US 5,614,550 A · Amide and urea derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses

Abstract

Compounds of formula (I) are provided: ##STR1## wherein: R.sup.1 represents an alkyl group; or a group of formula (II), (III), (IV) or (V): ##STR2## and wherein the groups R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are hydrogen or various organic groups; and pharmaceutically acceptable salts thereof; as well as methods for the preparation of such compounds and their use in the treatment and prophylaxis of hypercholesteremia and arteriosclerosis.

A compound of formula (I):

##STR17## wherein:
R.sup.1 represents an alkyl group having from 1 to 20 carbon atoms, or a group of formula (III), (IV) or (V):
##STR18## where R.sup.5 represents an alkyl group having from 1 to 15 carbon atoms;
m is an integer of from 1 to 4;
and, any aromatic ring in said group represented by R.sup.1 is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below;
R.sup.2 represents a hydrogen atom or an alkyl group having from 1 to 10 carbon atoms;
R.sup.3 represents
an alkyl group having from 1 to 10 carbon atoms,
an alkoxy group having from 1 to 10 carbon atoms,
an alkylthio group having from 1 to 10 carbon atoms,
an alkylsulfinyl group having from 1 to 10 carbon atoms,
an alkylsulfonyl group having from 1 to 10 carbon atoms,
a phenylthio group in which the phenyl part is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below,
a phenylsulfinyl group in which the phenyl part is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below,
a phenylsulfonyl group in which the phenyl part is unsubstituted or is substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below, or
an alkoxyalkyl group in which the alkoxy part has from 1 to 6 carbon atoms and the alkyl part has from 1 to 4 carbon atoms;
R.sup.4 represents a group of formula (VI), (VII), (VIII), (IX), (X) or (XI):
##STR19## where A.sup.1 represents a single bond or an alkylene group having from 1 to 4 carbon atoms, A.sup.2 represents a single bond or an alkylene group having from 1 to 6 carbon atoms, A.sup.3, A.sup.3a, A.sup.4 and A.sup.5 are independently selected from the group consisting of single bonds and alkylene groups having from 1 to 10 carbon atoms which may be saturated or may include a carbon-carbon double bond, provided that the total number of carbon atoms in A.sup.3, A.sup.4 and A.sup.5 and that in A.sup.3a, A.sup.4 and A.sup.5 does not exceed 10;
R.sup.6 represents an alkyl group having from 1 to 6 carbon atoms, a cycloalkyl group having from 3 to 9 carbon atoms in one or more aliphatic carbocyclic rings, said rings being unsubstituted or being substituted by at least one substituent selected from the group consisting of substituents .alpha., defined below, or an aryl group, as defined below;
and
in the groups of formulae (VI) and (VIII), the imidazolyl and benzimidazolyl groups may be unsubstituted or may be substituted by at least one substituent selected from the group consisting of substituents .beta., defined below;
R.sup.7 represents a hydrogen atom, a benzyl group, a phosphono group or a group of formula (XII):
##STR20## where:
z.sup.1 is 0 or 1;
z.sup.2 is 0, 1 or 2;
X is an oxygen or sulfur atom or a sulfinyl, sulfonyl or phenylene group, provided that, when z.sup.2 is 2, at least one X is a phenylene group;
z.sup.3 is 0 or an integer from 1 to 4;
and
R.sup.8 is a carboxy group, a phenyl group, a group of formula --NR.sup.9 R.sup.10,
where R.sup.9 and R.sup.10 are independently selected from the group consisting of hydrogen atoms and alkyl groups having from 1 to 4 carbon atoms,
or a heterocyclic group having 5 or 6 ring atoms of which 1 or 2 are hetero-atoms selected from the group consisting of oxygen and nitrogen atoms, said heterocyclic group being unsubstituted or being substituted on a carbon atom by an oxygen atom or by an alkyl group having from 1 to 4 carbon atoms;
and
said groups of formula (CH.sub.2).sub.z 1 and (CH.sub.2).sub.z 3 being unsubstituted or being substituted on a carbon atom by an alkyl group having from 1 to 4 carbon atoms or by a group of formula --NR.sup.9 R.sup.10, where R.sup.9 and R.sup.10 are as defined above;
n.sup.1 is 0 or 1;
n.sup.2 is 0 or 1;
M represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group;
said substituents .alpha. are selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms and halogen atoms;
and
said substituents .beta. are selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms and phenyl groups which are unsubstituted or are substituted by at least one substituent selected from the group consisting of said substituents .alpha.;
said aryl groups are aromatic carbocyclic groups having from 6 to 10 ring carbon atoms and are unsubstituted or are substituted by at least one substituent selected from the group consisting of substituents .alpha., defined above;
PROVIDED THAT, where R.sup.4 represents said group of formula (VII), (IX), (X) or (XI), R.sup.1 does not represent said alkyl group and that, where n.sup.2 is 1, A.sup.4 does not represent a single bond, and that, where n.sup.1 is 0, R.sup.3 is ethyl and R.sup.4 is 2-acetyl, R.sup.1 does not represent a methyl group;
or a pharmaceutically acceptable salt thereof.

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Amide and urea derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses

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Amide and urea derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses

Life of this patent

Abstract

Claims55