2,4,5-trisubstituted imidazoles and their use as anti-microbial agents 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
CA2496241 A1 2004-02-26 [CA2496241]CA2496241 C 2011-06-28 [CA2496241] / 2004-02-262011-06-28
申请号/申请日
2003CA-2496241 / 2003-08-19
发明人
AL-QAWASMEH RAED;HUESCA MARIO;LEE YOON S;YOUNG AIPING H;
申请人
APTOSE BIOSCIENCES;
主分类号
IPC分类号
A01N-043/50A01N-043/52A01N-043/90A61K-031/4164A61K-031/4178A61K-031/4184A61K-031/4188A61L-002/16C07D-233/22C07D-233/54C07D-235/02C07D-403/04C07D-403/14C07D-409/14C07D-471/14C07D-487/14
摘要
(CA2496241) The present invention provides therapeutically effective 2,4,5-trisubstituted imidazole compounds, methods of preparing the same, and compositions comprising the compounds alone or in combination with other agents.  The present invention further provides for the use of the compounds as anti-microbial agents.  The anti-microbial properties of the compounds include anti-bacterial and/or anti-fungal activity.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2002CA-2398765 2002-08-19 2003CA-2496241 2003-08-19 2003WO-CA01229 2003-08-19
主权利要求
(CA2496241)  THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS: 1. Use of a compound having structural formula (I) or a salt thereof, to inhibit the growth and/or proliferation of a microbial cell, wherein: R1 is aryl, substituted aryl, heterocycle, substituted heterocycle, heteroaryl, or substituted heteroaryl;  R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl or R2 and R3 when taken together along with the carbon atoms they are attached to, form a ring system having the formula: wherein x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R4 is hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  wherein said microbial cell is a bacterial cell or a fungal cell and said compound has anti-bacterial and/or anti-fungal activity. 2. Use of a compound having structural formula (I) or a salt thereof, wherein: R1 is aryl, substituted aryl, heterocycle, substituted heterocycle, heteroaryl, or substituted heteroaryl;  R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl or R2 and R3 when taken together along with the carbon atoms they are attached to, form a ring system having the formula: wherein x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R4 is hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  in the manufacture of a medicament for inhibiting the growth and/or proliferation of a microbial cell wherein said microbial cell is a bacterial cell or a fungal cell and said compound has anti-bacterial and/or anti-fungal activity. 3. The use according to claim 1 or 2, wherein said microbial cell is a bacterial cell and said compound has anti-bacterial activity. 4. The use according to claim 1 or 2, wherein said microbial cell is a fungal cell and said compound has anti-fungal activity. 5. The use according to claim 1 or 2, wherein said microbial cell is a drugresistant bacterial cell and said compound has anti-bacterial activity. 6. The use according to claim 5, wherein said drug-resistant bacterial cell is a methocillin-resistant Staphylococcus aureus cell or vancomycin-resistant Enterococcus cell. 7. The use according to claim 3, wherein said bacterial cell is a grampositive bacterial cell. 8. The use according to claim 3, wherein said bacterial cell is an Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus or Staphylococcus epidermidis cell. 9. The use according to claim 4, wherein said fungal cell is a Candida cell. 10. The use according to any one of claims 1 to 9, wherein said compound or medicament is formulated as a liposomal formulation. 11. Use of a compound having structural formula (I): or a salt thereof, for the treatment or prevention of a microbial infection in an animal in need thereof, wherein: R1 is aryl, or substituted aryl, heterocycle, substituted heterocycle, heteroaryl, or substituted heteroaryl;  R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl or R2 and R3 when taken together along with the carbon atoms they are attached to, form a ring system having the formula: wherein x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R4 is hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  wherein said microbial infection is a bacterial or fungal infection and said compound has anti-bacterial and/or anti-fungal activity. 