Claims
- 1. A compound having the formula
- 2. A compound in accordance with claim 2, wherein each q is 1 and said compound is a pharmaceutically acceptable salt.
- 3. A compound in accordance with claim 2, wherein said pharmaceutically acceptable salt is at least one quaternary nitrogen salt selected from the group consisting of a quaternary ammonium chloride, a quaternary ammonium iodide, a quaternary ammonium fluoride, a quaternary ammonium bromide, a quaternary ammonium oxyanion and a combination thereof.
- 4. A compound in accordance with claim 2, wherein said pharmaceutically acceptable salt is a quaternary ammonium iodide.
- 5. A compound in accordance with claim 1, wherein:
each R1 is a member selected from the group consisting of myristyl, oleyl, lauryl and palmityl.
- 6. A compound in accordance with claim 1 wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, secbutyl, hydroxymethyl, thiomethyl, carboxymethyl, guanidinopropyl, carbamoylmethyl, carbamoylethyl, benzyl, p-hydroxyphenylmethyl, 1-hydroxyethyl, 2-(methylthio)ethyl, 3-indolemethyl, carboxyethyl and aminobutyl.
- 7. A compound in accordance with claim 1, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl and isopropyl.
- 8. A compound in accordance with claim 1, wherein:
each Y1 and Y3 is a member independently selected from the group consisting of methyl, ethyl, propyl and butyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 9. A compound in accordance with claim 1, wherein at least one R2, Y1 and the atoms to which they are bound, join to form a member selected from the group consisting of a pyrrolidine ring, a 4-hydroxypyrrolidine ring and an imidazolylmethyl ring.
- 10. A compound in accordance with claim 1, wherein:
each R1 is a member independently selected from the group consisting of myristyl and oleyl; each R2 and R3 is hydrogen; each Y1 and Y3 is methyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 11. A compound in accordance with claim 10, wherein m is 1, n is 3, p is 0 and q is 0 or 1.
- 12. A compound in accordance with claim 10, wherein m is 3, n is 1, p is 0 and q is 0 or 1.
- 13. A compound in accordance with claim 10, wherein m is 2, n is 2, p is 0 and q is 0 or 1.
- 14. A compound in accordance with claim 10, wherein m is 1, n is 2, p is 1 and q is 0 or 1.
- 15. A transfection complex, said transfection complex comprising a nucleic acid and a compound of Formula I:
- 16. A transfection complex in accordance with claim 15, wherein each q is 1 and said compound is a pharmaceutically acceptable salt.
- 17. A transfection complex in accordance with claim 16, wherein said pharmaceutically acceptable salt is at least one quaternary nitrogen salt selected from the group consisting of a quaternary ammonium chloride, a quaternary ammonium iodide, a quaternary ammonium fluoride, a quaternary ammonium bromide, a quaternary ammonium oxyanion and a combination thereof.
- 18. A transfection complex in accordance with claim 15, wherein:
each R1 is a member selected from the group consisting of myristyl, oleyl, lauryl and palmityl.
- 19. A transfection complex in accordance with claim 15, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, secbutyl, hydroxymethyl, thiomethyl, carboxymethyl, guanidinopropyl, carbamoylmethyl, carbamoylethyl, benzyl, p-hydroxyphenylmethyl, 1-hydroxyethyl, 2-(methylthio)ethyl, 3-indolemethyl, carboxyethyl and aminobutyl.
- 20. A transfection complex in accordance with claim 15, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl and isopropyl.
- 21. A transfection complex in accordance with claim 15, wherein:
each Y1 and Y3 is a member independently selected from the group consisting of methyl, ethyl, propyl and butyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 22. A transfection complex in accordance with claim 15, wherein each R2, Y1 and the atoms to which they are bound, join to form a member independently selected from the group consisting of a pyrrolidine ring, a 4-hydroxypyrrolidine ring and an imidazolylmethyl ring.
- 23. A transfection complex in accordance with claim 15, wherein:
each R1 is a member selected from the group consisting of myristyl and oleyl; each R2 and R3 is hydrogen; each Y1 and Y3 is methyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 24. A transfection complex in accordance with claim 23, wherein m is 1, n is 3, p is 0 and q is 0 or 1.
