Claims
- 1. A compound of Formula I wherein: ##STR33## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is:
- (a) (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl or (C.sub.2 -C.sub.6)-alkynyl each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of:
- i) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of:
- 1) Cl, Br, I, F,
- 2) (C.sub.1 -C.sub.4)-alkyl,
- 3) (C.sub.1 -C.sub.4)-alkoxy,
- 4) NO.sub.2,
- 5) CF.sub.3,
- 6) SO.sub.2 NR.sup.2a R.sup.2a,
- 7) (C.sub.1 -C.sub.4)-alkylthio,
- 8) hydroxy,
- 9) amino,
- 10) (C.sub.3 -C.sub.7)-cycloalkyl,
- 11) (C.sub.3 -C.sub.10)-alkenyl; and
- ii) (C.sub.3 -C.sub.7)-cycloalkyl,
- iii) Cl, Br, I, F, or
- iv) COOR.sup.2,
- v) --CF.sub.2 CF.sub.3, or
- vi) --CH.sub.2 CF.sub.3 ; and
- (b) (C.sub.1 -C.sub.4)-perfluoroalkyl, or
- (c) (C.sub.3 -C.sub.6)-cycloalkyl, unsubstituted or substituted with one or more substituents from the group consisting of: (C.sub.1 -C.sub.4)-alkoxy, (C.sub.1 -C.sub.4)-alkyl- thio, perfluoro-(C.sub.1 -C.sub.4)-alkyl, hydroxy, or halogen (F,Cl,Br,I); and
- E is:
- (a) a single bond,
- (b) --S(O).sub.n (CH.sub.2).sub.s --, or
- --O--; and
- n is 0 to 2; and
- s is 0 to 5; and
- R.sup.2 is:
- (a) H, or
- (b) (C.sub.1 -C.sub.6)-alkyl; and
- R.sup.2a is:
- (a) R.sup.2,
- (b) CH.sub.2 -aryl, or
- (c) aryl; and
- (d) when R.sup.2 and R.sup.2a are alkyl substituents on the same nitrogen then can be joined to form a ring; and
- wherein there is more than one R.sup.2a group in the definition of a structure of Formula I they may be the same or different; and
- R.sup.9 and R.sup.10 are independently:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl, unsubstituted or substituted with (C.sub.3 -C.sub.7)-cycloalkyl,
- (c) (C.sub.2 -C.sub.6)-alkenyl,
- (d) (C.sub.2 -C.sub.6)-alkynyl,
- (e) Cl, Br, F, I,
- (f) (C.sub.1 -C.sub.6)-alkoxyl,
- (g) when R.sup.9 and R.sup.10 are on adjacent carbons, they can be joined to form an phenyl ring,
- (h) (C.sub.1 -C.sub.6)-perfluoroalkyl,
- (i) (C.sub.3 -C.sub.7)-cycloalkyl, unsubstituted or substituted with (C.sub.1 -C.sub.6)-alkyl,
- (j) aryl,
- (k) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --(CH.sub.2).sub.n --,
- (l) hydroxy-(C.sub.1 -C.sub.6)-alkyl,
- (m) --CO.sub.2 R.sup.2a,
- (n) --OH,
- (o) --NR.sup.2 R.sup.21,
- (p) --[(C.sub.1 -C.sub.6)-alkyl]NR.sup.2 R.sup.21,
- (q) --NO.sub.2,
- (r) --(CH.sub.2).sub.n --SO.sub.2 --N(R.sup.2).sub.2,
- (s) --NR.sup.2 CO--(C.sub.1 -C.sub.4)-alkyl, or
- (t) --CON(R.sup.2).sub.2 ;
- X is:
- (a) --O--,
- (b) --S(O).sub.n --,
- (c) --NR.sup.13 --,
- (d) --CH.sub.2 O--,
- (e) --CH.sub.2 S(O).sub.n,
- (f) --CH.sub.2 NR.sup.13 --,
- (g) --OCH.sub.2 --,
- (h) --NR.sup.13 CH.sub.2 --,
- (i) --S(O).sub.n CH.sub.2 --,
- (j) --CH.sub.2 --,