12. Use of a compound having general formula (I), or a salt thereof: wherein: R1 is aryl, or substituted aryl, heterocycle, substituted heterocycle, heteroaryl, or substituted heteroaryl;  R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl or R2 and R3 when taken together along with the carbon atoms they are attached to form a ring system having the formula: wherein x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  wherein Rll, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R4 is hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  in the manufacture of a medicament for the treatment or prevention of a microbial infection in an animal in need thereof, wherein said microbial infection is a bacterial infection or a fungal infection and said compound has anti-bacterial and/or anti-fungal activity. 13. The use according to claim 11 or 12, wherein said microbial infection is associated with a disease or disorder. 14. The use according to any one of claims 11 to 13, wherein said microbial infection is a bacterial infection and said compound has anti-bacterial activity. 15. The use according to any one of claims 11 to 13, wherein said microbial infection is a fungal infection and said compound has anti-fungal activity. 16. The use according to any one of claims 11 to 13, wherein said microbial infection is an infection by a drug resistant bacterium and said compound has anti-bacterial activity. 17. The use according to claim 16, wherein said drug resistant bacterium is methocillin-resistant Staphylococcus aureus or vancomycin-resistant Enterococcus. 18. The use according to claim 14, wherein said bacterial infection is a grampositive bacterial infection. 19. The use according to claim 14, wherein said bacterial infection is an Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus or Staphylococcus epidermidis infection. 20. The use according to claim 15, wherein said fungal infection is a Candida infection. 21. The use according to any one of claims 11 to 20, wherein said compound or medicament is formulated as a liposomal formulation. 22. The use according to any one of claims 1 to 21, wherein said compound or medicament is used in combination with one or more anti-microbial agent(s). 23. The use according to any one of claims 1 to 22, wherein said compound has the structural formula: or a salt thereof, wherein: R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl;  R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, -CH2-aryl, or -CH2-heteroaryl. 24. The use according to claim 23, wherein said compound has the structural formula: or a salt thereof, wherein: Ph1 and Ph2 are independently phenyl or substituted phenyl;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or acyl. 25. The use according to any one of claims 1 to 22, wherein said compound has the structural formula: or a salt thereof, wherein: R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or acyl;  x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  and R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, alkenyl, alkenyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano. 26. The use according to claim 25, wherein said compound has the structural formula: 27. The use according to any one of claims 1 to 22, wherein said compound is: 28. The use according to claim 27, wherein said compound is: 29. The use according to claim 23, wherein said compound is: 30. The use according to claim 29, wherein said compound is: 31. The use according to claim 25, wherein said compound is: 32. The use according to claim 31, wherein said compound is: 33. The use according to claim 32, wherein said compound is: 34. Use of a compound having structural formula (I), or a salt thereof, in the preparation of an anti-microbial composition: wherein: R1 is aryl, or substituted aryl, heterocycle, substituted heterocycle, heteroaryl, or substituted heteroaryl;  R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl or R2 and R3 when taken together along with the carbon atoms they are attached to, form a ring system having the formula: wherein x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R4 is hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  wherein said anti-microbial composition is an anti-bacterial or anti-fungal composition and said compound has anti-bacterial and/or anti-fungal activity. 35. The use according to claim 34, wherein said anti-microbial composition further comprises one or more anti-microbial agent(s). 36. The use according to claim 34 or 35, wherein said anti-microbial composition inhibits the growth and/or proliferation of a drug-resistant bacterium and said one or more compounds have anti-bacterial activity. 37. The use according to claim 36, wherein said drug-resistant bacterium is methocillin-resistant Staphylococcus aureus cell or vancomycin-resistant Enterococcus. 38. The use according to claim 34 or 35, wherein said anti-microbial composition is formulated for incorporation into a cosmetic product, personal care product, cleanser, polish, paint, spray, soap, or detergent. 