Claims
- 1. A compound of Formula 1 which is ##STR44## 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 a substituent selected from the group consisting of:
- i) aryl as defined below,
- ii) (C.sub.3 -C.sub.7)-cycloalkyl,
- iii) Cl, Br, I, F,
- iv) COOR.sup.2,
- vii) N[((C.sub.1 -C.sub.4)-alkyl)].sub.2,
- viii) NHSO.sub.2 R.sup.2,
- ix) CF.sub.3,
- x) COOR.sup.2, or
- xi) SO.sub.2 NHR.sup.2a ; and
- (b) aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of:
- i) Cl, Br, F, I,
- ii) (C.sub.1 -C.sub.4)-alkyl,
- iii) (C.sub.1 -C.sub.4)-alkoxy,
- iv) NO.sub.2
- v) CF.sub.3
- vi) SO.sub.2 NR.sup.2a R.sup.2a,
- vii) (C.sub.1 -C.sub.4)-alkylthio,
- viii) hydroxy,
- ix) amino,
- x) (C.sub.3 -C.sub.7)-cycloalkyl,
- xi) (C.sub.3 -C.sub.10)-alkenyl; and
- E is:
- (a) a single bond,
- (b) --S(O).sub.x (CH.sub.2).sub.s --, or
- (c) --O--; and
- x is 0 to 2,
- s is 0 to 5;
- m is 1 to 5;
- p is 0 to 3;
- n is 1 to 10;
- 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
- R.sup.3 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl or (C.sub.2 -C.sub.6)-alkynyl,
- (c) Cl, Br, I, F,
- (d) NO.sub.2
- (e) (C.sub.1 -C.sub.8)-perfluoroalkyl,
- (f) C.sub.6 F.sub.5,
- (g) CN,
- (h) NH.sub.2,
- (i) NH[(C.sub.1 -C.sub.4)-alkyl],
- (j) N[(C.sub.1 -C.sub.4)-alkyl].sub.2,
- (k) NH[CO(C.sub.1 -C.sub.4)-alkyl],
- (l) N[(C.sub.1 -C.sub.4)-alkyl)-(CO(C.sub.1 -C.sub.4)-alkyl)],
- (m) N(C.sub.1 -C.sub.4)-alkyl-COaryl,
- (n) N(C.sub.1 -C.sub.4)alkyl-SO.sub.2 aryl,
- (o) CO.sub.2 H,
- (p) CO.sub.2 R.sup.2a,
- (q) phenyl,
- (r) phenyl-(C.sub.1 -C.sub.3)-alkyl,
- (s) phenyl and phenyl-(C.sub.1 -C.sub.3)-alkyl substituted on the phenyl ring with one or two substituents selected from:
- i) (C.sub.1 -C.sub.4)-alkyl,
- ii) (C.sub.1 -C.sub.4)-alkoxyl,
- iii) F, Cl, Br, I,
- iv) hydroxyl,
- v) methoxyl,
- vi) CF.sub.3,
- vii) CO.sub.2 R.sup.2a, or
- viii) NO.sub.2 ; and
- R.sup.4 is:
- (a) H,
- (b) CN,
- (c) (C.sub.1 -C.sub.8)-alkyl,
- (d) (C.sub.3 -C.sub.6)-alkenyl,
- (e) (C.sub.1 -C.sub.8)-perfluoroalkyl,
- (f) (C.sub.1 -C.sub.8)-perfluoroalkenyl,
- (g) NH.sub.2,
- (h) NH(C.sub.1 -C.sub.4)-alkyl,
- (i) N[(C.sub.1 -C.sub.4)-alkyl].sub.2,
- (j) NH(C.sub.1 -C.sub.4)-acyl,
- (k) N[((C.sub.1 -C.sub.4)-acyl)((C.sub.1 -C.sub.4)-alkyl)],
- (l) CO.sub.2 H,
- (m) CO.sub.2 R.sup.24,
- (n) phenyl,
- (o) phenyl-(C.sub.2 -C.sub.6)-alkenyl, ##STR45## (z) (CH.sub.2).sub.n NHSO.sub.2 R.sup.16, (aa) (CH.sub.2).sub.n F,
- (ab) (CH.sub.2).sub.m -imidazol-1-yl,
- (ac) tetrazol-5-yl,
- (ad) --CONH--SO.sub.2 -aryl,
- (ae) --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
- (af) --CONH--SO.sub.2 --(C.sub.1 -C.sub.4)-perfluoroalkyl,
- (ag) --CONHSO.sub.2 NR.sup.2a R.sup.2a ; and ##STR46## R.sup.5 is: (a) CN,
- (b) NO.sub.2, or
- (c) CO.sub.2 R.sup.2a ; 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)-alkoxy,
- (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.x --(CH.sub.2).sub.n --,
- (l) hydroxy-(C.sub.1 -C.sub.6)-alkyl,
- (m) --CF.sub.3,
- (n) --CO.sub.2 R.sup.2a,
- (o) --OH,
