Discovery of highly potent and selective biphenylacylsulfonamide-based β3-adrenergic receptor agonists and evaluation of physical properties as potential overactive bladder therapies: Part 5

Journal of Medicinal Chemistry

Volumn 52, Issue 9, 2009, Pages 3063-3072

  Hattori, Kouji ^a   Toda, Susumu ^a   Imanishi, Masashi ^a   Itou, Shinji ^a   Nakajima, Yutaka ^a   Washizuka, Kenichi ^a   Araki, Takanobu ^a   Hamashima, Hitoshi ^a   Tomishima, Yasuyo ^a   Sakurai, Minoru ^a   Matsui, Shigeo ^a   Imamura, Emiko ^a   Ueshima, Koji ^a   Yamamoto, Takao ^a   Yamamoto, Nobuhiro ^a   Ishikawa, Hirofumi ^a   Nakano, Keiko ^a   Unami, Naoko ^a   Hamada, Kaori ^a   Matsumura, Yasuhiro ^a   Takamura, Fujiko ^a   more..

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

3 (CYCLOHEXYLOXY) 4' [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]ETHYL] N (METHYLSULFONYL)BIPHENYL 4 CARBOXAMIDE; 3 (CYCLOHEXYLOXY) 4' [2 [(2 HYDROXY 2 PYRIDIN 3 YLETHYL)AMINO]ETHYL] N (METHYLSULFONYL)BIPHENYL 4 CARBOXAMIDE; 4' [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]ETHYL] 3 (ISOPROPYLSULFANYL) N (METHYLSUFONYL)BIPHENYL 4 CARBOXAMIDE; 4' [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]ETHYL] 3 ISOBUTYL N (METHYLSULFONYL)BIPHENYL 4 CARBOXAMIDE; 4' [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]ETHYL] 3 ISOPROPYLAMINO] N [METHYLSULFONYL]BIPHENYL 4 CARBOXAMIDE; 4' [2 [[2 (6 AMINOPYRIDIN 3 YL) 2 HYDROXYETHYL]AMINO]ETHYL] 3 (CYCLOHEXYLOXY) N (METHYLSULFONYL)BIPHENYL 4 CARBOXAMIDE; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; CYCLIC AMP; POTASSIUM CHLORIDE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CHO CELL; CONTROLLED STUDY; DETRUSOR MUSCLE; DOG; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG STRUCTURE; DRUG SYNTHESIS; LIPOPHILICITY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OVERACTIVE BLADDER; STRUCTURE ACTIVITY RELATION;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; DRUG DISCOVERY; FEMALE; HUMANS; MICROSOMES, LIVER; RECEPTORS, ADRENERGIC, BETA-3; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SULFONAMIDES; URINARY BLADDER, OVERACTIVE;

EID: 65649106257     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9000709     Document Type: Article

References (37)