- (k) --(CH.sub.2).sub.2 --,
- (l) single bond, or
- (m) --CH.dbd., wherein Y and R.sup.12 are absent forming a --C.dbd.C-- bridge to the carbon bearing Z and R.sup.11 ; and
- Y is:
- (a) single bond,
- (b) --O--,
- (c) --S(O).sub.n --,
- (d) --NR.sup.13 --, or
- (e) --CH.sub.2 --; and
- except that X and Y are not defined in such a way that the carbon atom to which Z is attached also simultaneously is bonded to two heteroatoms (O, N, S, SO, SO.sub.2);
- R.sup.11 and R.sup.12 are independently:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl, unsubstituted or substituted with a substituent selected from the group consisting of:
- (i) aryl,
- (ii) (C.sub.3 -C.sub.7)-cycloalkyl,
- (iii) NR.sup.2 R.sup.21,
- (iv) morpholin-4-yl,
- (v) OH,
- (vi) CO.sub.2 R.sup.2a, or
- (vii) CON(R.sup.2).sub.2,
- (c) aryl or aryl-(C.sub.1 -C.sub.2)-alkyl, unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of:
- (i) Cl, Br, I, F,
- (ii) (C.sub.1 -C.sub.6)-alkyl,
- (iii) [(C.sub.1 -C.sub.5)-alkenyl]CH.sub.2 --,
- (iv) [(C.sub.1 -C.sub.5)-alkynyl]CH.sub.2 --,
- (v) (C.sub.1 -C.sub.6)-alkyl-S(O).sub.n --(CH.sub.2).sub.n --,
- (vi) --CF.sub.3,
- (vii) --CO.sub.2 R.sup.2a,
- (viii) --OH,
- (ix) --NR.sup.2 R.sup.21,
- (x) --NO.sub.2,
- (xi) --NR.sup.2 COR.sup.2,
- (xii) --CON(R.sup.2).sub.2,
- (xiii) --G--[(C.sub.1 -C.sub.6)-alkyl]-R.sup.23,
- (xiv) --N[CH.sub.2 CH.sub.2 ].sub.2 Q, or
- (xv) --P(O)[O-(C.sub.1 -C.sub.4)-alkyl].sub.2,
- and can additionally be substituted with 1 or 2 substituents selected from the group consisting of: Br, Cl or F,
- (d) (C.sub.3 -C.sub.7)-cycloalkyl;
- G is: a single bond, O, S(O).sub.n or NR.sup.23 ; and
- Q is: O, S(O).sub.n or NR.sup.22 ; and
- R.sup.13 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) aryl,
- (d) aryl-(C.sub.1 -C.sub.6)-alkyl-(C.dbd.0)--,
- (e) (C.sub.1 -C.sub.6)-alkyl--(C.dbd.0)--,
- (f) [(C.sub.2 -C.sub.5)-alkenyl]CH.sub.2 --,
- (g) [(C.sub.2 -C.sub.5)-alkynyl]CH.sub.2 --; or
- (h) aryl--CH.sub.2 --; and
- Z is:
- (a) --CO.sub.2 H,
- (b) --CO.sub.2 R.sup.24,
- (c) --tetrazol-5-yl,
- (d) --CO--NH(tetrazol-5-yl),
- (e) --CONHSO.sub.2 --aryl,
- (f) --CONH-SO.sub.2 --(C.sub.1 -C.sub.8)-alkyl, wherein the alkyl group is unsubstituted or substituted with a substituent chosen from the group consisting of: --OH, --SH, --O(C.sub.1 -C.sub.4)-alkyl, --S--(C.sub.1 -C.sub.4)-alkyl, --CF.sub.3, Cl, Br, F, I, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl, --NH.sub.2, --NH[(C.sub.1 -C.sub.4)-alkyl], --N[(C.sub.1 -C.sub.4)-alkyl].sub.2 ; and
- (g) --CONH--SO.sub.2 -perfluoro-(C.sub.1 -C.sub.4)-alkyl,
- (h) --CONH--SO.sub.2 -heteroaryl, wherein heteroaryl is as defined below,
- (i) --CONHSO.sub.2 NR.sup.2a R.sup.2a,
- (j) --SO.sub.2 NHCO-aryl,
