Patent CA-1253151-A (CA)
Inventor: SHEPARD KENNETH L
IPC: C07D409/12
Filed: 1984-06-18
Granted: 1989-04-25
Abstract: ABSTRACT OF THE DISCLOSURE         The invention relates to novel 2-sulfamoyl-benzo[b]thiophenes which are useful in the reduction of elevated intraocular pressure and having the formula:                                 wherein X is hydrogen, halo, such as chloro, bromo or fluoro, C1-3 alkyl, hydroxy or C1-3 alkoxy; and R is 1) hydroxY,  2) R1 wherein R? is  a) C1-18 alkyl either straight or branched chain substituted with one or more of  i) C3-6 cycloalkyl,  ii) halo, such as chloro, bromo or fluoro,  iii) aryl, wherein the aryl group is carbo-cyclic such as phenyl or naphthyl, or heterocyclic such as pyridinyl, furanyl, pyrazinyl, morpholinyl, oxazol-inyl, dioxolinonyl, imidazolyl, thienyl or the like and wherein the aryl group can be substituted with one or more of C1-10 alkyl, halo, C1-4 alkoxy, C2-5 alkanoyl, or trifluoromethyl,  iv) hydroxy,  v) C1-3 alkoxy,  vi) aryl-C1-3 alkoxy,  vii) C1-4 alkoxy-C1-3 alkoxy,  viii) amino,  ix) (C1-3 alkyl)amino,  x) di(C1-3 alkyl)amino, xi) R2-?-, wherein R2 is  1) HO-,  2) M+O-, wherein M+ is a pharmaceutically acceptable cation such as that from an alkali metal, or an ammonium,  3) C1-10 alkoxy, 4) R3R4N- wherein R3 and R4 are independently hydrogen, hydroxy, C1-15 alkyl, or taken together form a 3-7 membered heterocycle with the nitrogen to which they are attached such as piperidino or pyrrolidino, or  xii) C2-5 alkanoyl;  b) C3-6 cycloalkyl,  c) C1-18 alkyl-C3-6 cycloalkyl,  d) aryl as previously defined,  e) R3R4N-, f) C2-6 alkenyl,  g) aryl-C2-6 alkenyl, h) C2-6 alkynyl, or  i) heterocyclyl of 5 or 6 members with one or two heteroatoms selected from O, N and S, such as tetra-hydropyrrolyl, tetrahydrofuranyl, or imidazolidinyl, 3) R?-O-,  4) R1-?-, wherein R1 is R? or C1-18 alkyl, 5) R1-?-O-,  6) R1-O-?-O,  7)   wherein x is 0-2; y is 0-3; z is 0 or 1; and A is a heteroatom such as S, O or N,  8)   where R5 and R6 are independently:  a) hydrogen,  b) C1-18 alkyl, either straight or branched chain,  c) C3-6 cycloalkyl, d) C3-6 cycloalkyl-C1-3 alkyl,  e) aryl-C1-3 alkyl wherein the aryl group is either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C1-3 alkyl or C1-3 alkoxy,  f) R7?-, or R7O?- wherein R7 is  i) C1-18 alkyl, either straight or branched chain, ii) aryl, either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C1-3 alkyl, or C1-3 alkoxy,  iii) aryl-C1-3 alkyl wherein the aryl group is either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C1-3 alkyl or C1-3 alkoxy, iv) amino-C1-18 alkyl either straight or branched chain; or  g) R5 and R6 if lower alkyl, are joined together directly or through a heteroatom selected from O or N to form a 5 or 6 membered heterocycle with the nitrogen to which they are attached such as pyrrolidine, piperidine, morpholine, or piperazine,  9)   , wherein ? is an ophthalmologically acceptable cation selected from sodium, potassium, ammonium, tetra(C1-4 alkyl)ammonium, pyridinium, imidazolium, pralidoxime, and thiamine, 10)    wherein ? is as previously defined;     11)  , wherein R8 is C1-3 alkyl or phenyl-C1-3 alkyl; or  12)  (R8O)2 ?-O-, wherein R8 is as previously defined, and the two may be the same or different; and R and X, joined together, represent methylenedioxy, as well as the pharmaceutically and ophthalmologically acceptable salts thereof.