Sensitizing agents for use in boron neutron capture therapy

• US 5,462,724 A
• Filed: 01/30/1995
• Issued: 10/31/1995
• Est. Priority Date: 02/24/1992
• Status: Expired due to Term

• Current Assignee: Dennis C. Liotta, Raymond F. Schinazi
• Original Assignee: Dennis C. Liotta, Raymond F. Schinazi
• Inventors: Liotta, Dennis C., Schinazi, Raymond F.
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): AMBROSE, MICHAEL GEORGE
• Application Number:
  US08/380,520
• Time in Patent Office: 274 Days
• Field of Search: 558/72, 514/64, 424/1.77
• US Class Current: 424/1.77
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 41/0095 Boron neutron capture therapy, i.e. BNCT, e.g. using boronated porphyrins
• CPC Class Codes: C07D 411/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07F 5/027 Organoboranes and organoborohydrides
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C07F 9/12 with hydroxyaryl compounds
• CPC Class Codes: C07F 9/6596 having atoms other than oxygen, sulfur, selenium, tellurium, nitrogen or phosphorus as ring hetero atoms

Abstract

Compounds of formula I and II ##STR1## in which B contains a carboranyl group and one of R₃ and R₄ is a carboranyl group or a boronic acid or ester are useful sensitizing agents for boron neutron capture therapy.

Claims

1. A compound having the formula II ##STR15## R₃ and R₄ are each, independently, --H, --B(OH)₂, --B(OR₆)₂ (wherein R₆ is a C_1-4 alkyl), or a carboranyl group --B₁₀ H₁₀ C₂ R₈, wherein R₈ is --H, --OH, --CH₂ OH, --CH₂ X (wherein X is F, Cl, Br, or I) or --B₉ C₂ H₁₂^- (nidocarborane anion), provided that one of R₃ and R₄ is --H and the other of R₃ and R₄ is not --H, and pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein R₃ is --H.

3. The compound of claim 2, wherein R₄ is --B(OH)₂ or ##STR16##

4. A pharmaceutical composition for boron neutron capture therapy, comprising an effective amount of a compound having formula II ##STR17## R₃ and R₄ are each, independently, --H, --B(OH)₂, --B(OR₆)₂ (wherein R₆ is a C_1-4 alkyl), or a carboranyl group --B₁₀ H₁₀ C₂ R₈, wherein R₈ is --H, --OH, --CH₂ OH, --CH₂ X (wherein X is F, Cl, Br, or I) or --B₉ C₂ H₁₂^- (nidocarborane anion), provided that one of R₃ and R₄ is --H and the other of R₃ and R₄ is not --H, and pharmaceutically acceptable salts thereof.

5. A method of boron neutron capture therapy, comprising:

administering to a patient in need thereof an effective amount of a sensitizing agent which has the formula II, ##STR18## R₃ and R₄ are each, independently, --H, --B(OH)₂, --B(OR₆)₂ (wherein R₆ is a C_1-4 alkyl), or a carboranyl group --B₁₀ H₁₀ C₂ R₈, wherein R₈ is --H, --OH, --CH₂ OH, --CH₂ X (wherein X is F, Cl, Br, or I) or --B₉ C₂ H₁₂^- (nidocarborane anion), provided that one of R₃ and R₄ is --H and the other of R₃ and R₄ is not --H, and pharmaceutically acceptable salts thereof.

6. The method of claim 5, wherein R₃ is --H.

7. The method of claim 6, wherein R₄ is --B(OH)₂ or ##STR19##