- 25. A transfection complex in accordance with claim 23, wherein m is 3, n is 1, p is 0 and q is 0 or 1.
- 26. A transfection complex in accordance with claim 23, wherein m is 2, n is 2, p is 0 and q is 0 or 1.
- 27. A transfection complex in accordance with claim 23, wherein m is 1, n is 2, p is 1 and q is 0 or 1.
- 28. A transfection complex in accordance with claim 15, wherein said nucleic acid is RNA or DNA.
- 29. A transfection complex in accordance with claim 15, wherein said nucleic acid is plasmid DNA.
- 30. A transfection complex in accordance with claim 15, wherein said nucleic acid is antisense RNA or DNA.
- 31. A transfection complex in accordance with claim 23, wherein said transfection complex further comprises a second lipid.
- 32. A transfection complex in accordance with claim 23, wherein said second lipid is a member selected from the group consisting of DOSPA, DOPE, DMDHP, cholesterol and combinations thereof.
- 33. A method for transfecting a cell with a nucleic acid, said method comprising contacting said cell with a transfection complex comprising said nucleic acid and a compound of Formula I:
- 34. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein each q is 1 and said compound is a pharmaceutically acceptable salt.
- 35. A method for transfecting a cell with a nucleic acid in accordance with claim 34, wherein said pharmaceutically acceptable salt is at least one quaternary nitrogen salt selected from the group consisting of a quaternary ammonium chloride, a quaternary ammonium iodide, a quaternary ammonium fluoride, a quaternary ammonium bromide, a quaternary ammonium oxyanion and a combination thereof.
- 36. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein:
each R1 is a member independently selected from the group consisting of myristyl, oleyl, lauryl and palmityl.
- 37. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, secbutyl, hydroxymethyl, thiomethyl, carboxymethyl, guanidinopropyl, carbamoylmethyl, carbamoylethyl, benzyl, p-hydroxyphenylmethyl, 1-hydroxyethyl, 2-(methylthio)ethyl, 3-indolemethyl, carboxyethyl and aminobutyl.
- 38. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl and isopropyl.
- 39. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein:
each Y1 and Y3 is a members independently selected from the group consisting of methyl, ethyl, propyl and butyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 40. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein at least one R2, Y1 and the atoms to which they are bound, join to form a member selected from the group consisting of a pyrrolidine ring, a 4-hydroxypyrrolidine ring and an imidazolylmethyl ring.
- 41. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein:
each R1 is a member selected from the group consisting of myristyl and oleyl; each R2 and R3 is hydrogen; each Y1 and Y3 is methyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 42. A method for transfecting a cell with a nucleic acid in accordance with claim 41, wherein m is 1, n is 3, p is 0 and q is 0 or 1.
- 43. A method for transfecting a cell with a nucleic acid in accordance with claim 41, wherein m is 3, n is 1, p is 0 and q is 0 or 1.
- 44. A method for transfecting a cell with a nucleic acid in accordance with claim 41, wherein m is 2, n is 2, p is 0 and q is 0 or 1.
- 45. A method for transfecting a cell with a nucleic acid in accordance with claim 41, wherein m is 1, n is 2, p is 1 and q is 0 or 1.
- 46. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein said nucleic acid is RNA or DNA.
- 47. A method for transfecting a cell with a nucleic acid in accordance with claim 33, wherein said transfection complex further comprises a second lipid.
