Orally active and brain permeable proline amides as highly selective 5HT2c agonists for the treatment of obesity

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 7, 2010, Pages 2365-2369

  Liu, Kevin K C ^a   Lefker, Bruce A ^a   Dombroski, Mark A ^a   Chiang, Phoebe ^a   Cornelius, Peter ^a   Patterson, Terrell A ^a   Zeng, Yuan ^a   Santucci, Stephanie ^a   Tomlinson, Elizabeth ^a   Gibbons, Colleen P ^a   Marala, Ravi ^a   Brown, Janice A ^a   Kong, Jimmy X ^a   Lee, Eunsun ^a   Werner, Wendy ^a   Wenzel, Zane ^a   Giragossian, Craig ^a   Chen, Hou ^a   Coffey, Steven B ^a  

^a PFIZER INC   (United States)

Author keywords

5HT2c agonist; Binding selectivity; Obesity

Indexed keywords

AMINE; ANTIOBESITY AGENT; MONOAMINE OXIDASE INHIBITOR; PROLINE DERIVATIVE; SEROTONIN 2B RECEPTOR; SEROTONIN 2C AGONIST; SEROTONIN 2C RECEPTOR;

ANIMAL EXPERIMENT; ARTICLE; BRAIN; DOG; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG HALF LIFE; DRUG RECEPTOR BINDING; DRUG STRUCTURE; FOOD INTAKE; IN VIVO STUDY; NONHUMAN; OBESITY; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; AMIDES; ANIMALS; ANTI-OBESITY AGENTS; BRAIN; DOGS; EATING; HUMANS; OBESITY; PROLINE; RATS; RECEPTOR, SEROTONIN, 5-HT2C; STRUCTURE-ACTIVITY RELATIONSHIP;

RODENTIA;

EID: 77949491869     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.107     Document Type: Article

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16. Compound 8 did not exhibit any 5HT2b agonist activity in an ex vivo rat stomach fundus assay, and in a monkey heart valve interstitial cell (mVIC) mitogen activated protein kinase (MAPK) functional assay. Therefore, the potential risks related to activation of the 5HT2b receptor are deemed to be significantly reduced with compound 8. Compound 8 did not show any 5HT2a agonist activity as well in the above mentioned MAPK functional assay, and in the rat head twitch in vivo studies.
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