Claims for Patent: RE42152

Summary for Patent: RE42152

Title:	Aromatic-linked polyamine macrocyclic compounds with anti-HIV activity
Abstract:	Polyamine macrocyclic compounds, e.g. of 10 to 15 ring members and 3 to 6 ring amine nitrogens, linked through methylene groups to an aromatic moiety, show high selective activity against HIV.
Inventor(s):	Gary J. Bridger, Sreenivasan Padmanbhan, Renato Skerlj, David M. Thornton
Assignee:	Genzyme Corp
Application Number:	US12/192,704
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE42152
Patent Claims:	1. A pharmaceutical composition active against HIV comprising as an active ingredient a linked cyclic compound of formula I, Z-R-A-R′-Y (I) in which Z and Y are identical cyclic polyamine moieties having from 10 to 15 ring members and from 3 to 6 4 amine nitrogens in the ring spaced by 2 or more carbon atoms from each other, said amine nitrogens being the only ring heteroatoms, A is an unsubstituted aromatic or heteroaromatic moiety other than quinoline, R and R′ are each methylene linked to nitrogen atoms in Z and Y, the amine nitrogen atoms being otherwise unsubstituted, in admixture or association with a pharmaceutically acceptable diluent or carrier. 2. A composition according to claim 1, wherein in the compound of formula I, each moiety Z and Y has 14 ring members and 4 amine nitrogens in the ring. 3. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[1,3-phenylenebis(methylene)]-bis-1,4,8,11-tetra-azacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 4. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetra-azacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 5. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is a bis-zinc complex of 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 6. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is a bis-copper complex of 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 7. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[3,3′-biphenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 8. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 11,11′-[1,4-phenylene-bis-(methylene)]-bis-1,4,7,11-tetraazacyclotetradecane 11,11′-[1,4 -phenylene-bis-(methylene)]-bis- 1,4,7,11 -tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 9. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,11′-[1,4-phenylene-bis-(methylene)]-1,4,8,11-tetraazacyclotetradecane-1,4,7,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 10. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[2,6-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 11. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1-[3,5-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 12. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[2,5-thiophene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 13. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[4,4′-(2,2′-bipyridine)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 14. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[2,9-(1,10-phenanthroline)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 15. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[1,3-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 16. A pharmaceutical composition according to claim 1, wherein the active against HIV comprising as an active ingredient is 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 17. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[5-nitro-1,3-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 18. The compound of claim 1, which is 1′1′-[2,4,5,6-tetrachloro-1,3-phenyleneis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane A pharmaceutical composition active against HIV comprising as an active ingredient 1′1′-[2,4,5,6 -tetrachloro- 1,3 -phenylenebis(methylene)]bis- 1,4,8,11 -tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 19. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,3,5,6-tetrafluoro-1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 20. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4-naphthylene-bis-(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 21. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,3-phenylenebis-(methylene)]bis-1,5,9-triazacyclododecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 22. The compound of claim 1, which is 1,1′-[1,4-phenylene-bis-(methylene)]-1,5,9-triazacyclododecane A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4 -phenylene-bis-(methylene)]-bis- 1,5,9 -triazacyclododecane in acid addition salt form in admixture or association with a pharmaceutically acceptable diluent or carrier. 23. The compound of claim 1, which is a bis-zinc complex of 1,1′[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane. 24. The compound of claim 1, which is 1,1′-[3,3′-biphenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 25. The compound of claim 1, which is 1,1′-[2,6-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 26. The compound of claim 1, which is 1,1′-[3,5-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 27. The compound of claim 1, which is 1,1′-[2,5-thiophene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 28. The compound of claim 1, which is 1,1′-[4,4′-(2,2′-bipyridine)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 29. The compound of claim 1, which is 1,1′-[2,9-(1,10-phenanthroline)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 30. The compound of claim 1, which is 1,1′-[1,3-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form. 31. The compound of claim 1, which is 1,1′-[1,4-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form. 32. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,5-dimethyl-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 33. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,5-dichloro-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 34. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2-bromo-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 35. The compound of claim 1, which is A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[6-phenyl-2,4-pyridinebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 36. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,3 -phenylenebis(methylene)]-bis- 1,4,8,11 -tetra-azacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 37. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4 -phenylenebis(methylene)]-bis- 1,4,8,11 -tetra-azacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 38. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[3,3′-biphenylene-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 39. A pharmaceutical composition active against HIV comprising as an active ingredient 11,11′-[1,4 -phenylene-bis-(methylene)]-bis- 1,4,7,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 40. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,6 -pyridine-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 41. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1-[3,5 -pyridine-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 42. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,5 -thiophene-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 43. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[4,4′-( 2,2′-bipyridine)-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 44. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,9 -( 1,10 -phenanthroline)-bis-(methylene)]-bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 45. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,3 -phenylene-bis-(methylene)]-bis- 1,4,7,10 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 46. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4 -phenylene-bis-(methylene)]-bis- 1,4,7,10 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 47. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[5 -nitro- 1,3 -phenylenebis(methylene)]bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 48. A pharmaceutical composition active against HIV comprising as an active ingredient 1′1′-[2,4,5,6 -tetrachloro- 1,3 -phenylenebis(methylene)]bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 49. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[2,3,5,6 -tetra-fluoro- 1,4 -phenylenebis(methylene)]bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 50. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4 -naphthylene-bis-(methylene)]bis- 1,4,8,11 -tetraazacyclotetradecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 51. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,3 -phenylenebis-(methylene)]bis- 1,5,9 -triazacyclododecane in admixture or association with a pharmaceutically acceptable diluent or carrier. 52. A pharmaceutical composition active against HIV comprising as an active ingredient 1,1′-[1,4 -phenylene-bis-(methylene)]-bis- 1,5,9 -triazacyclododecane in admixture or association with a pharmaceutically acceptable diluent or carrier.