Claims for Patent: 9,062,047

Summary for Patent: 9,062,047

Title:	Crystalline form of pyrimido[6,1-A] isoquinolin-4-one compound
Abstract:	The current invention is directed towards a polymorph of N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea, in the form of a crystalline solid consisting of greater than 99% by weight of N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea, at least 95% in the polymorphic form of a thermodynamically stable polymorph (I) of N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea, wherein said polymorph is determined by single crystal X-ray structural analysis and X-ray powder diffraction pattern.
Inventor(s):	Walker Michael J. A., Plouvier Bertrand M. C., Northen Julian S., Fernandes Philippe
Assignee:	Verona Pharma plc
Application Number:	US13814877
Patent Claims:	3. The polymorph of wherein said powder X-ray diffraction pattern further comprises characteristics peaks claim 2 , in terms of 2θ claim 2 , at 15.3° and 17.6°.4. The polymorph of wherein said powder X-ray diffraction pattern comprises at least 5 characteristic peaks claim 2 , in terms of 2θ claim 2 , selected from 6.4° claim 2 , 10.1° claim 2 , 12.6° claim 2 , 12.9° claim 2 , 13.6° claim 2 , 14.2° claim 2 , 14.7° claim 2 , 15.3° claim 2 , 15.4° claim 2 , 15.8° claim 2 , 17.0° claim 2 , 17.6° claim 2 , 18.9° claim 2 , 20.9° claim 2 , 22.4° claim 2 , 22.8° claim 2 , and 28.7°.5. A solid composition comprising the polymorph of and a pharmaceutically acceptable carrier.6. The composition of wherein at least 50% by weight of total N-{2-[(2E)-2-(mesitylimino)-9 claim 5 ,10-dimethoxy-4-oxo-6 claim 5 ,7-dihydro-2H-pyrimido[6 claim 5 ,1-a]-isoquinolin-3(4H)-yl]ethyl}urea in said composition is present as said polymorph.7. The composition of wherein at least 70% by weight of total N-{2-[(2E)-2-(mesitylimino)-9 claim 5 ,10-dimethoxy-4-oxo-6 claim 5 ,7-dihydro-2H-pyrimido[6 claim 5 ,1-a]-isoquinolin-3(4H)-yl]ethyl}urea in said composition is present as said polymorph.8. The composition of wherein at least 90% by weight of total N-{2-[(2E)-2-(mesitylimino)-9 claim 5 ,10-dimethoxy-4-oxo-6 claim 5 ,7-dihydro-2H-pyrimido[6 claim 5 ,1-a]-isoquinolin-3(4H)-yl]ethyl}urea in said composition is present as said polymorph.9. The composition of wherein at least 97% by weight of total N-{2-[(2E)-2-(mesitylimino)-9 claim 5 ,10-dimethoxy-4-oxo-6 claim 5 ,7-dihydro-2H-pyrimido[6 claim 5 ,1-a]-isoquinolin-3(4H)-yl]ethyl}urea in said composition is present as said polymorph.10. A solid composition comprising the polymorph of and one or more additional compounds.11. The solid composition of claim 10 , wherein the additional compound is a known therapeutic.12. A process for preparing the polymorph of comprising:(a) combining N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea with a solvent to form a mixture, and(b) heating said mixture at or above a temperature of about 50° C. for a time and under conditions suitable for forming said polymorph.13. A process for preparing the polymorph of comprising:(a) combining N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea with a solvent to form a mixture,(b) filtering said mixture to form a filtered mixture(c) heating said filtered mixture at or above a temperature of about 55° C. for a time and under conditions suitable for forming said polymorph; and(d) filtering and drying said polymorph.14. The process of claim 12 , wherein the solvent is DMSO claim 12 , ethanol claim 12 , methanol claim 12 , isopropanol claim 12 , hexanes claim 12 , pentane claim 12 , ethyl acetate claim 12 , dichloromethane claim 12 , or chloroform.15. The process of claim 14 , wherein the solvent is DMSO or ethanol.16. The process of wherein said filtered mixture is maintained at or above a temperature of about 50° C. for about 24 to 96 hours.17. The process of claim 16 , wherein said filtered mixture is maintained at or above a temperature of about 50° C. for about 72 hours.18. The process of wherein said filtered mixture is maintained at or above a temperature of about 55° C. for about 24 to 96 hours.19. The process of claim 16 , wherein said filtered mixture is maintained at or above a temperature of about 55° C. for about 72 hours.20. The process of wherein said mixture is dried in vacuo at between 25 and 50° C.21. The process of wherein said mixture is dried in vacuo at 40° C.22. The polymorph of claim 2 , prepared by the method comprising(a) combining N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]ethyl}urea with a solvent to form a mixture, and(b) heating said mixture at or above a temperature of 50° C. for a time and under conditions suitable for forming said polymorph.23. The polymorph of claim 2 , prepared by the method comprising(a) combining N-{2-[(2E)-2-(mesitylimino)-9,10-dimethoxy-4-oxo-6,7-dihydro-2H-pyrimido[6,1-a]-isoquinolin-3(4H)-yl]thyl}urea with a solvent to form a mixture,(b) filtering said mixture to form a filtered mixture,(c) heating said filtered mixture at or above a temperature of 55° C. for a time and under condition suitable for forming said polymorph; and(d) filtering and drying said polymorph.25. The method of claim 24 , wherein the mammal is a human.