Synthesis and biological effects of novel 2-amino-3-naphthoylthiophenes as allosteric enhancers of the A1, adenosine receptor

Journal of Medicinal Chemistry

Volumn 46, Issue 5, 2003, Pages 794-809

  Baraldi, Pier Giovanni ^a   Romagnoli, Romeo ^a   Pavani, Maria Giovanna ^a   Del Carmen Nuñez, Maria ^a   Tabrizi, Mojgan Aghazadeh ^a   Shryock, John C ^b   Leung, Edward ^c   Moorman, Allan R ^c   Uluoglu, Canan ^d   Iannotta, Valeria ^a   Merighi, Stefania ^a   Borea, Pier Andrea ^a  

^a UNIVERSITY OF FERRARA   (Italy)

^b UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^c King Pharmaceuticals   (United States)

^d GAZI UNIVERSITY   (Turkey)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 3 NAPHTHOYLTHIOPHENE DERIVATIVE; 2 AMINO 4,5 DIMETHYL 3 (3 TRIFLUOROMETHYLBENZOYL)THIOPHENE; 2 CHLORO 6 N CYCLOPENTYLADENOSINE; 4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; 8 CYCLOPENTYL 1,3 DIPROPYLXANTHINE; ADENOSINE A1 RECEPTOR; ADENOSINE A1 RECEPTOR AGONIST; ADENOSINE A2A RECEPTOR; ADENOSINE A3 RECEPTOR; CYCLIC AMP; THIOPHENE DERIVATIVE; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL CELL; ARTICLE; CHO CELL; CONTROLLED STUDY; DRUG EFFECT; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; LIGAND BINDING; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ALLOSTERIC REGULATION; ANIMALS; BINDING, COMPETITIVE; BRAIN; CHO CELLS; CRICETINAE; CYCLIC AMP; HUMANS; MEMBRANES; NAPHTHALENES; RADIOLIGAND ASSAY; RATS; RECEPTORS, PURINERGIC P1; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 0037468418     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0210212     Document Type: Article

References (57)

1. (a) Birdsall, N. J.; Cohen, F.; Lazareno, S.; Matsui, H. Allosteric regulation of G-protein-linked receptors. Biochem. Soc. Trans. 1995, 23, 108-111.
2. (b) Birdsall, N. J.; Farries, T.; Gharagozloo, P.; Kobayashi, S.; Lazareno, S.; Sugimoto, M. Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: functional studies. Mol. Pharmacol. 1999, 55, 778-786.
3. (c) Linden, J. Allosteric enhancement of adenosine receptors. In Purinergic approaches in experimental therapeutics; Jacobson, K. A.; Jarvis, M. F., Eds.; Wiley-Liss: New York, 1997; pp 29-37.
4. (d) Christopoulos, A.; Lanzafame, A.; Mitchelson, F. Allosteric interactions at muscarinic cholinoceptors. Clin. Exp. Pharmacol. Physiol. 1998, 25, 185-194.
5. Barker, J. L.; Harrison, N. L.; Mariani, A. P. Benzodiazepine pharmacology of cultured mammalian CNS neurons. Life Sci. 1986, 39, 1959-1968.
6. (a) Ralevic, V.; Burnstock, G. Receptors for purines and pyrimidines. Pharmacol. Rev. 1998, 50, 413-492.
7. (b) Jacobson, K. A.; Knutsen, L. J. S. P1 and P2 purine and pyrimidine receptor ligands. In Handbook of Experimental Pharmacology; Abbracchio, M. P.; Williams, M., Eds.; Springer-Verlag: Berlin, 2001; Vol. 151, pp 129-175.
8. (a) DeNinno, M. P. Adenosine. In Annual Reports in Medicinal Chemistry; Doherty, A., Ed.; Academic press, San Diego, 1998; Vol. 33, pp 1111-1120.
9. (b) Stiles, G. L. Adenosine receptors subtypes: new insights from cloning and functional studies. Purinergic approaches in experimental therapeutics; Jacobson, K. A.; Jarvis, M. F., Eds.; Wiley-Liss: New York, 1997; pp 29-37.
