Naphthalenyl piperidines as renin inhibitors
AssigneeHoffman-La Roche Inc.
InventorsVolker Breu, Hans-Peter Märki, Eric Vieira, Wolfgang Wostl
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Abstract
Piperidine derivatives, their manufacture and use as medicaments is described. The compounds are useful for treating diseases associated with restenosis, glaucoma, cardiac infarct, high blood pressure and end organ damage, e.g. cardiac insufficiency and kidney insufficiency.
Claims30
A compound of the formula:
- wherein
- R1 is naphthyl substituted by one to three C1-C5-alkoxy groups;
- R2 is phenyl;
- phenyl substituted by one to three substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- benzyl;
- or benzyl substituted by one to three sub substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- R3 is hydroxymethyl;
- a pharmaceutically acceptable salt thereof.
The compound (3S,4R,5R)-[4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidin-3-yl]-methanol.
A compound of the formula:
- wherein
- R1 is naphthyl substituted by one to three C1-C5-alkoxy groups;
- R2 is phenyl;
- phenyl substituted by one to three substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- benzyl;
- or benzyl substituted by one to three substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- R3 is imidazolylmethyl;
- a pharmaceutically acceptable salt thereof.
The compound (3S,4R,5R)-3-imidazol-1-ylmethyl-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidine dihydrochloride.
A compound of the formula:
- wherein
- R1 is naphthyl substituted by one to three C1-C5-alkoxy groups;
- R2 is phenyl;
- phenyl substituted by one to three substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- benzyl;
- or benzyl substituted by one to three substituents independently selected from the group consisting of halogen, cyano, C1-C3-alkoxy, and nitro;
- R3 is R3a—(CH2)k—[CH(OR4)]1—CH2—O—;
- R3a is hydrogen, hydroxy, imidazolyl, triazolyl, C1-C3-alkoxy, C1-C3-alkoxy-C2-C3-alkoxy, hydroxy-C2-C3-alkoxy, C1-C3-alkylamino or C1-C3-dialkylamino;
- R4 is hydrogen or C1-C3-alkyl;
- k is 1 or 2, when R3a is hydrogen, k is 0;
- l is 1 is or 2;
- or
- a pharmaceutically acceptable salt thereof.
The compound 2-[3-[4-[(3S,4R,5R)-3-[(2R)-2-hydroxy-3-(2-methoxy-ethoxy)-propoxy]-5-(4-methoxy-naphthalen-2-ylmethoxy)-piperidin-4-yl]-phenoxy]-propoxy]-benzonitrile.
The compound (R)-3-[(3S,4R,5R)-5-(4-methoxy-naphthalen-2-ylmethoxy)-4-[4-[3-(2-nitro-phenoxy)-propoxy]-phenyl]-piperidin-3-yloxy]-propane-1,2-diol.
The compound (R)-1-[(3S,4R,5R)-5-(4-methoxy-naphthalen-2-ylmethoxy)-4-[4-[3-(2-nitro-phenoxy)-propoxy]-phenyl]-piperidin-3-yloxy]-3-[1,2,4]triazol-1-yl-propan-2-ol.
The compound (R)-1-imidazol-1-yl-3-[(3S,4R,5R)-5-(4-methoxy-naphthalen-2-ylmethoxy) -4-[4-[3-(2-nitro-phenoxy)-propoxy]-phenyl]-piperidin-3-yloxy)-propan-2-ol.
A compound of the formula:
- wherein
- R1 is naphthyl substituted by one to three C1-C5-alkoxy groups;
- R2 is phenyl substituted by one to three C1-C3-alkoxy groups or benzyl substituted by one to three C1-C3-alkoxy groups;
- R3 is hydroxymethyl;
- or
- a pharmaceutically acceptable salt thereof.
A compound of the formula:
- wherein
- R1 is naphthyl substituted by one to three C1-C5-alkoxy groups;
- R2 is phenyl substituted by one to three C1-C3-alkoxy groups or benzyl substituted by one to three C1-C3-alkoxy groups;
- R3 is imidiazolylmethyl;
- or
- a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.