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US 2017/0362260 A1Published application
Neprilysin inhibitors
AssigneeTheravance Biopharma R&D IP, LLC
InventorsAdam D. Hughes, Melissa Fleury
Life of this patent
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Abstract
In one aspect, the invention relates to compounds having the formula X: where Ra, Rb, R2, R7, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.
Claims2
1-24. (canceled)
A compound of:
- (a) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid;
- (b) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyi soxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid 5-methyl-2-oxo-[1,39 dioxol-4-ylmethyl ester;
- (c) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 2,2,3,3,3 -pentafluoropropyl ester;
- (d) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid acetoxymethyl ester;
- (e) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 2-methoxy-ethyl ester;
- (f) butyric acid (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl ester;
- (g) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid ethoxycarbonyloxymethyl ester;
- (h) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 2-morpholin-4-ylethyl ester;
- (i) (S)-2-methoxycarbonylamino-3 -methylbutyric acid (R)-3 -[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3 -methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionyloxymethyl ester;
- (j) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropoxycarbonyloxymethyl ester;
- (k) (R)-2-(2-aminoacetoxy)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]propionic acid ethyl ester;
- (l) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-propionyloxypropionic acid;
- (m)(S)-2-amino-3-methylbutyric acid (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)-hydrazino]-2-hydroxypropionyloxymethyl ester;
- (n) (S)-2-methoxycarbonylamino-3-methylbutyric acid (R)-1-carboxy-24N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]ethyl ester;
- (o) (S)-2-aminopropionic acid (R)-1-carboxy-2-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]ethyl ester;
- (p) (S)-2-amino-3-methylbutyric acid (R)-1-carboxy-2-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]ethyl ester;
- (q) (R)-2-(2-aminoacetoxy)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]propionic acid;
- (r) (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 1-cyclohexyloxycarbonyloxyethyl ester;
- or
- a pharmaceutically-acceptable salt thereof.
17 more elements
Dependencies are inferred from the claim text.