10. Fredholm, B. B. Adenosine and neuroprotection. Int. Rev. Neurobiol. 1997, 40, 259-280.
11. 2 receptors. Can. J. Physiol. Pharmacol. 1987, 65, 365-376.
12. (a) Mehta, R. C.; Salazar-Bookaman, M. M.; Fertel, R. H.; De Los Angeles, J.; Nikulin, V. I.; Fraundorfer, P. F.; Miller, D. D.; Feller, D. R. Biochemical and functional characterization of 1-benzyl substituted trimetoquinol affinity analogues on rat and human beta-adrenoceptors. Biochem. Pharmacol. 2000, 59, 517- 529.
13. (b) Leppik, R. A.; Birdsall, N. J. Agonist binding and function at the human alpha(2A)-adrenoceptor: allosteric modulation by amilorides. Mol. Pharmacol. 2000, 58, 1091-1099.
14. (a) Schetz, J. A.; Sibley, D. R. Zinc allosterically modulates antagonist binding to cloned D1 and D2 dopamine receptors. J. Neurochem. 1997, 68, 1990-1997.
15. (b) Hoare, S. R.; Strange, P. G. Regulation of D2 dopamine receptors by amiloride and amiloride analogues. Mol. Pharmacol. 1996, 50, 1295-308.
16. (a) Hedlund, P. B.; Carson, M. J.; Sutcliffe, J. G.; Thomas, E. A. Allosteric regulation by oleamide of the binding properties of 5-HT7 receptors. Biochem. Pharmacol. 1999, 58, 1807-1813.
17. (b) Thomas, E. A.; Cravatt, B. F.; Sutcliffe, J. G. The endogenous lipid oleamide activates serotonin 5-HT7 neurons in mouse thalamus and hypothalamus. J. Neurochem. 1999, 72, 2370-2378.
18. Croci, T.; Aureggi, G.; Manara, L.; Emonds-Alt, X.; Le Fur, G.; Maffrand, J. P.; Mukenge, S.; Ferla, G. In vitro characterization of tachykinin NK2-receptors modulating motor responses of human colonic muscle strips. Br. J. Pharmacol. 1998, 124, 1321-1327.
19. Purdy, R. E.; Prins, B. A.; Weber, M. A.; Bakhtiarian, A.; Smith, J. R.; Kim, M. K.; Nguyen, T. H.; Weiler, E. W. Possible novel action of ouabain: allosteric modulation of vascular serotonergic (5-HT2) and angiotensinergic (AT1) receptors. J. Pharmacol. Exp. Ther. 1993, 267, 228-237.
20. Nepveu, F.; Souchard, J. P.; Rolland, Y.; Dorey, G.; Spedding, M. 2-2′-Pyridylisatogen, a selective allosteric modulator of P2 receptors, is a spin trapping agent. Biochem. Biophys. Res. Commun. 1998, 242, 272-276.
21. Grazzini, E.; Guillon, G.; Mouillac, B.; Zingg, H. H. Inhibition of oxytocin receptor function by direct binding of progesterone. Nature 1998, 392, 509-512.
22. (a) Bruns, R. F.; Fergus, J. H. Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol. Pharmacol. 1990, 38, 939-949.
23. (b) Bruns, R. F.; Fergus, J. H.; Coughenour, L. L.; Courtland, G. G.; Pugsley, T. A.; Dodd, J. H.; Tinney, F. J. Structure-activity relationships for enhancement of adenosine A1 receptor binding by 2-amino-3-benzoylthiophenes. Mol. Pharmacol. 1990, 38, 950-958.
24. 1, receptor. J. Pharmacol. Exp. Ther. 1997, 281, 761-768.
25. 1 receptor-dependent and -independent effects of the allosteric enhancer PD 81, 723. J. Pharmacol. Exp. Ther. 1999, 288, 446-454.
26. (e) Kourounakis, A. P.; Visser, C.; De Groote, M.; IJzerman, A. P. Differential effects of the allosteric enhancer (2-amino-4,5-dimethyl-thienyl)] [3-(trifluoromethyl) phenyl] methanone (PD 81, 723) on agonist and antagonist binding and function at the human wild-type and a mutant (T277A) adenosine A1 receptor. Biochem. Pharmacol. 2001, 61, 137-144.
