University of California

Goethe-university Frankfurt

Karen Wagner

Bruce D Hammock

Christophe H Morisseau

Sung Hee Hwang

Kin Sing Lee

Guodong Zhang

Bora Inceoglu

Aaron Wecksler

Yang Kevin Xiang

Todd Harris

Raghavender Reddy Gopireddy

Eugen Proschak

Rene Bloecher

Provided herein are novel bioavailable dual inhibitors capable of inhibiting both soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4), and methods of using the same.

Orally available sEH/PDE4 dual inhibitors

Provided are methods for treating, reducing, alleviating, and/or inhibiting neuropathic pain by orally, intravenously or intrathecally administering an effective amount of an inhibitor of soluble epoxide hydrolase ('sEH'), to a patient in need thereof. The neuropathic pain treated is selected from the group consisting of post-herpetic neuralgia, trigeminal neuralgia, focal peripheral nerve injury, and anesthesia dolorosa, central pain due to stroke or mass lesion, spinal cord injury, or multiple sclerosis, and peripheral neuropathy due to diabetes, HIV, or chemotherapy.

Substituted piperidines as soluble epdxide hydrolase inhibitors

The present invention provides compounds and compositions, e.g., a series of compounds wherein a 1,5-biarylpyrazole group is conjugated to a urea group by a non-cleavable covalent chain, that are useful as dual COX-2/sEH inhibitors. The compounds disclosed herein have activity associated with the arachidonate cascade. The activity of these compounds was demonstrated using a lipopolysaccharide (LPS) induced model of pain in the rat. The compounds of the present invention demonstrated superior anti-allodynic activity as compared to the same dose of celecoxib, i.e., a COX-2 inhibitor, also as compared to the same dose of t-AUCB, i.e., a sEH inhibitor, and also as compared to the co-administered same dose of both celecoxib and t-AUCB. The dual inhibitors of the present invention demonstrate enhanced in vivo anti-allodynic activity in a nociceptive behavioral assay. In addition, the compounds of the present invention also demonstrated to have potent anti-angiogenic effects toward endothelial cells (HUVEC) and inhibit angiogenesis in vitro, ex vivo and in vivo. The dual inhibitors of the present invention also demonstrate anti-angiogenic effect to slow breast tumor growth in vivo.

Pyrazole inhibitors of COX-2 and sEH

Growing community of inventors

Davis, CA, United States of America

Karen Wagner