1. Abrams, P.; Cardozo, L.; Fall, M.; Griffiths, D.; Rosier, P.; Ulmsten, U.; Van Kerrebroeck, P.; Victor, A.; Wein, A. The standardisation of terminology of lower urinary tract function. Neurourol. Urodyn. 2002, 21, 167-178.
2. Stewart, W. F.; Van Rooyen, J, B.; Cundiff, G. W.; Abrams, P.; Herzog, A. R.; Corey, R.; Hunt, T. L.; Wein, A. J. Prevalence and burden of overactive bladder in the United States. World J. Urol 2003, 20, 327-336.
3. Abrams, P.; Andersson, K. E. Muscarinic receptor antagonists for overactive bladder. BJU Int. 2007, 100, 987-1004.
4. Andersson, K. E. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev. 1993, 45, 253-308. (Pubitemid 23292873)
5. 3- adrenoceptors on brown adpocytes as target for anti-obesity drugs. Nature (London) 1984, 309, 163-165.
6. 3-adrenergic receptor. Science 1989, 245, 1118-1121.
7. (a) 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.
8. (b) Arch, J. R.; Ainsworth, A. T.; Cawthorne, M. A.; Piercy, V.; Sennitt, M. V.; Thod, V. E.; Wilson, C.; Wilson, S. Atypical β-adrenoceptors on brown adpocytes as target for anti-obesity drugs. Nature 1983, 309, 163-165.
9. (a) Levin, R. M.; Ruggieri, M. R.; Wein, A. J. Identification of receptor subtypes in the rabbit and human urinary bladder by selective radioligand binding. J. Urol. 1988, 139, 844-848. (b) Morita, T.; Ando, M.; Kihara, K. Species differences in cAMP production and contractile response induced by β-adrenoceptor subtype in urinary bladder smooth muscle. Neurourol. Urodyn. 1993, 12, 185-190. (Pubitemid 18105037)
10. 3-adrenoceptor in the human detrusor muscle. Br. J. Pharmacol. 1999, 126, 819-825.
11. 3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders. J. Urol. 2001, 165, 240-244.
12. 3-Adrenoceptors in human detrusor muscle. Urology 2002, 59, 25-29.
13. 3-adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro. Neurourol. Urodyn. 2006, 25, 815-819.
14. 3 adrenergic receptor agonists with good oral bioavailability. Part I. J. Med. Chem. 2008, 51, 1925-1944.
15. 3 binding selectivity. Bioorg. Med. Chem. Lett. 1997, 7, 1583-1588.
16. 3 adrenergic receptor. Med. Chem. Res 2000, 10, 164-177.
17. 3 adrenergic receptor agonists containing acylsulfonamide, sulfonylsulfonamide, and sulfonylurea carboxylic acid isosteres. J. Med. Chem. 2002, 45, 567-583.
18. 3 adrenergic receptor agonists with good oral bioavailability. Part II. J. Med. Chem. 2008, 51, 4002-4020.
19. The metabolites were determined by LC/MS/MS and authentic compound analysis. See Experimental Section.
20. (a) Aithal, G.; Day, C. Nonsteroidal anti-inflammatory drug-induced hepatotoxicity. Clin. Liver Dis. 2007, 11 (3), 563-575.
21. (b) Benet, L. Z.; Spahn-Langguth, H.; Iwakawa, S.; Volland, C.; Mizuma, T.; Mayer, S.; Mutschler, E.; Lin, E. T. Predictability of the covalent binding of acidic drugs in man. Life Sci. 1993, 53, 141-146.
22. Hattori, K.; Tomishima, Y.; Imanishi, M. Aminoalcohol Derivatives. Patent US 7037938, May 2, 2006.
23. Experimental method was described in refs 9 and 11.
24. 9
25. Zhu, C.; Jiang, L.; Chen, T. M.; Hwang, K. K. A. Comparative study of artificial membrane permeability assay for high throughput profiling of drug absorption potential. Eur. J. Med. Chem. 2002, 37, 399-407. (Pubitemid 34465549)
26. Experimental method was described in refs 9 and 11.
27. 3-adrenergic receptor agonist, evokes bladder relaxation and increases micturiation reflex threshold in the dog. J. Pharmacol. Exp. Ther. 2007, 323, 202-209.
28. 3- adrenoceptor agonist, on bladder function. J. Pharmacol. Exp. Ther. 2007, 321, 642-647.
29. The biphenyl analogues (FGB SGB and acylsulfonamide analogues) and the active compound of FK175 were included.
30. 50(cAMP accumulation on dogs)].
31. For clogp: ClogP, version 4.3; BioByte Corp.: Claremont, CA.
32. For clogD: Pallas PrologD, version 3.0; CompuDrug: Sedona, AZ.
33. Leach, A. G.; Jones, H. D.; Cosgrove, D. A.; Kenny, P. W.; Ruston, L.; MacFaul, P.; Wood, J. M.; Colclough, N.; Law, B. Matched molecular pairs as a guide in the optimization of pharmaceutical properties; a study of aqueous solubility, plasma protein binding and oral exposure. J. Med. Chem. 2006, 49, 6672-6682.
34. (a) Rowley, M.; Kulagowski, J. J.; Watt, A. P.; Rathbone, D.; Stevenson, G. I.; Carling, R. W.; Baker, R.; Marshall, G. R.; Kemp, J. A.; Foster, A. C.; Grimwood, S.; Hargeaves, R.; Hurley, C.; Saywell, K. L.; Tricklebank, M. D.; Leeson, P. D. Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA receptor antagonists. J. Med. Chem. 1997, 40, 4053-4068.
35. (b) Climenarejo, G.; Alvarez-Pedraglio, A.; Lavandera, J. L. Cheminformatic models to predict binding affinities to human serum albumin. J. Med. Chem. 2001, 44, 4370-4378.
36. (c) Reference 22.
37. (d) Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decisionmaking in medicinal chemistry. Nat. Rev. Drug Discovery 2007, 6, 881-890, and references cited therin.