5-arylindole derivatives

C - Chemistry – Metallurgy – 07 – D

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C07D 403/14 (2006.01) A61K 31/44 (2006.01) A61K 31/505 (2006.01) A61K 31/53 (2006.01) C07D 401/14 (2006.01) C07D 403/04 (2006.01) C07F 7/22 (2006.01)

Patent

CA 2169179

Compounds of formula (I), wherein A, B, D, E, and F are each independently nitrogen or carbon; R1 is hydrogen, C1 to C6 alkyl, -(CH2)nR7, or C1 to C3 alkyl-aryl; R2, R3, R4, R5, and R6 are each independently hydrogen, C1 to C6 alkyl, aryl, C1 to C3 alkyl- aryl, halogen, cyano, nitro, -(CH2)mNR8R9, -(CH2)mOR9, -SR9, -SO2NR8R9, -(CH2)mNR8SO2R9, -(CH2)mNR8CO2R9, -(CH2)mNR8COR9, -(CH2)mCONR7R9, or -(CH2)mCO2R9; R2 and R3, R3 and R4, R4 and R5, and R5 and R6 may be taken together to form a 5- to 7-membered alkyl ring, a 6-membered aryl ring, a 5- to 7-membered heteroalkyl ring, having 1 heteroatom of N, O, or S, or a 5- to 6-membered heteroaryl ring having 1 or 2 heteroatoms of N, O, or S; R7 is -OR10, -SR10, -SO2NR10R11, -NR10SO2R11, -NR10CO2R11, -NR10COR11, -CONR10R11, or -CO2R10; R8, R9, R10 and R11 are each independently hydrogen, C1 to C6 alkyl, or C1 to C3 alkyl-aryl; m is 0, 1, or 2; n is 2, 3, or 4; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are each independently phenyl or substituted phenyl, wherein said substituted phenyl may be substituted with 1 to 3 of C1 to C4, alkyl, halogen hydroxy, cyano, carboxamido, nitro, or C1 to C4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders and are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, and chronic paroxysmal hermicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

Procédé de séparation et de quantification de transferrine pauvre en hydrate de carbone (CDT), permettant de déterminer la consommation d'alcool récente d'une personne. Des lipoprotéines sont précipitées dans du sérum sanguin et saturées avec du fer, après quoi l'échantillon est centrifugé après une courte période de stockage. La substance surnageante du mélange centrifugé est ensuite diluée avec de l'eau. Le mélange est ensuite injecté dans une colonne d'échange d'ions, et un gradient salin est utilisé pour la séparation des isoformes de transferrine. Un chromatogramme est développé par chromatographie liquide haute performance (HPLC) et un filtre permettant l'absorbance à 460 nm. Si le profil chromatographique indique des valeurs accrues de CDT (*, **), notamment une valeur dépassant 0,8 % de transférrine totale, il agit comme un indicateur à spécificité élevée d'une forte consommation d'alcool.

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