- (p) --NR.sup.2 R.sup.21,
- (q) --[(C.sub.1 -C.sub.6)-alkyl]NR.sup.2 R.sup.21,
- (r) --NO.sub.2,
- (s) --(CH.sub.2).sub.n --SO.sub.2 --N(R.sup.2).sub.2,
- (t) --NR.sup.2 CO--(C.sub.1 -C.sub.4)-alkyl, or
- (u) --CON(R.sup.2).sub.2 ; and
- X is:
- (a) --O--,
- (b) --S(O).sub.x --,
- (c) --NR.sup.13 --
- (d) --CH.sub.2 O--,
- (e) --CH.sub.2 S(O).sub.x,
- (f) --CH.sub.2 NR.sup.13 --,
- (g) --OCH.sub.2 --,
- (h) --NR.sup.13 CH.sub.2 --,
- (i) --S(O).sub.x 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.x --,
- (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) OH,
- (v) CO.sub.2 R.sup.2a, or
- (vi) CON(R.sup.2).sub.2,
- (c) aryl or aryl-(C.sub.1 -C.sub.2)-alkyl, unsubstituted or substituted with 1 to 3 substitutents 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.x --(CH.sub.2).sub.x --,
- (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) --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.x or NR.sup.23 ; 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.O)--,
- (e) (C.sub.1 -C.sub.6)-alkyl--(C.dbd.O)--,
- (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) --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) --CONHSO.sub.2 --(C.sub.1 -C.sub.4)-perfluoroalkyl,
- (i) --CONHSO.sub.2 NR.sup.2a R.sup.2a ; and
- (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 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
- (l) --SO.sub.2 NHCO--(C.sub.1 -C.sub.4)-perfluoroalkyl,
- (n) --SO.sub.2 NHCONR.sup.2a R.sup.2a ;
- (o) --PO(OH).sub.2,
- (p) --PO(OR.sup.2).sub.2, or
- (q) --PO(OH)(OR.sup.2); and
- R.sup.14 is:
- (a) H,
- (b) (C.sub.1 -C.sub.8)-alkyl,
- (c) (C.sub.1 -C.sub.8)-perfluoroalkyl,
- (d) (C.sub.3 -C.sub.6)-cycloalkyl,
- (e) phenyl, or
- (f) benzyl; and
- R.sup.15 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) (C.sub.3 -C.sub.6)-cycloalkyl,
- (d) (CH.sub.2).sub.p -phenyl,
- (e) OR.sup.17,
- (f) NR.sup.18 R.sup.19 ; and
- R.sup.16 is:
- (a) (C.sub.1 -C.sub.8)-alkyl,
- (b) (C.sub.1 -C.sub.8)-perfluoroalkyl,
- (c) 1-adamantyl,
- (d) 1-naphthyl,
- (e) (1-naphthyl)ethyl, or
- (f) --(CH.sub.2).sub.p -phenyl; and
- R.sup.17 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) (C.sub.3 -C.sub.6)-cycloalkyl,
- (d) phenyl, or
- (e) benzyl; and
- R.sup.18 and R.sup.19 are independently:
- (a) H,
- (b) (C.sub.1 -C.sub.4)-alkyl,
- (c) phenyl,
- (d) benzyl, or
- (e) .alpha.-methylbenzyl; 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 (C.sub.1 -C.sub.4)-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,
- (e) S(O).sub.x --(C.sub.1 -C.sub.4)-alkyl,
- R.sup.24 is:
- (a) (C.sub.1 -C.sub.4)-alkyl,
- (b) CHR.sup.25 --O--COR.sup.26,
- (c) CH.sub.2 CH.sub.2 --N[(C.sub.1 -C.sub.2)-alkyl].sub.2,
- (d) (CH.sub.2 CH.sub.2 O).sub.y --O--[(C.sub.1 -C.sub.4)-alkyl], wherein y is 1 or 2,
- (e) aryl, or --CH.sub.2 -aryl, where aryl is as defined above or optionally substituted with --CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl, ##STR47## R.sup.25 and R.sup.26 independently are (C.sub.1 -C.sub.6)-alkyl or phenyl.
