Claims
- 1. A method for the prevention or treatment of conditions which require the inhibition of an enzyme whose preferred mode of action is to catalyse the hydrolysis of an ester functionality which method comprises administering to a subject a therapeutically effective amount of a compound comprising formula (I):
- 2. The method of claim 1 wherein the compound (I) is a compound of formula (II):
- 3. The method of claim 2, wherein in the compound of formula (II), R1 is either a branched or unbranched alkyl group having up to 25 carbon atoms; an aryl group; an arylalkyl group wherein the alkyl moiety has up to 25 carbon atoms; or an aryl aryl group, wherein the aryl alkyl group or the aryl aryl group may be separated by a spacer, and where the spacer can be one or more of an ester, amide, O, CH2 or a ketone;
R8 is hydrogen or fluorine; R9 is lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 10 carbon atoms; haloalkyl; or a halogen; R10 is hydrogen lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 10 carbon atoms; haloalkyl; or a halogen; and R11 is hydrogen lower branched or unbranched alkyl having 1 to 10 carbon atoms or a halogen.
- 4. The method of any one of claims 1-3 wherein said condition is selected from obesity, hyperlipaemia, hyperlipidaemia, hyperglycaemia (type II diabetes), hypertension, cardiovascular disease, stroke, gastrointestinal disease and gastrointestinal conditions.
- 5. The method of claim 1, wherein said method is for reducing levels of toxins in body fat.
- 6. The method of claim 1, wherein the step of administering the compound to a subject comprises administering the compound to humans.
- 7. The method of claim 1, wherein the step of administering the compound to a subject comprises administering the compound to animals.
- 8. A compound formula (IIa):
- 9. The compound of claim 8 wherein R1a is C10-20 branched or unbranched alkyl, optionally interrupted by one or two oxygen atoms and/or optionally substituted by one or more of aryl, aryloxy, heteroaryl, heteroaryloxy, cyano, nitro, —CO2R13, —NR13R14, —CONR13R14, OH and halogen, wherein R13 and R14 each independently represent hydrogen or C1-6alkyl.
- 10. The compound of claim 8 or 9 wherein R1a is an unbranched alkyl chain having 14, 15, 16, 17 or 18 carbon atoms.
- 11. The compound of claim 8 or 9 wherein R8a is hydrogen or halogen.
- 12. The compound of claim 10, wherein R8a is hydrogen or halogen.
- 13. The compound of claim 8 or 9 wherein wherein R9a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 14. The compound of claim 10 wherein R9a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 15. The compound of claim 11, wherein R9a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 16. The compound of claim 8 or 9 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 17. The compound of claim 10 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 18. The compound of claim 11 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 19. The compound of claim 12 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 20. The compound of claim 13 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 21. The compound of claim 14 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 22. The compound of claim 15 wherein R10a is hydrogen; lower branched or unbranched alkyl having 1 to 10 carbon atoms; cyclic alkyl having 3 to 6 carbon atoms; haloC1-6alkyl or a halogen.
- 23. The compound of claim 8 or 9 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 24. The compound of claim 10 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 25. The compound of claim 11 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 26. The compound of claim 12 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 27. The compound of claim 13 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 28. The compound of claim 14 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 29. The compound of claim 15 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 30. The compound of claim 16 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 31. The compound of claim 17 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 32. The compound of claim 18 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 33. The compound of claim 19 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 34. The compound of claim 20 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 35. The compound of claim 21 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 36. The compound of claim 22 wherein R11a is hydrogen, halogen or branched or unbranched alkyl having 1 to 10 carbon atoms.
