Phosphonate Compounds

• US 20140045794A1
• Filed: 10/21/2013
• Published: 02/13/2014
• Est. Priority Date: 12/03/1999
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Hostetler, Karl Y., Beadle, James R.
• Granted Patent: US 8,889,658 B2
• Time in Patent Office: Days
• US Class Current: 514/81
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: C07F 9/3873 containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
• CPC Class Codes: C07F 9/404 containing hydroxy substituents in the hydrocarbon radicals
• CPC Class Codes: C07F 9/405 : containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
• CPC Class Codes: C07F 9/48 : Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
• CPC Class Codes: C07F 9/5728 : condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C07F 9/6512 : having the nitrogen atoms in positions 1 and 3
• CPC Class Codes: C07F 9/65583 : each of the hetero rings containing nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/65616 : containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
• CPC Class Codes: C07H 19/04 : Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/10 : with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein R¹ is hydrogen and B is guanin-9-yl.

3. The compound of claim 1, wherein R⁸ is alkylglycerol.

4. The compound of claim 1, wherein R⁸ is 1-S-alkylthioglycerol.

5. The compound of claim 1, wherein R⁸ is alkoxyalkanol.

6. The compound of claim 5, wherein R⁸ is alkoxyethanol.

7. The compound of claim 5, wherein R⁸ is alkoxypropanol.

8. The compound of claim 7, wherein R⁸ is hexadecyloxypropanol.

9. The compound of claim 7, wherein R⁸ is octadecyloxypropanol.

10. The compound of claim 1, wherein R¹ is —

CH₂OH and B is cytosin-1-yl.

11. The compound of claim 10, wherein R⁸ is alkylglycerol.

12. The compound of claim 10, wherein R⁸ is 1-S-alkylthioglycerol.

13. The compound of claim 10, wherein R⁸ is alkoxyalkanol.

14. The compound of claim 13, wherein R⁸ is alkoxyethanol.

15. The compound of claim 13, wherein R⁸ is alkoxypropanol.

16. The compound of claim 15, wherein R⁸ is hexadecyloxypropanol.

17. The compound of claim 15, wherein R⁸ is octadecyloxypropanol.

18. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.

19. The pharmaceutical composition of claim 18, wherein the composition is formulated as a solid dosage form.

20. The pharmaceutical composition of claim 18, wherein the composition is formulated as a capsule, tablet, aerosol, solution, or suspension, or is a topical formulation or a solution.