Azolium and purinium salt anticancer and antimicrobial agents

Patent metadata

Field	Value
Publication number	US-9278951-B2
Application number	US-201214114324-A
Country	US
Kind code	B2
Filing date	Apr 30, 2012
Priority date	Apr 29, 2011
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

Singly and multiply charged imidazolium cations (ICs) have been identified as a class of chemical compositions that possess potent antineoplastic, antibacterial and antimicrobial properties. The imidazolium cations disclosed demonstrate greater or equivalent potency towards cancerous cells as the current clinical standard, cisplatin. These imidazolium cations, however, achieve this efficacy without any of the known toxic side effects caused by heavy metal-based antineoplastic drugs such as cisplatin.

First claim

What is claimed is:

1. An azolium or purinium salt composition having one of the formulas (I) to (VIII):

wherein dashed lines in formulas (I) to (VIII) represent a variable attachment of either R or X to a corresponding ring atom;
wherein each X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , and X 15 when present, may be the same or different, and is a halogen;
wherein R 1 is selected from C 1 to C 20 alkyl, C 1 to C 20 substituted alkyl, C 1 to C 20 alkyl heteroatom groups where the heteroatom is selected from S, O, or N, C 3 to C 12 cycloalkyl, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkenyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted cycloalkenyl, C 2 to C 12 alkynyl, C 6 to C 12 aryl, C 5 to C 12 substituted aryl, polycyclic aromatics, substituted polycyclic aromatics, C 6 to C 12 arylalkyl, C 6 to C 12 alkylaryl, C 3 to C 12 heterocyclic, C 3 to C 12 substituted heterocyclic, C 1 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl biphenyl, C 2 to C 6 alkenyl biphenyl, C 2 to C 6 alkynyl biphenyl, fluoroquinolone compounds, penicillin compounds, aminoglycoside compounds; cephalosporin compounds, glycopeptides, sulfonamides, tetracycline, anti-microbial compounds, steroids, anti-inflammatory compounds, anti-fungal compounds, anti-bacterial compounds, antagonist compounds, chemotherapy compounds; and tumor suppressor compounds;
wherein R 2 is selected from C 1 to C 20 substituted allkyl, C 1 to C 20 alkyl heteroatom groups where heteroatom is selected from S, O, or N, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkenyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted cycloalkenyl, C 2 to C 12 alkynyl, C 6 to C 12 aryl, C 6 to C 12 substituted aryl, polycyclic aromatics, substituted polycyclic aromatics, C 6 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl heterocyclic, C 1 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl biphenyl, C 2 to C 6 alkenyl biphenyl, C 2 to C 6 alkynyl biphenyl, fluoroquinolone compounds, penicillin compounds, aminoglycoside compounds; cephalosporin compounds, glycopeptides, sulfonamides, tetracycline, anti-microbial compounds, steroids, anti-inflammatory compounds, anti-fungal compounds, anti-bacterial compounds, antagonist compounds, chemotherapy compounds, and tumor suppressor compounds;
wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and R 19 , when present, are each independently selected from hydrogen, C 1 to C 20 alkyl, C 1 to C 20 substituted alkyl, C 1 to C 20 alkyl heteroatom groups where the heteroatom is selected from S, O, or N; C 3 to C 12 cycloalkyl, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkenyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted cycloalkenyl, C 2 to C 12 alkynyl, C 6 to C 12 aryl, C 5 to C 12 substituted aryl, polycyclic aromatics, substituted polycyclic aromatics, C 6 to C 12 arylalkyl, C 6 to C 12 alkylaryl, C 3 to C 12 heterocyclic, C 3 to C 12 substituted heterocyclic, C 1 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl biphenyl, C 2 to C 6 alkenyl biphenyl, C 2 to C 6 alkynyl biphenyl, hydroxyl, carbonyl, amino, acetyl, acetoxy, oxo, nitro, cyano, isocyano, cyanato, isocyanato, fluoroquinolone compound, penicillin compounds, aminoglycoside compounds; cephalosporin compounds, glycopeptides, sulfonamides, tetracycline, anti-microbial compounds, steroids, anti-inflammatory compounds, anti-fungal compounds anti-bacterial compounds, antagonist compounds, chemotherapy compounds; and tumor suppressor compounds;
wherein at least one X is always present in each of the formulas (I) to (VIII); and
wherein A is defined as an anion independently selected as a halide, hydroxide, alkoxide, aryloxide, carboxylate, sulfate, phosphate, triflate, tosylate or borate.

