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US 4,544,667 AGranted
2-Sulfamoylbenzo[b]furan derivatives for the treatment of elevated intraocular pressure
AssigneeMerck & Co., Inc.
InventorsKenneth L. Shepard, Samuel L. Graham
Life of this patent
Estimating the term…
Abstract
Novel 2-sulfamoylbenzo[b]furans and derivatives thereof are shown to be useful for the treatment of elevated intraocular pressure in compositions including opthalmic drops and inserts.
Claims18
A compound of structural formula:
- ##STR26## or an ophthalmologically or pharmaceutically acceptable salt thereof, wherein:
- X is halogen, chloro, bromo or fluoro, C.sub.1-3 alkyl, hydroxy or C.sub.1-3 alkoxy;
- and
- R is
- (1) hydroxy,
- (2) R.sub.a.sup.1 wherein R.sub.a.sup.1 is
- (a) C.sub.1-18 alkyl either straight or branched chain and substituted with one or more of
- (i) C.sub.3-6 cycloalkyl,
- (ii) halo,
- (iii) aryl, wherein the aryl group is phenyl, naphthyl, pyridinyl, furanyl, pyrazinyl, imidazolyl or thienyl and wherein the aryl group can be substituted with one or more of C.sub.1-10 alkyl, halo, C.sub.1-4 alkoxy or C.sub.2-5 alkanoyl,
- (iv) hydroxy,
- (v) C.sub.1-3 alkoxy,
- (vi) aryl-C.sub.1-3 alkoxy, wherein aryl is as previously defined,
- (vii) amino,
- (viii) (C.sub.1-3 alkyl)amino,
- (ix) di(C.sub.1-3 alkyl)amino
- (x) ##STR27## wherein R.sup.2 is (1) HO--,
- (2) M.sup.+ O.sup.-, wherein M.sup.+ is a pharmaceutically acceptable cation,
- (3) C.sub.1-10 alkoxy,
- (4) R.sup.3 R.sup.4 N-- wherein R.sup.3 and R.sup.4 are independently hydrogen, C.sub.1-15 alkyl, or taken together form a 3-7 membered heterocycle, selected from piperidino and pyrrolidino, with the nitrogen to which they are attached,
- (b) C.sub.3-6 cycloalkyl,
- (c) C.sub.1-18 alkyl-C.sub.3-6 cycloalkyl,
- (d) aryl as previously defined,
- (e) C.sub.2-6 alkenyl,
- (f) aryl-C.sub.2-6 alkenyl, wherein aryl is as previously defined, or
- (g) C.sub.2-6 alkynyl;
- (3) R.sub.a.sup.1 --O--,
- (4) ##STR28## wherein R.sup.1 is R.sub.a.sup.1 or C.sub.1-18 alkyl, (5) ##STR29## (6) ##STR30## (7) ##STR31## wherein x is 0-2;
- y is 0-3;
- z is 0 or 1;
- and A is a heteroatom selected from S, O and N,
- (8) ##STR32## wherein R.sup.5 and R.sup.6 are independently:
- (a) hydrogen,
- (b) C.sub.1-18 alkyl, either straight or branched chain,
- (c) C.sub.3-6 cycloalkyl,
- (d) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl,
- (e) aryl-C.sub.1-3 alkyl wherein the aryl group is as previously defined and is either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C.sub.1-3 alkyl or C.sub.1-3 alkoxy,
- (f) ##STR33## wherein R.sup.7 is (i) C.sub.1-18 alkyl, either straight or branched chain,
- (ii) aryl as previously defined, either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C.sub.1-3 alkyl, or C.sub.1-3 alkoxy,
- (iii) aryl-C.sub.1-3 alkyl wherein the aryl group is as previously defined and is either unsubstituted or substituted with one or more of chloro, bromo, fluoro, C.sub.1-3 alkyl or C.sub.1-3 alkoxy,
- (iv) amino-C.sub.1-18 alkyl either straight or branched chain;
- or
- (g) R.sup.5 and R.sup.6 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 selected from pyrrolidine, piperidine, morpholine and piperazine;
- (9) ##STR34## wherein M.sup.+ is an ophthalmologically acceptable cation selected from sodium, potassium, ammonium, tetra(C.sub.1-4 alkyl)ammonium, pyridinium, imidazolium, pralidoxime, and thiamine
- (10) ##STR35## wherein M.sup.+ is as previously defined;
- (11) ##STR36## wherein R.sup.8 is C.sub.1-3 alkyl or phenyl-C.sub.1-3 alkyl;
- or (12) ##STR37## wherein R.sup.8 is as previously defined, and the two may be the same or different.
44 more elements
Dependencies are inferred from the claim text.