Claims
- 1. A compound according to formula I
- 2. The compound of claim 1, wherein at least one of the following pairs is deleted and the valency of the ring carbon atoms at these deleted positions is completed with a double bond: R5 and R9; R8 and R10; and R13 and R14.
- 3. The compound of claim 1, wherein at least three of R1 through R14 are independently selected from the group consisting of a substituted or unsubstituted (C1-C10) aminoalkyloxy, (C1-C10) alkylcarboxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, a substituted or unsubstituted arylamino-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, H2N—HC(Q5)—C(O)—O—, H2N—HC(Q5)—C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkyloxy, (C1-C10) quaternaryammoniumalkylcarboxy, P.G.—HN—HC(Q5)—C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy.
- 4. The compound of claim 3, wherein the 3 of R1 through R14 independently selected from the group consisting of a substituted or unsubstituted (C1-C10) alkylcarboxy-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkyl, (C1-C10) alkylamino-(C1-C10) alkylamino, (C1-C10) alkylamino-(C1-C10) alkylamino-(C1-C10) alkylamino, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted arylamino-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkyloxy-(C1-C10) alkyl, and (C1-C10) quaternaryammoniumalkylcarboxy.
- 5. The compound of claim 1, wherein the second steroid is a compound of formula I.
- 6. The compound of claim 1, wherein the linking group is (C1-C10) alkyl-oxy-(C1-C10) alkyl.
- 7. The compound of claim 1, wherein none of R5, R8, R9, R13, and R14 is deleted.
- 8. The compound of claim 1, wherein each of R3, R7, and R12 is independently selected from the group consisting of a substituted or unsubstituted (C1-C10) aminoalkyloxy, a substituted or unsubstituted (C1-C10) aminoalkylcarboxy, a substituted or unsubstituted (C1-C10) aminoalkylaminocarbonyl, a substituted or unsubstituted (C1-C10) aminoalkylcarboxamido, H2N—HC(Q5)—C(O)—O—, H2N—HC(Q5)—C(O)—N(H)—, (C1-C10) azidoalkyloxy, (C1-C10) cyanoalkylcarboxy, P.G.—HN—HC(Q5)—C(O)—O—, (C1-C10) guanidinoalkyloxy, and (C1-C10) guanidinoalkylcarboxy, where Q5 is a side chain of any amino acid, P.G. is an amino protecting group or a pharmaceutically acceptable salt thereof.
- 9. The compound of claim 8, wherein R1, R2, R4, R5, R6, R8, R10, R11, R13, R14, R15, and R16 are hydrogen.
- 10. The compound of claim 9, wherein R17 is —CR18R19R20, where each of R18, R19, and R20, is independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C1-C10) alkyl, (C1-C10) hydroxyalkyl, (C1-C10) alkyloxy-(C1-C10) alkyl, a substituted or unsubstituted (C1-C10) aminoalkyl, a substituted or unsubstituted aryl, (C1-C10) haloalkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, oxo, and a linking group attached to a second steroid.
- 11. The compound of claim 8, wherein each of R3, R7, and R12, is independently selected from the group consisting of —O—(CH2)n-NH2, —O—CO—(CH2)n-NH2, —O—(CH2)n-NH—C(NH)—NH2, —O—(CH2)n-N3, —O—(CH2)n-CN, where n is 1 to 3, and —O—C(O)—HC(Q5)—NH2, where Q5 is a side chain of any amino acid.
- 12. The compound of claim 8, wherein each of R3, R7, and R12, is —O—CO—(CH2)n-NH2, where n is 1 to 4.
- 13. The compound of claim 12, wherein R17 is —CH(CH3)(CH2)3—O—(CH2)n—NH2, wherein n is 1-7.
- 14. The compound of claim 12, wherein R17 is —CH(CH3)—(CH2)n—NR1R2, wherein n is 0-2, R1 and R2 are independently (C1-C6) alkyl, aryl or aralkyl.
- 15. The compound of claim 1, wherein R17 is —CH(CH3)(CH2)n1—CO—OR3, where R3 is selected from —(CH2)n2N+(CH3)3, wherein n1 and n2 are independently 1-4.
- 16. The compound of claim 15, wherein R3, R7, and R12 are —O—C(O)—(CH2)n—NH2, wherein n is 1-5.
- 17. The compound of claim 1 having the following formula:
- 18. The compound of claim 1 having the following formula:
- 19. The compound of claim 1 having the formula:
- 20. A method of preparing the compound according to formula I
- 21. The method of claim 20, wherein the electrophile is allylbromide.
- 22. A method of producing a compound of formula I:
- 23. The method of claim 22, wherein the guanidino producing electrophile is HSO3—C(NH)—NH2.
- 24. A pharmaceutical composition comprising an effective amount of a compound of claim 1.