39. The use according to claim 34 or 35, wherein said anti-microbial composition is an anti-bacterial composition and said one or more compounds have antibacterial activity. 40. The use according to claim 39, wherein said anti-bacterial composition inhibits the growth of one or more gram-positive bacteria. 41. The use according to claim 40, wherein said anti-bacterial composition inhibits the growth of one or more bacteria selected from the group of: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus and Staphylococcus epidermidis. 42. The use according to any one of claims 34 to 41, wherein said composition is a liposomal formulation. 43. The use according to any one of claims 34 to 42, wherein said compound has the structural formula: or a salt thereof, wherein: R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl;  R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, -CH2-aryl, or -CH2-heteroaryl. 44. The use according to claim 43, wherein said one or more compounds have the structural formula: or a salt thereof, wherein: Ph1 and Ph2 are independently phenyl or substituted phenyl;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or acyl. 45. The use according to any one of claims 34 to 42, wherein said one or more compounds have the structural formula: or a salt thereof, wherein: R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, or acyl;  x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  r' is CR18 or N;  and R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, alkenyl, alkenyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano. 46. The use according to claim 45, wherein said one or more compounds have the structural formula: 47. The use according to any one of claims 34 to 42, wherein said compound is selected from: 48. The use according to claim 47, wherein said compound is: 49. The use according to claim 43, wherein said compound is: 50. The use according to claim 49, wherein said compound is: 51. The use according to claim 45, wherein said compound is: 52. The use according to claim 51, wherein said compound is: 53. The use according to claim 52, wherein said compound is: 54. A compound having the structural formula: or a salt thereof, wherein: R2 and R3 are independently aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, or substituted heteroaryl;  R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, -CH2-aryl, or -CH2-heteroaryl;  with the proviso that the compounds are other than: 3,3'-[5-(4-methoxyphenyl)-1H-imidazole-2,4-diyl]bis-1H-indole;  4,5-Bis(4-methoxyphenyl)-2-(3-indolyl)imidazole;  3-(4,5-diphenyl-1H-imidazol-2-yl)-1-methyl-1H-indole;  3-[4-(4-chlorophenyl)-5-phenyl-1H-imidazol-2-yl]-1-methyl-1H-indole; 3. [4-(4-bromophenyl)-5-phenyl-1H-imidazol-2-yl]-1-methyl-1H-indole;  3-[4-(4-methylphenyl)-5-phenyl-1H-imidazol-2-yl]-1-methyl-1H-indole;  3-[4-(4-methoxyphenyl)-5-phenyl-1H-imidazol-2-yl]-1-methyl-1H-indole;  3-[4-(4-ethoxyphenyl)-5-phenyl-1H-imidazol-2-yl]-1-methyl-1H-indole;  3-[4,5-bis (4-methoxydiphenyl)-1H-imidazol-2-yl]-1-methyl-1H-indole;  2-(3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(3-indolyl)-4, 5-bis[4-(diethylamino)phenyl]imidazole;  2-(2-phenyl-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(2-chloro-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(2-ethylcarboxylate-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(5-chloro-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(5-cyano-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(5-nitro-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  2-(5-ethylcarboxylate-3-indolyl)-4,5-bis[4-(dimethylamino)phenyl]imidazole;  3-(4,5-di-2-furanyl-1H-imidazol-2-yl)-1H-indole;  3-[4,5-bis(4-methylphenyl)-1H-imidazol-2-yl]-1H-indole;  3-[4,5-bis(4-chlorophenyl)-1H-imidazol-2-yl]-1-methyl-1H-indole;  3-(4,5-diphenyl-1H-imidazol-2-yl)-1H-indole;  3-[5-(4-nitrophenyl)-4-phenyl-1H-imidazol-2-yl]-1H-indole;  3-[5-(4 p-methoxyphenyl)-4-(3-indolyl)-1H-imidazol-2-yl]-1H-indole;  and when R4 to R9 are H, and R10 is CH3, then R2 and R3 are not both phenyl substituted at para position with -CH=CH-COOH or -CH=CH-COO-t-Bu. 55. The compound according to claim 54 having the structural formula: or a salt thereof, wherein: Ph1 and Ph2 are independently selected from phenyl and substituted phenyl;  and R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl. 56. A compound having the structural formula: or a salt thereof, wherein: R4, R5, R6, R7, R8 and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  R10 is H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl;  x is CR11 or N;  y is CR12 or N;  z is CR13 or N;  r is CR14 or N;  x' is