Claims for Patent: 5,583,131

Summary for Patent: 5,583,131

Title:	Aromatic-linked polyamine macrocyclic compounds with anti-HIV activity
Abstract:	PCT No. PCT/GB92/02334 Sec. 371 Date Aug. 18, 1994 Sec. 102(e) Date Aug. 18, 1994 PCT Filed Dec. 16, 1992 PCT Pub. No. WO93/12096 PCT Pub. Date Jun. 24, 1993Polyamine 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 T. Skerlj, David M. Thornton
Assignee:	Genzyme Corp
Application Number:	US08/244,863
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 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 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. 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 composition according to claim 1, wherein the active ingredient is 1,1'-[1,3-phenylenebis(methylene)]-bis-1,4,8,11-tetra-azacyclotetradecane in acid addition salt form. 4. A composition according to claim 1, wherein the active ingredient is 1,1'-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetra-azacyclotetradecane in acid addition salt form. 5. A composition according to claim 1, wherein the active ingredient is a bis-zinc complex of 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane 6. A composition according to claim 1, wherein the active ingredient is a bis-copper complex of 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane. 7. A composition according to claim 1, wherein the active ingredient is 1,1'-[3,3'-biphenylene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 8. A composition according to claim 1, wherein the active ingredient is 11,11'-[1,4-phenylene-bis-(methylene)]-bis-1,4,7,1 1-tetraazacyclotetradecane in acid addition salt form. 9. A composition according to claim 1, wherein the 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. 10. A composition according to claim 1, wherein the active ingredient is 1,1'-[2,6-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 11. A composition according to claim 1, wherein the active ingredient is 1,1-[3,5-pyridine-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 12. A composition according to claim 1, wherein the active ingredient is 1,1'-[2,5-thiophene-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 13. A composition according to claim 1, wherein the active ingredient is 1,1'-[4,4'-(2,2'-bipyridine)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 14. A composition according to claim 1, wherein the active ingredient is 1,1'-[2,9-(1,10-phenanthroline)-bis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 15. A composition according to claim 1, wherein the active ingredient is 1,1'-[1,3-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form. 16. A composition according to claim 1, wherein the active ingredient is 1,1'-[1,4-phenylene-bis-(methylene)]-bis-1,4,7,10-tetraazacyclotetradecane in acid addition salt form. 17. The compound of claim 1, which is 1,1'-[5-nitro-1,3-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 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 in acid addition salt form. 19. The compound of claim 1, which is 1,1'-[2,3,5,6-tetra-fluoro-1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 20. The compound of claim 1, which is 1,1'-[1,4-naphthylene-bis-(methylene)]bis-1,4,8,11-tetraazacyclotetradecane in acid addition salt form. 21. The compound of claim 1, which is 1,1'-[1,3-phenylenebis-(methylene)]bis-1,5,9-triazacyclododecane in acid addition salt form. 22. The compound of claim 1, which is 1,1'-[1,4-phenylene-bis-(methylene)]-1,5,9-trlazacyclododecane in acid addition salt form. 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 1,1'-[2,5-dimethyl-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane. 33. The compound of claim 1, which is 1,1'-[2,5-dichloro-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane. 34. The compound of claim 1, which is 1,1'-[2-bromo-1,4-phenylenebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane. 35. The compound of claim 1, which is 1,1'-[6-phenyl-2,4-pyridinebis-(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane.