Biarylaniline phenethanolamines as potent and selective β3 adrenergic receptor agonists

Journal of Medicinal Chemistry

Volumn 49, Issue 9, 2006, Pages 2758-2771

  Uehling, David E ^a   Shearer, Barry G ^a   Donaldson, Kelly H ^a   Chao, Esther Y ^a   Deaton, David N ^a   Adkison, Kim K ^a   Brown, Kathleen K ^a   Cariello, Neal F ^a   Faison, Walter L ^a   Lancaster, Mary E ^a   Lin, Jasmine ^a   Hart, Robert ^a   Milliken, Tula O ^a   Paulik, Mark A ^a   Sherman, Bryan W ^a   Sugg, Elizabeth E ^a   Cowan, Conrad ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [3 [2 [2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PHENYL] 4 PYRIDINECARBOXYLIC ACID; 3' [[2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]ETHYL]AMINO][1,1' BIPHENYL] 3 CARBOXYLIC ACID; ANILINE DERIVATIVE; BETA 3 ADRENERGIC RECEPTOR; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; CARBOXYLIC ACID DERIVATIVE; PHENYLETHANOLAMINE DERIVATIVE; PHENYLPYRIDYL DERIVATIVE; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BETA ADRENERGIC STIMULATION; CHO CELL; CONTROLLED STUDY; DIABETES MELLITUS; DOG; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; IN VITRO STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN;

ANILINE COMPOUNDS; ANIMALS; BLOOD GLUCOSE; CELL LINE; CRICETINAE; CYCLIC AMP; DOGS; ETHANOLAMINE; GLYCOSYLATION; HEMOGLOBINS; HUMANS; MALE; MICE; MOLECULAR STRUCTURE; RECEPTORS, ADRENERGIC, BETA-3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33646457171     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0509445     Document Type: Article

References (45)