- (k) --SO.sub.2 NHCO--(C.sub.1 -C.sub.8)-alkyl, wherein the alkyl group is unsubstituted or substituted with a substituent chosen from the group consisting of: --OH, --SH, --O(C.sub.1 -C.sub.4)-alkyl, --S--(C.sub.1 -C.sub.4)-alkyl, --CF.sub.3, Cl, Br, F, I, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 --(C.sub.1 -C.sub.4 -alkyl, --NH.sub.2, --NH[(C.sub.1 -C.sub.4)-alkyl], --N[(C.sub.1 -C.sub.4)-alkyl].sub.2,
- (l) --SO.sub.2 NHCO--(C.sub.1 -C.sub.4)-perfluoroalkyl,
- (m) --SO.sub.2 NHCO-heteroaryl, or
- (n) --SO.sub.2 NHCONR.sup.2a R.sup.2a ; and
- T is --S(O).sub.n --, --O--, --NHCH.sub.2 --, --NHC(.dbd.O)--, --C(.dbd.O)N(R.sup.20)-, or --N(R.sup.20)-; and
- b is 0 or 1; and
- R.sup.15 is
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) phenyl, or
- (d) benzyl; and
- R.sup.16 is
- (a) (C.sub.1 -C.sub.10)-alkyl;
- (b) substituted (C.sub.1 -C.sub.10)-alkyl in which one or more substituent(s) is selected from
- (1) I, Br, Cl, F,
- (2) hydroxy,
- (3) (C.sub.1 -C.sub.10)-alkoxy,
- (4) (C.sub.1 -C.sub.5)-alkoxycarbonyl,
- (5) (C.sub.1 -C.sub.5)-acyloxy,
- (6) (C.sub.3 -C.sub.8)-cycloalkyl,
- (7) aryl,
- (8) substituted aryl in which the substituents are V and W,
- (9) (C.sub.1 -C.sub.10)-alkyl--S(O).sub.n,
- (10) (C.sub.3 -C.sub.8)-cycloalkyl--S(O).sub.n,
- (11) phenyl-S(O).sub.n,
- (12) substituted phenyl-S(O).sub.n in which the substituents are V and W,
- (13) oxo,
- (14) carboxy,
- (15) NR.sup.2 R.sup.2a,
- (16) (C.sub.1 -C.sub.5)-alkylaminocarbonyl,
- (17) di(C.sub.1 -C.sub.5)-alkylaminocarbonyl, or
- (18) cyano,
- (c) perfluoro-(C.sub.1 -C.sub.4)-alkyl,
- (d) (C.sub.2 -C.sub.10)-alkenyl,
- (e) (C.sub.2 -C.sub.10)-alkynyl,
- (f) (C.sub.3 -C.sub.8)-cycloalkyl,
- (g) substituted (C.sub.3 -C.sub.8)-cycloalkyl in which the substituent is selected from:
- (1) (C.sub.1 -C.sub.5)-alkyl, or
- (2) (C.sub.1 -C.sub.5)-alkoxy,
- (3) (C.sub.1 -C.sub.5)-alkoxycarbonyl,
- (4) (C.sub.1 -C.sub.5)-acyloxy,
- (5) (C.sub.1 -C.sub.5)-acyl,
- (6) hydroxy,
- (7) Br, Cl, F, I,
- (8) (C.sub.3 -C.sub.8)-cycloalkyl,
- (9) aryl,
- (10) substituted aryl in which the substituents are V and W,
- (11) (C.sub.1 -C.sub.10)-alkyl-S(O).sub.n,
- (12) (C.sub.3 -C.sub.8)-cycloalkyl-S(O).sub.n,
- (13) phenyl-S(O).sub.n,
- (14) substituted phenyl-S(O).sub.n in which the substituents are V and W,
- (15) oxo,
- (16) carboxy,
- (17) NR.sup.2 R.sup.2a,
- (18) (C.sub.1 -C.sub.5)-alkylaminocarbonyl,
- (19) di(C.sub.1 -C.sub.5)-alkylaminocarbonyl, or
- (20) cyano,
- (h) CO.sub.2 R.sup.2a,
- (i) aryl,
- (j) substituted aryl in which the substituents are V and W,
- (k) aryl--(CH.sub.2).sub.r --(M.sub.1).sub.z --(CH.sub.2).sub.t --
- (l) substituted aryl--(CH.sub.2).sub.r --(M.sub.1).sub.z --(CH.sub.2).sub.t -- in which the aryl group is substituted with V and W, ##STR34## M.sub.1 is O, S, --N(R.sup.15)--, or --C(O)--; and z is 0 or 1; and
