Methods for inhibiting angiogenesis
AssigneesLarge Scale Biology Corporation, SRI International
InventorsDaniel Tuse, Charles Hiebert, Keith R. Laderoute, Nahid Waleh
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Abstract
The present invention relates to methods for effectively inhibiting unwanted angiogenesis. More particularly, this invention relates to methods of treating diseases that show unwanted angiogenesis and to delivering anti-angiogenic activity to a mammal. In other aspects this invention relates to methods of reducing the level of tumor necrosis factor .alpha..
Claims24
A method of inhibiting angiogenesis in a tissue or organ in which same is intended, said method comprising contacting said tissue or organ with an anti-angiogenic amount of a compound having the formula:
- ##STR9## or a pharmaceutically acceptable salt thereof;
- wherein:
- R.sup.1 is C.sub.1 -C.sub.6 -alkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- Y is O or S;
- and
- X is selected from the group consisting of oxygen, sulfur, --CH.sub.2 -- and carboxy or is nil.
A method of treating a mammalian disease associated with undesired and uncontrolled angiogenesis and treatable by inhibiting same, said method comprising administering to a mammal in need thereof an anti-angiogenic amount of a compound having the formula ##STR10## or a pharmaceutically acceptable salt thereof;
- wherein:
- R.sup.1 is C.sub.1 -C.sub.6 -alkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- Y is O or S;
- and
- X is selected from the group consisting of oxygen, sulfur, --CH.sub.2 -- and carboxy or is nil.
A method of inhibiting the vascularization of endothelial cells, said method comprising contacting a tissue or organ comprising said endothelial cells in which same is intended with an anti-angiogenic amount of a compound having the formula ##STR11## or a pharmaceutically acceptable salt thereof;
- wherein:
- R.sup.1 is C.sub.1 -C.sub.6 -alkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- Y is O or S;
- and
- X is selected from the group consisting of oxygen, sulfur, --CH.sub.2 -- and carboxy or is nil.
A method of inhibiting the growth of a tumor in a mammal in need thereof, said method comprising:
- (a) administering to said mammal an anti-angiogenic amount of a compound having the formula:
- ##STR12## or a pharmaceutically acceptable salt thereof;
- wherein:
- R.sup.1 is C.sub.1 -C.sub.6 -alkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- Y is O or S;
- and
- X is selected from the group consisting of oxygen, sulfur, --CH.sub.2 -- and carboxy or is nil;
- and
- (b) histologically examining the vascularization of said tumor, thereby determining the inhibition of tumor growth.
A method for reducing the level of tumor necrosis factor .alpha. (TNF-.alpha.) produced by a cell in which same is intended, said method comprising contacting said cell with a compound having the formula:
- ##STR13## or a pharmaceutically acceptable salt thereof;
- wherein:
- R.sup.1 is C.sub.1 -C.sub.6 -alkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, aryl, hydroxyl, C.sub.1 -C.sub.6 -alkoxy, halogen, NO.sub.2 and NH.sub.2 ;
- Y is O or S;
- and
- X is selected from the group consisting of oxygen, sulfur, --CH.sub.2 -- and carboxy or is nil.
Dependencies are inferred from the claim text.