6-Methoxy-7-benzofuranoxy and 6-methoxy-7-indolyloxy analogues of 2-[2-(2,6-Dimethoxyphenoxy)ethyl]aminomethyl-1,4-benzodioxane (WB4101):1 Discovery of a potent and selective α1D-adrenoceptor antagonist

Journal of Medicinal Chemistry

Volumn 56, Issue 16, 2013, Pages 6402-6412

  Fumagalli, Laura ^a   Pallavicini, Marco ^a   Budriesi, Roberta ^b   Bolchi, Cristiano ^a   Canovi, Mara ^c   Chiarini, Alberto ^b   Chiodini, Giuseppe ^a   Gobbi, Marco ^c   Laurino, Paola ^d   Micucci, Matteo ^b   Straniero, Valentina ^a   Valoti, Ermanno ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^d WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[2 (2,6 DIMETHOXYPHENOXY)ETHYL]AMINOMETHYL] 1,4 BENZODIOXAN; 2 [[[2 (6 METHOXY 2,3 DIHYDRO 7 BENZOFURANOXY)ETHYL]AMINO]METHYL] 1,4 BENZODIOXANE; 2 [[[2 (6 METHOXY 2,3 DIHYDRO 7 INDOLYLOXY)ETHYL]AMINO]METHYL] 1,4 BENZODIOXANE; 2 [[[2 (6 METHOXY 7 BENZOFURANOXY)ETHYL]AMINO]METHYL] 1,4 BENZODIOXANE; 2 [[[2 (6 METHOXY 7 INDOLYLOXY)ETHYL]AMINO]METHYL] 1,4 BENZODIOXANE; 8 [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] 8 AZASPIRO[4.5]DECANE 7,9 DIONE; ALPHA 1 ADRENERGIC RECEPTOR; BENZOFURAN DERIVATIVE; INDOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENANTIOMER; MALE; NONHUMAN; PROSTATE; RAT; SPLEEN; STRUCTURE ACTIVITY RELATION; THORACIC AORTA; VAS DEFERENS;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; DIOXANES; MAGNETIC RESONANCE SPECTROSCOPY; RECEPTORS, ADRENERGIC, ALPHA-1;

EID: 84883182712     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400867d     Document Type: Article

References (28)

1. Green, P. N.; Shapero, M.; Wilson, C. Synthesis and pharmacological properties of a series of 2-substituted aminomethyl-1,4-benzodioxanes J. Med. Chem. 1969, 12, 326-329
2. Docherty, J. R. Subtypes of functional α1-adrenoceptor Cell. Mol. Life Sci. 2010, 67, 405-417
3. 1-adrenoceptors Eur. J. Pharmacol. 1995, 272, R5-R6
4. 1-adrenoreceptor antagonists (or inverse agonists?) J. Med. Chem. 2006, 49, 7140-7149
5. 1-adrenoceptor recognition Farmaco 1994, 49, 587-606
6. Valoti, E.; Pallavicini, M.; Villa, L.; Pezzetta, D. Synthesis of homochiral 5- and 8-substituted 2-[((2-(2,6-dimethoxyphenoxy)ethyl)amino)methyl] -1,4-benzodioxanes and electrophoretic determination of their enantiomeric excess J. Org. Chem. 2001, 66, 1018-1025
7. 1 antagonist WB-4101 Bioorg. Med. Chem. 2004, 12, 4937-4951
8. 1B- adrenoceptor antagonist Eur. J. Med. Chem. 2012, 58, 184-191
9. Ferri, V.; Pallavicini, M.; Piccini, D.; Valoti, E.; Villa, L.; Brunello, N.; Racagni, G. Synthesis, Binding affinities for α-adrenoceptor and eudismic analysis of chiral benzodioxane derivatives and their chiral opened analogues Farmaco 1988, 49, 1153-1163
10. 1-adrenoceptor antagonist WB4101 Bioorg. Med. Chem. 2005, 13, 2547-2559
11. 1- adrenoceptor antagonist WB4101 Eur. J. Med. Chem. 2006, 41, 1025-1040
12. Bolchi, C.; Fumagalli, L.; Moroni, B.; Pallavicini, M.; Valoti, E. A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods Tetrahedron: Asymmetry 2003, 14, 3779-3885
13. Bolchi, C.; Pallavicini, M.; Fumagalli, L.; Marchini, N.; Moroni, B.; Rusconi, C.; Valoti, E. Highly efficient resolutions of 1,4-benzodioxane-2- carboxylic acid with para substituted 1-phenylethylamines Tetrahedron: Asymmetry 2005, 16, 1639-1643
14. Marchini, N.; Bombieri, G.; Artali, R.; Bolchi, C.; Pallavicini, M.; Valoti, E. Influence of (S)-1-phenylethylamine para substitution on the resolution of (±)-1,4-benzodioxane-2-carboxylic acid: A crystallographic, theoretical and morphologic approach Tetrahedron: Asymmetry 2005, 16, 2099-2106
15. Bolchi, C.; Pallavicini, M.; Fumagalli, L.; Rusconi, C.; Binda, M.; Valoti, E. Resolution of 2-substituted benzodioxanes by entrainment Tetrahedron: Asymmetry 2007, 18, 1038-1041
16. Pallavicini, M.; Valoti, E.; Villa, L.; Piccolo, O. Synthesis of (R)- and (S)-isopropylidene glycerol Tetrahedron: Asymmetry 1994, 5, 5-8
17. Bolchi, C.; Pallavicini, M.; Fumagalli, L.; Ruggeri, P.; Valoti, E. Diastereomeric 2-aminomethyl-1,4-benzodioxane mandelates: Phase diagrams and resolution Tetrahedron: Asymmetry 2013, 24, 796-800
18. White, J. D.; Yager, K. M.; Yakura, T. Synthetic studies of the pyrroloquinoline nucleus of the makaluvamine alkaloids. Synthesis of the topoisomerase II inhibitor makaluvamine D J. Am. Chem. Soc. 1994, 116, 1831-1838
19. Dharmasena, P.; Oliveira-Campos, A. M. R.; Queiroz, M. J. R. P.; Shannon, P. V. R. Anti-tumour heterocycles. Part 12. The synthesis of new hydroxypyrrolocarbazoles and hydroxypyridocarbazoles J. Chem. Res., Miniprint 1996, 316-363
20. 1A-adrenoreceptors Eur. J. Pharmacol. 1991, 202, 33-44
21. 1D-adrenoreceptor antagonist, isolated from Fissistigma glaucescens Br. J. Pharmacol. 1994, 112, 1174-1180
22. 1a-adrenergic receptor subtype-selective antagonists J. Pharmacol. Exp. Ther. 2000, 294, 224-229
23. Arunlakshana, O.; Schild, H. O. Some quantitative uses of drug antagonists Br. J. Pharmacol. 1959, 14, 48-58
24. 2 and receptor differentiation: a statistical analysis of competitive antagonism Life Sci. 1979, 25, 637-654
25. 1d-adrenergic receptor antagonists J. Med. Chem. 2005, 48, 3076-3079
26. 1D-adrenoceptor antagonist Bioorg. Med. Chem. Lett. 1998, 8, 1353-1358
27. Kenakin, T. New concepts in pharmacological efficacy at 7TM receptors: IUPHAR Review 2 Br. J. Pharmacol. 2013, 168, 554-575
28. Noguera, M. A.; Ivorra, M. D.; D'Ocon, P. Functional evidence of inverse agonism in vascular smooth muscle Br. J. Pharmacol. 1996, 119, 158-164