Pyridopyrimidine based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation.

Debenham, John S; Madsen-Duggan, Christina B; Wang, Junying; Tong, Xinchun; Lao, Julie; Fong, Tung M; Schaeffer, Marie-Therese; Xiao, Jing Chen; Huang, Cathy C R-R; Shen, Chun-Pyn; Sloan Stribling, D; Shearman, Lauren P; Strack, Alison M; Euan Macintyre, D; Hale, Jeffrey J; Walsh, Thomas F

Debenham, John S; Madsen-Duggan, Christina B; Wang, Junying; Tong, Xinchun; Lao, Julie; Fong, Tung M; Schaeffer, Marie-Therese; Xiao, Jing Chen; Huang, Cathy C R-R; Shen, Chun-Pyn; Sloan Stribling, D; Shearman, Lauren P; Strack, Alison M; Euan Macintyre, D; Hale, Jeffrey J; Walsh, Thomas F.

Affiliation

Debenham JS; Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA.

Bioorg Med Chem Lett ; 19(9): 2591-4, 2009 May 01.

Article in En | MEDLINE | ID: mdl-19328684

ABSTRACT

ABSTRACT

The synthesis, SAR and binding affinities are described for cannabinoid-1 receptor (CB1R) specific inverse agonists based on pyridopyrimidine and heterotricyclic scaffolds. Food intake and pharmacokinetic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R.

Subject(s)

Cannabinoid Receptor Agonists; Obesity/drug therapy; Pyrimidines/chemistry; Administration, Oral; Animals; Cannabinoids/chemistry; Chemistry, Pharmaceutical/methods; Drug Design; Humans; Inhibitory Concentration 50; Protein Structure, Tertiary; Rats; Receptor, Cannabinoid, CB1/agonists; Receptor, Cannabinoid, CB2/agonists; Structure-Activity Relationship

Fulltext

XML

PubMed Links

Search on Google

Full text: 1 Database: MEDLINE Main subject: Pyrimidines / Cannabinoid Receptor Agonists / Obesity Limits: Animals / Humans Language: En Year: 2009 Type: Article

Fulltext

XML

PubMed Links

Search on Google

Full text: 1 Database: MEDLINE Main subject: Pyrimidines / Cannabinoid Receptor Agonists / Obesity Limits: Animals / Humans Language: En Year: 2009 Type: Article