2. A multicationic azolium or purinium salt composition having one of the formulas (IX) to (XI):

wherein at least two of the R groups present in formulas (IX) to (XI) are independently selected from one of the cationic structural portions defined in formulas (I) to (VIII)

wherein dashed lines in formulas (I) to (VIII) represent a variable attachment of either R or X to a corresponding ring atom;
wherein at least one X is always present, wherein each X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , and X 15 may be the same or different, and is a halogen;
wherein R 1 is selected from C 1 to C 20 alkyl, C 1 to C 20 substituted alkyl, C 1 to C 20 alkyl heteroatom groups where the heteroatom is selected from S, O, or N, C 3 to C 12 cycloalkyl, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkenyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted cycloalkenyl, C 2 to C 12 alkynyl, C 6 to C 12 aryl, C 5 to C 12 substituted aryl, polycyclic aromatics, substituted polycyclic aromatics, C 6 to C 12 arylalkyl, C 6 to C 12 alkylaryl, C 3 to C 12 heterocyclic, C 3 to C 12 substituted heterocyclic, C 1 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl biphenyl, C 2 to C 6 alkenyl biphenyl, C 2 to C 6 alkynyl biphenyl, fluoroquinolone compounds, penicillin compounds, aminoglycoside compounds; cephalosporin compounds, glycopeptides, sulfonamides, tetracycline, anti-microbial compounds, steroids, anti-inflammatory compounds, anti-fungal compounds, anti-bacterial compounds, antagonist compounds, chemotherapy compounds; and tumor suppressor compounds;
wherein R 2 is selected from C 1 to C 20 substituted alkyl, C 1 to C 20 alkyl heteroatom groups where the heteroatom is selected from S, O, or N, C 3 to C 12 cycloalkyl, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkynyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted cycloalkenyl, C 2 to C 12 alkynyl, C 6 to C 12 aryl, C 5 to C 12 substituted aryl, polycyclic aromatics, substituted polycyclic aromatics, C 6 to C 12 arylalkyl, C 6 to C 12 alkylaryl, C 3 to C 12 heterocyclic, C 3 to C 12 substituted heterocyclic, C 1 to C 12 alkoxy, C 1 to C 12 alcohols, C 1 to C 12 carboxy; biphenyl, C 1 to C 6 alkyl biphenyl, C 2 to C 6 alkenyl biphenyl, C 2 to C 6 alkynyl biphenyl, fluoroquinolone compounds, penicillin compounds, aminoglycoside compounds; cephalosporin compounds, glycopeptides, sulfonamides, tetracycline, anti-microbial compounds, steroids, anti-inflammatory compounds, anti-fungal compounds, anti-bacterial compounds, antagonist compounds, chemotherapy compounds; and tumor suppressor compound;
wherein R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , and R 19 , are each independently selected from any of the cationic structural portions of formulas (I) to (VIII) above, hydrogen, C 1 to C 20 alkyl, C 1 to C 20 substituted alkyl, C 1 to C 20 alkyl heteroatom groups where the heteroatom is selected from S, O, or N, C 3 to C 12 cycloalkyl, C 3 to C 12 substituted cycloalkyl, C 2 to C 12 alkenyl, C 3 to C 12 cycloalkenyl, C 3 to C 12 substituted

Assignees

• Youngs Wiley
• Panzner Matthew
• Tessier Claire
• Deblock Michael
• Wright Brian
• Wagers Patrick
• Robishaw Nikki
• Univ Akron

Inventors

• Youngs Wiley
• Panzner Matthew
• Tessier Claire
• Deblock Michael
• Wright Brian
• Wagers Patrick
• Robishaw Nikki

Classifications

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D233/58

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms · CPC title