CR15 or N;  y' is CR16 or N;  z' is CR17 or N;  x' is CR18 or N;  R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, substituted lower alkyl, alkenyl, alkenyl, alkylalkenyl, alkyl alkynyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, substituted aryl, heterocycle, heteroaryl, substituted heterocycle, heteroalkyl, cycloalkyl, substituted cycloalkyl, alkylcycloalkyl, alkylcycloheteroalkyl, nitro, or cyano;  with the proviso that the compound is other than: 57. The compound according to claim 56 having the structural formula: 58. The compound according to claim 56, wherein: x is CR11 or N;  y is CR12;  z is CR13;  r is CR14 or N;  x' is CR15 or N;  y' is CR16;  z' is CR17;  and r' is CR18 or N. 59. The compound according to claim 58, wherein: x is CR11;  y is CR12;  z is CRl3;  r is CR14 or N;  x' is CR15;  y' is CR16;  z' is CR17;  and r' is CR18 or N. 60. The compound according to any one of claims 56 to 59, wherein: R11, R12, R13, R14, R15, R16, R17 and R18 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, nitro or cyano. 61. The compound according to claim 60, wherein: R11, R12, R13, R14, R15, R16, R17 and R18 are each hydrogen or halogen. 62. The compound according to claim 61, wherein: R11, R12, R13, R14, R15, R16, R17 and R18 are each hydrogen. 63. The compound according to claim 61, wherein: R12 and R17 are halogen;  and R11, R13, R14, R15, R16 and R18 are hydrogen. 64. The compound according to any one of claims 54 to 63, wherein: R5, R6, R7, R8 and R9 are independently hydrogen, halogen, lower alkyl, amino, carboxyl or nitro. 65. The compound according to claim 64, wherein: R5, R6, R7, R8 and R9 are independently hydrogen, halogen, lower alkyl, or carboxyl. 66. The compound according to claim 65, wherein: R5, R6, R7, R8 and R9 are independently hydrogen or halogen. 67. The compound according to any one of claims 54 to 66, wherein: R4 is hydrogen or acyl. 68. The compound according to claim 67, wherein: R4 is hydrogen. 69. The compound according to any one of claims 54 to 63, wherein: R4 is hydrogen, lower alkyl or acyl;  R5, R6, R7, R8, and R9 are independently hydrogen, halogen, hydroxyl, thiol, lower alkyl, lower alkenyl, alkoxy, alkylthio, acyl, aryloxy, amino, amido, carboxyl, aryl, heterocycle, nitro or cyano;  and R10 is H, lower alkyl, alkenyl, alkynyl, aryl, or acyl. 70. The compound according to claim 69 wherein: R4 is hydrogen or acyl;  R5, R6, R7, R8, and R9 are independently hydrogen, halogen, lower alkyl, amino, carboxyl or nitro;  and R10 is H, lower alkyl or acyl. 71. The compound according to claim 70, wherein: R4 is hydrogen;  R5, R6, R7, R8, and R9 are independently hydrogen, halogen or lower alkyl;  and R10 is H or lower alkyl. 72. The compound according to claim 71, wherein: R6 is hydrogen or halogen;  R9 is hydrogen or lower alkyl;  and R5, R7, R8 and R10 are each hydrogen. 73. The compound according to claim 54, wherein said compound is: 74. The compound according to claim 56, wherein said compound is: 75. The compound according to claim 73, wherein said compound is: 76. The compound according to claim 74, wherein said compound is: 77. The compound according to claim 76, wherein said compound is: 78. A pharmaceutical composition comprising a compound according to any one of claims 54 to 77, and a pharmaceutically acceptable carrier, diluent or excipient. 79. The pharmaceutical composition according to claim 78, wherein said composition is a liposomal formulation. 80. An anti-microbial composition comprising a compound according to any one of claims 54 to 77, and a carrier, diluent or excipient.
法律状态
(CA2496241) LEGAL DETAILS FOR CA2496241  Actual or expected expiration date=2023-08-19    Legal state=ALIVE    Status=GRANTED     Event publication date=2003-08-19  Event code=CA/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=CA CA2496241  Application date=2003-08-19  Standardized application number=2003CA-2496241     Event publication date=2004-02-26  Event code=CA/A1  Event type=Examination events  Application laid open  Publication country=CA  Publication number=CA2496241  Publication stage Code=A1  Publication date=2004-02-26  Standardized publication number=CA2496241     Event publication date=2008-05-09  Event code=CA/EEER  Event indicator=Pos  Event type=Examination events  Examination request    Event publication date=2011-06-28  Event code=CA/C  Event indicator=Pos  Event type=Event indicating In Force  Patent (second level)  Publication country=CA  Publication number=CA2496241  Publication stage Code=C  Publication date=2011-06-28  Standardized publication number=CA2496241
专利类型码
A1C
国别省市代码
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