- r and t are 0 to 2; and
- heteroaryl is: a 5- or 6-membered aromatic ring containing from one to three heteroatoms selected from the group consisting of N, O or S; and
- V and W are each independently selected from:
- (a) H,
- (b) (C.sub.1 -C.sub.5)-alkoxy,
- (c) (C.sub.1 -C.sub.5)-alkyl,
- (d) hydroxy,
- (e) ((C.sub.1 -C.sub.5)-alkyl)S(O).sub.n,
- (f) --CN,
- (g) --NO.sub.2,
- (h) --NR.sup.2 R.sup.2a,
- (i) ((C.sub.1 -C.sub.5)-alkyl)CO--NR.sup.2 R.sup.2a,
- (j) --CO.sub.2 R.sup.2a,
- (k) ((C.sub.1 -C.sub.5)--alkyl)CO--,
- (l) CF.sub.3,
- (m) I, Br, Cl, F,
- (n) hydroxy--(C.sub.1 -C.sub.4)--alkyl--,
- (o) carboxy--(C.sub.1 -C.sub.4)--alkyl--,
- (p) -tetrazol-5-yl,
- (q) --NH--SO.sub.2 CF.sub.3,
- (r) aryl,
- (s) --O--CONR.sup.2 R.sup.2a,
- (t) --NR.sup.2a --CO.sub.2 R.sup.2a,
- (u) --NR.sup.2a --CONR.sup.2a R.sup.2a,
- (v) --NR.sup.2a --CON(CH.sub.2 CH.sub.2).sub.2 Q,
- (w) --OCON(CH.sub.2 CH.sub.2).sub.2 Q; or
- (x) --CONR.sup.2 R.sup.2a ; and
- Q.sub.1 is O, S(O).sub.n, or NR.sup.2a ; and
- R.sup.18 is: phenyl, unsubstituted or substituted with: V and W, (C.sub.1 -C.sub.4)-alkyl, or perfluoro-(C.sub.1 -C.sub.4)-alkyl; and
- R.sup.20 is
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) allyl,
- (d) (C.sub.3 -C.sub.6)-cycloalkyl,
- (e) (C.sub.1 -C.sub.4)-acyl,
- (f) benzyl, or
- (g) phenyl; and
- R.sup.21 is:
- (a) H, or
- (b) (C.sub.1 -C.sub.4)-alkyl, is unsubstituted or substituted with:
- i) NH.sub.2,
- ii) NH[(C.sub.1 -C.sub.4)-alkyl],
- iii) N[(C.sub.1 -C.sub.4)-alkyl].sub.2,
- iv) CO.sub.2 H,
- v) CO.sub.2 (C.sub.1 -C.sub.4)-alkyl,
- vi) OH,
- vii) SO.sub.3 H, or
- viii) SO.sub.2 NH.sub.2 ; and
- R.sup.22 is:
- (a) H,
- (b) (C.sub.1 -C.sub.4)-alkyl,
- (c) (C.sub.1 -C.sub.4)-alkoxyl,
- (d) aryl,
- (e) aryl-(C.sub.1 -C.sub.4)-alkyl,
- (f) CO.sub.2 R.sup.2a,
- (g) CON(R.sup.2).sub.2,
- (h) SO.sub.2 R.sup.2a,
- (i) SO.sub.2 N(R.sup.2).sub.2,
- (j) P(O)[(C.sub.1 -C.sub.4)-alkoxyl].sub.2, or
- (k) imidazol-2-yl or imidazol-4-yl, in which the imidazole can be substituted with (C1-C4)-alkyl; and
- R.sup.23 is:
- (a) OH,
- (b) NR.sup.2 R.sup.21,
- (c) CO.sub.2 R.sup.2a,
- (d) CON(R.sup.2).sub.2, or
- (e) S(O).sub.n -(C.sub.1 -C.sub.4)-alkyl; and
- R.sup.24 is:
- (a) (C.sub.1 -C.sub.4)-alkyl,
- (b) CHR.sup.26 --O--COR.sup.27,
- (c) CH.sub.2 CH.sub.2 --N[(C.sub.1 -C.sub.2)--alkyl].sub.2,
- (d) CH.sub.2 CH.sub.2 --N[CH.sub.2 CH.sub.2 ].sub.2 O,
- (e) (CH.sub.2 CH.sub.2 O).sub.y --O--[(C.sub.1 -C.sub.4)-alkyl], wherein y is 1 or 2,
- (f) aryl, ##STR35## R.sup.25 is: (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) aryl, or
- (d) aryl-(C.sub.1 -C.sub.5)-alkyl; and
- R.sup.26 and R.sup.27 are (C.sub.1 -C.sub.6)-alkyl or phenyl.
