CA2350882A1 - Transfection reagents - Google Patents

Transfection reagents Download PDF

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CA2350882A1
CA2350882A1 CA002350882A CA2350882A CA2350882A1 CA 2350882 A1 CA2350882 A1 CA 2350882A1 CA 002350882 A CA002350882 A CA 002350882A CA 2350882 A CA2350882 A CA 2350882A CA 2350882 A1 CA2350882 A1 CA 2350882A1
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group
alkyl
independently
alkenyl
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CA2350882C (en
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Yongliang Chu
Malek Masoud
Gulilat Gebeyehu
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Life Technologies Corp
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
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    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/20—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
    • C07C211/21—Monoamines
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C211/63—Quaternary ammonium compounds having quaternised nitrogen atoms bound to acyclic carbon atoms
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract

Disclosed are compounds capable of facilitating transport of biologically active agents or substances into cells having general structure (A).

Claims (109)

1. A compound having the formula:
wherein Q is selected from the group consisting of N, O and S;
L is C, CH, (CH2)l, or {(CH2)i -Y-(CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine , a carbonyl, and a secondary amino group and wherein Y is optionally substituted by -X1-L'-X2-Z or -Z;
R1 - R6, independently of one another, are selected from the group consisting of H, -(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms; and R1 and R4 or R3 and R6 may optionally be covalently linked with each other, with Y or with L when L is C or CH to form a cyclic moiety;
Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein;
X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene;
L' is selected from the group consisting of alkyl, alkenylene, alkynylene, arylene, alkylene ether, and polyether;
D is Q or a bond;

A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C(NH), C(S) and (CH2)t;
X is a physiologically acceptable anion;
m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0;
i, j, k, l, p and t are integers from 0 to about 100;
q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
2. The compound as claimed in claim 1, wherein at least one of R1, R3, R4 and is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl having from about 8 to about 24 carbon atoms.
3. The compound as claimed in claim 1, wherein the alkyl ether optionally substituted by one or more alcohol groups comprises a carbohydrate.
4. The compound as claimed in claim 3, wherein the carbohydrate is selected from the group consisting of galactose, fructose, glucose, maltose, sucrose, cellobiose, lactose, mannose, glucopyranose, mannopyranose and galactopyranose.
5. A compound as claimed in claim 1, wherein said compound has the formula:
wherein L is (CH2)l or {(CH2)i -Y- (CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, and a secondary amino group;

R1 - R6, independently of one another, are selected from the group consisting of H, -(CH2)p-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms; and R1 and R4 or R3 and R6 may optionally be covalently linked with each other to form a cyclic moiety;
Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein;
A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C(NH), C(S) and (CH2)t;
X is a physiologically acceptable anion;
m,n,v and w are 0 or 1;
i, j, k, l, p and t are integers from 1 to about 100;
q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion, wherein when m and n are 0, then a is 0.
6. The compound as claimed in claim 5, wherein at least one of R1, R3, R4 and is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl having from about 8 to about 24 carbon atoms.
7. The compound as claimed in claim 5, wherein the alkyl ether optionally substituted by one or more alcohol groups comprises a carbohydrate.
8. The compound as claimed in claim 7, wherein the carbohydrate is selected from the group consisting of galactose, fructose, glucose, maltose, sucrose, cellobiose, lactose, mannose, glucopyranose, mannopyranose and galactopyranose.
9. The compound as claimed in claim 5, wherein said compound has the formula:
wherein R1, R3, R4 and R6, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms; and 1, b and c are integers independently selected from 1 to about 4.
10. The compound as claimed in claim 9, which is:
11. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Q and L are as defined in claim 1;
R1, R3, R4 and R6, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
r, s, u and y are 0 or 1; and R7 and R8 are independently H or a carbohydrate.
12. The compound as claimed in claim 11, wherein said compound has the formula:
wherein R1, R3, R4 and R6, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkenyl or aryl group having from about 8 to about 24 carbon atoms;
R7 and R8 are independently H or a carbohydrate; and 1 is an integer from 1 to about 4.
13. The compound as claimed in claim 12, which is:

wherein R7 and R8 are independently H or a carbohydrate.
14. The compound as claimed in claim 13, wherein R7 and R8 are H.
15. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Q is as defined in claim 1;
R1, R2, R4 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
Z is selected from the group consisting of spermiyl, spermidiyl, amino acid, peptidyl, diaminoalkyl, and polyamine;
m, n, r and a are 0 or 1; and 1, b and c are integers independently selected from 1 to about 4.
16. The compound as claimed in claim 5, wherein said compound has the formula:
wherein R1, R2, R4 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R2, R4 and R5 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
Z is selected from the group consisting of spermiyl, spermidiyl, amino acid, peptidyl, diaminoalkyl, and polyamine;
m and n are 0 or 1; and 1, b and c are integers independently selected from 1 to about 4.
17. The compound as claimed in claim 16, which is:

