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US 2012/0259113 A1Published application
Dual-acting pyrazole antihypertensive agents
AssigneeTheravance, Inc.
InventorsBrooke Blair, Paul R. Fatheree, Melissa Fleury, Roland Gendron, Ryan Hudson, Robert Murray McKinnell, Michael Wilson
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.
Claims12
A compound of formula I:
- where:
- Z is
- Ar is selected from:
- R1 is selected from —SO2NHC(O)R1a, tetrazolyl, —C(O)OR1b,
- where R1a is —C1-6alkyl, —C0-6alkylene-OR, —C3-7cycloalkyl, —C0-5alkylene-NR1bR1b, pyridyl, isoxazolyl, methylisoxazolyl, pyrrolidinyl, morpholinyl, or phenyl optionally substituted with halo;
- where each R1b 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(OR4d), and —CH(R4b)C(O)OR4c;
- where R4a is H or —C(O)—C1-6alkyl;
- R4b is H or —OH;
- R4c is H, —C1-6alkyl, —C0-6alkylenemorpholine, —CH2OC(O)O—C1-6alkyl, —CH(CH3)OC(O)O—C1-6alkyl, —CH(CH3)OC(O)O—C3-7cycloalkyl, or:
- R4d is H or —C(O)—R4e;
- and R4e is —C1-6alkyl, —C1-6alkyl-NH2 or aryl;
- 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.
16 more elements
(canceled)
12-16. (canceled)
Dependencies are inferred from the claim text.