title: A novel series of glucagon receptor antagonists with reduced molecular weight and lipophilicity.
abstract: A novel series of glucagon receptor antagonists has been discovered. These pyrazole ethers and aminopyrazoles have lower molecular weight and increased polarity such that the molecules fall into better drug-like property space. This work has culminated in compounds 44 and 50 that were shown to have good pharmacokinetic attributes in dog, in contrast to rats, in which clearance was high; and compound 49, which demonstrated a dose-dependent reduction in glucose excursion in a rat glucagon challenge experiment.
authors: Pfizer Worldwide Research & Development, Eastern Point Rd, Groton, CT 06442, USA. kevin.filipski@pfizer.com
authors: Kevin J
authors: KJ
authors: Filipski
authors: Jianwei
authors: J
authors: Bian
authors: David C
authors: DC
authors: Ebner
authors: Esther C Y
authors: EC
authors: Lee
authors: Jian-Cheng
authors: JC
authors: Li
authors: Matthew F
authors: MF
authors: Sammons
authors: Stephen W
authors: SW
authors: Wright
authors: Benjamin D
authors: BD
authors: Stevens
authors: Mary T
authors: MT
authors: Didiuk
authors: Meihua
authors: M
authors: Tu
authors: Christian
authors: C
authors: Perreault
authors: Janice
authors: J
authors: Brown
authors: Karen
authors: K
authors: Atkinson
authors: Beijing
authors: B
authors: Tan
authors: Christopher T
authors: CT
authors: Salatto
authors: John
authors: J
authors: Litchfield
authors: Jeffrey A
authors: JA
authors: Pfefferkorn
authors: Angel
authors: A
authors: Guzman-Perez
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004986:Ether / Q000737:chemistry; D005934:Glucagon / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008970:Molecular Weight; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013696:Temperature
chemical_list: D011720:Pyrazoles; D018027:Receptors, Glucagon; D004986:Ether; D005934:Glucagon; D005947:Glucose