1-/2-Substituted-1H/-2H-[1,2,3]triazolo[4,5-G]phthalazine-4,9-dione compound, process for the preparation thereof and pharmaceutical composition comprising the same
AssigneeEwha University-Industry Collaboration Foundation
InventorsHea Young Choo, Jin Kim, Hee Rhee, Hyun Park, Sang Lee, Chong Lee
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Abstract
The present invention relates to 1-/2-substituted-1H/-2H-[1,2,3]triazolo[4,5-g]phthalazine-4,9-dione compounds and their pharmaceutically acceptable salts, a process for preparing the compounds and a pharmaceutical composition comprising the compounds. The compounds are shown to effectively inhibit cell proliferation and are thus expected to be used for treatment or prevention or treatment of various cancers or as an ancillary(auxiliary) means of the same.
Claims16
A compound of Formula I or a pharmaceutically acceptable salt thereof:
- wherein R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-metylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, 1-methylpentyl, 2-methylpeptyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, benzyl, 4-methoxybenzyl, phenyl, toluenyl, xylyl and cumenyl.
A compound of Formula II or a pharmaceutically acceptable salt thereof:
- wherein R is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, benzyl, 4-methoxybenzyl, phenyl, toluenyl, xylenyl and cumenyl.
A compound selected from the group consisting of:
- (i) 1-(4-methoxybenzyl)-1H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (ii) 1H-[1,2,3] triazolo [4,5-g]phthalazin-4,9-dione,
- (iii) 1-methyl-1H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (iv) 2-methyl-2H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (v) 1-ethyl-1H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (vi) 2-ethyl-2H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (vii) 1-n-propyl-1H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione,
- (viii) 2-n-propyl-2H-[1,2,3]triazolo[4,5-g]phthalazin4,9-dione,
- (ix) 1-n-butyl-1H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione, and
- (x) 2-n-butyl-2H-[1,2,3]triazolo[4,5-g]phthalazin-4,9-dione.
A process for preparing a mixture of compounds of Formulas I and II or a pharmaceutically acceptable salt thereof, the process comprising:
- (a) preparing phthalazin-5,8-dione from phthalazine,
- (b) preparing 1-(4-methoxybenzyl)-1H-[1,2,3]triazolo[4,5-g]phthalazin4,9-dione by reacting the phthalazine with 4-methoxybenzyl azide in a molar ratio of about 3 to about 1 in the presence of ethyl acetate,
- (c) preparing 1H-[1,2,3]triazolo[4,5-g]phthalazin4,9-dione by dissolving the 1-(4-methoxybenzyl)-1H-[1,2,3]triazolo[4,5-g]phthalazin4,9-dione in trifluoroacetic acid and subsequently performing reflux, and
- (d) alkylating the 1H-[1,2,3]triazolo[4,5-g]phthalazin4,9-dione by using about 2-3 times molar equivalent of potassium carbonate and about 2-3 times molar equivalent of halogenated alkylating agent;
- wherein R is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylbutyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, phenyl, toluenyl, xylenyl and cumenyl.
Dependencies are inferred from the claim text.