4-amino-2-[4-[1-(benzyloxycarbonyl)-2(s)- [[(1,1- dimethylethyl)amino]carbonyl]- piperazinyl]-6,7-dimethoxyquinazoline (L- 765,314): A potent and selective α(1b) adrenergic receptor antagonist

Journal of Medicinal Chemistry

Volumn 41, Issue 8, 1998, Pages 1205-1208

  Patane, Michael A ^c   Scott, Ann L ^a   Broten, Theodore P ^a   Chang, Raymond S L ^a   Ransom, Richard W ^a   DiSalvo, Jerry ^a   Forray, Carlos ^b   Bock, Mark G ^c  

^a MERCK RESEARCH LABORATORIES   (United States)

^b H LUNDBECK A S   (Denmark)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 2 [4 [1 (BENZYLOXYCARBONYL) 2 [[(1,1 DIMETHYLETHYL)AMINO]CARBONYL]PIPERAZINYL] 6,7 DIMETHOXYQUINAZOLINE; 8 [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] 8 AZASPIRO[4.5]DECANE 7,9 DIONE; ALPHA 1 ADRENERGIC RECEPTOR BLOCKING AGENT; ALPHA 1 ADRENERGIC RECEPTOR STIMULATING AGENT; ALPHA 1B ADRENERGIC RECEPTOR; ALPHA 1B ADRENERGIC RECEPTOR BLOCKING AGENT; BMY 7376; N [5 (4,5 DIHYDRO 1H IMIDAZOL 2 YL) 5,6,7,8 TETRAHYDRO 2 HYDROXY 1 NAPHTHYL]METHANESULFONAMIDE; PHENYLEPHRINE; PRAZOSIN; TERAZOSIN; UNCLASSIFIED DRUG;

ALPHA ADRENERGIC RECEPTOR BLOCKING; ANTIHYPERTENSIVE ACTIVITY; ARTICLE; DRUG INHIBITION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; NONHUMAN; RAT; RECEPTOR AFFINITY; SMOOTH MUSCLE RELAXATION; THORACIC SPINAL CORD; VASCULAR SMOOTH MUSCLE;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; ANTIHYPERTENSIVE AGENTS; BLOOD PRESSURE; HUMANS; MALE; ORGAN SPECIFICITY; PRAZOSIN; RATS; RATS, INBRED SHR; RATS, SPRAGUE-DAWLEY; RECEPTORS, ADRENERGIC, ALPHA-1; SPINAL CORD; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032499276     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980053f     Document Type: Article

References (20)

1. For example, Prazosin: Graham, R. M.; Pettinger, W. A. Drug Therapy: Prazosin. N. Engl. J. Med. 1979, 300, 232-236.
2. Caine, M.; Raz, S.; Zeigler, M. Adrenergic and Cholinergic Receptors in the Human Prostate, Prostatic Capsule and Bladder Neck. Br. J. Urol. 1975, 47, 193-202.
3. Caine, M.; Pfau, A.; Perlberg, S. The Use of Alpha-adrenergic Blockers in Benign Prostatic Obstruction. Br. J. Urol. 1976, 48, 255-263.
4. 1-Adrenergic Receptor Subtype. J. Biol. Chem. 1990, 265, 8183-8189.
5. (b) Schwinn, D. A.; Johnston, G. L.; Page, S. O.; Mosley, M. J.; Wilson, K. H.; Worman, N. P.; Campbell, S.; Roock, M. O.; Furness, L. M.; Parry-Smith, D. J.; Peter, B.; Beiley, D. S. Cloning and Pharmacological Characterization of Human Alpha-1 Adrenergic Receptors: Sequence Corrections and Direct Comparison With Other Species. J. Pharmacol. Exp. Ther. 1995, 272, 134-142.
6. (a) Price, D. T.; Schwinn, D. A.; Lomasney, J. W.; Allen, L. F.; Caron, M. G.; Lefkowitz, R. J. Identification, Quantification, and Localization of mRNA for Three Distinct Alpha-1 Adrenergic Receptor Subtypes in Human Prostate. J. Urol. 1993, 150, 546-551.
7. (b) Forray, C.; Bard, J. A.; Wetzel, J. M.; Chiu, G.; Shapiro, E.; Tang, R.; Lepor, H.; Hartig, P. R.; Weinschank, R. L.; Branchek, T. A.; Gluchowski, C. The Alpha-1-Adrenergic Receptor that Mediates Smooth Muscle Contraction in the Human Prostate has the Pharmacological Properties of the Cloned Human Alpha-1c Subtype. Mol. Pharmacol. 1994, 45, 703-708.
8. Chapple, C. R.; Burt, R. P.; Andersson, P. O.; Greengrass, P.; Wyllie, M.; Marshall, I. Alpha-1-Adrenoceptor Subtypes in the Human Prostate. Br. J. Urol. 1994, 74, 585-589.
9. 1a-Adrenoceptor-Selective Antagonist: Characterization Using Recombinant Human α1-Adrenoceptors and Native Tissues. Mol. Pharmacol. 1995, 48, 250-258.
10. (b) For Rec 15/2739: Testa, R.; Guarneri, L.; Taddei, C.; Poggesi, E.; Angelico, P.; Sartani, A.; Leonardi, A.; Gofrit, O. N.; Meretyk, S.; Caine, M. Functional Antagonistic Activity of Rec 15/2739, a Novel Alpha-1 Antagonist Selective for the Lower Urinary Tract, on Noradrenaline-Induced Contraction of Human Prostate and Mesenteric Artery. J. Pharmcol. Exp. Ther. 1996, 277, 1237-1246.
11. 1-Adrenoceptors in Human Prostate: Implications for Adrenoceptor Classification. Mol. Pharmacol. 1996, 49, 209-215.
12. 1a Receptor Agonist. J. Med. Chem. 1996, 39, 4116-4119.
13. 1a-Adrenoceptor Agonist, Selectivity Increases Intraurethral Pressure in Dogs. Eur. J. Pharmacol. 1996, 318, 117-122.
14. 1B-Adrenoceptor Antagonist. Eur. J. Pharmacol. 1995, 287, 13-16.
15. 1B-Adrenoceptor Antagonist. J. Med. Chem. 1996, 39, 4602-4607.
16. Goetz, A. S.; King, H. K.; Ward, S. D. C.; True, T. A.; Rimele, T. J.; Saussy, D. L. BMY 7378 is a Selective Antagonist of the D Subtype of α1-Adrenoceptors. Eur. J. Pharmacol. 1995, 272, R5-R6.
17. Rossen, K.; Weissman, S. A.; Sager, J.; Reamer, R. A.; Askin, D.; Volante, R. P.; Reider, P. J. Asymmetric Hydrogenation of Tetrahydropyrazines: Synthesis of (S) Piperazine-2-tert-butyl-carboxamide, an Intermediate in the Preparation of HIV Protease Inhibitor Indinavir. Tetrahedron Lett. 1995, 36, 6419-6422.
18. 1-Adrenergic Subtypes in the Rat Spinal Cord. Eur. J. Pharmacol. 1996, 312, 263-266.
19. 1/2 was 0.5 h.
20. 2a adrenergic receptors from human and rodent sources. For a discussion of this example, please see: Heible, J. P.; Bondinell, W. E.; Ruffolo, R. R. J. Med. Chem. 1995, 38, 3415-3444.