Benzothiazinone derivative substituted with trifluoromethyl at 6-position, and preparation method therefor and use thereof
A benzothiazinone derivative substituted with trifluoromethyl at 6-position, and a preparation method therefor and the use thereof. A series of compounds are obtained by means of changing the benzene ring of the benzothiazinone backbone, especially by means of changing a substituent thereof. Compared with other benzothiazinone derivatives, the benzothiazinone derivative substituted with trifluoromethyl at 6-position is more stable with regard to hepatic microsomal enzymes, and has longer metabolic half-life T 1/2 and better water solubility.
1 . A 6-trifluoromethyl-substituted benzothiazinone derivative selected from the group consisting of:
wherein: R 1 is hydrogen, methyl or ethyl; R 2 is hydrogen, methyl or ethyl; and R 3 is hydrogen or halogen.
2 . The 6-trifluoromethyl-substituted benzothiazinone derivative according to claim 1 , selected from the group consisting of:
3 . A method of inhibiting tubercle bacillus in a subject, comprising:
administering to said subject a 6-trifluoromethyl-substituted benzothiazinone derivative according to claim 1 .
4 . A pharmaceutical composition comprising the 6-trifluoromethyl-substituted-benzothiazinone derivative according to claim 1 as an active ingredient.
5 . A method of preparing the 6-trifluoromethyl-substituted benzothiazinone derivative according to claim 1 , comprising: reacting a compound A5,
with an azide compound,
or reacting a compound A4,
with a compound BC,
or reacting the compound A4,
with a compound D2,
wherein: R 1 is hydrogen, methyl or ethyl; R 2 is hydrogen, methyl or ethyl; and R3 is hydrogen or halogen; X is O or S.
6 . The method according to claim 5 , wherein the reaction of the compound A5 and the azide compound is carried out at room temperature in the presence of a copper salt, a reducing agent and inorganic base; the reaction of compound A4 with the compound BC is carried out at room temperature; the reaction of compound A4 with compound D2 is carried out at room temperature.
7 . The method according to claim 5 , wherein the compound A4 is prepared by a process comprising: reacting compound A1,
with oxalyl chloride.