Glucuronate salt of a piperazine compound
The present invention provides a salt form, and compositions thereof, useful as a modulator of one or more GPCRs and which exhibits desirable characteristics for the same. The present invention also provides methods for preparing said salt form.
1. Compound 2:
2. The compound according to claim 1 , wherein said compound is in solid form.
3. The compound according to claim 2 , wherein said compound is crystalline.
4. The compound according to claim 3 , wherein said compound is a crystalline solid substantially free of amorphous compound 2.
5. The compound according to claim 1 , wherein said compound is substantially free of impurities.
6. A method for preparing compound 2:
comprising the steps of:
providing compound 1:
combining compound 1 with glucuronic acid in a suitable solvent; and
optionally isolating compound 2.
7. The method according to claim 6 , wherein said suitable solvent is a protic solvent, a polar aprotic solvent, or a mixture thereof.
8. A method for preparing compound 2:
comprising the steps of:
combining compound 1:
with a suitable solvent and heating to form a solution thereof;
adding glucuronic acid to said solution; and
optionally isolating compound 2.
9. A pharmaceutically acceptable composition comprising the compound according to claim 1 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.
10. The composition according to claim 9 , wherein said composition is an injectable formulation for intravascular delivery.
11. The composition according to claim 9 , wherein said composition is an injectable formulation for intramuscular delivery.
12. A method of modulating one or more GPCRs in a biological sample, comprising contacting said biological sample with a compound according to claim 1 .
13. A method of treating, or lessening the severity of, one or more disorders selected from Parkinson's disease, psychoses including schizophrenia, mania, psychotic depression, bipolar disorder, depression, stress/anxiety, Alzheimer's disease, Huntington's disease, panic disorder, obsessive compulsive disorder, an eating disorder, drug addiction, social phobias, aggression or agitation, migraine, scleroderma, Raynaud's phenomenon, emesis, a GI tract disorder related to the regulation of peristalsis, RLS, or prolactin secretion arising from tumours of the pituitary gland, wherein said method comprises administering to a patient a composition according to either of claims 9 or 10 .
14. The method according to claim 13 , wherein said disorder is Parkinson's disease.
15. The method according to claim 13 , wherein said disorder is a psychosis selected from schizophrenia, mania, psychotic depression, and bipolar disorder.
16. The method according to claim 13 , wherein said disorder is depression, stress/anxiety, panic disorder, obsessive compulsive disorder, an eating disorder, drug addiction, or a social phobia.
17. The method according to claim 13 , wherein said disorder is aggression or agitation.
18. The method according to claim 13 , wherein said disorder is Alzheimer's disease, Huntington's disease, migraine, scleroderma, Raynaud's phenomenon, emesis, a GI tract disorder related to the regulation of peristalsis, RLS, or prolactin secretion arising from tumours of the pituitary gland.
19. The crystalline compound according to claim 3 , wherein said compound is Form I.
20. The crystalline compound according to claim 18 , having one or more peaks in its powder X-ray diffraction pattern selected from those at about 17.5, 22.5, 19.9, 3.9, and 12.2 degrees 2-theta.
21. The crystalline compound according to claim 3 , wherein said compound is Form II.
22. The crystalline compound according to claim 3 , wherein said compound is a hydrate of compound 2.
23. The crystalline compound according to claim 22 , wherein said hydrate is selected from Hydrate I or Hydrate II.
24. The crystalline compound according to claim 3 , wherein said compound is a solvate of compound 2.
25. The crystalline compound according to claim 24 , wherein said solvate is selected from the Methanolate, Ethanolate I, Ethanolate II, Isopropanolate I, Isopropanolate II, or the Acetonate.