C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 257/04 (2006.01) A61K 31/19 (2006.01) A61K 31/215 (2006.01) A61K 31/275 (2006.01) A61K 31/41 (2006.01) A61K 31/445 (2006.01) A61K 31/495 (2006.01) A61K 31/535 (2006.01) A61K 31/54 (2006.01) C07C 45/62 (2006.01) C07C 45/74 (2006.01) C07C 49/83 (2006.01) C07C 49/835 (2006.01) C07C 59/90 (2006.01) C07C 69/712 (2006.01) C07C 235/78 (2006.01)
Patent
CA 2267047
The present invention relates to the use derivatives of phenoxy acetic acid and of phenoxymethyl tetrazole of formula (I) Image wherein: - the -O-C(R1)(R2)-(CH2)P A group can be in ortho, meta or para position; - A is selected from -COOH, -COO-(C1-C4)alkyl, -CN or a group of formula Image in which R' is hydrogen or (C1-C4)alkyl; or the group A-(CH2)P C(R1)(R2)- is selected from phenyl, benzyl or (indolyl)methyl, which may be subsituted by R4 groups; - p is 0, 1 or 2; - R1 and R2 are independently selected from hydrogen or (C1-C8)alkyl or they form, together with the carbon atom to which they are linked, a (C3-C7)cycloalkyl group; - R4 are from 0 to 2 substituents independently selected from chlorine, bromine, iodine, fluorine, linear or branched (C1-C8)alkyl, hydroxy, (C1-C4)alkoxy, (C1-C4)acyl groups; or the group Image in formula (I) is a naphtyl group which may be on its turn substituted by R4 groups; - n is an integer from 1 to 4; - m is 0 or 1; - B is selected from linear or branched C1-C10 alkyl, -CO-C(R3)=CH-R, - CH=C(R3)-CO-Ar, -CO-CH(R3)-CH2-R or -CO-CH(R3)-CH2-NR5R6 when m is 0 or is -CH=C(R3)-CO-Ar when m is 1; - R is selected from hydrogen, -Ar or -CO-Ar; - R3 is hydrogen or a (C1-C8)alkyl group; - R5 and R6 are independently a (C1-C4)alkyl group or they form, together with the nitrogen atom to which they are linked, a piperidino, piperazino, (C1-C8)alkylpiperazino, morpholino or thiomorpholino group; - Ar is a phenyl group which can be unsubstituted or substituted with from 1 to 3 groups independently selected from chlorine, bromine, iodine, fluorine, linear or branched (C1-C8)alkyl, hydroxy, (C1-C4)alkoxy, (C1-C4)acyl groups, stereoisomers thereof or salts thereof with pharmaceuticaly acceptable acids or basis, for the preparation of a medicament having MDM2 antagonistic activity, new compounds of the above formula, and pharmaceutical compositions containing at least one of those compounds.
Di Domenico Roberto
Hansen Silke
Kaluza Brigitte
Menta Ernesto
Schumacher Ralf
F. Hoffmann-La Roche Ag
Gowling Lafleur Henderson Llp
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