title: Substituted 2-phenyl-benzimidazole derivatives: novel compounds that suppress key markers of allergy.
abstract: The pharmacotherapy of allergy and asthma has traditionally focused on the effecter molecules of the allergic cascade, while neglecting targets that play an early role in their development. Reasoning that IgE is central to the expansion of atopic diseases, we identified and extended a novel family of 2-(substituted phenyl)-benzimidazole inhibitors of IgE response. Pharmacological activity depends on an intact phenylbenzimidazole-bis-amide backbone, and is optimized by the presence of lipophilic terminal groups composed of either bis cycloalkyl or combinations of aliphatic and halogen-substituted aromatic groups. These compounds also inhibit IL-4 and IL-5 responses in T cells and CD23 expression on B cells, with potencies that parallel their inhibition of IgE. The broad profile of these compounds thus underscores their potential for treating the multifarious pathology of asthma.
authors.affiliation: Avanir Pharmaceuticals, 11388 Sorrento Valley Road, San Diego, CA 92121, USA. mrichards@avanir.com
authors.forename: Mark L
authors.initials: ML
authors.lastname: Richards
authors.forename: Shirley Cruz
authors.initials: SC
authors.lastname: Lio
authors.forename: Anjana
authors.initials: A
authors.lastname: Sinha
authors.forename: Homayon
authors.initials: H
authors.lastname: Banie
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Thomas
authors.forename: Michael
authors.initials: M
authors.lastname: Major
authors.forename: Mark
authors.initials: M
authors.lastname: Tanji
authors.forename: Jagadish C
authors.initials: JC
authors.lastname: Sircar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001682:Biological Availability; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D016207:Cytokines; D007073:Immunoglobulin E; C117755:2-phenylbenzimidazole