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US 8,263,629 B2Granted
Substituted aminobutyric derivatives as neprilysin inhibitors
AssigneeNovartis AG
InventorsGary Mark Coppola, Yuki Iwaki, Rajeshri Ganesh Karki, Toshio Kawanami, Gary Michael Ksander, Muneto Mogi, Robert Sun
Life of this patent
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Abstract
The present invention provides a compound of formula I′; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, X and n are defined herein. The invention also relates to a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
Claims15
A compound of the formula (I′):
- or a pharmaceutically acceptable salt or tautomer thereof, wherein:
- R1 is C1-7alkyl;
- for each occurrence, R2 is independently C1-7alkyl, NO2, CN, halo, C3-7cycloalkyl, hydroxy, C1-7alkoxy, halo-C1-7alkyl, NRbRc, C6-10aryl, heteroaryl or heterocyclyl;
- wherein Rb and Rc for each occurrence, are independently H or C1-7alkyl;
- R3 is A2-R4;
- R4 is C6-10aryl or a heteroaryl, which can be monocyclic or bicyclic and which can be optionally substituted with one or more substituents independently selected from hydroxy, hydroxy-C1-7alkyl, NRbRc, nitro, C1-7alkoxy, halo, C1-7alkyl, halo-C1-7alkyl, C2-7alkenyl, C6-10aryl, heteroaryl, —C(O)C1-7alkyl, —NHS(O)2-C1-7alkyl, —SO2C1-7alkyl and benzyl;
- R5 is H, halo, hydroxy, C1-7alkoxy, halo, C1-7alkyl or halo-C1-7alkyl;
- and
- X is OH, —O—C1-7alkyl, —NRbRc, —NHS(O)2—C1-7alkyl, —NHS(O)2-benzyl or —O—C6-10aryl;
- wherein alkyl is optionally substituted with one or more substituents independently selected from the group consisting of aryl, heteroaryl, heterocyclyl, —C(O)NH2, —C(O)NH—C1-6alkyl, and —C(O)N(C1-6alkyl)2;
- A2 is a bond or a linear or branched C1-7alkylene which is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-7alkoxy, hydroxy, O-Acetate and C3-7cycloalkyl;
- n is 0, 1, 2, 3, 4 or 5;
- wherein each heteroaryl is a monocyclic or bicyclic aromatic ring comprising 5-10 ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and
- each heterocyclyl is a monocyclic saturated or partially saturated but non-aromatic moiety comprising 4-7 ring atoms selected from carbon atoms and 1-5 heteroatoms, wherein each heteroatom of a heteroaryl or a heterocyclyl is independently selected from O, N and S.
11 more elements
Dependencies are inferred from the claim text.