Thiopyrimidinecarboxamides as CXCR1/2 modulators
There is disclosed a pyrimidinecarboxamide compound useful as a pharmaceutical agent, synthetic processes, and pharmaceutical compositions which include the pyrimidinecarboxamide compound. More specifically, there is disclosed a CXCR1/2 inhibitor useful for treating a variety of inflammatory and neoplastic disorders.
1. A compound having formula SX-682
or a pharmaceutically acceptable salt or solvate thereof.
2. A pharmaceutical formulation comprising the compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof.
3. The pharmaceutical formulation of claim 2 , wherein the compound of claim 1 is in a powder, solution, suspension, emulsion, or surface deposited on a suitable pharmaceutical excipient for inhalation or oral administration.
4. A method for treating rheumatoid arthritis, stroke and ischemia reperfusion injury, psoriasis, chronic obstructive pulmonary disease, or bronchopulmonary dysplasia in a patient in need of such treatment, comprising administering an effective amount of the compound having formula SX-682:
or a pharmaceutically acceptable salt or solvate thereof.
5. The method of claim 4 , wherein the compound having formula SX-682 is administered orally, transdermally, parenterally, intranasally, or by inhalation.
6. The method of claim 4 , wherein the compound having formula SX-682 is co-administered with a chemotherapeutic agent.
7. The method of claim 4 , wherein the compound having formula SX-682 is administered in a 0.01 mg to 1000 mg dose.
8. The method of claim 4 , wherein the compound having formula SX-682 is administered in a 0.01 mg to 7500 mg dose.
9. The method of claim 4 , wherein the compound having formula SX-682 is administered in a 0.01 mg to 500 mg dose.
10. The method of claim 4 , wherein the compound having formula SX-682 is administered orally or by inhalation in a daily, twice-weekly or once-weekly dose of 0.04 mg to 4000 mg, given in two to four divided doses or as a single dose.
11. The method of claim 10 , wherein the dose of the compound having formula SX-682 is 10 mg to 2000 mg.
12. The method of claim 10 , wherein the dose of the compound having formula SX-682 is 10 mg to 1000 mg.
13. The method of claim 10 , wherein the dose of the compound having formula SX-682 is 50 mg to 600 mg.
14. A method of making a compound having the formula SX-682
comprising reacting 2-chloro-pyrimidine-5-carboxylic acid with 4-fluoroaniline to produce N-(4-fluorophenyl)-2-chloro-pyrimidinamide.
15. The method of claim 14 , further comprising reacting N-(4-fluorophenyl)-2-chloro-pyrimidinamide with sodium hydrogen sulfide to produce 2-mercapto-pyrimidine-5-carboxylic acid (4-fluoro-phenyl)-amide.
16. The method of claim 15 , further comprising reacting 2-mercapto-pyrimidine-5-carboxylic acid (4-fluoro-phenyl)-amide with 2-bromomethyl-4-trifluoromethoxy-phenylboronic acid, pinacol ester to produce a pinacol ester derivative having the formula I
17. The method of claim 15 , further comprising deprotection of the boronic acid pinacol ester of formula I by reaction with potassium hydrogen fluoride.