Synthesis, absolute configuration, and biological profile of the enantiomers of trans-[2-(2,6-dimethoxyphenoxy)ethyl][(3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2- yl)methyl]amine (mephendioxan), a potent competitive α1A-adrenoreceptor antagonist

Journal of Medicinal Chemistry

Volumn 39, Issue 11, 1996, Pages 2253-2258

  Quaglia, Wilma ^a   Pigini, Maria ^a   Tayebati, Seyed K ^a   Piergentili, Alessandro ^a   Giannella, Mario ^a   Leonardi, Amedeo ^b   Taddei, Carlo ^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

[2 (2,6 DIMETHOXYPHENOXY)ETHYL][(3,4 TOLYL 2,3 DIHYDRO 1,4 BENZODIOXIN 2 YL)METHYL]AMINE; ADRENERGIC RECEPTOR BLOCKING AGENT; ALPHA 1A ADRENERGIC RECEPTOR; MEPHENDIOXAN; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ARTICLE; CHIRALITY; COMPETITIVE INHIBITION; DRUG CONFORMATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENANTIOMER; NONHUMAN; PROTEIN MODIFICATION; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; BINDING, COMPETITIVE; CELL LINE; CERCOPITHECUS AETHIOPS; CEREBRAL CORTEX; CIRCULAR DICHROISM; CLONING, MOLECULAR; DIOXANES; DIOXINS; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MOLECULAR STRUCTURE; MUSCLE, SMOOTH; PRAZOSIN; RADIOLIGAND ASSAY; RATS; RECEPTORS, ADRENERGIC, ALPHA-1; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION; VAS DEFERENS;

EID: 0029946632     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960069a     Document Type: Article

References (30)

1. 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. 1D-Adrenoceptor Antagonist Isolated from Fissistigma Glauceseens. Br. J. Pharmacol. 1994, 112, 1174-1180.
3. 1-Adrenoceptors. Eur. J. Pharmacol. 1995, 272, R5-R6.
4. 1d-Adrenoceptor Subtype Is Involved in the Noradrenaline-Induced Contractions of Rat Aorta. Life Sci. 1995, 57, PL 159-163.
5. 1-Adrenergic Receptor. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7159-7163.
6. 1-Adrenergic Receptor Subtype. J. Biol. Chem. 1990, 265, 8183-8189.
7. 1A-Adrenergic Receptor, the Gene for Which Is Located on Human Chromosome 5. J. Biol. Chem. 1991, 266, 6365-6369.
8. 1-Adrenoceptor Classification: Sharpening Occam's Razor. Trends Pharmacol. Sci. 1994, 15, 167-170.
9. 1-Adrenoceptors: Consensus Update. Pharmacol. Rev. 1995, 47, 267-270.
10. 1-Adrenoceptor Classification. Eur. J. Pharmacol. Mol. Pharmacol. Sect. 1994, 268, 141-149.
11. Melchiorre, C.; Giardinà, D.; Gallucci, P.; Brasili, L. Structural Requirements for Competitive α-Adrenoreceptor Occupancy by Cyclic and Open Analogues of WB 4101. J. Pharm. Pharmacol. 1982, 34, 683-644.
12. 1-Adrenoreceptors. J. Med. Chem. 1984, 27, 1535-1536.
13. 1-Adrenoreceptor Blocking Activity. J. Med. Chem. 1988, 31, 2300-2304.
14. 1-Adrenoreceptor Antagonists. J. Med. Chem. 1990, 33, 2946-2948.
15. Quaglia, W.; Pigini, M.; Tayebati, S. K.; Piergentili, A.; Giannella, M.; Marucci, G.; Melchiorre, C. Structure-Activity Relationships in 1,4-Benzodioxan-Related Compounds. 4. Effect of Aryl and Alkyl Substituents at Position 3 on α-Adrenoreceptor Blocking Activity. J. Med. Chem. 1993, 36, 1520-1528.
16. Nelson, W. L.; Powell, M. L.; Dyer, D. C. Absolute Configuration of Glycerol Derivatives. 7. Enantiomers of 2-[[[2-(2,6-Dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane (WB-4101), a Potent Competitive α-Adrenergic Antagonist. J. Med. Chem. 1979, 22, 1125-1127.
17. Andrisano, V.; Marucci, G.; Melchiorre, C.; Tumiatti, V. Stereoselectivity at α-Adrenoreceptor Subtypes: Observations With the Enantiomers of WB 4101 Separated Through Their Amides of N-Tosyl-(S)-proline. Chirality 1992, 4, 16-20.
18. Arnoldi, A.; Merlini, L. Asymmetric Synthesis of 3-Methyl-2-phenyl-1,4-benzodioxanes. Absolute Configuration of the Neolignans Eusiderin and Eusiderin C and D. J. Chem. Soc., Perkin Trans. 1 1985, 2555-2557.
19. Woolley, D. W. Probable Evolutionary Relations of Serotonin and Indole-Acetic Acid, and Some Practical Consequences Therefrom. Nature (London) 1957, 180, 630-633.
20. Villani, F. J., Jr.; Costanzo, M. J.; Inners, R. R.; Mutter, M. S.; McClure, D. E. Determination of Enantiomeric Purity of Tertiary Amines by Proton NMR of α-Methoxy-α-(trifluoromethyl)phenyl Acetic Complexes. J. Org. Chem. 1986, 51, 3715-3718.
21. Arunlakshana, O.; Schild, H. O. Some Quantitative Uses of Drug Antagonists. Br. J. Pharmacol. 1959, 14, 48-58.
22. 2 and Receptor Differentiation: a Statistical Analysis of Competitive Antagonism. Life Sci. 1979, 25, 637-654.
23. Van Rossum, J. M. Cumulative Dose-response Curves. II. Technique for the Making of Dose-response Curves in Isolated Organs and the Evaluation of Drug Parameters. Arch. Int. Pharmacodyn. 1963, 143, 299-330.
24. 50) of an Enzymatic Reaction. Biochem. Pharmacol 1973, 22, 3099-3108.
25. Ruffolo, R. R., Jr.; Bondinell, W.; Hieble, J. P. α- and β-Adrenoceptors. From the Gene to the Clinic. 2. Structure-Activity Relationships and Therapeutic Applications. J. Med. Chem. 1996, 38, 3681-3716.
26. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. Modeling of G-Protein-Coupled Receptors: Application to Dopamine, Acetylcholine, and Mammalian Opsin Receptors. J. Med. Chem. 1992, 35, 3448-3462.
27. 2+ Channel Antagonist Niguldipine. J. Med. Chem. 1995, 38, 1579-1581.
28. 1A Receptor Agonist with High Potency and Selectivity. J. Pharmacol. Exp. Ther. 1994, 270, 1270-1281.
29. 1-Adrenoceptor Subtypes in Prostate and Prostatic Urethra of Rat, Rabbit, Dog and Man. Eur. J. Pharmacol. 1994, 249, 307-315.
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.