Human β3 adrenergic receptor agonists containing cyclic ureidobenzenesul fonamides

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 5, 1999, Pages 749-754

  Parmee, Emma R ^a   Naylor, Elizabeth M ^a   Perkins, Leroy ^a   Colandrea, Vincent J ^a   Ok, Hyun O ^a   Candelore, Mari R ^a   Cascieri, Margaret A ^a   Deng, Liping ^a   Feeney, William P ^a   Forrest, Michael J ^a   Hom, Gary J ^a   MacIntyre, D Euan ^a   Miller, Randall R ^a   Stearns, Ralph A ^a   Strader, Catherine D ^a   Tota, Laurie ^a   Wyvratt, Matthew J ^a   Fisher, Michael H ^a   Weber, Ann E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZENESULFONAMIDE DERIVATIVE; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; CARBANILAMIDE; HYDANTOIN DERIVATIVE; IMIDAZOLE DERIVATIVE; ISOPRENALINE; L 760087; L 764646; PARTIAL AGONIST; PHENOL DERIVATIVE; PYRIDINE DERIVATIVE; TRIAZOLE DERIVATIVE; TRIAZOLINE DERIVATIVE; TRIFLUOROACETIC ACID; UNCLASSIFIED DRUG; UREA DERIVATIVE; BETA 1 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; BETA 3 ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; DRUG DERIVATIVE; L 755507; L 757793; SULFONAMIDE; UREA;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CYCLIZATION; DOG; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; HEART RATE; INTRAVENOUS DRUG ADMINISTRATION; LIPOLYSIS; NONHUMAN; ORAL DRUG ADMINISTRATION; RHESUS MONKEY; ANIMAL; DRUG POTENTIATION; HUMAN; MACACA; METABOLISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADMINISTRATION, ORAL; ADRENERGIC BETA-AGONISTS; ANIMALS; DOGS; HEART RATE; HUMANS; MACACA MULATTA; RECEPTORS, ADRENERGIC, BETA; RECEPTORS, ADRENERGIC, BETA-1; RECEPTORS, ADRENERGIC, BETA-2; RECEPTORS, ADRENERGIC, BETA-3; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; UREA;

EID: 0033535160     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00073-6     Document Type: Article

References (20)

1. Present address: Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033.
2. For recent reviews see: (a) Dow, R. L. Exp. Opin. Invest. Drugs 1997, 6, 1811.
3. (b) Lowell, B. B.; Flier, J. S. Annu. Rev. Med. 1997, 48, 307.
4. (c) Arch, J. R. S.; Wilson, S. Int. J. Obesity 1996, 20, 191.
5. (d) Himms-Hagen, J.; Danforth, E. Curr. Opin. Endocrin. Diabetes 1996, 3, 59.
6. (e) Claus, T. H.; Bloom, J. D. Ann. Rep. Med. Chem. 1995, 30, 189.
7. (a) Weber, A. E.; Mathvink, R. J.; Perkins L.; Hutchins, J. E.; Candelore, M. R.; Tota, L.; Strader, C. D.; Wyvratt, M. J.; Fisher, M. H. Bioorg. Med. Chem. Lett. 1998, 8, 1101.
8. (b) Parmee, E. R.; Ok, H. O.; Candelore, M. R.; Tota, L.; Deng, L.; Strader, C. D.; Wyvratt, M. J.; Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 1998, 8, 1107.
9. (c) Weber, A. E.; Ok, H. O.; Alvaro, R. F.; Candelore, M. R.; Cascieri, M. A.; Chiu, S-H. L.; Deng, L.; Forrest, M. J.; Hom, G. H.; Hutchins, J. E.; Kao, J.; MacIntyre, D.E.; Mathvink, R. J.; McLoughlin, D.; Miller, R.R., Newbold, R. C.; Olah, T. V.; Parmee, E. R.; Perkins L.; Stearns, R. A.; Strader, C.D.; Szumiloski, J.; Tang, Y.S.; Tota, L.; Vicario, P. P.; Wyvratt, M. J.; Fisher, M. H. Bioorg. Med. Chem. Lett. 1998, 8, 2111.
10. (d) Naylor, E. M.; Colandrea, V. J.; Candelore, M. R.; Cascieri, M. A.; Colwell, L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. H.; MacIntyre, D.E.; Strader, C.D.; Tota, L.; Wang, P.-R.; Wyvratt, M. J.; Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 1998, 8, 3087.
11. Fisher, M. H.; Amend, A. M.; Bach, T. J.; Barker, J. M.; Brady, E. J.; Candelore, M. R.; Carroll, D.; Cascieri, M. A.; Chiu, S-H. L.: Deng, L.; Forrest, M. J.; Hegarty-Friscino, B.; Guan, X.-M.; Hom, G. H.; Hutchins, J. E.; Kelly, L. J.; Mathvink, R. J.; Metzger, J. M.; Miller, R. R.; Ok, H.O.; Parmee, E. R.; Saperstein, R.; Strader, C. D.; Stearns, R. A.; Thompson, G. M.; Tota, L.; Vicario, P. P.; Weber, A. E.; Woods, J. W.; Wyvratt, M. J.; Zafian, P. T.; MacIntyre, D. E. J. Clin. Invest. 1998, 707, 2387.
12. 1H NMR, mass spectrometry, and HPLC analysis prior to submission for biological evaluation. For experimental details see: Fisher, M. H.; Mathvink, R. J.; Ok, H.O.; Parmee, E. R.; Weber, A. E. U. S. Patent 5 451 677, 1995; Chem. Abstr. 1996, 124, 116877 and Fisher, M. H.; Naylor, E. M.; Weber, A. E. U. S. Patent 5 541 197, 1996; Chem. Abstr. 1996, 125, 221588.
13. 1H NMR, mass spectrometry, and HPLC analysis prior to submission for biological evaluation. For experimental details see: Fisher, M. H.; Mathvink, R. J.; Ok, H.O.; Parmee, E. R.; Weber, A. E. U. S. Patent 5 451 677, 1995; Chem. Abstr. 1996, 124, 116877 and Fisher, M. H.; Naylor, E. M.; Weber, A. E. U. S. Patent 5 541 197, 1996; Chem. Abstr. 1996, 125, 221588.
14. 3 AR agonist activity examined. In each case, in line with expectation, the (R)-isomer was 5- to 190-fold more potent than the respective (S)-isomer.
15. 125I-cyanopindolol binding, repectively.
16. 125I-cyanopindolol binding, repectively.
17. 125I-cyanopindolol binding, repectively.
18. 50 values.
19. All in vivo experiments were performed as described in ref 4.
20. 3H]-L-760,087 was prepared from aniline 3 as described in ref 3c.