(2R,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid
In one aspect, the invention relates to a compound of the structure: or a pharmaceutically acceptable salt thereof, and a crystalline form of this compound, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising this compound; methods of using this compound; and processes for preparing this compound.
1. A composition comprising a crystalline form of a compound or salt of Formula (1):
2. The composition of claim 1 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 14.19±0.2 and 21.15±0.2 degrees 2θ.
3. The composition of claim 1 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 8.48±0.2, 17.03±0.2, and 25.41±0.2 degrees 2θ.
4. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 8.48±0.2, 17.03±0.2, and 25.41±0.2 degrees 2θ.
5. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises peaks at 8.48±0.2, 17.03±0.2, and 25.41±0.2 degrees 2θ.
6. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 20.59±0.2, 24.45±0.2, 24.78±0.2, 25.67±0.2, 27.67±0.2, and 30.73±0.2 degrees 2θ.
7. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises peaks at 20.59±0.2, 24.45±0.2, 24.78±0.2, 25.67±0.2, 27.67±0.2, and 30.73±0.2 degrees 2θ.
8. The composition of claim 5 , wherein the powder x-ray diffraction pattern further comprises peaks at 20.59±0.2, 24.45±0.2, 24.78±0.2, 25.67±0.2, 27.67±0.2, and 30.73±0.2 degrees 2θ.
9. The composition of claim 1 , wherein the crystalline form is characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 165 to 169° C.
10. The composition of claim 5 , wherein the crystalline form is further characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 165 to 169° C.
11. The composition of claim 8 , wherein the crystalline form is further characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 165 to 169° C.
12. The composition of claim 1 , wherein the crystalline form is non-solvated.
13. The composition of claim 1 , wherein the compound of Formula (1) is a free acid.
14. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising the composition of claim 2 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising the composition of claim 10 and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the pharmaceutically acceptable carrier is magnesium stearate.
18. An oral dosage form comprising the composition of claim 1 .
19. An oral dosage form comprising the composition of claim 2 .
20. An oral dosage form comprising the composition of claim 10 .