Doxazosin-related α1-adrenoceptor antagonists with prostate antitumor activity

Journal of Medicinal Chemistry

Volumn 52, Issue 15, 2009, Pages 4951-4954

  Giardinà, Dario ^a   Martarelli, Daniele ^a   Sagratini, Gianni ^a   Angeli, Piero ^a   Ballinari, Dario ^b   Gulini, Ugo ^a   Melchiorre, Carlo ^d   Poggesi, Elena ^c   Pompei, Pierluigi ^a  

^a UNIVERSITY OF CAMERINO   (Italy)

^b NERVIANO MEDICAL SCIENCES   (Italy)

^c Recordati SpA   (Italy)

^d UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 (2,3 DIHYDRO 1,4 BENZODIOXIN 2 YLCARBON)OCTAHYDROQUINOXALIN 1(2H) YL] 6,7 DIMETHOXYQUINAZOLIN 4 AMINE; 2 [4 (2,3 DIHYDRO 1,4 BENZODIOXIN 2 YLCARBONYL)OCTAHYDROQUINOXALIN 1(2H) YL] 6,7 DIMETHOXYQUINAZOLIN 4 AMINE; ALPHA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; CYCLODOXAZOSIN; DOXAZOSIN; N [6 [(4 AMINO 6,7 DIMETHOXYQUINAZOLIN 2 YL)(METHYL)AMINO]HEXYL] N METHYL 2,3 DIHYDRO 1,4 BENZODIOXINE 2 CARBOXAMIDE; UNCLASSIFIED DRUG; ALPHA 1 ADRENERGIC RECEPTOR; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; ANTINEOPLASTIC AGENT; DRUG DERIVATIVE;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BINDING AFFINITY; CANCER CELL CULTURE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; PROSTATE CANCER; ANIMAL; CHO CELL; CRICETULUS; DRUG ANTAGONISM; HAMSTER; MALE; METABOLISM; MOUSE; PATHOLOGY; PROSTATE TUMOR; RAT; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CHO CELLS; CRICETINAE; CRICETULUS; DOXAZOSIN; HUMANS; MALE; MICE; PROSTATIC NEOPLASMS; RATS; RECEPTORS, ADRENERGIC, ALPHA-1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 68549101741     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8016046     Document Type: Article

References (24)

1. Young, R. A.; Brogden, R. N. Doxazosin: A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in mild or moderate hypertension. Drugs 1988, 35, 525-541.
2. 1-adrenoceptor subtype-specific blockade. Br. J. Urol. 1998, 81 (Suppl. 1), 34-47.
3. 1-Adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia. J. Urol. 1999, 161, 2002-2008.
4. Djavan, B.; Marberger, M. A meta-analysis on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Eur. Urol. 1999, 36, 1-13.
5. 1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res. 2000, 60, 4550-4555.
6. 1- adrenoceptor antagonists induce prostate cancer cell apoptosis via an β1-adrenoceptor-independent action. Cancer Res. 2002, 62, 597-602.
7. Garrison, J. B.; Shaw, Y.-J.; Chen, C.-S.; Kyprianou, N. Novel quinazoline-based compounds impair prostate tumorigenesis by targeting tumor vascularity. Cancer Res. 2007, 67, 11344-11352.
8. Giardinà, D.; Gulini, U.; Massi, M.; Piloni, M. G.; Pompei, P.; Rafaiani, G.; Melchiorre, C. Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on Rblocking activity. J. Med. Chem. 1993, 36, 690-698.
9. 1B- adrenoceptor antagonist. Eur. J. Pharmacol. 1995, 287, 13-16.
10. Giardinà, D.; Crucianelli, M.; Marucci, G.; Melchiorre, C.; Polidori, C.; Pompei, P.; Massi, M. Pharmacological evaluation of prazosin- and doxazosin-related compounds with modified piperazine ring. Arzneim.-Forsch. Drug Res. 1996, 46, 1054-1059.
11. Koo, J.; Avakian, S.; Martin, G. J. Derivatives of 1,4-benzodioxan. I. 1,4-Benzodioxan-2-carboxamides. J. Am. Chem. Soc. 1955, 77, 5373-5374.
12. Giardinà, D.; Polimanti, O.; Sagratini, G.; Angeli, P.; Gulini, U.; Marucci, G.; Melchiorre, C.; Poggesi, E.; Leonardi, A. Searching for cyclazosin analogues as R1B-adrenoceptor antagonists. Il Farmaco 2003, 58, 477-487.
13. Brill, E.; Schultz, H. P. Quinoxaline studies. XII. Stereodirective syntheses of cis- and trans-decahydroquinoxalines and cis- and trans-decahydroquinoxalones-2. J. Org. Chem. 1964, 29, 211-220.
14. 1-adrenoceptor antagonist activity of derivatives of the furan portion of (+)-cyclazosin. Bioorg.Med. Chem. 2007, 15, 2334-2345.
15. 1A-adrenoceptors. Eur. J. Pharmacol. 1991, 202, 33-44.
16. 1D-adrenoceptor antagonist, isolated from Fissistigma glaucescens. Br. J. Pharmacol. 1994, 112, 1174-1180.
17. Buckner, S. A.; Oheim, K. W.; Morse, P. A.; Knepper, S. M.; Hancock, A. A. Alpha 1-adrenoceptor-induced contractility in rat aorta is mediated by the alpha1Dsubtype. Eur. J. Pharmacol. 1996, 297, 241-248.
18. Arunlakshana, D.; Schild, H. O. Some quantitative uses of drug antagonists. Br. J. Pharmacol. 1959, 14, 48-58.
19. van Rossum, J. M.Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drugs parameters. Arch. Int. Pharmacodyn. Ther. 1963, 143, 299-330.
20. 1-adrenoceptor antagonist. Pharmacol. Commun. 1995, 6, 79-86.
21. 50) of an enzyme reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
22. Antonello, A.; Hrelia, P.; Leonardi, A.; Marucci, G.; Rosini, M.; Tarozzi, A.; Tumiatti, V.; Melchiorre, C. Design, synthesis, and biological evaluation of prazosin-related derivatives as multipotent compounds. J. Med. Chem. 2005, 48, 28-31.
23. Hanahan, D.; Weinberg, R. A. The hallmarks of cancer. Cell 2000, 100, 57-70.
24. 1B-adrenoceptors. Drug Development Research 1998, 44, 140-162.