18. The compound as claimed in claim 16, which is:

19. The compound as claimed in claim 16, which is:
20. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Q, R1, R4, m, n, r and a are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
Z is selected from the group consisting of spermiyl, spermidiyl, amino acid, peptidyl, diaminoalkyl, and polyamine;
R7 and R8 are independently H or a carbohydrate; and 1 is an integer from 1 to about 4.
21. The compound as claimed in claim 20, wherein said compound has the formula:
wherein Q as defined in claim 1;
at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
Z is selected from the group consisting of spermiyl, spermidiyl, amino acid, peptidyl, diaminoalkyl, and polyamine;
R7 and R8 are independently H or a carbohydrate; m and n are as defined in claim 1; and 1 is an integer from 1 to about 4.
22. The compound as claimed in claim 21, wherein Q is N and R7 and R8 are H.
23. The compound as claimed in claim 21 which is:

wherein R7 and R8 are independently H or a carbohydrate.
24. The compound according to claim 23, wherein R7 and R8 are H.
25. The compound as claimed in claim 21, which is:
wherein R7 and R8 are independently H or a carbohydrate.
26. The compound as claimed in claim 25, wherein R7 and R8 are H.
27. The compound as claimed in claim 21, which is:

wherein R7 and R8 are independently H or a carbohydrate.
28. The compound as claimed in claim 27, wherein R7 and R8 are H.
29. The compound as claimed in claim 5, wherein said compound has the formula:
wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms; and 1, b and c are integers independently selected from 1 to about 4.
30. The compound as claimed in claim 29, which is:

31. The compound as claimed in claim 29, which is:
32. The compound as claimed in claim 5, wherein said compound has the formula:
wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms; R7 and R8 are independently hydrogen or a carbohydrate; and 1 is an integer from 1 to about 4.
33. The compound as claimed in claim 32, which is:
wherein R7 and R8 are independently H or a carbohydrate.
34. The compound as claimed in claim 33, wherein R7, and R8 are H.
35. The compound as claimed in claim 32, which is:

wherein R7 and R8 are independently H or a carbohydrate.
36. The compound as claimed in claim 35, wherein R7 and R8 are H.
37. The compound as claimed in claim 32, which is:
wherein R7 and R8 independently are H or a carbohydrate.
38. The compound as claimed in claim 37, wherein R7 and R8 are H.
39. The compound as claimed in claim 32, which is:

wherein R7 and R8 are H or a carbohydrate.
40. The compound as claimed in claim 39, wherein R7 and R8 are H.
41. The compound as claimed in claim 5, wherein said compound has the formula:

wherein Z is as defined in claim 5;
at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
R7 and R8 are independently H or a carbohydrate;
m and n are 0 or 1;
i and j are integers from about 2 to about 3; and k is an integer from 1 to about 3.
42. The compound as claimed in claim 5, wherein said compound has the formula:

wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3; and k is an integer from 1 to about 3.
43. The compound as claimed in claim 42, which is:

44. The compound as claimed in claim 42, which is:

45. The compound as claimed in claim 1, wherein said compound has the formula:

wherein Q, R1, R4, r, u, m and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3; and k is an integer from 1 to about 3.
46. The compound as claimed in claim 5, wherein said compound has the formula:

wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3; and k is an integer from 1 to about 3.
47. The compound as claimed in claim 46, which is:

48. The compound as claimed in claim 1, wherein said compound has the formula:

wherein Q, R1, R4, r, u, m and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
49. The compound as claimed in claim 5, wherein said compound has the formula:

wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1- C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
50. The compound as claimed in claim 49, which is:

51. The compound as claimed in claim 49, which is:

wherein R7 and R8 are independently H or a carbohydrate.
52. The compound as claimed in claim 51, wherein R7 and R8 are H.
53. The compound as claimed in claim 49, which is:

54. The compound as claimed in claim 5, which is:

55. The compound as claimed in claim 1, wherein said compound has the formula:

wherein Q, R1, R4, r, u, m and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1-C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
56. The compound as claimed in claim 5, wherein said compound has the formula:

wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one-another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;

m and n are 0 or 1;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
57. The compound as claimed in, claim 56, which is:

58. The compound as claimed in 56, which is:

wherein R7 and R8 are independently H or a carbohydrate.
59. The compound as claimed in claim 58, wherein R7 and R8 are H.
60. The compound as claimed in 56, which is:

61. The compound as claimed in claim 5, which is:

wherein R7 and R8 are independently H or a carbohydrate.
62. The compound as claimed in claim 61, wherein R7 and R8 are H.
63. The compound as claimed in claim 1, wherein said compound has the formula:

wherein Q, R1, R4, r, u, m and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
64. The compound as claimed in claim 5, wherein said compound has the formula:
wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
65. The compound as claimed in claim 64, which is:

