Alkynyl indazole derivative and use thereof
The main object of the present invention is to provide a novel compound which has a VEGF receptor tyrosine kinase inhibitory activity and is useful as an active ingredient for the treatment of diseases accompanying angiogenesis or edema, for example, age-related macular degeneration or the like. The present invention includes, for example, an alkynyl indazole derivative represented by the following general formula (I), a pharmaceutical acceptable salt thereof, and a medicine containing thereof.
1. An alkynyl indazole derivative represented by the following general formula (I):
wherein
R 1 represents a lower alkyl,
X and Y are the same or different and each represents CH or N, with the proviso that X and Y are not simultaneously N; and
Z is a group represented by the following general formula (a):
wherein
R 2 represents a lower alkyl which may have a substituent,
n is an integer of 1 to 7; and
A is a partial structure represented by the following formula:
or a pharmaceutically acceptable salt thereof.
2. The alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof, wherein X and Y are simultaneously CH.
3. The alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof, wherein Z is bound in the para-position.
4. The alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof, wherein A is a partial structure represented by the following formula:
5. A medicine characterized by containing the alkynyl indazole derivative according to claim 1 or the pharmaceutically acceptable salt thereof.
6. The medicine according to claim 5 , which is a vascular endothelial cell growth factor (VEGF) receptor tyrosine kinase inhibitor.
7. The medicine according to claim 5 , which is used for treatment or prevention of a retinal disease accompanying angiogenesis or edema.
8. The medicine according to claim 7 , wherein the retinal disease accompanying angiogenesis or edema is age-related macular degeneration, macular edema, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, secondary cataract, myopic choroidal neovascularization, or glaucoma.
9. A method for treating a disease or condition accompanying angiogenesis or edema in a mammal, the method comprising the step of administering the alkynyl indazole derivative according to claim 1 , or the pharmaceutically acceptable salt thereof, to the mammal.
10. The method according to claim 9 , wherein the disease or condition accompanying angiogenesis or edema to be treated is a retinal disease accompanying angiogenesis or edema.
11. The method according to claim 10 , wherein the retinal disease accompanying angiogenesis or edema is age-related macular degeneration, macular edema, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, secondary cataract, myopic choroidal neovascularization, or glaucoma.