- 2. A compound which is ##STR36## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is:
- (a) (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl or (C.sub.2 -C.sub.6)-alkynyl, each of which is unsubstituted with a substituent selected from the group consisting of:
- ii) (C.sub.3 -C.sub.7)-cycloalkyl,
- iii) Cl, Br, I, F, or
- iv) COOR.sup.2,
- v) --CF.sub.2 CF.sub.3, or
- vi) --CH.sub.2 CF.sub.3 ; and
- (b) perfluoro-(C.sub.1 -C.sub.4)-alkyl, or
- (c) (C.sub.3 -C.sub.6)-cycloalkyl; and
- R.sup.2 is: H, or (C.sub.1 -C.sub.6)-alkyl; and
- R.sup.2a is: R.sup.2, benzyl, or phenyl; and when R.sup.2 and R.sup.2a are alkyl substituents on the same nitrogen then can be joined to form a ring;
- R.sup.9 and R.sup.10 are independently: H, (C.sub.1 -C.sub.6 -alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, Cl, Br, F, I, (C.sub.1 -C.sub.6)-alkoxy, aryl, or R.sup.9 and R.sup.10 join to form a phenyl ring; and
- X and Y are: --CH.sub.2 --, --O--, --S--, --NR.sup.13 --, single bond, or --CH.dbd., which is double bonded to the carbon bearing Z and R.sup.11, except that X and Y are not defined in such a way that the carbon atom to which Z is attached also simultaneously bonded to two heteroatoms (O, N, or S(O).sub.n); and
- Z is:
- (a) --CO.sub.2 H,
- (b) --CO.sub.2 --(C.sub.1 -C.sub.6)-alkyl,
- (c) -tetrazol-5-yl,
- (d) --CO--NH(tetrazol-5-yl)
- (e) --CONH--SO.sub.2 --aryl,
- (f) --CONH--SO.sub.2 --(C.sub.1 -C.sub.8)-alkyl, wherein the alkyl group is unsubstituted or substituted with a substituent selected from the group consisting of: --OH, --SH, --O(C.sub.1 -C.sub.4)-alkyl, --S--(C.sub.1 -C.sub.4)-alkyl, --CF.sub.3, Cl, Br, F, I, --NO.sub.2, --CO.sub.2 H, --CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl, --NH.sub.2, --NH[(C.sub.1 -C.sub.4)-alkyl], --N[(C.sub.1 -C.sub.4)-alkyl].sub.2 ; and
- (g) --CONH--SO.sub.2 --perfluoro-(C.sub.1 -C.sub.4)-alkyl,
- (h) --CONH--SO.sub.2 -heteroaryl, or
- (i) --CONHSO.sub.2 NR.sup.2 R.sup.2a ; and
- R.sup.11 and R.sup.12 are independently: H, (C.sub.1 -C.sub.6)-alkyl, or aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of: Br, I. Cl, F, (C.sub.1 -C.sub.4)-alkyl, (C.sub.2 -C.sub.4)-alkenyl, (C.sub.2 -C.sub.4)-alkynyl, (C.sub.1 -C.sub.4)-alkoxyl, NO.sub.2, CF.sub.3, SO.sub.2 NR.sup.2a R.sup.2a, (C.sub.1 -C.sub.4)-alkylthio, hydroxyl, --NR.sup.2a R.sup.2a ; and
- R.sup.13 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) aryl, wherein aryl is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of: Br, I, Cl, F, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxy, NO.sub.2, CF.sub.3, SO.sub.2 NR.sup.2a R.sup.2a, (C.sub.1 -C.sub.4)-alkylthio, hydroxy, --NR.sup.2a R.sup.2a,
- (c) [(C.sub.2 -C.sub.5)-alkenyl]CH.sub.2 --,
- (d) [(C.sub.2 -C.sub.5)-alkynyl]CH.sub.2 --,
