New tetrahydroisoquinoline substituted sulfonamide compounds useful as 5-HT7 receptor antagonist in the treatment of e.g. central nervous system disorders

摘要

Tetrahydroisoquinoline substituted sulfonamide compounds or their salts, isomers, prodrugs or solvates are new. Tetrahydroisoquinoline substituted sulfonamide compounds or their salts, isomers, prodrugs or solvates are new. W : T; T : alkyl, alkenyl, cycloalkyl, aryl or heterocyclyl (all optionally substituted); R 1 - R 7T, H, COR 8, C(O)OR 8, C(O)NR 8R 9, C=NR 8, CN, OR 8, OC(O)R 8, S(O) t-R 8, NR 8R 9, NR 8C(O)R 9, NO 2, N=CR 8R 9, NO 2, N=CR 8R 9 or halogen; t : 1 - 3; R 8 and R 9alkoxy, aryloxy (both optionally substituted), H, T or halogen. An independent claim is included for preparation of (I). [Image] ACTIVITY : CNS-Gen.; Analgesic; Antidepressant; Antimigraine; Tranquilizer; Neuroleptic; Neuroprotective; Nootropic; Hypnotic; Antiinflammatory; Hypotensive; Uropathic; Cardiovascular-Gen.; Gastrointestinal-Gen. MECHANISM OF ACTION : 5-HT 7 receptor antagonist. Radioligand binding assay was performed using Cloned Human Serotonin Receptor, subtype 7 (h5-HT 7), expressed in CHO cells, coated on Flashplate. The mass member protein/well (12 mu g) and receptor/well (9 - 10 fmoles) were taken. The flashplate was equilibrated at room temperature for 1 hour before the addition of the components of the assay mixture. The binding buffer was tris-HCl (50 mM), pH 7.4 containing MgCl 2 (10 mM), EDTA (0.5 mM) and bovine serum albumin (0.5 %). The radioligand was [ 125>I]LSD (0.82 nM). Nonspecific binding was determined with Clozapine (50 mu M) and the inhibiting compound used was 5-chloro-N-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-2,4-difluorobenzenesulfonamide (A). The flashplate was sealed and incubated at room temperature for 240 minutes in darkness. The radioactivity was quantified and IC 50 value was calculated. The IC 50 value for (A) was 64.8 nM.