ANTAGONIST; PIPERIDINE DERIVATIVE; TACHYKININ RECEPTOR ANTAGONIST; TETRAHYDROPYRAN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHEMICAL MODIFICATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; NONHUMAN; PROCESS OPTIMIZATION; SMOOTH MUSCLE CONTRACTILITY; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; CACO-2 CELLS; COLON; CYCLOPENTANES; DIPEPTIDES; FEMALE; GUINEA PIGS; HUMANS; ILEUM; INJECTIONS; INTESTINAL ABSORPTION; MALE; MIDDLE AGED; MUSCLE CONTRACTION; MUSCLE, SMOOTH; PERMEABILITY; PIPERIDINES; PYRANS; RADIOLIGAND ASSAY; RECEPTORS, NEUROKININ-2; STEREOISOMERISM; THIOPHENES; URINARY BLADDER;

EID: 34948830134     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070289w     Document Type: Article

References (30)

1. (a) Maggi, C. A.; Patacchini, R.; Rovero, P.; Giachetti, A. Tachykinin receptors and tachykinin receptor antagonists. J. Auton. Pharmacol. 1993, 13, 23-93.
2. (b) Buck, S. H. The Tachykinin Receptors; Humana Press: Totowa, NJ, 1995.
3. (c) Quartara, L.; Altamura, M. Tachykinin receptor antagonists: from research to clinic. Curr. Drug Targets 2006, 7, 975-992.
4. (a) Lecci, A.; Maggi, C. A. Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases. Expert Opin. Ther. Targets 2003, 343-362.
5. (b) Patacchini, R.; Maggi, C. A. Peripheral tachykinin receptors as targets for new drugs. Eur. J. Pharmacol. 2001, 429, 13-21.
6. (c) Lecci, A.; Capriati, A.; Altamura, M.; Maggi, C. A. Tachykinins and tachykinin receptors in the gut, with special reference to NK2 receptor in human. Auton. Neurosci. 2006, 126-127, 232-249.
7. (a) Joos, G. F.; De Swert, K. O.; Pauwels, R. A. Airway inflammation and tachykinins: prospects for the development of tachykinin receptor antagonists. Eur. J. Pharmacol. 2001, 429, 239-250.
8. (b) Lecci, A.; Valenti, C.; Maggi, C. A. Tachykinin receptor antagonists in irritable bowel syndrome. Curr. Opin. Invest. Drugs 2002, 3, 589-601.
9. (c) Holzer, P.; Holzer-Petsche, U. Tachykinin receptors in the gut: physiological and pathological implications. Curr. Opin. Pharmacol. 2001, 1, 583-590.
10. (d) Bensaid, M.; Faucheux, B. A.; Hirsch, E.; Agid, Y.; Soubrie, P.; Oury-Donat, F. Expression of fachykinin NK2 receptor mRNA in human brain. Neurosci. Lett. 2001, 303, 25-28.
11. Emonds-Alt, X.; Vilain, P.; Goulaouic, P.; Proietto, V.; Van Broeck, D.; Advenier, C.; Naline, E.; Neliat, G.; Le Fur, G.; Breliere, J. C. A potent and selective non-peptide antagonist of the neurokinin A (NK2) receptor. Life Sci. 1992, 50, 101-106.
12. 2 receptor antagonist. Br. J. Pharmacol. 1998, 123, 81-91.
13. 2 receptor. J. Med. Chem. 2004, 47, 6935-6947.
14. Sisto, A.; Altamura, M.; Cardinali, F.; D'Andrea, P.; Rossi, C.; Fattori, D. α,α-Cyclic amino-acids as useful scaffolds for the preparation of hNK2 receptor antagonists. Bioorg. Med. Chem. Lett. 2007, 17, 4841-4844.
15. 2 receptor to define the binding site of a novel class of antagonists. Eur. J. Pharmacol. 2004, 488, 61-69.
16. α,α-dialkylated glycines. Br. Biopolym. J. 1986, 4, 221-225.
17. 2 receptor antagonist. Eur. J. Pharmacol. 2006, 549, 140-148.
18. 2 receptor antagonists. J. Med. Chem. 2000, 43, 4041-4044.
19. 2 receptor antagonists as evolution of a potent bicyclic antagonist: QSAR and site-directed mutagenesis studies. J. Med. Chem. 2002, 45, 3418-3429.
20. 2 antagonists retaining the β-turn feature. X-ray and molecular modelling studies. Acta Crystallogr. 2006, B62, 889-896.
21. (a) Fukuyama, T.; Chung-Kuang, J.; Cheung, M. 2- and 4- Nitrobenzenesulfonamides: exceptionally versatile means for preparation of secondary amines and protection of amines. Tetrahedron Lett. 1995, 36, 6373.
22. (b) Pelletier, J. C.; Kincaid, S. Mitsunobu reaction modifications allowing product isolation without chromatography: application to a small parallel library. Tetrahedron Lett. 2000, 41, 797.
23. Dess, D. B.; Martin, J. C. Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehyde and ketones. J. Org, Chem. 1983, 48, 4155-4156.
24. (a) Bridges, A. J.; Lee, A.; Maduakor, E. C.; Schwartz, C. E. Fluorine as an ortho-directing group in aromatic metalation: a two step preparation of substituted benzo[b]thiophene-2-carboxylates. Tetrahedron Lett. 1992, 33, 7499-7502.
25. (b) Beck, J. R. Direct synthesis of benzo[b]thiophene-2- carboxylate esters involving nitro displacement. J. Org. Chem. 1972, 37, 3224-3226.
26. Palm, K.; Stenberg, P.; Luthman, K. G.; Artursson, P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 1997, 14, 568-571.
27. Palm, K.; Luthman, K.; Ungell, A. L.; Strandlund, G.; Artursson, P. Correlation of drug absorption with molecular surface properties. J. Pharm. Sci. 1996, 85, 32-39.
28. Balacco, G. SwaN-MR: a complete and expansible NMR software for the Macintosh. J. Chem. Inf. Comput. Sci. 1994, 34, 1235-1241.
29. 2 receptor antagonists in human and rat urinary bladder. Eur J. Pharmacol., 2000, 388, 177-182.
30. Larger, P.; Altamura, M.; Catalioto, R.-M.; Giuliani, S.; Maggi, C. A.; Valenti, C.; Triolo, A. Simultaneous LC-MS/MS determination of reference pharmaceuticals as a method for the characterization of the Caco-2 cell monolayer absorption properties. Anal. Chem. 2002, 74, 5273-5281.