- 37. A compound of formula (IIb)
- 38. A compound of formula (II), selected from:
2-(4-Methylphenoxy)-4H-3,1-benzoxazin-4-one; 2-(4-Chlorophenoxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-phenoxy-4H-3,1-benzoxazin-4-one, 2-(2-Ethylhexyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-octyloxy-4H-3,1-benzoxazin-4-one, 2-Hexyloxy-6-methyl-4H-3,1-benzoxazin-4-one, 2(2-Ethylhexyloxy)-6-methyl-4H -3,1-benzoxazin-4-one, 2-Ethyl-2-hexyloxy-4H-3,1-benzoxazin-4-one, 7-Ethyl-2-hexyloxy-4H-3,1-benzoxazin-4-one, 7-Ethyl-2-octyloxy-4H-3,1-benzoxazin-4-one, 2-Octyloxy-4H-3,1-benzoxazin-4-one, 6-Methoxy-2-octyloxy-4H-3,1-benzoxazin-4-one, 2-Hexyloxy-4H-3,1-benzoxazin-4-one, 6-Iodo-2-octyloxy-4H-3,1-benzoxazin-4-one, 2-Octyloxy-7-propyl-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(8-phenyloctyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(4-phenylbutyloxy)-4H-3,1-benzoxazin-4-one, 5-Methyl-2-octyloxy-4H-3,1-benzoxazin-4-one; or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 39. A compound of formula (IIa) selected from:
2-Decyloxy-6-methyl-4H-3,1-benzoxazin-4-one, 6-Methyl-2-tetradecyloxy-4H-3,1-benzoxazin-4-one, 6-Methyl-2-pentadecyloxy-4H-3,1-benzoxazin-4-one, 2-Heptadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one, 6-Methyl-2-octadecyloxy-4H-3,1-benzoxazin-4-one, 2-(3,7-Dimethyloctyloxy)-6-methyl-4H-3,1-benzoxazin-4-one, 2-[2-(2-Hexyloxyethoxy)ethoxy]-6-methyl-4H-3,1-benzoxazin-4-one, 2-(Octadeca-9-enyloxy)-6-methyl-4H-3,1-benzoxazin-4-one, 2-(10-Phenyldecyloxy)-6-methyl-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(4-phenoxyphenoxy)-4H-3,1-benzoxazin-4-one, 2-Dodecyloxy-6-methyl-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(12-phenyldodecyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(octadeca-11-enyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(octadeca-11-ynyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-[-10-(thien-2-yl)-decyloxy]-4H-3,1-benzoxazin-4-one, 7-Octyl-2-octyloxy-4H-3,1-benzoxazin-4-one, 6-Octyl-2-octyloxy-4H-3,1-benzoxazin-4-one, 2-(5-Chloropentyloxy)-6-methyl-4H-3,1-benzoxazin-4-one, 2,2′-(1,16-Hexadecylidenedioxy)-bis-4H-3,1-benzoxazin-4-one, 6-Methyl-2-(6-phenoxyhexyloxy)-4H-3,1-benzoxazin-4-one, 6-Methyl-2-[6-(4-phenoxyphenoxy)hexyloxy]-4H-3,1-benzoxazin-4-one; or a pharmaceutically acceptable salt, ester amide or prodrug thereof.
- 40. A compound of formula (IIa) which is:
2-Hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one or a pharmaceutically acceptable salt, ester, amid or prodrug thereof.
- 41. A process for the preparation of a compound of formula (II) which process comprises:
Process (A) reacting a compound of formula (IV): 117with a compound of formula (V): 118or Process (B) cyclising a compound of formula (VI) 119wherein R1 and R8-R11 are as hereinbefore defined and R18 is hydrogen or C1-6alkyl. or: Process (C) reacting a compound of formula (VII) 120with a compound of (VIII)R1OH (VIII)or: Process (D) converting a compound of formula (I), (II) or (IIa) into a different compound of formula (IIa)
- 42. A pharmaceutical composition comprising a compound of formula (II) or a pharmaceutically acceptable salt, ester, amide or pro-drug thereof, in combination with a pharmaceutically acceptable carrier or diluent.
- 43. A food product comprising a compound of formula (II) or a pharmaceutically acceptable salt, ester, amide or pro-drug thereof.
- 44. A method for inhibiting an enzyme whose preferred mode of action is to catalyse the hydrolysis of an ester functionality comprising:
contacting the enzyme with a compound of formula (I), (II), (IIa) or (IIb) or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 45. The method of claim 44, wherein the step of contacting the compound with the enzyme controls and inhibits unwanted enzymes in a process or product.
- 46. The method of claim 45, wherein the step of contacting the compound with the enzyme controls and inhibits unwanted enzymes in the process of manufacturing healthcare goods comprising surfactants, soap or detergents.
- 47. The method of claim 45, wherein the step of contacting the compound with the enzyme prevents the degradation of foodstuff which comprises a fat.
- 48. A method for the prevention or treatment of obesity or an obesity related disorder, the method comprising administering to a subject a compound of formula (I), (II), (IIa), or (IIb), or pharmaceutically acceptable salt, ester, amide or pro-drug thereof.
- 49. A method for preventing or treating obesity or an obesity related disorder, the method comprising administering to a subject a composition of claim 42.
- 50. A method for preventing or treating obesity or an obesity related disorder, the method comprising administering to a subject the food product of claim 43.
- 51. A method of reducing the fat content of animals which provide meat for human consumption comprising administering to the animal a compound of formula (I), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 52. A method for maintaining a given weight or for cosmetic weight loss, the method comprising administering to a subject a compound of formula (I), (II), (IIa), or (IIb), or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.
- 53. An intermediate of formula (VI):
Priority Claims (2)
Number |
Date |
Country |
Kind |
9900413.7 |
Jan 1999 |
GB |
|
9917294.2 |
Jul 1999 |
GB |
|
PRIORITY INFORMATION
[0001] This application is a continuation of international application number PCT/GB00/00032, filed on Jan. 6, 2000, entitled “2-Oxy-Benzoxazinone Derivatives for the Treatment of Obesity”, which PCT application claims priority to GB 9900413.7, filed on Jan. 8, 1999, and GB 9917294.2, filed on Jul. 22, 1999, and the entire contents of each of these is hereby incorporated by reference.
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCT/GB00/00032 |
Jan 2000 |
US |
Child |
09901887 |
Jul 2001 |
US |