Synthesis and SAR of derivatives 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 7, 2010, Pages 2074-2077

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

^a MERCK RESEARCH LABORATORIES   (United States)

^b AMRI   (United States)

Author keywords

Agonist; Bombesin receptor subtype 3 (BRS 3); Obesity

Indexed keywords

2 [2 [4 (PYRIDIN 2 YL)PHENYL]ETHYL] 5 (2,2 DIMETHYLBUTYL) 1H IMIDAZOLE; BOMBESIN RECEPTOR; BOMBESIN RECEPTOR SUBTYPE 3; IMIDAZOLE DERIVATIVE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; BODY WEIGHT; CONTROLLED STUDY; DIET; DRUG BINDING; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFICACY; DRUG EXPOSURE; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; FOOD INTAKE; MOUSE; NONHUMAN; OBESITY; PHARMACOPHORE; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; SUBSTITUTION LINE; WEIGHT REDUCTION;

ANIMALS; BODY WEIGHT; EATING; HUMANS; IMIDAZOLES; MICE; OBESITY; RATS; RECEPTORS, BOMBESIN; STRUCTURE-ACTIVITY RELATIONSHIP;

BOVINE RESPIRATORY SYNCYTIAL VIRUS; MUS;

EID: 77949488938     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.02.076     Document Type: Article

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21. The synthesis of some compounds needed additional transformation of functional groups, such as ester to acid (2, 3a, 3b and 3c).
22. 50 was reported as the inflection point of the resulting sigmoidal curve.
23. 50 for activation was reported as the inflection point of the resulting sigmoidal curve. The percentages of activation are the maxim activations of tested compounds relative to that of dY-peptide.
24. Extensive SAR with various acid isosteres were carried out and the results will be published separately.
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