CHROMENONE DERIVATIVES AS TRPV3 ANTAGONISTS

摘要

Disclosed herein are chromenone compounds of formula (II), wherein the substituents are as defined within the specification; processes for their preparation, compositions comprising said compounds and uses thereof. Said compounds are useful the their Transient Receptor Potential Vanilloid 3 (TRPV3) activity and as such are useful in the treatement of pain, acute pain, chronic pain, nociceptive pain, neuropathic pain, post-operative pain, dental pain, cancer pain, cardiac pain arising from an ischemic myocardium, pain due to migraine, arthralgia, neuropathies, neuralgia, trigeminal neuralgia nerve injury, diabetic neuropathy, neurodegeneration, retinopathy, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, urinary incontinence, vulvodynia, gastrointestinal disorders such as irritable bowel syndrome, gastro-esophageal reflux disease, enteritis, ileitis, stomach-duodenal ulcer, inflammatory bowel disease, Crohn's disease, celiac disease, an inflammatory disease such as pancreatitis, a respiratory disorder such as allergic and non-allergic rhinitis, asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, dermatitis, pruritic conditions such as uremic pruritus, fervescence, muscle spasms, emesis, dyskinesias, depression, Huntington's disease, memory deficits, restricted brain function, amyotrophic lateral sclerosis (ALS), dementia, arthritis, osteoarthritis, diabetes, obesity, urticaria, actinic keratosis, keratocanthoma, alopecia, Meniere's disease, tinnitus, hyperacusis, anxiety disorders and benign prostate hyperplasia. Examples of particularly preferred compounds include: 4-{ 2-[(E)-2-(2-Cyclopentyloxy-3-methoxyphenyl)-1-ethenyl]-7-fluoro-4-oxo-4H-3-chromenyl} benzonitrile, 4-{ 7-Fluoro-2-[(E)-2-(3-methoxy-2-neopentyloxyphenyl)-1-ethenyl]-4-oxo-4H-3-chromenyl} benzonitrile, 4-{ 2-[(E)-2-[2-Cyclopentyloxy-3-methoxyphenyl)-1-ethenyl]-6,7-difluoro-4-oxo-4H-3-chromenyl} benzonitrile; 4-{ 6-Fluoro-2-[(E)-2-(2-isobutoxy-3-methoxyphenyl)-1-ethenyl]-4-oxo-4H-3-chromenyl} benzonitrile.