| abstract |
A compound of Formula II or a salt thereof, or a solvate or hydrate of the compound or its salt: ** Formula ** where n is an integer from 1 to 3 and R2 represents substituted heteroaryl; and where said compound in hibe a current mediated by TRPA1 with an IC50 of less than 10 micromolar, for use in a method of treatment or prevention of a condition selected from asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, osteoarthritis, inflammatory bowel disease , glomerulonephritis, neuroinflammatory diseases such as multiple sclerosis, immune system disorders, acute and / or chronic pain, touch sensitivity, burns, inflammation, diabetic neuropathy, psoriasis, eczema, dermatitis, postherpetic neuralgia (shingles), migraine, incontinence, fever , hot flashes, oral mucositis, pain due to cancer, bladder cystitis, pain associated with Crohn's disease and Irritable Bowel Syndrome (IBS), Grierson-Gopalan syndrome (better known as burning feet syndrome), syndrome the bocaardiente (SBA) and cough, or as a depilatory to promote the loss, or inhibit the growth, of the pel or in a patient, where said IC50 is determined by a zonal membrane clamp register performed in the mode of whole cells with a clamping potential of -40 mV by the following steps: (a) dispose of HEK293 commercial line cells / TREx (Invitrogen) expressing TRPA1 from a construct encoding a TRPA1 protein with an amino acid sequence shown in SEQ ID NO: 1; (b) have an internal solution of 140 mM cesium aspartate, 10 mM EGTA, 2.2 mM CaCl2, 2.08mM MgCl2 and 10 mM HEPES, pH 7.2, and with the addition of 60 mg / ml amphotericin before of the experiment; (c) having an external solution of 150 mM NaCl, 4.5 mM KCl, 3 mM MgCl2, 10 mM HEPES, 10 mM glutamine, 1 mM EGTA, pH 7.4; (d) apply a voltage ramp from -120 to +100 mV, of 400 ms duration, every 5 seconds; (e) study the ability of the compound to block current inward or outward in the continuous presence of micromolar AITC 5; and (f) determine the value of the IC50. |