Synthesis and biological profile of the enantiomers of [4-(4-amino-6,7- dimethoxyquinazolin-2-yl)-cis-octahydroquinoxalin-1-yl]furan-2-ylmethanone (cyclazosin), a potent competitive α(1B)-adrenoceptor antagonist

Journal of Medicinal Chemistry

Volumn 39, Issue 23, 1996, Pages 4602-4607

  Giardinà, Dario ^a   Crucianelli, Mauro ^a   Romanelli, Roberta ^a   Leonardi, Amedeo ^b   Poggesi, Elena ^b   Melchiorre, Carlo ^c  

^a UNIVERSITY OF CAMERINO   (Italy)

^b Recordati SpA   (Italy)

^c UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIHYDRO 2,6 DIMETHYL 4 (4 NITROPHENYL) 3,5 PYRIDINEDICARBOXYLIC ACID [3 (4,4 DIPHENYL 1 PIPERIDINYL)PROPYL]AMIDE METHYL ESTER; 2 [[2 (2,6 DIMETHOXYPHENOXY)ETHYL]AMINOMETHYL] 1,4 BENZODIOXAN; 2 DIPROPYLAMINO 8 HYDROXYTETRALIN; 8 [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] 8 AZASPIRO[4.5]DECANE 7,9 DIONE; AH 11110A; ALPHA 1A ADRENERGIC RECEPTOR; ALPHA 1B ADRENERGIC RECEPTOR; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; CYCLAZOCINE; NIGULDIPINE; PRAZOSIN; RAUWOLSCINE; SPIPERONE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BRAIN HOMOGENATE; CONTROLLED STUDY; DRUG COMPETITION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; ENANTIOMER; HUMAN; NONHUMAN; RAT; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; BINDING SITES; CATTLE; CEREBRAL CORTEX; CHO CELLS; COS CELLS; CRICETINAE; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; QUINAZOLINES; QUINOXALINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ADRENERGIC, ALPHA-1; STEREOISOMERISM;

EID: 0029803747     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960510x     Document Type: Article

References (30)

1. (a) Bylund, D. B.; Eikenberg, D. C.; Hieble, J. P.; Langer, S. Z.; Lefkowitz, R. J.; Minneman, K. P.; Molinoff, P. B.; Ruffolo, R. R., Jr.; Trendelenburg, U. IV. International Union of Pharmacology Nomenclature of Adrenoceptors. Pharmacol. Rev. 1994, 46, 121-136.
2. 1-Adrenoceptors: Consensus Update. Pharmacol. Rev. 1995, 47, 267-270.
3. Hieble, J. P.; Bondinell, W. E.; Ruffolo, R. R., Jr. α- and β-Adrenoceptors: From the Gene to the Clinic. 1. Molecular Biology and Adrenoceptor Subclassification. J. Med. Chem. 1995, 38, 3415-3444.
4. 1-Adrenoceptor. Eur J. Pharmacol. 1995, 272, R5-R6.
5. 1A-subtype in Rat Submaxillary Gland. Br. J. Pharmacol. 1989, 98, 883-889.
6. 1A-Subtype. Eur. J. Pharmacol. (Mol. Pharmacol. Sect.) 1995, 289, 81-86.
7. 1A-Adrenoceptors. Eur. J. Pharmacol. 1991, 202, 33-44.
8. 1-Adrenoceptor Subtypes in Prostate and Prostatic Urethra of Rat, Rabbit, Dog and Man. Eur. J. Pharmacol. 1993, 249, 307-315.
9. 2+ in Smooth Muscle. Nature 1987, 329, 333-335.
10. 1-Adrenoceptor Mediating Contractions of Rat Aorta, Vas Deferens and Spleen. Br. J. Pharmacol. 1993, 109, 80-87.
11. 1d-Adrenoceptor Subtype is Involved in the Noradrenaline-Induced Contractions of Rat Aorta. Life Sci. 1995, 57, PL 159-163.
12. 1-Adrenegic Receptors. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7159-7163.
13. 1-Adrenegic Receptors Subtype. J. Biol. Chem. 1990, 265, 8183-8189.
14. 1A-Adrenergic Receptor. J. Biol. Chem. 1991, 266, 6365-6369.
15. 1D-Adrenegic Receptor cDNA. Mol. Pharmacol. 1991, 40, 876-883.
16. 1c-Adrenoceptors are the Same Subtype. Eur. J. Pharmacol. 1995, 290, 49-53.
17. 1-Adrenoceptor Classification. Eur. J. Pharmacol. (Mol. Pharmacol. Sect.) 1994, 268, 141-149.
18. 1-Adrenoceptor Classification: Sharpening Occam's Razor. Trends Pharmacol. Sci. 1994, 15, 167-170.
19. 1-Adrenoceptors. Neurosci. Abstr. 1994, 20, 526.
20. 1-Adrenoreceptor Blocking Activity. J. Med. Chem. 1989, 32, 50-55.
21. 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 α-Blocking Activity. J. Med. Chem. 1993, 36, 690-698.
22. 1B-Adrenoceptor Antagonist. Eur. J. Pharmacol. 1995, 287, 13-16.
23. 1-Adrenoceptors. Eur. J. Pharmacol. 1989, 172, 131-145.
24. 1A-Adrenoreceptor Antagonist. J. Med. Chem. 1996, 39, 2253-2258.
25. Hancock, A. A.; Buckner, S. A.; Ireland, L. M.; Knepper, S. M.; Kerwin, J. F., Jr. Actions of Terazosin and its Enantiomers at Subtypes of Alpha 1- and Alpha 2-Adrenoceptors in Vitro. J. Recept. Signal Transduct. Res. 1995, 15, 863-885.
26. 50) of an Enzyme Reaction. Biochem. Pharmacol. 1973, 22, 3099-3108.
27. Goetz, A. S.; Lutz, M. W.; Rimele, T. J.; Saussy, D. L., Jr. Characterization of Alpha-1 Adrenoceptor Subtypes in Human and Canine Prostate Membranes. J. Pharmacol. Exp. Ther. 1994, 271, 1228-1233.
28. Schwinn, D. A.; Johnston, G. I.; Page, S. O.; Mosley, M. J.; Wilson, K. A.; Worman, N. P.; Campbell, S.; Fidock, M. D.; Furness, L. M.; Parry-Smith, D. J.; Peter, B.; Bailey, D. S. Cloning and Pharmacological Characterization of Human Alpha-1 Adrenergic Receptors: Sequence Corrections and Direct Comparison with Other Species Homologues. J. Pharmacol. Exp. Ther. 1995, 272, 134-142.
29. Testa, R.; Taddei, C.; Poggesi, E.; Destefani, C.; Cotecchia, S.; Hieble, J. P.; Sulpizio, A. C.; Naselsky, D.; Bergsma, D.; Ellis, C.; Swift, A.; Ganguly, S.; Ruffolo, R. R., Jr.; Leonardi, A. REC 15/2739 (SB 216469): A Novel Prostate Selective on-Adrenoceptor Antagonist. Pharmacol. Commun. 1995, 6, 79-86.
30. De Lean, A.; Munson, P. J.; Rodbard, D. Simultaneous Analysis of Families of Sigmoidal Curves: Application to Bioassay, Radioligand Assay, and Physiological Dose-Response Curves. Am. J Physiol. 1978, 235, E97-E102.