Thiazolo (2,3-b) benzo (and azabenzo) thiazole derivatives, process for their preparation and pharmaceutical compositions containing them

Claim 2

A compound having the formula: or wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl or substituted phenyl; R 3 is hydrogen or lower alkanoyl; X is CH or N; Y is a pharmaceutically acceptable anion the dotted lines represent optional double bonds in the 5,6 and 7,8 positions; subject to the proviso that where the group having the formula is ortho-phenylene in formula II, then R 2 is other than lower alkyl or phenyl and where the group having the formula III is ortho-phenylene in formula I whilst R 2 is lower alkyl and R 3 is hydrogen, then Y is other than acetate.

Claim 3

A compound as claimed in claim 1, which has formula I where Y is trifluoroacetate or halide.

Claim 4

A compound as claimed in claim 1 or 2, wherein R 1 is hydrogen, halo or lower alkoxy.

Claim 5

A compound as claimed in any on claims 1 to 3, where R 2 is trifluoroacetyl, phenyl or halophenyl.

Claim 6

A compound as claimed in any one of claims 1 to 4, which has formula I in which R 3 is hydrogen or lower alkanoyl.

Claim 7

6-Chloro-2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative.

Claim 8

6-Chloro-2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative.

Claim 9

A compound selected from 6-chloro-3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 3-hydroxy-2-phenylthiazolo[2',3'-2,3]thiaz,olo[4,5-b] pyridinium trifluoroacetate; 2-phenylthiazolo[2'-,3'-2,3]thiazolo[5,4-b]pyridin-3(2H)-one mesoionic dideh y dro derivative; 6-chloro-2-trifluoroacetylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 6-chloro-2-(p-chlorophenyl)thiazolo[2,3-b]benzothiazolium bromide; 6-chloro-2-(p-chlorophenyl)thiazolo[2,3-b]benzothiazol - 3(2H)-one mesoionic didehydro derivative; 7-ethoxy-3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 7-ethoxy-2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 3-hydroxy-2-phenyl-5,6,7,8-tetrahydaothiazolo[2,3,b] benzothiazolium bromide; 2-phenyl-5,6,7,B-tetrahydrothiazolo[2,3,-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 3-acetoxy-7-chloro-2-phenylthiazolo[2',3'-2,3]thiazolo [5,4-b]pyridinium bromide; 7-chlora-3-hydroxy-2-phenylthiazolo[2',3'-2,3]thiazolo [5,4,-b]pyridinium bromide and 7-chloro-2-phenylthiazolo[2',3'-2,3]thiazolo[5,4-b] pyridin-3(2H)-one mesoionic didehydro derivative.

Claim 10

A compound selected from 6-chloro-3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 3-hydroxy-2-phenylthiazolo[2',3'-2,3]thiaz,olo[4,5-b] pyridinium trifluoroacetate; 2-phenylthiazolo[2'-,3'-2,3]thiazolo[5,4-b]pyridin-3(2H)-one mesoionic dideh y dro derivative; 6-chloro-2-trifluoroacetylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 6-chloro-2-(p-chlorophenyl)thiazolo[2,3-b]benzothiazolium bromide; 6-chloro-2-(p-chlorophenyl)thiazolo[2,3-b]benzothiazol - 3(2H)-one mesoionic didehydro derivative; 7-ethoxy-3-hydroxy-2-phenylthiazolo[2,3-b]benzothiazolium bromide; 7-ethoxy-2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 3-hydroxy-2-phenyl-5,6,7,8-tetrahydaothiazolo[2,3,b] benzothiazolium bromide; 2-phenyl-5,6,7,B-tetrahydrothiazolo[2,3,-b]benzothiazol-3(2H)-one mesoionic didehydro derivative; 3-acetoxy-7-chloro-2-phenylthiazolo[2',3'-2,3]thiazolo [5,4-b]pyridinium bromide; 7-chlora-3-hydroxy-2-phenylthiazolo[2',3'-2,3]thiazolo [5,4,-b]pyridinium bromide and 7-chloro-2-phenylthiazolo[2',3'-2,3]thiazolo[5,4-b] pyridin-3(2H)-one mesoionic didehydro derivative.

Claim 11

As a pharmaceutical a compound having the general formula or wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl, or substituted phenyl; R 3 is hydrogen or lower alkanoyl; X is CH or N: and Y is a pharmaceutically acceptable anion and the dotted lines represent optional double bonds in.the 5,6 and 7,8 positions.

Claim 12

As a pharmaceutical a compound having the general formula or wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl, or substituted phenyl; R 3 is hydrogen or lower alkanoyl; X is CH or N: and Y is a pharmaceutically acceptable anion and the dotted lines represent optional double bonds in.the 5,6 and 7,8 positions.

Claim 13

As a pharmaceutical 2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative.

Claim 14

As a pharmaceutical 2-phenylthiazolo[2,3-b]benzothiazol-3(2H)-one mesoionic didehydro derivative.

Claim 15

A pharmaceutical composition comprising a compound having the formula or wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl, or substituted phenyl; R3 is hydrogen or lower alkanoyl; X is CH or N, and Y is a pharmaceutically acceptable anion and the dotted lines represent optional double bonds in the 5,6 and 7,8 positions, in association or combination with a pharmaceutically acceptable carrier.