- (e) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of: Cl, Br, I, F, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxyl, NO.sub.2, CF.sub.3, SO.sub.2 NR.sup.2a R.sup.2a, (C.sub.1 -C.sub.4)-alkylthio, hydroxy, amino, (C.sub.3 -C.sub.7)-cycloalkyl, or (C.sub.3 -C.sub.10)-alkenyl,
- (f) aryl[(C.sub.1 -C.sub.6)-alkyl]CO--, or
- (g) [(C.sub.1 -C.sub.6)-alkyl]CO--; and
- T is --S(O)n--, --O--, --NHCH.sub.2 --, NHC(.dbd.O)--, --C(.dbd.O)NR.sup.30, or --N(R.sup.20); and
- b is 0 or 1; and
- R.sup.16 is
- (a) (C.sub.1 -C.sub.10)-alkyl in which one or more substituent(s) is selected from the group consisting of: hydroxy, oxy, carboxy, (C.sub.1 -C.sub.5)-alkoxy-carbonyl, (C.sub.3 -C.sub.8)-cycloalkyl, aryl, or substituted aryl in which the substituents are V and W, and
- (b) aryl, unsubstituted or substituted in which the substituents are V and W;
- V and W are each independently selected from:
- (a) H,
- (b) (C.sub.1 -C.sub.5)-alkoxy,
- (c) (C.sub.1 -C.sub.5)-alkyl,
- (d) hydroxy,
- (e) ((C.sub.1 -C.sub.5)-alkyl)S(O).sub.n,
- (f) --CN,
- (g) --NO.sub.2,
- (h) --NR.sup.2 R.sup.2a,
- (i) [(C.sub.1 -C.sub.5)-alkyl]CO-NR.sup.2 R.sup.2a,
- (j) --CO.sub.2 R.sup.2a,
- (k) [(C.sub.1 -C.sub.5)-alkyl]CO-,
- (l) CF.sub.3,
- (m) I, Br, Cl, F,
- (n) hydroxy-(C.sub.1 -C.sub.4)-alkyl-,
- (o) carboxy-(C.sub.1 -C.sub.4)-alkyl-,
- (p) -tetrazol-5-yl,
- (q) --NH--SO.sub.2 CF.sub.3,
- (r) aryl,
- (s) --O--CONR.sup.2 R.sup.2a,
- (t) NR.sup.2a --CO.sub.2 R.sup.2a,
- (u) --NR.sup.2a --CONR.sup.2a R.sup.2a,
- (v) --NR.sup.2a --CON(CH.sub.2 CH.sub.2).sub.2 Q,
- (w) --OCON(CH.sub.2 CH.sub.2).sub.2 Q, or
- (x) --CONR.sup.2 R.sup.2a ; and
- Q is: O, S(O).sub.n, or NR.sup.2a ; and
- R.sup.20 is: H or (C.sub.1 -C.sub.6)-alkyl; and
- heteroaryl is: pyridyl, thienyl, furyl, imidazolyl or thiazolyl.
- 3. A compound of claim 2 which is ##STR37## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is (C.sub.1 -C.sub.6)-alkyl; and
- T is S, or S(.dbd.O); and
- R.sup.9 and R.sup.10 are: (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkenyl or (C.sub.1 -C.sub.6)-alkynyl, (C.sub.1 -C.sub.4)-alkoxyl, (C.sub.3 -C.sub.8)-cycloalkyl, Cl, Br, I, F, or aryl; and
- X is --CH.sub.2 --, O or --NR.sup.13 --; and
- R.sup.11 is phenyl, unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of: Br, Cl, F, I, (C.sub.1 -C.sub.4)-alkyl, (C.sub.1 -C.sub.4)-alkoxyl, CF.sub.3, NO.sub.2, (C.sub.1 -C.sub.4)-alkylthio, OH or NR.sup.2a R.sup.2a ; and
- R.sup.13 is: H, (C.sub.1 -C.sub.6)-alkyl, [(C.sub.2 -C.sub.5)-alkenyl]CH.sub.2 --, [(C.sub.2 -C.sub.5)-alkynyl]CH.sub.2 -- or aryl; and
- Z is carboxyl, CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl or tetrazol-5-yl; and
- R.sup.16 is benzyl, unsubstituted or substituted in the 2-position or in the 4-position with a substituent selected from the group consisting of: carboxyl, (C.sub.1 -C.sub.4)-alkyl, Br, Cl, F, or I, methoxy or nitro.
