Identification of a novel, orally bioavailable histamine H(3) receptor antagonist based on the 4-benzyl-(1H-imidazol-4-yl) template

Robert Aslanian; Mwangi W Mutahi; Neng Yang Shih; Kevin D McCormick; John J Piwinski; Pauline C Ting; Margaret M Albanese; Michael Y Berlin; Xiaohong Zhu; Shing Chun Wong; Stuart B Rosenblum; Yueheng Jiang; Robert West; Susan She; Shirley M Williams; Matthew Bryant; John A Hey

doi:10.1016/s0960-894x(02)00055-0

Identification of a novel, orally bioavailable histamine H(3) receptor antagonist based on the 4-benzyl-(1H-imidazol-4-yl) template

Bioorg Med Chem Lett. 2002 Mar 25;12(6):937-41. doi: 10.1016/s0960-894x(02)00055-0.

Authors

Robert Aslanian¹, Mwangi W Mutahi, Neng Yang Shih, Kevin D McCormick, John J Piwinski, Pauline C Ting, Margaret M Albanese, Michael Y Berlin, Xiaohong Zhu, Shing Chun Wong, Stuart B Rosenblum, Yueheng Jiang, Robert West, Susan She, Shirley M Williams, Matthew Bryant, John A Hey

Affiliation

¹ The Schering Plough Research Institute, Kenilworth, NJ 07033, USA. [email protected]

PMID: 11958998
DOI: 10.1016/s0960-894x(02)00055-0

Abstract

A novel series of histamine H(3) receptor antagonists, based on the 4-benzyl-(1H-imidazole-4-yl) template, incorporating urea and carbamate linkers has been prepared. Compound 3j is a selective H(3) antagonist and demonstrates excellent oral plasma levels in the rat and monkey.

MeSH terms

Administration, Oral
Animals
Biological Availability
Haplorhini
Histamine Antagonists / chemical synthesis*
Histamine Antagonists / pharmacokinetics
Histamine Antagonists / pharmacology
Imidazoles / chemical synthesis
Imidazoles / pharmacokinetics*
Imidazoles / pharmacology
Protein Binding
Rats
Receptors, Histamine H3 / drug effects
Receptors, Histamine H3 / metabolism*
Structure-Activity Relationship

Substances

Histamine Antagonists
Imidazoles
Receptors, Histamine H3