Claim 16

A pharmaceutical composition comprising a compound having the formula or wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl, or substituted phenyl; R3 is hydrogen or lower alkanoyl; X is CH or N, and Y is a pharmaceutically acceptable anion and the dotted lines represent optional double bonds in the 5,6 and 7,8 positions, in association or combination with a pharmaceutically acceptable carrier.

Claim 17

A process for the preparation of a compound having the general formula wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl or substituted phenyl; R 3 is hydrogen or lower alkanoyl; X is CH or N; and Y is a pharmaceutically acceptable anion the dotted lines represent optional double bonds in the 5,6 and 7,8 positions; wherein (a) a compound having the formula or a salt thereof is cyclized with a compound having the formula Hal-CHR 2 *-CCOH (U) in the presence of a condensing agent (wherein X and the dotted lines are as explained above, - R 1 * and R 2 * are the same as R 1 and R 2 respectively save that, where necessary or-desired, an amino or hydroxy group may be protected by a removable protecting group and Hal is chlorine or bromine); or (b) a compound having the formula is cyclized with a condensing agent (wherein R 1 *, R 2 *, X and the dotted lines are as defined above); subject to the proviso that where the group having the formula isortho-phenylene when R 2 * is lower alkyl or phenyl and acetic anhydride is used as condensing agent then the cyclization product is for use as a pharmaceutical (c) a compound having the formula wherein R 1 , X and the dotted lines are as defined above) is cyclized with trifluoroacetic anhydride to form a product wherein R 2 is trifluoroacetyl; or (d) a compound having the formula or a salt thereof, is cyclized with a compound having the formula Hal-CHR 2 *-Z (IX) (wherein R 1 , R 2 , X, Hal and the dotted lines are as defined above and Z is a reactive derivative of carboxyl); subject to the proviso that where 2-xerceptobenzothiazole is cyclized with a-bromophenylacetyl chloride in the presence of triethylamine so as to form 2-phenylthiazolo[2,3-b] benzothiazol-3(2H)-one, then the cyclization product is for use as a pharmaceutical; or (e) a compound having the formula (wherein R 1 , R 2 , R 3 , X, and the dotted lines are as defined above and Y is the anion is subjected to (i) deacylation and removal of the acid HY, if R 3 is lower alkanoyl, or (ii) removal of the acid HY, if R 3 is hydrogen; or (f) a compound having the formula (uherein R 1 , R 2 , X and the dotted lines are as defined above, Y is a pharmaceutically acceptable anion and R 3 is lower alkanoyl) is subjected to deacylation to form a compound where R 3 is hydrogen; and, where necessary a protecting group is removed.

Claim 18

A process for the preparation of a compound having the general formula wherein R 1 is hydrogen, halo, amino, lower alkyl, lower alkoxy, trifluoromethyl or hydroxy; R 2 is lower alkyl, acetyl, trifluoroacetyl, phenyl or substituted phenyl; R 3 is hydrogen or lower alkanoyl; X is CH or N; and Y is a pharmaceutically acceptable anion the dotted lines represent optional double bonds in the 5,6 and 7,8 positions; wherein (a) a compound having the formula or a salt thereof is cyclized with a compound having the formula Hal-CHR 2 *-CCOH (U) in the presence of a condensing agent (wherein X and the dotted lines are as explained above, - R 1 * and R 2 * are the same as R 1 and R 2 respectively save that, where necessary or-desired, an amino or hydroxy group may be protected by a removable protecting group and Hal is chlorine or bromine); or (b) a compound having the formula is cyclized with a condensing agent (wherein R 1 *, R 2 *, X and the dotted lines are as defined above); subject to the proviso that where the group having the formula isortho-phenylene when R 2 * is lower alkyl or phenyl and acetic anhydride is used as condensing agent then the cyclization product is for use as a pharmaceutical (c) a compound having the formula wherein R 1 , X and the dotted lines are as defined above) is cyclized with trifluoroacetic anhydride to form a product wherein R 2 is trifluoroacetyl; or (d) a compound having the formula or a salt thereof, is cyclized with a compound having the formula Hal-CHR 2 *-Z (IX) (wherein R 1 , R 2 , X, Hal and the dotted lines are as defined above and Z is a reactive derivative of carboxyl); subject to the proviso that where 2-xerceptobenzothiazole is cyclized with a-bromophenylacetyl chloride in the presence of triethylamine so as to form 2-phenylthiazolo[2,3-b] benzothiazol-3(2H)-one, then the cyclization product is for use as a pharmaceutical; or (e) a compound having the formula (wherein R 1 , R 2 , R 3 , X, and the dotted lines are as defined above and Y is the anion is subjected to (i) deacylation and removal of the acid HY, if R 3 is lower alkanoyl, or (ii) removal of the acid HY, if R 3 is hydrogen; or (f) a compound having the formula (uherein R 1 , R 2 , X and the dotted lines are as defined above, Y is a pharmaceutically acceptable anion and R 3 is lower alkanoyl) is subjected to deacylation to form a compound where R 3 is hydrogen; and, where necessary a protecting group is removed.