1. 3-Adrenergic receptors: Really relevant targets for anti-obesity drugs? Curr. Med. Chem.: Cent. Nerv. Syst. Agents 2003, 3, 257-273.
2. (b) Moneva, M. H.; Dagogo-Jack, S. Multiple drug targets in the management of type 2 diabetes. Curr. Drug Targets 2002, 3, 203-221.
3. Arch, J. R. S.; Ainsworth, A. T. Thermogenic and antiobesity activity of a novel β-adrenoceptor agonist (BRL 26830A) in mice and rats. Am. J. Clin. Nutr. 1983, 38, 549-558.
4. Arch, J. R. S.; Ainsworth, A. T.; Cawthorne, M. A.; Piercy, V.; Sennitt, M. V.; Thody, V. E.; Wilson, C.; Wilson, S. Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 1984, 309, 163-165.
5. 3- adrenoceptors. Br. J. Clin. Pharmacol. 1996, 42, 291-300.
6. 3-adrenergic receptor. Science 1989, 245, 1118-1121.
7. 3-adrenergic receptor. Mol. Pharmacol. 1991, 40, 895-899.
8. 3- adrenergic receptor: relationship with the atypical receptor of adipocytes. EMBO J. 1991, 10, 3721-3727.
9. 3-adrenoceptor. Trends Pharm. Sci. 1996, 17, 373-381.
10. 3 adrenergic receptor agonist, (R)-N-[4-[2-[[2-hydroxy-2-(3- pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl] thiazol-2-yl]benzenesulfonamide. J. Med. Chem. 2000, 43, 3832-3836.
11. (b) Ikemoto, N.; Liu, J.; Brands, K. M. J.; McNamara, J. M.; Reider, P. J. Practical routes to the triarylsulfonyl chloride intermediate of a ft adrenergic receptor agonist. Tetrahedron 2003, 59, 1317-1325.
12. 3-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am. J. Clin. Nutr. 2002, 76, 780-788.
13. (b) Van Baak, M. A.; Hul, G. B. J.; Toubro, S.; Astrume, A.; Gottesdiener, K. M.; DeSmet, M.; Saris, W. H. M. Clin. Pharmacol. Ther. 2002, 71, 272-279.
14. 3-adrenergic receptor agonist with high cell permeability. Bioorg. Med. Chem. 2005, 13, 855-868.
15. (b) Washburn, W. N.; Sun, C.-Q., Bisacchi, G.; Wu, G.; Cheng, P. T.; Sher, P. M.; Ryono, D.; Gavai, A. V.; Poss, K.; Girotra, R. J.; McCann, P. J.; Mikkilineni, A. B.; Dejneka, T. C.; Wang, T. C.; Merchant, Z.; Morella, M.; Arbeeny, C. M.; Harper, T. W.; Slusarchyk, D. A.; Skwish, S.; Russell, A. D.; Allen, G. T.; Tesfamariam, B.; Frohlich, B. H.; Abboa-Offei, B. E.; Cap, M.; Waldron, T. L.; George, R. J.; Young, K. E.; Dickinson, K. E.; Seymour, A. A. BMS-201620: a selective beta 3 agonist. Bioorg. Med. Chem. Lett. 2003, 14, 3525-3529.
16. 3-adrenoceptor agonistic activity of 4′-hydroxynorephedrine derivative as an agent for treatment of frequent urination and urinary incontinence. J. Med. Chem. 2003, 46, 105-112.
17. (d) Ashwell, M. A.; Solvibile, W. R.; Han, S.; Largis, E.; Mulvey, R.; Tillet, J. 4-Aminopiperidine ureas as potent selective agonists of the human β3-Adrenergic receptor. Biorg. Med. Chem. Lett. 2001, 11, 3123-3127.
18. 3-adrenoceptor-mediated relaxation of the human detrusor. Acta Physiol. Scand. 1998, 164, 117-118.
19. 3-adrenoceptor in the human detrusor muscle. Br. J. Pharmacol. 1999, 126, 819-825.
20. 3- adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J. Pharmacol. Exp. Ther. 1999, 288, 1367-1373.
21. 3 adrenoceptor agonists ZD7114 and CGP 12177A in rats. Pharmacol. Res. 2002, 46, 351-356.
22. 3 adrenoceptors in vitro with their gastroprotective effects in the conscious rat. Br. J. Pharmacol. 1996, 117, 580-586.
23. 3 adrenergic receptor agonists containing acylsulfonamide, sulfonylsulfonamide, and sulfonylurea carboxylic acid isosteres. J. Med. Chem. 2002, 45, 567-583.
24. Foxton, M. W. WO 9533724, 1995.
25. (a) Deaton, D. N.; Shearer, B. G.; Uehling, D. E. Synthesis of aminoarylheterocyclic carboxylic acids as β-3 agonists used for obesity. WO 02060885.
26. (b) Donaldson, K. H.; Shearer, B. G.; Uehling, D. E. Preparation of β-3 adrenoceptor agonists. WO 0142217.
27. Ananthakrishnanadar, P.; Kannan, N. The effects of substituents on the rate of saponification of biphenyl-4-carboxylates. J. Chem. Soc., Perkin Trans. 2 1984, 1, 35-37.
28. Thompson, W. J.; Gaudino, J. A general synthesis of 5-arylnicotinates. J. Org. Chem. 1984, 49, 5237-5243.
29. Rozen, S.; Lerman, O. Bromination of deactivated aromatics using bromine trifluoride without a catalyst. J. Org. Chem. 1993, 58, 239-240.
30. Rozen, S.; Brand, M.; Rami, L. Aromatic bromination using bromine fluoride with no Friedel-Crafts catalyst. J. Org. Chem. 1988, 53, 5545-5547.
31. Ulrich, G.; Bedel, S.; Picard, C.; Tisnes, P. Synthesis of bisfunctionalized-oligopyridines bearing an ester group. Tetrahedron Lett. 2001, 42, 6113-6115.
32. (a) Yoo, B. W.; Choi, K. H.; Choi, K.; Kim, J. H. Mild and efficient deoxygenation of amine N-oxides with the titanium tetrachloride-indium system. Synth. Comm. 2003, 33, 4185-4189.
33. (B) Bennasar, M. L.; Zulaica, E.; Roca, T.; Alonso, Y. I.; Monerris, M. A synthetic entry to 3,5-disubstituted pyridines. Tetrahedron Lett. 2003, 44, 4711-4714.
34. (c) Dyke, C. A.; Bryson, T. A. Esterification of carboxylic acids with boron trichloride. Tetrahedron Lett. 2001, 42, 3959-3961.
35. Meier, P.; Legraverant, S.; Mueller, S.; Schaub, J. Synthesis of formylphenylpyridinecarboxylic acids using Suzuki-Miyaura coupling reactions. Synthesis 2003, 551-554.
36. Epsztajn, J.; Plotka, M. W.; Grabowska, A. Application of organolithium compounds in organic synthesis. Part 19. Synthetic strategies based on aromatic metallation. A concise regiospecific synthesis of 3-halogenated picolinic and isonicotinic acids. Synth. Comm. 1997, 27, 1075-1086.
37. 3 binding selectivity. Bioorg. Med. Chem. Lett. 1997, 7, 1583-1588.
38. ? agonists for metabolic staging of insulin responsive target tissues both in vivo and in vitro. Exp. Clin. Endocrinol. Diabetes 1997, 105, 73-74.
39. Although functional data on rodent β ARs would be useful in interpreting the rodent in vivo data, the appropriate reagents were unavailable to us during this program. Therefore, caution should be taken in extrapolating the relative potency of these compounds in the rodent in vivo setting to humans.
40. Paulik, M. A.; Buckholz, R. G.; Lancaster, M. E.; Dallas, W. S.; Hull-Ryde, E. A.; Weiel, J. E. and Lenhard, J. M. Development of infrared imaging to measure thermogenesis in cell culture: thermogenic effects of uncoupling protein-2, troglitazone, and β-adrenoceptor agonists. Pharm. Res. 1998, 15, 944-949.
41. Brooks, T. M. The use of a streamlined bacterial mutagenicity assay, the MINISCREEN. Mutagenesis 1995, 10, 447-448.
42. Burke, D. A.; Wedd, D. J.; Burlinson, B. Use of the miniscreen assay to screen novel compounds for bacterial mutagenicity in the pharmaceutical industry. Mutagenesis 1996, 11, 201-205.
43. Nagano, H.; Yoshiharu, N.; Masatomo, H. Mechanism of the reaction of nicotinic acid 1-oxide with acetic anhydride. Chem. Pharm. Bull 1987, 35, 4068-4077.
44. Brody, M. S.; Finn, M. G. Palladium-catalyzed coupling of functionalized bromoarenes to a polystyrene-bound aryl tributylstannane. Tetrahedron. Lett. 1999, 40, 415-418.
45. Smith, C.; Teitler, M. Cardiovasc. Drugs Ther. 1999, 13, 123-126.