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US 2014/0194426 A1Published application
Dual-acting oxazole antihypertensive agents
AssigneeTheravance, Inc.
InventorsPaul R. Fatheree, Ryan Hudson, Robert Murray McKinnell
Life of this patent
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Abstract
In one aspect, the invention relates to compounds having the formula: wherein: Ar, Z, R3, R4 and R5 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have AT1 receptor antagonist activity and neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
Claims16
A compound of formula I:
- where:
- Z is:
- where the amide portion of the compound of formula I is on the carbon atom between the oxygen ring atom and the nitrogen ring atom and the R3 moiety is on the carbon ring atom adjacent to the oxygen ring atom;
- Ar is selected from:
- R1 is selected from —COOR, —SO2NHC(O)R1a, tetrazolyl,
- where R1a is —C1-6alkyl, —C0-6alkylene-OR, —C3-7cycloalkyl, —C0-5alkylene-NRR, pyridyl, isoxazolyl, methylisoxazolyl, pyrrolidinyl, morpholinyl, and phenyl optionally substituted with halo;
- where each R is independently selected from H and —C1-6alkyl;
- a is 0, 1, or 2;
- R2 is F;
- R3 is selected from —C2-5alkyl and —O—C1-5alkyl;
- R4 is selected from —CH2—SR4a, —CH2—N(OH)C(O)H, —CH(R4b)C(O)NH(OH), and —CH(R4b)COOR4c;
- where R4a is H or —C(O)—C1-6alkyl;
- R4b is H or —OH;
- and R4a is H or —C1-6alkyl;
- and
- R5 is selected from —C1-6alkyl, —CH2-furanyl, —CH2-thiophenyl, benzyl, and benzyl substituted with one or more halo, —CH3, or —CF3 groups;
- where each ring in Ar is optionally substituted with 1 to 3 substituents independently selected from —OH, —C1-6alkyl, —C2-4alkenyl, —C2-4alkynyl, —CN, halo, —O—C1-6alkyl, —S—C1-6alkyl, —S(O)—C1-6alkyl, —S(O)2—C1-4alkyl, -phenyl, —NO2, —NH2, —NH—C1-6alkyl and —N(C1-6alkyl)2, wherein each alkyl, alkenyl and alkynyl is optionally substituted with 1 to 5 fluoro atoms;
- or a pharmaceutically acceptable salt thereof.
15 more elements
(canceled)
Dependencies are inferred from the claim text.