66. The compound as claimed in claim 64, which is:
wherein R7 and R8 are independently H or a carbohydrate.
67. The compound as claimed in claim 66, wherein R7 and R8 are H.
68. The compound as claimed in claim 64, which is:

wherein R7 and R8 are independently H or a carbohydrate.
69. The compound as claimed in claim 68, wherein R7 and R8 are H.
70. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Q, R1, R2, r, u, m and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;

L1 and L2 independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
71. The compound as claimed in claim 5, wherein said compound has the formula:
wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
72. The compound as claimed in claim 71, which is:

73. The compound as claimed in claim 71, which is:
wherein R7 and R8 are independently H or a carbohydrate.
74. The compound according to claim 73, wherein R7 and R8 are H.
75. The compound as claimed in claim 71, which is:
wherein R7 and R8 independently are H or a carbohydrate.
76. The compound as claimed in claim 75, wherein R7 and R8 are H.
77. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Q, R1, R4, r, u, m, and n are as defined in claim 1;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;

L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
78. The compound as claimed in claim 5, wherein said compound has the formula:
wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms;
R2 and R5, independently of one another, are selected from the group consisting of H and a C1 - C8 alkyl, alkenyl, aryl, and alkyl optionally substituted by one or more of an alcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group;
m and n are 0 or 1;
i and j are integers from about 2 to about 3;
k is an integer from 1 to about 3;
L1 and L2, independently from one another, are an alkylene or an alkylene ether;
and Y is selected from the group consisting of CH2, O, S and NH.
79. The compound as claimed in claim 78, which is:

80. The compound as claimed in claim 78, which is:
wherein R7 and R8 are independently H or a carbohydrate.
81. The compound as claimed in claim 80, wherein R7 and R8 are H.
82. The compound as claimed in clam 78, which is:

wherein R7 and R8 are independently H or a carbohydrate.
83. The compound as claimed in claim 82, wherein R7 and R8 are H.
84. The compound as claimed in claim 5, which is:
85. The compound as claimed in claim 1, wherein said compound has the formula:
wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by -X1-L'-X2 -Z or -Z;
R1, R3, R4 and R6, independently of one another, are selected from the group consisting of H, -(CH2)P-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or an alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from 6 to about 64 carbon atoms; and R1, R3, R4 and R6 may optionally be covalently linked with each other or with Y, to form a cyclic moiety;
Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein;
X1 and X2, independently of one another, are selected from the group consisting of NH, O, S, alkylene, and arylene;
L' is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether;
D is Q or a bond;
m and n are 0 or 1; and i, j, k, l and p are integers from 1 to about 10.
86. The compound as claimed in claim 85, wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms.
87. The compound as claimed in claim 85, wherein the alkyl ether optionally substituted by one or more alcohol groups is a carbohydrate.
88. The compound as claimed in claim 87, wherein the carbohydrate is selected from the group consisting of galactose, fructose, glucose, maltose, sucrose, cellobiose, lactose, mannose, glucopyranose, mannopyranose and galactopyranose.
89. The compound as claimed in claim 85, wherein said compound has the formula:
wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, and a secondary amino group;
R1, R3, R4 and R6, independently of one another, are selected from the group consisting of H, -(CH2)P -Z, an alkyl, an alkenyl, an aryl, and an alkyl or an alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms; and R1, R3, R4 and R6 may optionally be covalently linked with each other, to form a cyclic moiety;
Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein;

m and n are 0 or 1; and i, j, k, l and p are integers from 1 to about 10.
90. The compound as claimed in claim 89, wherein at least one of R1 and R4 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms.
91. The compound as claimed in claim 89, wherein the alkyl ether optionally substituted by one or more alcohol groups is a carbohydrate.
92. The compound as claimed in claim 91, wherein the carbohydrate is selected from the group consisting of galactose, fructose, glucose, maltose, sucrose, cellobiose, lactose, mannose, glucopyranose, mannopyranose and galactopyranose.
93. A compound having the formula:
wherein Q is selected from the group consisting of N, O and S;
L is a bivalent organic radical capable of covalently linking each Q;
R1 - R6, independently of one another, are selected from the group consisting of H, -(CH2)p-D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms; and R1 and R4 or R3 and R6 may optionally be covalently linked with each other, or with L to form a cyclic moiety;

Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, peptide, and protein;
D is Q or a bond;
A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C(NH), C(S) and (CH2)t;
X is a physiologically acceptable anion;
m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, a and y is other than 0;
i, j, k, l, p and t are integers from 0 to about 100;
q is an integer from 1 to about 1000; and a is the number of positive charge divided by the valence of the anion.
94. The compound as claimed in any one of claims 1, 2, 5, 6, 9, 11, 12, 15, 16, 20, 21, 22, 29, 32, 41, 42, 45, 46, 48, 49, 55, 56, 63, 64, 70, 71, 77, 78, 85, 86, 87, 88, 89, 90, 91, 92 and 93, wherein said cyclic group is a cholesteryl group.
95. A compound or a polycation having the formula:

wherein L is C, CH, (CH2)l, or {(CH2)i-Y-(CH2)j)k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, a phosphate, a sulfate, a sulfoxide, an imine, a carbonyl, and a secondary amino group and wherein Y is optionally substituted by -X,-L'-X2-Z or -Z;
R1-R6, independently of one another, are selected from the group consisting of H, -(CH2)p -D-Z, an alkyl, an alkenyl, an aryl, and an alkyl or an alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, an alkylthio, a urea, a thiourea, a guanidyl, or a carbamoyl group, and wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms;

Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, amino acid derivative, peptide, and protein;

X1 and X2, independently of ode another, are selected from the group consisting of NH, O, S, alkylene and arylene;

L' is selected from the group consisting of alkylene, alkenylene, alkynylene, arylene, alkylene ether, and polyether;

A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C(NH), C(S) and (CH2)t;

m, n, r, s, u, v, w and y are 0 or 1, with the proviso that when both m and n are 0 at least one of r, s, u and y is other than 0;

i, j, k, l, p and t are integers from 0 to about 100; and q is an integer from 1 to about 1000.
96. The compound or the polycation as claimed in claim 95, wherein at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms.
97. A compound or a polycation having the formula:

wherein L is (CH2)1 or {(CH2)i -Y- (CH2)j}k, wherein Y is selected from the group consisting of CH2, an ether, a polyether, an amide, a polyamide, an ester, a sulfide, a urea, a thiourea, a guanidyl, a carbamoyl, a carbonate, and a secondary amino group;

R1-R6, independently of one another, are selected from the group consisting of H, -(CH2)p -Z, an alkyl, an alkenyl, an aryl, and an alkyl or an alkyl ether optionally substituted by one or more of an alcohol, an aminoalcohol, an amine, an amide, an ether, a polyether, a polyamide, an ester, a mercaptan, a urea, a thiourea, a guanidyl, or a carbamoyl group, and at least one of R1, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 6 to about 64 carbon atoms;

Z is selected from the group consisting of amine, spermiyl, carboxyspermiyl, guanidyl, spermidinyl, putricinyl, diaminoalkyl, pyridyl, piperidinyl, pyrrolidinyl, polyamine, amino acid, amino acid derivative, peptide, and protein;

A1 and A2, independently of one another, are selected from the group consisting of CH2O, CH2S, CH2NH, C(O), C(NH), C(S) and (CH2)t;

m, n,v and w are 0 or 1;

i, j, k, l, p and t are integers from 1 to about 100; and q is an integer from 1 to about 1000.
98. The compound or the polycation as claimed in claim 97, wherein at least one of R,, R3, R4 and R6 is a straight chain or branched, cyclic, alkyl, alkenyl, alkynyl or aryl group having from about 8 to about 24 carbon atoms.
99. The compound or the polycation as claimed in claim 95 or 97, wherein the alkyl ether optionally substituted by one or more alcohol groups is a carbohydrate.
100. The compound or the polycation as claimed in claim 99, wherein the carbohydrate is selected from the group consisting of galactose, fructose, glucose, maltose, sucrose, cellobiose, lactose, mannose, glucopyranose, mannopyranose and galactopyranose.
101. A composition comprising one or more compounds of any one of claims 1 to 93.
102. A composition comprising one or more compounds of any one of claims 1 to and at least one additional component selected from the group consisting of a cell, cells, a cell culture, a cell culture media, a neutral lipid, a nucleic acid, and a transfection enhancer.
103. The composition of claim 102, which comprises a nucleic acid.
104. A lipid aggregate comprising one or more compounds of any one of claims 1 to 93.
105. The lipid aggregate of claim 104, which comprises at least one lipid aggregate-forming compound.
106. The lipid aggregate of claim 105, wherein said lipid aggregate-forming compound is selected from the group consisting of DOPE, DOPC and cholesterol.
107. A kit comprising one or more compounds of any one of claims 1 to 93 and at least one additional component selected from the group consisting of a cell, cells, a cell culture media, a nucleic acid, a transfection enhancer and instructions for transfecting a cell or cells.
108. A method for introducing a polyanion into a cell or cells, said method comprising forming a liposome from a positively charged compound of any one or claims 1 to 93, contacting the liposome with a polyanion to form a positively-charged polyanion-liposome complex and incubating the complex with a cell or cells.
109. A method for introducing a biologically active substance into a cell, said method comprising forming a liposome of a compound of any one of claims 1 to 93 and a biologically active substance and incubating the liposome with a cell or cell culture.
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