Human β3 adrenergic receptor agonists containing imidazolidinone and imidazolone benzenesulfonamides

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 5, 1999, Pages 755-758

  Naylor, Elizabeth M ^a   Parmee, Emma R ^a   Colandrea, Vincent J ^a   Perkins, Leroy ^a   Brockunier, Linda ^a   Candelore, Mari R ^a   Cascieri, Margaret A ^a   Colwell Jr , Lawrence F ^a   Deng, Liping ^a   Feeney, William P ^a   Forrest, Michael J ^a   Hom, Gary J ^a   MacIntyre, D Euan ^a   Strader, Catherine D ^a   Tota, Laurie ^a   Wang, Pei Ran ^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

ANILINE DERIVATIVE; BENZENESULFONAMIDE DERIVATIVE; BETA 1 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; ETHANOLAMINE DERIVATIVE; GLYCEROL; HYDANTOIN DERIVATIVE; IMIDAZOLINE DERIVATIVE; L 766892; TRIFLUOROACETIC ACID; UNCLASSIFIED DRUG; UREA DERIVATIVE; BETA 3 ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; CYCLOPENTANE DERIVATIVE; CYCLOPENTYLPROPYLIMIDAZOLIDINONE; IMIDAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOG; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; GLYCEROL BLOOD LEVEL; HEART RATE; INTRAVENOUS DRUG ADMINISTRATION; NONHUMAN; ORAL DRUG ADMINISTRATION; RHESUS MONKEY; ANIMAL; CHO CELL; DOSE RESPONSE; DRUG POTENTIATION; HAMSTER; HUMAN; MACACA; METABOLISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADRENERGIC BETA-AGONISTS; ANIMALS; CHO CELLS; CRICETINAE; CYCLOPENTANES; DOSE-RESPONSE RELATIONSHIP, DRUG; HEART RATE; HUMANS; IMIDAZOLES; MACACA MULATTA; RECEPTORS, ADRENERGIC, BETA; RECEPTORS, ADRENERGIC, BETA-1; RECEPTORS, ADRENERGIC, BETA-2; RECEPTORS, ADRENERGIC, BETA-3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033535161     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00072-4     Document Type: Article

References (8)

1. Present address: Schering Plough Research Institute, Kenilworth, NJ 07033, U.S.A.
2. Parmee, E. R.; Naylor, E. M.; Perkins, L.; Colandrea, V. J.; Ok, H. O.; Candelore, M. R.; Cascieri, M. A.; Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. J.; MacIntyre, D. E.; Miller, R. R.; Stearns, R. A.; Strader, C. D.; Tota, L.; Wyvratt, M. J.; Fisher, M. H.; Weber, A. E. Bioorg. Med. Chem. Lett. 1999, 9, 749.
3. The enantiomeric excess of aniline 3 was estimated to be 90%. For details of the synthesis and the determination of the enantiomeric excess see Naylor, E. M.; Colandrea, V. J.; Candelore, M. R.; Cascieri, M. A.; Colwell, Jr., L. F.; Deng, L.; Feeney, W. P.; Forrest, M. J.; Hom, G. J.; 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.
4. The sulfonyl chlorides, with the exception of those required for the synthesis of sulfonamides 1j-k, were prepared according to the procedure outlined in the preceding paper. The sulfonyl chorides, required for the synthesis of sulfonamides 1j-k, were prepared from the appropriately substituted 4-bromophenylimidazolidinone according to the procedure described in Graham, S. L.; Hoffman, J. M.; Gautheron, P.; Michelson, S. R.; Scholz, T. H.; Schwam, H.; Shepard, K. L.; Smith, A. M.; Smith, R. L.; Sondey, J. M.; Sugrue, M. F. J. Med. Chem. 1990, 33, 749.
5. 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. All final compounds were characterized by NMR, mass spectrometry and HPLC. For experimental details see: Fisher, M. H.; Naylor, E. M.; Weber, A. E. U.S. Patent 5 541 197, 1996; Chem. Abstr. 1996, 125, 221588.
6. 50 values.
7. (b) For experimental details see 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. J.; 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, 101, 2387.
8. Personal communication from Dr. Karen A. Owens and Ms. Dorothy A. Levorse.