- 48. A pharmaceutical composition comprising:
(a) a transfection complex comprising a nucleic acid and a compound of Formula I: 9 or a pharmaceutically acceptable salt thereof, wherein:
each R1 is independently selected from the group consisting of optionally substituted C8-C24 alkyl and optionally substituted C8-C24 alkenyl; each R2 and R3 is independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted arylalkyl, optionally substituted C1-C8 alkylthioalkyl, optionally substituted guanidinoalkyl, optionally substituted carboxyalkyl, optionally substituted aminoalkyl, optionally substituted carbamoyl C1-C8 alkyl and optionally substituted heteroarylalkyl; each Y1 and Y2 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted arylalkyl, optionally substituted C1-C6 alkylthioalkyl, optionally substituted guanidinoalkyl, optionally substituted carboxyalkyl, optionally substituted aminoalkyl, optionally substituted carbamoyl C1-C8 alkyl and optionally substituted heteroarylalkyl; each Y3, if present, is independently selected from the group consisting of hydrogen, optionally substituted C1-C8 alkyl, optionally substituted arylalkyl, optionally substituted C1-C8 alkylthioalkyl, optionally substituted guanidinoalkyl, optionally substituted carboxyalkyl, optionally substituted aminoalkyl, optionally substituted carbamoyl C1-C8 alkyl and optionally substituted heteroarylalkyl; m is an integer selected from the group consisting of 1, 2, 3 and 4, n is an integer selected from the group consisting of 0, 1, 2 and 3, and p is an integer selected from the group consisting of 0 and 1, wherein the sum of m, n and p is 4; each k is an integer independently selected from the group consisting of 1, 2, 3, 4 and 5; and each q is an integer independently selected from the group consisting of 0 and 1; or, each R2, Y1 and the atoms to which they are bound, join to form an optionally substituted 5- or 6-membered heterocyclic ring, with the proviso that if m is 2, n is 2, q is 0 and Y1 is hydrogen, then Y2 is not an optionally substituted aminoalkyl; and (b) a pharmaceutically acceptable carrier.
- 49. A pharmaceutical composition in accordance with claim 49, wherein each q is 1 and said compound is a pharmaceutically acceptable salt.
- 50. A pharmaceutical composition in accordance with claim 49, wherein said pharmaceutically acceptable salt is at least one quaternary nitrogen salt selected from the group consisting of a quaternary ammonium chloride, a quaternary ammonium iodide, a quaternary ammonium fluoride, a quaternary ammonium bromide, a quaternary ammonium oxyanion and a combination thereof.
- 51. A pharmaceutical composition in accordance with claim 49, wherein:
each R1 is a member independently selected from the group consisting of myristyl, oleyl, lauryl and palmityl.
- 52. A pharmaceutical composition in accordance with claim 49, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, isobutyl, secbutyl, hydroxymethyl, thiomethyl, carboxymethyl, guanidinopropyl, carbamoylmethyl, carbamoylethyl, benzyl, p-hydroxyphenylmethyl, 1-hydroxyethyl, 2-(methylthio)ethyl, 3-indolemethyl, carboxyethyl and aminobutyl.
- 53. A pharmaceutical composition in accordance with claim 49, wherein:
each R2 and R3 is a member independently selected from the group consisting of hydrogen, methyl and isopropyl.
- 54. A pharmaceutical composition in accordance with claim 49, wherein:
each Y1 and Y3 is a member independently selected from the group consisting of methyl, ethyl, propyl and butyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 55. A pharmaceutical composition in accordance with claim 49, wherein at least one R2, Y1 and the atoms to which they are bound, join to form a member selected from the group consisting of a pyrrolidine ring, a 4-hydroxypyrrolidine ring and an imidazolylmethyl ring.
- 56. A pharmaceutical composition in accordance with claim 49, wherein:
each R1 is a member independently selected from the group consisting of myristyl and oleyl; each R2 and R3 is hydrogen; each Y1 and Y3 is methyl; and each Y2 is a member independently selected from the group consisting of N,N-dimethylethylamine, N,N-dimethylpropylamine and N,N-dimethylbutylamine.
- 57. A pharmaceutical composition in accordance with claim 56, wherein m is 1, n is 3, p is 0 and q is 0 or 1.
- 58. A pharmaceutical composition in accordance with claim 56, wherein m is 3, n is 1, p is 0 and q is 0 or 1.
- 59. A pharmaceutical composition in accordance with claim 56, wherein m is 2, n is 2, p is 0 and q is 0 or 1.
- 60. A pharmaceutical composition in accordance with claim 56, wherein m is 1, n is 2, p is 1 and q is 0 or 1.
- 61. A pharmaceutical composition in accordance with claim 49, wherein said nucleic acid is DNA or RNA.
- 62. A pharmaceutical composition in accordance with claim 49, wherein said transfection complex further comprises a second lipid.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Provisional Patent Application Nos. 60/384,514 and 60/385,234, both filed on May 31, 2002, the disclosures of which are hereby incorporated by reference in their entireties for all purposes.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60384514 |
May 2002 |
US |
|
60385234 |
May 2002 |
US |