Quinuclidine derivatives as substance p antagonists

Details Quinuclidine derivatives as substance p antagonists Quinuclidine derivatives as substance p antagonists

C - Chemistry, Metallurgy

07

D

C07D 453/02 (2006.01) A61K 31/435 (2006.01)

Patent

CA 2132541

Compounds useful in the treatment of inflammatory disorders, central nervous system disorders and other disorders of formula (I) and the pharmaceutically-acceptable salts thereof, wherein X1 is alkoxy or halosubstituted alkoxy; X2 is hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halosubstituted alkyl, halosubstituted alkoxy, alkylamino, dialkylamino, alkylsulfonylamino (which may be substituted), N-alkyl-N-alkylsulfonylamino (which may be substituted), alkanoylamino (which may be substituted) or N-alkyl-N-alkanoylamino (which may be substituted); Ar1 and Ar2 are each, independently, thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl; A is Y-(CH2)m-CH(R2)-(CH2)n- NR1-; R1 is hydrogen, alkyl, benzyl or -(CH2) -Y; R2 is hydrogen, alkyl (which may be substituted), benzyl, 4-hydroxybenzyl, 3-indolylmethyl or -(CH2)p-Y; Y is -CN, -CH2Z or -COZ; Z is hydroxy, amino, alkoxy, alkylamino or dialkylamino; m, n and p are each, independently, 0, 1, 2 or 3; and R1 and R2 may be connected to form a ring.

Composés de formule (I) et leurs sels acceptables en pharmacie, utiles pour le traitement des troubles inflammatoires, des troubles du SNC et d'autres affections; X1 est un alcoxy ou un alcoxy avec halosubstitution; X2 est un hydrogène, un halogène, un groupe alkyle, alcényle, alcynyle, alcoxy, alkylthio, alkylsulfinyle, alkylsulfonyle, alkyle avec halosubstitution, alcoxy avec halosubstitution, alkylamino, dialkylamino, alkylsulfonylamino (avec substitution facultative), N-alkyl-N-alkylsulfonylamino (avec substitution facultative), alcanoylamino (avec substitution facultative) ou N-alkyl-N-alcanoylamino (avec substitution facultative); Ar1 et Ar2 sont chacun indépendamment l'un de l'autre un groupe thiényle, phényle, fluorophényle, chlorophényle ou bromophényle; A est Y-(CH2)m-CH(R2)-(CH2)n-NR1-; R1 est de l'hydrogène, le groupe alkyle, benzyle ou -(CH2) -Y; R2 est de l'hydrogène, le groupe alkyle (avec substitution facultative), benzyle, 4-hydroxybenzyle, 3-indolylméthyle ou -(CH2)p-Y; Y est -CN, -CH2Z ou -COZ; Z est un groupe hydroxy, amino, alcoxy, alkylamino ou dialkylamino; m, n et p sont chacun indépendamment l'un de l'autre 0, 1, 2 ou 3; R1 et R2 peuvent être connectés pour former un cycle.

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