Synthesis and SAR of heterocyclic carboxylic acid isosteres based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 9, 2010, Pages 2912-2915

  Hadden, Mark ^a   Goodman, Allan ^a   Guo, Cheng ^a   Guzzo, Peter R ^a   Henderson, Alan J ^a   Pattamana, Kevin ^a   Ruenz, Megan ^a   Sargent, Bruce J ^a   Swenson, Brian ^a   Yet, Larry ^a   Liu, Jian ^b   He, Shuwen ^b   Sebhat, Iyassu K ^b   Lin, Linus S ^b   Tamvakopoulos, Constantin ^b   Peng, Qianping ^b   Kan, Yanqing ^b   Palyha, Oksana ^b   Kelly, Theresa M ^b   Guan, Xiao Ming ^b   Metzger, Joseph M ^b   Reitman, Marc L ^b   Nargund, Ravi P ^b   more..

^a ALBANY MOLECULAR RESEARCH INC   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Acid isosteres; BRS 3; Obesity

Indexed keywords

2 BIETHYLIMIDAZOLE; HETEROCYCLIC CARBOXYLIC ACID; IMIDAZOLE; PHENOL; TETRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG PENETRATION; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN TISSUE; NONHUMAN; OBESITY; STRUCTURE ACTIVITY RELATION; SUZUKI REACTION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-OBESITY AGENTS; BRAIN; HUMANS; IMIDAZOLES; MICE; OBESITY; RATS; RECEPTORS, BOMBESIN; STRUCTURE-ACTIVITY RELATIONSHIP;

BOVINE RESPIRATORY SYNCYTIAL VIRUS;

EID: 77950857663     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.03.028     Document Type: Article

References (16)

1. CDC. Morbidity and Mortality Weekly Report 55 (2006) 985
2. Mokdad A.H., Bowman B.A., Ford E.S., Vinicor F., Marks J.S., and Koplan J.P. J. Am. Med. Assoc. 282 (2001) 1519
3. Mokdad A.H., Ford E.S., Bowman B.A., Dietz W.H., Vinicor F., Bales V.S., and Marks J.S. J. Am. Med. Assoc. 289 (2003) 76
4. Luque C.A., Rey J.A., and Fernandez A. Formulary 32 (1997) 1025
5. McNeely W., and Benfield P. Drugs 56 (1998) 241
6. Liu J., Lao Z.J., Zhang J., Schaeffer M.T., Jiang M.M., Guan X.M., Van der Ploeg L.H., and Fong T.M. Biochemistry 41 (2002) 8954
7. Ohki-Hamazaki H., Watase K., Yamamoto K., Ogura H., Yamano M., Yamada K., Maeno H., Imaki J., Kikuyama S., Wada E., and Wada K. Nature 390 (1997) 165
8. He S., Dobbelaar P.H., Liu J., Jian T., Sebhat I.K., Lin L.S., Goodman A., Guo C., Guzzo P.R., Hadden M., Henderson A.J., Ruenz M., Sargent B.J., Yet L., Kelly T.M., Palyha O., Kan Y., Pan J., Chen H., Marsh D.J., Shearman L.P., Strack A.M., Metzger J.M., Feighner S.D., Tan C., Howard A.D., Tamvakopoulos C., Peng Q., Guan X., Reitman M.L., Patchett A.A., Wyvratt M.J., and Nargund N.P. Bioorg. Med. Chem. Lett. (2009) 'Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists' accompanying manuscript
9. Liu J., He S.H., Jian T., Dobbelaar P., Sebhat I.K., Lin L.S., Goodman A., Guo C., Guzzo P.R., Hadden M., Henderson A.J., Ruenz M., Pattamana K., Sargent B.J., Swenson B., Yet L., Tamvakopoulos C., Kelly T.M., Peng Q., Kan Y., Pan J., Palyha O., Marsh D.J., Shearman L.P., Strack A.M., Metzger J.M., Howard A.D., Guan X., Reitman M.L., Wyvratt M.J., and Nargund N.P. Bioorg. Med. Chem. Lett. (2009) 'Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity' accompanying manuscript
10. Poonian M.S., and Nowowsiat E.F. J. Org. Chem. 45 (1980) 203
11. Tilley J.W., Danho W., Lovey K., Wagner R., Swistok J., Makofske R., Michalewsky J., Triscari J., Nelson D., and Weatherford S. J. Med. Chem. 34 (1991) 1125
12. Rostovtsev V.V., Green L.G., Fokin V.V., and Sharpless K.B. Angew. Chem., Int. Ed. 41 (2002) 2596
13. a's were calculated online using the Marvin calculator from Chemaxon.
14. Dobson P.D., and Kell D.B. Nat. Rev. Drug Discovery 7 (2008) 205
15. Zhang H., Cai Q., and Ma D. J. Org. Chem. 70 (2005) 5164
16. Pipecolic acid has been shown to be actively transported into mouse brain;. Kim J.S., and Giacobini E. Dev. Brain Res. 22 (1985) 181