- 25. The pharmaceutical composition of claim 24, wherein the composition includes additional antibiotics.
- 26. A method of treating a microbial infection of a host by administering to the host an effective amount of an anti-microbial composition comprising a compound according to claim 1.
- 27. The method of claim 26 wherein the host is a human.
- 28. The method of claim 26 wherein the anti-microbial composition further comprises a second anti-microbial substance to be delivered into a microbial cell.
- 29. The method of claim 28 wherein the second anti-microbial substance is an anti-biotic.
- 30. The method of claim 26 wherein the infection is a bacterial infection.
- 31. The method of claim 30 wherein the infection is a infection a Gram-negative bacterial infection.
- 32. The method of claim 30 wherein the bacterial infection is an infection with a bacterium characterized by an outer membrane comprising a substantial percentage of lipid A.
- 33. A method of enhancing cell permeability by administering to the cell a permeability-enhancing amount of the compound of claim 1.
- 34. The method of claim 33 further comprising administering to the cell a substance to be introduced into the cell.
- 35. The method of claim 34 in which the cell is a bacterium.
- 36. The method of claim 35 in which the bacterium is a Gram-negative bacterium.
- 37. The method of claim 34 in which the cell is a sperm cell and the compound is part of a spermicidal composition.
- 38. A method of identifying compounds effective against a microbe comprising administering a candidate compound and a compound according to claim 1 to the microbe and determining whether the candidate compound has a static or toxic effect on the microbe.
- 39. The method of claim 38 in which the microbe is a Gram-negative bacterium.
- 40. A method of microbial growth control comprising contacting a microbe with an effective amount of anti-microbial composition comprising a compound according to claim 1.
- 41. A composition of matter comprising the compound of claim 1 in combination with an anti-microbial substance to be introduced into a cell.
- 42. A compound comprising a ring system of at least 4 fused rings, each of the rings having from 5-7 atoms, the ring system having two faces, wherein the compound comprises 3 chains attached to the same face of the ring system, each of the chains containing a multiple nitrogen-containing group, wherein the multiple nitrogen-containing group is separated from the ring system by at least one atom, and wherein the multiple nitrogen-containing group is a (C1-C10) alkylamino (C1-C1) alkyamino group or a (C1-C10) alkylamino (C1-C1) alkyamino (C1-C1) alkyamino group.
- 43. The compound of claim 42, wherein each of the mulitiple nitrogen-containing groups is separated from the steroid backbone by at least two atoms.
- 44. The compound of claim 43, wherein each of the multiple nitrogen-containing groups is separated from the steroid backbone by at least three atoms.
- 45. The compound of claim 44, wherein each of the multiple nitrogen-containing groups is separated from the steroid backbone by at least four atoms.
- 46. The compound of claim 42, wherein the compound further comprises a hydrophobic group attached to the steroid backbone.
- 47. The compound of claim 42, wherein the hydrophobic group is selected from the group consisting of a substituted (C3-10) aminoalkyl group, a (C1-10) alkyloxy (C3-10) alkyl group, and a (C1-10) alkylamino (C3-10)alkyl group.
- 48. A pharmaceutical composition comprising an effective amount of a compound of claim 42.
- 49. A method of enhancing cell permeability by administering to the cell a permeability enhancing amount of the compound of claim 42.
- 50. A compound of claim 1 having the formula:
- 51. The compound of claim 1, wherein R1 is hydrogen and R2 is (C1-C10) alkylamino-(C1-C10) alkylamino.
- 52. The compound of claim 1, wherein R1 is (C1-C10) alkylamino, and R2 is (C1-C10) alkylamino.
- 53. A compound according to formula I
- 54. The compound of claim 53, wherein the compound has the formula:
- 55. The compound of claim 53, wherein the compound has the formula:
- 56. The compound of claim 53, wherein the compound has the formula:
- 57. The compound of claim 53, wherein the compound has the formula:
- 58. The compound of claim 53, wherein the compound has the formula:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation-in-part of U.S. patent application Ser. No. 09/234,008, filed Jan. 19, 1999, which is a continuation-in-part of PCT/US 98/04489, filed Mar. 6, 1998, each of which is hereby incorporated by reference in its entirety. This application claims priority from provisional application U.S. No. 60/225,467, filed Aug. 15, 2000, which is hereby incorporated by reference in its entirety.
STATEMENT OF GOVERNMENT INTEREST
[0002] This invention was made with support from the National Institutes of Health (GM 54619). The government has certain rights in this invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60225467 |
Aug 2000 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
09234008 |
Jan 1999 |
US |
Child |
09930316 |
Aug 2001 |
US |
Parent |
PCT/US98/04489 |
Mar 1998 |
US |
Child |
09234008 |
Jan 1999 |
US |