27. (a) Amoah-Apraku, B.; Xu, J.; Lu, J. Y.; Pelleg, A.; Bruns, R. F.; Belardinelli, L. Selective potentiation by an A1 adenosine receptor enhancer of the negative dromotropic action of adenosine in the guinea pig heart. J. Pharmacol. Exp. Ther. 1993, 266, 611-617.
28. (b) Bhattacharya, S.; Linden, J. The allosteric enhancer, PD 81, 723, stabilizes human A1 adenosine receptor coupling to G proteins. Biochim. Biophys. Acta 1995, 1265, 15-21.
29. (c) Bhattacharya, S.; Linden, J. Effects of long-term treatment with the allosteric enhancer, PD81, 723, on Chinese hamster ovary cells expressing recombinant human A1 adenosine receptors. Mol. Pharmacol. 1996, 50:, 104-111.
30. (d) Janusz, C. A.; Bruns, R. F.; Berman, R. F. Functional activity of the adenosine binding enhancer, PD 81, 723, in the in vitro hippocampal slice. Brain Res. 1991, 567, 181-187.
31. (e) Janusz, C. A.; Berman, R. F. The adenosine binding enhancer, PD 81, 723, inhibits epileptiform bursting in the hippocampal brain slice. Brain Res. 1993, 619, 131-136.
32. (f) Mudumbi, R. V.; Montamat, S. C.; Bruns, R. F.; Vestal R. E. Cardiac functional responses to adenosine by PD 81, 723, an allosteric enhancer of the adenosine A1 receptor. Am. J. Physiol. 1993, 264, H1017-1022.
33. Bruns, R. F. Conformational induction versus conformational selection: evidence from allosteric enhancers. Trends Pharmacol. Sci. 1996, 17, 189-191.
34. (a) Baraldi, P. G. Thiophenes useful for modulating the adenosine receptor. US Patent 5, 939, 432, 1997.
35. (b) Baraldi, P. G.; Zaid, A. N.; Lampronti, I.; Fruttarolo, F.; Pavani, M. G.; Tabrizi, M. A.; Shryock, J. C.; Leung, E.; Romagnoli, R. Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor. Bioorg. Med. Chem. Lett. 2000, 10, 1953-1957.
36. (c) Baraldi, P. G. Preparation of acyl-amino-(fused) thiophenes as allosteric adenosine receptor modulators. US Pat. Appl. 20010047008, 2001.
37. (a) Van der Klein, P. A. M.; Kourounakis, A. P.; IJzerman, A. P. Allosteric modulation of the adenosine A1 receptor. Synthesis and biological evaluation of novel 2-amino-3-benzoylthiophenes as allosteric enhancers of agonist binding, J. Med. Chem. 1999, 42, 3629-3635.
38. (b) Kourounakis, A. P.; Visser, C.; de Groote, M.; IJzerman, A. P. Allosteric modulation of the rat adenosine A1 receptor: differential effects on agonist and antagonist binding. Drug Dev. Res. 2000, 51, 207-215.
39. Tranberg, C. E.; Zickgraf, A.; Giunta, B. N.; Luetjens, H.; Figler, H.; Murphree, L. J.; Falke, R.; Fleischer, H.; Linden, J.; Scammells, P. J.; Olsson, R. A. 2-Amino-3-aroyl-4,5-alkyl-thiophenes: agonist allosteric enhancers at human A1 adenosine receptors. J. Med. Chem. 2002, 45, 382-389.
40. Gewald, K.; Schinke, E.; Böettcher, H. Heterocycles from CH-acidic nitriles. VIII. 2-Aminothiophenes from methylene-active nitriles, carbonyl compounds and sulfur. Chem. Ber. 1966, 99, 94-100.
41. Seneci, P.; Nicola, M.; Inglesi, M.; Vanotti, E.; Resnati, G. Synthesis of mono-and disubstituted 1H-imidazo[1,2-b] pyrazoles. Synth. Commun. 1999, 2, 311-341.