- 2. A compound which is ##STR48## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is (C.sub.2 -C.sub.4)-alkyl, or cyclopropyl; and
- R.sup.3 is H, Cl, (C.sub.1 -C.sub.4)-perfluoroalkyl, (C.sub.1 -C.sub.4)-alkyl, aryl, CH.sub.2 -aryl; and
- R.sup.4 is CO.sub.2 H, CH.sub.2 OH, or CO.sub.2 (C.sub.1 -C.sub.4)-alkyl; and
- R.sup.9 and R.sup.10 are independently: (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkenyl, (C.sub.1 -C.sub.6)-alkynyl, (C.sub.1 -C.sub.4)-alkoxyl, Cl, Br, I, F, (C.sub.3 -C.sub.8)-cycloalkyl, or 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, F, I, (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, amino, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.10)-alkenyl; and
- R.sup.11 is phenyl, unsubstituted or substituted with Br, Cl, F, I, (C.sub.1 -C.sub.4)-alkyl or (C.sub.1 -C.sub.4)-alkoxyl, (C.sub.1 -C.sub.6)-alkyl--S(O).sub.n --(CH.sub.2).sub.n --, hydroxy-(C.sub.1 -C.sub.6)-alkyl, --CF.sub.3, --CO.sub.2 R.sup.2a, --OH, --NR.sup.2 R.sup.21, --[(C.sub.1 -C.sub.6)-alkyl]NR.sup.2 R.sup.21, --NO.sub.2, --(CH.sub.2).sub.n --SO.sub.2 --N(R.sup.2).sub.2, --NR.sup.2 CO--(C.sub.1 -C.sub.4)-alkyl, or CON(R.sup.2)2; and
- Z is tetrazol-5-yl, carboxyl or CO.sub.2 (C.sub.1 -C.sub.4)-alkyl; and
- R.sup.21 is: H, or (C.sub.1 -C.sub.4)-alkyl, wherein the alkyl is unsubstituted or substituted with a substituent selected from the group consisting of: NH.sub.2, NH[(C.sub.1 -C.sub.4)-alkyl], N[(C.sub.1 -C.sub.4)-alkyl].sub.2, CO.sub.2 H, OH, SO.sub.3 H, CO.sub.2 (C.sub.1 -C.sub.4)-alkyl or SO.sub.2 NH.sub.2.
- 3. A compound which is ##STR49## or a pharmaceutically acceptable salt thereof wherein: Z is CO.sub.2 H, CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl or 1H-tetrazol-5-yl; and
- R.sup.9 and R.sup.10 are independently: (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, Cl, Br, I, F, (C.sub.3 -C.sub.8)-cycloalkyl, or 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, F, I, (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, amino, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.10)-alkenyl; and
- R.sup.11 is H, or benzyl; and
- R.sup.13 is H, CH.sub.3 (CH.sub.2).sub.3 C(.dbd.O)--, C.sub.6 H.sub.5 CH.sub.2 CH.sub.2 C(.dbd.O)--, or C.sub.6 H.sub.5 CH.sub.2 C(.dbd.O)--.
