| 主权项 |
1. A method for relieving the symptoms or inhibiting arresting or reducing a disease or condition associated with TRPA1 function in a subject in need thereof comprising administering to the subject an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof,wherein,
R1 and R2, which may be the same or different, are independently selected from hydrogen, substituted or unsubstituted alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, (CRxRy)nORx, CORx, COORx, CONRxRy, and (CH2)—CHRxRy; R3 is selected from hydrogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, and cycloalkenyl; L is a linker selected from —(CRxRy)n—, —O—(CRxRy)n—, —C(O)—, —NRx—, —S(O)mNRx—, —NRx(CRxRy)n— and —S(O)mNRx(CRxRy)n; Z1 and Z2 are independently sulfur or CRa; with a proviso that either of Z1 or Z2 is always sulfur; Ra is selected from hydrogen, cyano, halogen, substituted or unsubstituted alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, ORx, (CRxRy)nORx, CORx, COORx, CONRxRy, S(O)mNRxRy, NRxRy, NRx(CRxRy)nORx, (CH2)nNRxRy, (CH2)nCHRxRy, NRx(CRxRy)nCONRxRy, (CH2)nNHCORx, (CH2)nNH(CH2)nSO2Rx, (CH2)nNHSO2Rx, SRx and ORx; U is selected from substituted or unsubstituted aryl, substituted or unsubstituted five membered heterocycles selected from the group consisting of thiazole, isothiazole, oxazole, isoxazole, thiadiazole, oxadiazole, pyrazole, imidazole, furan, thiophene, pyrrole, 1,2,3-triazole, and 1,2,4-triazole, or substituted or unsubstituted six membered heterocycle selected from the group consisting of pyrimidine, pyridine and pyridazine; V is selected from hydrogen, cyano, nitro, —NRxRy, halogen, hydroxyl, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, haloalkyl, haloalkoxy, cycloalkylalkoxy, aryl, arylalkyl, biaryl, heteroaryl, heteroarylalkyl, heterocyclic ring and heterocyclylalkyl, —C(O)ORx, —ORx, —C(O)NRxRy, —C(O)Rx, and —SO2NRxRy; or U and V together may form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring that may optionally include one or more heteroatoms selected from O, S and N; at each occurrence, Rx and Ry are independently selected from hydrogen, hydroxyl, halogen, substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclic ring and heterocyclylalkyl; and at each occurrence, ‘m’ and ‘n’ are independently selected from 0 to 2, both inclusive;wherein the disease or condition is selected from pain, complex regional pain syndrome, postoperative pain, rheumatoid arthritic pain, back pain, visceral pain, cancer pain, algesia, neuralgia, migraine, neuropathies, diabetic neuropathy, sciatica, HIV-related neuropathy, post-herpetic neuralgia, fibromyalgia, nerve injury, ischaemia, neurodegeneration, stroke, post stroke pain, multiple sclerosis, respiratory diseases, cough, inflammatory disorders, oesophagitis, gastroeosophagal reflux disorder (GERD), irritable bowel syndrome, inflammatory bowel disease, pelvic hypersensitivity, urinary incontinence, cystitis, burns, psoriasis, eczema, emesis, stomach duodenal ulcer and pruritus. |
