3-'Hydroxy-(-4-trifluoromethylphenyl)-methyl-7-spirocyclobutyl-5,6,7 8-tetrahydroquinolin-5-ol derivatives and the use of the same as cholesterol ester transfer protein (cetp) inhibitors
The application relates to substituted tetrahydroquinoline derivatives, processes for their preparation and their use in medicaments.
1 . A compound of the formula (I)
in which
A represents a radical
—(CH 2 ) 2 CH 3 and
B represents a radical
or a pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , in which A represents para-fluorophenyl.
3 . The compound according to claim 1 , in which B represents isopropyl.
4 . The compound according to claim 1 having the anti isomer form.
5 . (Cancelled)
6 . A pharmaceutical composition comprising a compound as defined in claim 1 , 2 , 3 , or 4 and at least one inert, non-toxic, pharmaceutically suitable vehicle, solvent or excipient.
7 . (Cancelled)
8 . (Cancelled)
9 . A method for inhibition of the cholesterol ester transfer protein (CETP) and for stimulation of reverse cholesterol transport, comprising administering an effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , or 6 .
10 . A method for lowering the LDL cholesterol level in the blood and simultaneously increasing the HDL cholesterol level comprising administering an effective amount of a compound of claim 1 , 2 , 3 , 4 , 5 , or 6 .
11 . A method for the treatment of hypolipoproteinaemia, dyslipidaemias, hypertriglyceridaemias, hyperlipidaemias, arteriosclerosis adiposity and obesity stroke or Alzheimer's disease, comprising administering an effective amount of a compound of claim 1 .
12 . (Cancelled)
13 . A process for the preparation of compounds of the formula (I) as defined in claim 1 , characterized in that a compound of the general formula (II)
in which
A and B have the meanings indicated in claim 1 ,
is first oxidized to a compound of the general formula (III)
in which
A and B have the meanings indicated in claim 1 ,
these are reacted in a next step by means of an asymmetric reduction to give a compound of the general formula (IV)
in which
A and B have the meanings indicated in claim 1 ,
this is then
(A) converted by the introduction of a hydroxy protective group into a compound of the general formula (V)
in which
R 1 represents a hydroxy protective group,
in which
R 2 , R 3 and R 4 are identical or different and denote C 1 -C 4 -alkyl,
in a subsequent step the compound of the general formula (VI)
in which
R 1 , A and B have the meanings indicated in claim 1 ,
is prepared from this by means of diastereoselective reduction
and finally the hydroxy protective group is cleaved according to customary methods,
or
(B) the compound of the formula (IV) is reduced directly.
14 . The process of claim 13 , in which R 1 of formula (V) is a radical of the formula —SiR 2 R 3 R 4 .