Bi-aryl amide compounds as CRTh2 receptor modulators
AssigneeAstraZeneca AB
InventorsRoger Victor Bonnert, Timothy Jon Luker, Anil Patel, Aaron Rigby
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Abstract
The present invention relates to (2S)-2-({3′-Chloro-4′-[(2,2-dimethylpyrrolidin-1-yl) carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid and (2R)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl) carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid of formula (I), and crystalline forms and pharmaceutically acceptable salts thereof useful as pharmaceuticals.
Claims17
A mixture of (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid, or a pharmaceutically acceptable salt thereof;
- and (2R)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid,-or a pharmaceutically acceptable salt thereof.
A compound of formula (I):
- or a pharmaceutically acceptable salt thereof.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid 2-methylpropan-2-amine salt characterised by an X-ray powder diffraction pattern with peaks at at least one of the following 2-theta values measured using CuKαradiation:
- 14.6, 17.4 and 21.1.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid 2-methylpropan-2-amine salt characterised by an X-ray powder diffraction pattern substantially as shown in FIG. 1.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid characterised by an X-ray powder diffraction pattern with peaks at at least one of the following 2-theta values measured using CuKαradiation:
- 15.0, 19.2 and 21.4.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid characterised by an X-ray powder diffraction pattern substantially as shown in FIG. 2.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid characterised by an X-ray powder diffraction pattern with peaks at at least one of the following 2-theta values measured using CuKαradiation:
- 10.6, 13.2 and 15.1.
A crystalline form of the compound (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid characterised by an X-ray powder diffraction pattern substantially as shown in FIG. 3.
A compound of formula (1c):
A compound of formula (1d):
A compound of formula (1f):
A pharmaceutical product comprising, in combination, a first active ingredient which is a mixture of (2S)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid, or a pharmaceutically acceptable salt thereof;
- and (2R)-2-({3′-chloro-4′-[(2,2-dimethylpyrrolidin-1-yl)carbonyl]-5-fluorobiphenyl-2-yl}oxy)propanoic acid,-or a pharmaceutically acceptable salt thereof, and a second active ingredient which is selected from one or more of:
- a PDE4 inhibitor;
- a selective β2 adrenoceptor agonist;
- a modulator of chemokine receptor function;
- an inhibitor of p38 kinase function;
- a glucocorticoid;
- an anticholinergic agent and
- a non-steroidal glucocorticoid receptor antagonist.
A pharmaceutical product comprising, in combination, a first active ingredient which is
- or a pharmaceutically acceptable salt thereof, and
- a second active ingredient which is selected from one or more of:
- a PDE4 inhibitor;
- a selective β2 adrenoceptor agonist;
- a modulator of chemokine receptor function;
- an inhibitor of p38 kinase function;
- a glucocorticoid;
- an anticholinergic agent and
- a non-steroidal glucocorticoid receptor antagonist.
Dependencies are inferred from the claim text.