Phosphonic acid derivatives with metallopeptidase inhibitory activity
AssigneeZambon Group S.p.A.
InventorsGabriele Norcini, Daniela Botta, Francesco Santangelo
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Abstract
Compounds of formula (I) wherein R is an alkyl, aryl or arylalkyl group wherein the aryl is phenyl naphthyl or heterocycle; R1 and R2, the same or different, are hydrogen atoms or alkyl groups; R3 is an aryl or arylalkyl group wherein the aryl is as above; R4 is a heterocycle optionally substituted with a heterocycle or phenyl, or it is a phenyl group substituted with a heterocycle (R4 is not imidazole or indole); X is a bond or —OCONH or —CONH— group, processes for their preparation and pharmaceutical compositions thereof, are described. The compounds of formula (I) are endowed with a dual ACE-inhibitory and NEP-inhibitory activity and are useful in the treatment of cardiovascular disease.
Claims8
A compound of formula
- wherein
- R is a straight or branched C1-C6 alkyl group optionally substituted with one or more fluorine atoms, an aryl or arylalkyl group with from 1 to 6 carbon atoms in the alkyl moiety wherein the aryl is a phenyl, 1-naphthyl 2-napithyl group or a 5 or 6 membered aromatic heterocycle with 1 or 2 heteroatoms selected among nitrogen, oxygen and sulphur, optionally substituted with one or more substituents, the same or different, selected among halogen atoms, hydroxy groups, alkyl alkoxy, alkylthio, alkylsuphonyl or alkoxycarbonyl groups with from 1 to 3 carbon atoms in the alkyl moiety, carboxy groups, aminocarbonyl groups, acylamino groups, aminosulphonyl groups, mono- or di-alkylaminocarbonyl groups with from 1 to 3 carbon atoms in the alkyl moiety;
- R1 and R2, the same or different, represent a hydrogen atom or a straight or branched C1-C4 alkyl group;
- R3 is a straight or branched C1-C6 alkyl group or an arylalkyl group with from 1 to 6 carbon atoms in the alkyl moiety wherein the aryl is a phenyl, 1-naphthyl, 2-naphthyl group or a 5 or 6 membered aromatic heterocycle with one or two heteroatoms selected among nitrogen, oxygen and sulphur, optionally substituted as indicated for R;
- R4 is a 5 or 6 membered aromatic heterocyclic group with one or two heteroatoms selected among nitrogen, oxygen and sulphur, substituted with a 5 or 6 membered aromatic heterocyclic group with one or two heteroatoms selected among nitrogen, oxygen and sulphur or with a phenyl group, or it is a phenyl group substituted with a 5 or 6 membered aromatic heterocyclic group with one or two heteroatoms selected among nitrogen, oxygen and sulphur, wherein the phenyl and the heterocyclic groups are optionally substituted with one or more substituents, the same or different, selected among halogen atoms, alkyl, alkoxy, alkylthio or alkoxycarbonyl groups with from 1 to 3 carbon atoms in the alkyl moiety;
- X is a single bond or an —O—CONH— or —CONH— group;
- the carbon atoms marked with an asterisk are asymmetric carbon atoms;
- and pharmaceutically acceptable salts thereof;
- provided that R4 is not an imidazolyl or indolyl group.
Dependencies are inferred from the claim text.