42. For the synthesis of compounds having general formula A see the following articles: (a) methyl ester both of 1- and 2-naphthoic acid: Forbes, D. C.; Barrett, E. J.; Lewis, D. L.; Smith, M. C. A new and efficient route toward the preparation of diazo ketones using cyanuric chloride and diazomethane. Tetrahedron Lett. 2000, 41, 9943-9947. (b) Methyl ester of 4-methyl and 4-meth-oxy 1-naphthoic acid: Nishino, H.; Tsunoda, K.; Kurosawa, K. Manganese (III)-mediated formylation of aromatic compounds in the presence of malonic acid. Bull. Chem. Soc. Jpn. 1989, 62, 545-550. (c) Methyl ester of 4-bromo-1-naphthoic acid: Mayer, F.; Sieglitz, A. Untersuchungen und Ringschlüsse in der Reihe der Methyl-naphthaline. Chem. Ber. 1922, 55, 1841-1859.
43. For the synthesis of compounds having general formula A see the following articles: (a) methyl ester both of 1- and 2-naphthoic acid: Forbes, D. C.; Barrett, E. J.; Lewis, D. L.; Smith, M. C. A new and efficient route toward the preparation of diazo ketones using cyanuric chloride and diazomethane. Tetrahedron Lett. 2000, 41, 9943-9947. (b) Methyl ester of 4-methyl and 4-meth-oxy 1-naphthoic acid: Nishino, H.; Tsunoda, K.; Kurosawa, K. Manganese (III)-mediated formylation of aromatic compounds in the presence of malonic acid. Bull. Chem. Soc. Jpn. 1989, 62, 545-550. (c) Methyl ester of 4-bromo-1-naphthoic acid: Mayer, F.; Sieglitz, A. Untersuchungen und Ringschlüsse in der Reihe der Methyl-naphthaline. Chem. Ber. 1922, 55, 1841-1859.
44. For the synthesis of compounds having general formula A see the following articles: (a) methyl ester both of 1- and 2-naphthoic acid: Forbes, D. C.; Barrett, E. J.; Lewis, D. L.; Smith, M. C. A new and efficient route toward the preparation of diazo ketones using cyanuric chloride and diazomethane. Tetrahedron Lett. 2000, 41, 9943-9947. (b) Methyl ester of 4-methyl and 4-meth-oxy 1-naphthoic acid: Nishino, H.; Tsunoda, K.; Kurosawa, K. Manganese (III)-mediated formylation of aromatic compounds in the presence of malonic acid. Bull. Chem. Soc. Jpn. 1989, 62, 545-550. (c) Methyl ester of 4-bromo-1-naphthoic acid: Mayer, F.; Sieglitz, A. Untersuchungen und Ringschlüsse in der Reihe der Methyl-naphthaline. Chem. Ber. 1922, 55, 1841-1859.
45. Ethyl ester both of 4-methyl- and 4-methyl-6-chloronaphthoic acid (compounds with general formula B) were prepared following the procedure reported in the article: Kim, J. N.; Im, Y. J.; Gong, J. H.; Lee, K. Y. An expedient synthesis of 2-substituted naphthalenes from the Baylis-Hillman adducts. Tetrahedron. Lett. 2001, 42, 4195-4197.
46. Rosowsky, A.; Papoulis, A. T.; Forsch, R. A.; Qeener, S.F. Synthesis and antiparasitic activity of 2,4-diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of Piritrexim. J. Med. Chem. 1999, 42, 1007-1017.
47. Luettringhaus, A.; Mohr, M.; Engelhard, N. Thiaaromatics. VII. 1,2-Dithiolium salt from 1,3-dithiacyclohexenes by dehydrogenation with ring contraction. Justus Liebigs Ann. Chem. 1963, 661, 84-94.
48. For the N-alkylated piperidones 12-18, only the compounds 15 and 18 were not previously reported. For 1-(3-chlorobenzyl)-4- piperidone 13 and 1-(4-chlorobenzyl)-4-piperidone 14, see the ref 18b; for 1-(2-chlorobenzyl)-4-piperidone 12 see the article: Gooding, O. W.; Beard, C. C. Use of mercaptoacetaldehyde dimer in a novel thienoannelation sequence. A short synthesis of ticlopidine. Heterocycles 1991, 32, 1777-1780; for the 1-(4-fluorobenzyl)-4-piperidone 16 see the article: Massa, S.; Mai, A.; Artico, M. Spiro-[4-H-pyrrolo[1,2-a] [1,4]benzodiazepine-4,4′- piperidine] derivatives as potential nootropic agents: a simple one-pot synthesis. Synth. Comm. 1990, 20, 3537-3545; for the 1-(4- nitrobenzyl)-4-piperidone 17, see the article: Lavey, B. J.; Janda, K. D. Catalytic antibody-mediated hydrolysis of paraoxon. J. Org. Chem. 1996, 61, 7633-7636.
