Claims
- 1. A quaternary nitrogen-containing phosphonate and the pharmaceutically-acceptable salts and esters thereof, having the following structure: ##STR24## wherein m and n are integers from 0 to 10; m+n is from 0 to 10; (a) Q is a covalent bond or a moiety selected from O, S, or NR.sup.1 ;
- (b) Y is N.sup.+ (R.sup.8).sub.2 or C(R.sup.1).sub.2, and when Y is C(R.sup.1).sub.2, at least one R.sup.2 must be N.sup.+ R.sup.8).sub.3 ;
- (c) Z is a six-membered saturated, unsaturated, or aromatic, monocyclic heterocycle containing one heteroatom, wherein said heteroatom is nitrogen;
- (d) R is PO.sub.3 H.sub.2 or P(O)(OH)R.sup.4, wherein R.sup.4 is substituted or unsubstituted alkyl of 1-8 carbon atoms;
- (e) each R.sup.1 is independently selected from the group consisting of nil; SR.sup.6 ; R.sup.9 SR.sup.6 ; hydrogen; hydroxy; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; --OR.sup.3 ; --CO.sub.2 R.sup.3 ; --O.sub.2 CR.sup.3 ; --NR.sup.3.sub.2 ; --N(R.sup.3)C(O)R.sup.3 --C(O)N(R.sup.3).sub.2 ; halogen; --C(O)R.sup.3 ; arylalkyl; nitro; substituted or unsubstituted aryl; and combinations thereof;
- (f) R.sup.2 is one or more substituents on the Z moiety independently selected from the group consisting of N.sup.+ (R.sup.8).sub.3 ; SR.sup.6 ; R.sup.9 SR.sup.6 ; hydrogen; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; --OR.sup.3 ; --CO.sub.2 R.sup.3 ; --O.sub.2 CR.sup.3 ; --NR.sup.3.sub.2 ; --N(R.sup.3)C(O)R.sup.3 ; --C(O)N(R.sup.3).sub.2 ; halogen; hydroxy; --C(O)R.sup.3 ; arylalkyl; nitro; and substituted or unsubstituted aryl;
- (g) each R.sup.3 is independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl having from 1-8 carbon atoms, and R.sup.9 SR.sup.6 ;
- (h) R.sup.5 is selected from the group consisting of hydrogen; halogen; SR.sup.6 ; R.sup.9 SR.sup.6 ; amino; hydroxy; and substituted or unsubstituted C.sub.1 -C.sub.8 alkyl;
- (i) each R.sup.6 is independently selected from the group consisting of H; --C(O)R.sup.7 ; --C(S)R.sup.7 ; --C(O)NR.sup.7.sub.2 ; --C(S)N(R.sup.7).sub.2 ; --C(S)OR.sup.7 ; and --C(O)OR.sup.7 ; wherein R.sup.7 is hydrogen or substituted or unsubstituted C.sub.1 -C.sub.8 alkyl;
- (j) each R.sup.8 is independently selected from the group consisting of nil, substituted or unsubstituted alkyl having 1-35 carbon atoms, substituted or unsubstituted phenyl, benzyl, and R.sup.9 SR.sup.6 ; and
- (k) R.sup.9 is substituted or unsubstituted C.sub.1 -C.sub.8 alkyl.
- 2. A quaternary nitrogen-containing phosphonate compound, according to claim 1, wherein Y is N.sup.+ (R.sup.8).sub.2.
- 3. A compound, according to claim 2, wherein Z is pyridinium or piperidinium.
- 4. A compound, according to claim 3, wherein Z is pyridinium.
- 5. A compound, according to claim 1, wherein Q is N or NR.sup.1.
- 6. A compound, according to claim 1, wherein R.sup.1 is independently selected from --SR.sup.6 ; R.sup.9 SR.sup.6 ; hydrogen; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; --NR.sup.3.sub.2 ; or --CO.sub.2 R.sup.3.
- 7. A compound, according to claim 6, wherein R.sup.1 is --SR.sup.6 ; R.sup.9 SR.sup.6 ; or hydrogen.
- 8. A compound, according to claim 1, wherein R.sup.2 is --SR.sup.6 ; R.sup.9 SR.sup.6 ; hydrogen; substituted or unsubstituted C.sub.1 -C.sub.8 alkyl; --NR.sup.3.sub.2 ; --OR.sup.3 ; or --CO.sub.2 R.sup.3.
- 9. A compound, according to claim 8, wherein R.sup.2 is --SR.sup.6 ; R.sup.9 SR.sup.6 ; or hydrogen.
- 10. A compound, according to claim 1, wherein R.sup.3 is hydrogen; R.sup.9 SR.sup.6 ; or unsubstituted or substituted C.sub.1 -C.sub.8 alkyl.
- 11. A compound, according to claim 6, wherein R.sup.3 is hydrogen; or R.sup.9 SR.sup.6.
- 12. A compound, according to claim 10, wherein R.sup.3 is hydrogen or R.sup.9 SR.sup.6.
- 13. A compound, according to claim 6, wherein R.sup.6 is H; --C(O)R.sup.7 ; C(S)R.sup.7 ; or C(O)N(R.sup.7).sub.2.
- 14. A compound, according to claim 13, wherein R.sup.6 is H; --C(O)R.sup.7 ; or C(S)R.sup.7.
- 15. A compound, according to claim 11, wherein R.sup.6 is H; --C(O)R.sup.7 ; C(S)R.sup.7 ; or C(O)N(R.sup.7).sub.2.
- 16. A compound, according to claim 13, wherein R.sup.6 is H; --C(O)R.sup.7 ; C(S)R.sup.7 ; or C(O)N(R.sup.7).sub.2.
- 17. A compound, according to claim 8, wherein R.sup.6 is H; --C(O)R.sup.7 ; C(S)R.sup.7 ; or C(O)N(R.sup.7).sub.2.
- 18. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a quaternary nitrogen-containing heterocyclic phosphonate compound according to claim 1; and
- (b) a pharmaceutically-acceptable excipient.
- 19. A pharmaceutical composition comprising:
- (a) a safe and effective amount of a quaternary nitrogen-containing heterocyclic phosphonate compound according to claim 2; and
- (b) a pharmaceutically-acceptable excipient.
- 20. A compound according to claim 1, wherein R.sup.8 is an unsubstituted or substituted alkyl having 10 to 20 carbon atoms.
- 21. An anti-calculus, anti-plaque, and anti-gingivitis oral composition comprising:
- (a) a safe and effective amount of a quaternary nitrogen-containing heterocyclic phosphonate compound according to claim 20; and
- (b) a pharmaceutically-acceptable excipient.
- 22. A method for treating or preventing dental calculus, plaque, and gingivitis in humans and other mammals in need of such treatment comprising administering to a human or other mammal a safe and effective amount of a quaternary nitrogen-containing heterocyclic phosphonate compound of claim 20.
Parent Case Info
This application is a continuation-in-part application of U.S. Ser. No. 07/890,885, which was filed May 29, 1992 now abandoned.
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Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
890885 |
May 1992 |
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