title: Prodrugs of CL316243: a selective beta3-adrenergic receptor agonist for treating obesity and diabetes.
abstract: CL316243 is a highly selective and potent beta3-adrenergic receptor agonist, and has been shown in rodent models to be an effective agent for treating obesity and Type II diabetes. To improve the oral absorption and pharmacokinetic profiles of CL316243, a number of prodrugs have been synthesized and evaluated. Several ester-type prodrugs show significant improvements in oral bioavailability in both rodent and primate models.
authors.affiliation: Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Sum
authors.forename: A
authors.initials: A
authors.lastname: Gilbert
authors.forename: A M
authors.initials: AM
authors.lastname: Venkatesan
authors.forename: K
authors.initials: K
authors.lastname: Lim
authors.forename: V
authors.initials: V
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: O'Dell
authors.forename: G
authors.initials: G
authors.lastname: Francisco
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Grosu
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: Ellingboe
authors.forename: M
authors.initials: M
authors.lastname: Malamas
authors.forename: I
authors.initials: I
authors.lastname: Gunawan
authors.forename: J
authors.initials: J
authors.lastname: Primeau
authors.forename: E
authors.initials: E
authors.lastname: Largis
authors.forename: K
authors.initials: K
authors.lastname: Steiner
mesh_terms: D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001682:Biological Availability; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004149:Dioxoles / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
chemical_list: D000318:Adrenergic beta-Agonists; D004149:Dioxoles; D004952:Esters; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D011355:Prodrugs; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate