Discovery and optimization of novel 4-[(aminocarbonyl)amino]-N-[4-(2-aminoethyl)phenyl]benzenesulfonamide ghrelin receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 21, 2009, Pages 6237-6240

  Pasternak, Alexander ^a   Goble, Stephen D ^a   deJesus, Reynalda K ^a   Hreniuk, Donna L ^a   Chung, Christine C ^a   Tota, Michael R ^a   Mazur, Paul ^a   Feighner, Scott D ^a   Howard, Andrew D ^a   Mills, Sander G ^a   Yang, Lihu ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Antagonist; Ghrelin; Inverse agonist; Obesity

Indexed keywords

1 AMINO 3 (ARYLOXY)PROPAN 2 OL; 4 [(AMINOCARBONYL)AMINO]N[ 4 ( 2 AMINOETHYL)PHENYL]BENZENESULFONAMIDE; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; GHRELIN ANTAGONIST; GHRELIN RECEPTOR ANTAGONIST; HORMONE ANTAGONIST; HORMONE RECEPTOR BLOCKING AGENT; SULFONAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CELL LINE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; HUMAN; HUMAN CELL; NONHUMAN; PHARMACOLOGICAL PARAMETERS; RAT; SUBSTITUTION REACTION;

ANIMALS; ANTI-OBESITY AGENTS; CELL LINE; DRUG DESIGN; DRUG INVERSE AGONISM; HUMANS; MALE; OBESITY; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GHRELIN; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 71749098026     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.08.076     Document Type: Article

References (25)