- 4. A compound which is ##STR38## or a pharmaceutically acceptable salt thereof. wherein: V is: H, 4-Cl, 4-Br, 4-I, 4-F, 4-NO.sub.2, 4-OCH.sub.3, 4-CH.sub.3, 2-CO.sub.2 H; and
- R.sup.9 and R.sup.10 are independently: H, Cl, Br, F, I, (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.2 -C.sub.6)-alkynyl, (C.sub.1 -C.sub.4)-alkoxyl, (C.sub.3 -C.sub.7)-cycloalkyl, and
- R.sup.11 is: phenyl, unsubstituted or substituted with substituents selected from the group consisting of: H, Cl, Br, F, I, CH.sub.3, or OCH.sub.3 ; and
- X is: O or --NR.sup.13 --; and
- R.sup.13 is: H, (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl, or (C.sub.2 -C.sub.6)-alkynyl; and
- Z is: carboxyl, CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl or tetrazol-5-yl; and
- 5. The compound of claim 1 wherein said compound or its pharmaceutically acceptable salt is selected from the group consisting of:
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)phenyl]methyl]-5-(4-chlorobenzylthio)-4-H-1,2,4-triazole;
- 3-Butyl-4-[[4-[1-carboxy-1-phenylmethoxy]phenyl]methyl]-5-(4-methoxybenzylthio) -4H-1,2,4-triazole;
- 3-Butyl-4-(1-carboxy-1-phenylmethoxy)phenyl]methyl]-5-(4-nitrobenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-[1-carboxy-1-(2-chlorophenyl)methoxy]phenyl]methyl]-5-(4-methoxybenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-[1-carboxy-1-(2-chlorophenyl)methoxy]phenyl]methyl]-5-(4-chlorobenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-5-(2-carboxybenzylthio)-4-[[4-(1-carboxy-1-phenylmethoxy)phenyl]methyl]-4H-1,2,4-triazole;
- 3-Butyl-5-(4-nitrobenzylthio)-4-[[4-[1-phenyl-1-(tetrazol-5-yl)methoxy]phenyl]methyl]-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)-3-propylphenyl]methyl-5-(4-chlorobenzylthio)-4H1,2,4-triazole;
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)-3-propylphenyl]methyl-5-(4-methoxybenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)-3,5-dipropylphenyl]methyl]-5-(4-chlorobenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)-3,5-dipropylphenyl]methyl]-5-(4-methoxybenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-[1-carboxy-1-(2,5-dibromo-3,4-dimethoxyphenyl)methoxy]phenyl]methyl]-5-(4-chlorobenzylthio)4H-1,2,4-triazole;
- 3-Butyl-4-[[4-[1-carboxy-1-(2,5-dibromo-3,4-dimethoxyphenyl)methoxy]phenyl]methyl]-5-(4-methoxybenzylthio)4H-1,2,4-triazole;
- 4-[[[N-allyl-N-[(1-carboxy-1-phenyl)methyl]amino]phenyl]methyl]-3-butyl-5-(4-chlorobenzylthio)-4H-1,2,4-triazole;
- 3-Butyl-4-[[4-(1-carboxy-1-phenylmethoxy)-3-propylphenyl]methyl]-5-phenyl-4H-1,2,4-triazole;
- 4-[[[N-allyl-N[(1-carboxy-1-phenyl)methyl]amino]phenyl]methyl]-3-butyl-5-(4-methoxybenzylthio)-4H-1,2,4-triazole; or
- 3-Butyl-4-[[[N-[(1-carboxy-1-phenyl)methyl]-N-ethylamino]phenyl]methyl]-5-(4-chlorobenzylthio)-4H-1,2,4-triazole.
- 6. A pharmaceutical composition useful in the treatment of hypertension which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1.
- 7. A method of treating hypertension which comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 1.
- 8. A method of treating ocular hypertension comprising topical ocular administration to a patient in need of such treatment of an effective ocular antihypertensive amount of a compound of claim 1.
- 9. A method of treating cognitive dysfunction, anxiety, or depression comprising administering to a patient in need of such treatment, a therapeutically effective amount of a compound of claim 1.
Parent Case Info
The present application is a continuation in part of copending application Ser. No. 671,598 filed on Mar. 19, 1991, now abandoned which is a continuation in part application of copending Ser. No. 479,779 filed on Feb. 13, 1990 (now abandoned).
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EPX |
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Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
671598 |
Mar 1991 |
|
Parent |
479779 |
Feb 1990 |
|