Novel 2-(substituted phenyl)benzimidazole derivatives with potent activity against IgE, cytokines, and CD23 for the treatment of allergy and asthma.
The effectiveness of the injectable anti-IgE antibody omalizumab has validated IgE as an important target for allergic diseases, thus spawning the development of small-molecule IgE inhibitors. Herein, a brief SAR is described for novel phenylbenzimidazole compounds that potently suppress IgE responses. In addition to IgE, these agents inhibit other targets critical for allergic response. The profile of orally active AVP-13358, the lead compound of this series currently in clinical trials, is described.
Richards
Mark L
ML
Avanir Pharmaceuticals, 11388 Sorrento Valley Road, San Diego, California 92121, USA. mrichards@avanir.com
Lio
Shirley Cruz
SC
Sinha
Anjana
A
Tieu
Kenneth K
KK
Sircar
Jagadish C
JC
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors*; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D017455:Receptors, IgE / Q000037:antagonists & inhibitors*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000276:immunology
D018926:Anti-Allergic Agents; D001562:Benzimidazoles; D016207:Cytokines; D017455:Receptors, IgE; D007073:Immunoglobulin E