49. For the N-alkylated piperidones 12-18, only the compounds 15 and 18 were not previously reported. For 1-(3-chlorobenzyl)-4- piperidone 13 and 1-(4-chlorobenzyl)-4-piperidone 14, see the ref 18b; for 1-(2-chlorobenzyl)-4-piperidone 12 see the article: Gooding, O. W.; Beard, C. C. Use of mercaptoacetaldehyde dimer in a novel thienoannelation sequence. A short synthesis of ticlopidine. Heterocycles 1991, 32, 1777-1780; for the 1-(4-fluorobenzyl)-4-piperidone 16 see the article: Massa, S.; Mai, A.; Artico, M. Spiro-[4-H-pyrrolo[1,2-a] [1,4]benzodiazepine-4,4′- piperidine] derivatives as potential nootropic agents: a simple one-pot synthesis. Synth. Comm. 1990, 20, 3537-3545; for the 1-(4- nitrobenzyl)-4-piperidone 17, see the article: Lavey, B. J.; Janda, K. D. Catalytic antibody-mediated hydrolysis of paraoxon. J. Org. Chem. 1996, 61, 7633-7636.
50. For the N-alkylated piperidones 12-18, only the compounds 15 and 18 were not previously reported. For 1-(3-chlorobenzyl)-4- piperidone 13 and 1-(4-chlorobenzyl)-4-piperidone 14, see the ref 18b; for 1-(2-chlorobenzyl)-4-piperidone 12 see the article: Gooding, O. W.; Beard, C. C. Use of mercaptoacetaldehyde dimer in a novel thienoannelation sequence. A short synthesis of ticlopidine. Heterocycles 1991, 32, 1777-1780; for the 1-(4-fluorobenzyl)-4-piperidone 16 see the article: Massa, S.; Mai, A.; Artico, M. Spiro-[4-H-pyrrolo[1,2-a] [1,4]benzodiazepine-4,4′- piperidine] derivatives as potential nootropic agents: a simple one-pot synthesis. Synth. Comm. 1990, 20, 3537-3545; for the 1-(4- nitrobenzyl)-4-piperidone 17, see the article: Lavey, B. J.; Janda, K. D. Catalytic antibody-mediated hydrolysis of paraoxon. J. Org. Chem. 1996, 61, 7633-7636.
51. Jarvis, M. F.; Gessner, G.; Shapiro, G.; Merkel, L.; Myers, M.; Cox, B. F.; Martin, G. E. Differential effects of the adenosine A1 receptor allosteric enhancer PD 81,723 on agonist binding to brain and adipocyte membranes. Brain Res. 1999, 840, 75-83.
52. Hansch, C.; Leo, A.; Unger, S. H.; Kim, K. H.; Nikaitani, D.; Lien, E. J. "Aromatic" substituent constants for structure-activity correlations. J. Med. Chem. 1973, 16, 1207-1216.
53. Gao, Z. G.; Van Muijlwijk-Koezen, J. E.; Chen, A.; Muller, C. E.; IJzerman, A. P.; Jacobson, K. A. Allosteric modulation of A3 adenosine receptors by a series of 3-(2-pyridinyl) isoquinoline derivatives. Mol. Pharmacol. 2001, 60, 1057-1063.
54. Shryock J. C.; Ozeck M. J.; Belardinelli L. Inverse agonists and neutral antagonists of recombinant human A1 adenosine receptors stably expressed in Chinese hamster ovary cells. Mol. Pharmacol. 1998, 53, 886-893.
55. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248-254.
56. Cheng, Y.; Prusoff, W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (IC50) of an enzymatic reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
57. Munson, P. J.; Rodbard, D.; Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem. 1980, 107, 220-239.