Patent NZ-595778-A (NZ)
Title: Fused pyrimidineone compounds as trpv3 modulators
Inventor: KATTIGE VIDYA G
IPC: C07D513/04
Filed: 2009-04-15
Abstract: 595778 Disclosed are 7-[2-aryl-vinyl]-6-(aryl)-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives as represented by the general formula (I), wherein X is O, S or NRb; Y is CR3 or N; ring A is aryl, heterocyclyl or heteroaryl; R1 and R3, are each independently selected from hydrogen, halogen, nitro, cyano, -COOH, substituted or unsubstituted alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclic group, -NR4R5, -S(O)pNR4R5 and -S(O)pR4; or R1 and R3 together with the carbon atoms to which they were attached may form a 5 to 7 membered cyclic ring, which may be substituted or unsubstituted, saturated, unsaturated or partially saturated, which cyclic ring may optionally contain one or more heteroatoms selected from O, NRb and S; R2 is aryl, heteroaryl, or heterocyclic group, each of which may be optionally mono- or polysubstituted with substituent(s) independently selected from the group consisting of halogen, hydroxyl, nitro, cyano, -COOH, -NR4R5, acyl, substituted or unsubstituted alkyl, alkenyl, alkoxy, cyanoalkoxy, haloalkyl, haloalkyloxy, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, aryl, heterocyclic group and heteroaryl; and wherein the remaining substituents are as defined herein. Representative compounds include 7-{ (E)-2-[2-(cyclopropylmethoxy)-3-methoxyphenyl]-1-ethenyl} -6-(4-trifluoromethoxy-phenyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one, 7-[(E)-2-(2-hydroxy-3-methoxyphenyl)-1-ethenyl]-6-[4-(trifluoromethoxy)phenyl]-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one, 7-[(E)-2-{ (2,3-dihydroxy)phenyl} -1-ethenyl]-6-(4-trifluoromethoxy-phenyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one and 7-{ (E)-2-[2-cyclopropylmethoxy-3-hydroxyphenyl]-1-ethenyl} -6-(4-trifluoromethoxyphenyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one; or a pharmaceutically acceptable salt thereof. Further disclosed is a pharmaceutical composition comprising a compound as defined above and a pharmaceutically acceptable carrier or diluent; for 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. .