1. Hemling S., Jarosch F., and Klussmann S. Drug News Perspect. 19 (2006) 13-20
2. Zhao H., and Liu G. Curr. Opin. Drug Discovery Dev. 9 (2006) 509-515
3. Esler W.P., Rudolph J., Claus T.H., Tang W., Barucci N., Brown S.-E., Bullock W., Daly M., DeCarr L., Li Y., Milardo L., Molstad D., Zhu J., Gardell S.J., Livingston J.N., and Sweet L.J. Endocrinology 148 (2007) 5175-5185
4. Dezaki K., Hosoda H., Kakei M., Hashiguchi S., Watanabe M., et al. Diabetes 53 (2004) 3142-3151
5. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., and Kangawa K. Nature 402 (1999) 656-660
6. Tschop M., Smiley D.L., and Heiman M.L. Nature 407 (2000) 908-913
7. Wren A.M., Small C.J., Ward H.L., Murphy K.G., Dakin C.L., Taheri S., Kennedy A.R., Roberts G.H., Morgan D.G., Ghatei M.A., and Bloom S.R. Endocrinology 141 (2000) 4325-4328
8. Wren A.M., Seal L.J., Cohen M.A., Brynes A.E., Frost G.S., Murphy K.G., Dhillo W.S., Ghatei M.A., and Bloom S.R.J. Clin. Endocrinol. Metab. 86 (2001) 5992
9. Howard A.D., Feighner S.D., Cully D.F., Arena J.P., Liberator P.A., Rosenblum C.I., Hamelin M.J., Hreniuk D.L., Palyha O.C., Anderson J., Paress P.S., Diaz C., Chou M., Liu K., Mckee K.K., Pong S.S., Chaung L.Y., Elbrecht A., Heavens R., Rigby M., Sirinathsinghji D.J.S., Dean D.C., Melillo D.G., Patchett A.A., Nargund R., Griffon P.R., DeMartino J.A., Gupta S.K., Schaeffer J.M., Smith R.G., and Van Der Ploeg L.H.T. Science 273 (1996) 974-977
10. Holst B., Cygankeiwicz A., Jensen T.H., Ankersen M., and Schwartz T.W. Mol. Endocrinol. 17 (2003) 2201-2210
11. Holst B., Holliday N.D., Bach A., Heding A., and Schwartz T.W. J. Biol. Chem. 279 (2004) 53806-53817
12. Holst B., and Schwartz T.W. Trends Pharm. Sci. 25 (2004) 113-117
13. Cummings D.E., Foster-Schubert K.E., and Overduin J. Curr. Drug Targets 6 (2005) 153-169
14. Several very recent classes are described in the following:. Rudoph J., Esler W.P., O'Connor S., Coish P.D.G., Wickens P.L., Brands M., Bierer D.E., Bloomquist B.T., Bondar G., Chen L., Chuang C.-Y., Claus T.H., Fathi Z., Fu W., Khire U.R., Kristie J.A., Liu X.-G., Lowe D.B., McClure A.C., Michels M., Ortiz A.A., Ramsden P.D., Schoenleber R.W., Shelekhin T.E., Vakalapoulos A., Tang W., Wang L., Yi L., Gardell S.J., Livingston J.N., Sweet L.J., and Bullock W.H. J. Med. Chem. 50 (2007) 5202-5216
15. Moulin A., Demange L., Berge G., Gagne D., Ryan J., Mousseaux D., Heitz A., Perrissoud D., Locatelli V., Torsello A., Galleyrand J.-C., Fehrentz J.-A., and Martinez J. J. Med. Chem. 50 (2007) 5790-5806
16. Xin Z., Serby M.D., Zhao H., Kosogof C., Szczepankiewicz B.G., Liu M., Liu B., Hutchins C.W., Sarris K.A., Hoff E.D., Falls D., Lin C.W., Ogiela C.A., Collins C.A., Brune M.E., Bush E.N., Droz B.A., Fey T.A., Knourek-Segel V.E., Shapiro R., Jacobson P.B., Beno D.W.A., Turner T.M., Sham H.L., and Liu G. J. Med. Chem. 49 (2006) 4459
17. Carpino P.A., and Ho G. Expert Opin. Ther. Patents 18 (2008) 1253-1263
18. Moulin A., Demange L., Ryan J., Mousseaux D., Sanchez P., Berge G., Gagne D., Perrissoud D., Locatelli V., Torsello A., Galleyrand J.-C., Fehrentz J.-A., and Martinez J. J. Med. Chem. 51 (2008) 689-693
19. Esler W.P., Rudolph J., Claus T.H., Tang W., Barucci N., Brown S.-E., Bullock W., Daly M., DeCarr L., Li Y., Milardo L., Molstad D., Zhu J., Gardell S.J., Livingston J.N., and Sweet L.J. Endocrinology 148 (2007) 5175-5185
20. Bednarek M.A., Feighner S.D., Pong S.-S., McKee K.K., Hreniuk D.L., Silva M.V., Warren V.A., Howard A.D., Van der Ploeg L.H.Y., and Heck J.V. J. Med. Chem. 43 (2000) 4370-4376
21. Weber A.E., Mathvink R.J., Perkins L., Hutchins J.E., Candelore M.R., Tota L., Strader C.D., Wyvratt M.J., and Fisher M.H. Bioorg. Med. Chem. Lett. 8 (1998) 1101-1106
22. Parmee E.R., Ok H.O., Candelore M.R., Tota L., Deng L., Strader C.D., Wyvratt M.J., Fisher M.H., and Weber A.E. Bioorg. Med. Chem. Lett. 8 (1998) 1107-1112
23. Shih T.L., Candelore M.R., Cascieri M.A., Chiu S.-H.L., Colwell Jr. L.F., Deng L., Feeney W.P., Forrest M.J., Hom G.J., MacIntyre E., Miller R.R., Stearns R.A., Strader C.D., Tota L., Wyvratt M.J., Fisher M.H., and Weber A.E. Bioorg. Med. Chem. Lett. 9 (1999) 1251-1254
24. Cheng K., Chan W.W.-S., Butler B., Wei L., Schoen S., Wyvratt M.J., Fisher M.H., and Smith R.G. Endocrinology 132 (1993) 2729-2731
25. Brandish P.E., Hill L.A., Zheng W., and Skolnick E.M. Anal. Biochem. 313 (2003) 311-318 Also see details in Supplementary data