- 4. A compound which is ##STR50## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is: (C.sub.1 -C.sub.4)-alkyl and cyclopropyl; and
- R.sup.2a is: H, (C.sub.1 -C.sub.6)-alkyl, benzyl, or phenyl; and
- R.sup.3 is H, Cl, (C.sub.1 -C.sub.4)-perfluoroalkyl, (C.sub.1 -C.sub.4)-alkylamino, (C.sub.1 -C.sub.4)-acylamino; and
- R.sup.4 is CO.sub.2 H, CH.sub.2 OH, or CO.sub.2 (C.sub.1 -C.sub.4)-alkyl; and
- R.sup.9 and R.sup.10 are independently: (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, Cl, Br, I, F, (C.sub.3 -C.sub.8)-cycloalkyl, or aryl; and
- R.sup.11 is: aryl or aryl--CH.sub.2 --, wherein the aryl is unsubstituted or substituted with 1 or 2 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, NO.sub.2, CF.sub.3, (C.sub.1 -C.sub.4)-alkylthio, OH, --NR.sup.2a R.sup.2a and
- X is: O, NR.sup.13, CH.sub.2, or --CH.dbd., which is double bonded to the carbon bearing Z and R.sup.11 ; and
- R.sup.13 is: H, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkenyl, aryl; and
- Z is: CO.sub.2 H, CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl, 1H-tetrazol-5-yl, --CONHSO.sub.2 -aryl, wherein aryl is defined as phenyl or naphthyl, unsubstituted, mono- or disubstituted with substituents selected from the group consisting of: H, (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, amino, (C.sub.3 -C.sub.7)-cycloalkyl, (C.sub.3 -C.sub.10)-alkenyl.
- 5. A compound which is ##STR51## or a pharmaceutically acceptable salt thereof wherein: R.sup.1 is: (C.sub.1 -C.sub.4)-alkyl and cyclopropyl; and
- R.sup.2a is: H, (C.sub.1 -C.sub.6)-alkyl, benzyl, or phenyl; and
- R.sup.3 is H, Cl, (C.sub.1 -C.sub.4)-perfluoroalkyl, (C.sub.1 -C.sub.4)-alkylamino, (C.sub.1 -C.sub.4)-acylamino; and
- R.sup.4 is CO.sub.2 H, CH.sub.2 OH, or CO.sub.2 (C.sub.1 -C.sub.4)-alkyl; and
- R.sup.9 and R.sup.10 are independently: (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, Cl, Br, I, F, (C.sub.3 -C.sub.8)-cycloalkyl, or aryl; and
- R.sup.11 is: aryl or aryl--CH.sub.2 --, wherein the aryl is unsubstituted or substituted with 1 or 2 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, NO.sub.2, CF.sub.3, (C.sub.1 -C.sub.4)-alkylthio, OH, --NR.sup.2a R.sup.2a ; and
- R.sup.12 is H, OH, or (C.sub.1 -C.sub.4)-alkyl; and
- Z is CO.sub.2 H, CO.sub.2 --(C.sub.1 -C.sub.4)-alkyl or 1H-tetrazol-5-yl.
- 6. A compound or its pharmaceutically acceptable salt selected from the group consisting of:
- 2-Butyl-1-[4-(N-(1(R)-carbomethoxy-1-benzyl)methyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(R)-carboxy-1-benzyl)methyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(R)-carbomethoxy-1-benzyl)methyl-methyl-N-pentanoyl)aminomethylphenyl]-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(R)-carboxy-1-benzyl)methyl-N-pentanoyl)aminomethyl-phenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1-(R)-carboxy-1-benzyl)methyl-N-(3-phenyl)propionyl)aminomethylphenyl]methyl-4-chloroimidazole;
- 2-Butyl-1-[4-N-(1(R)-carbomethoxy-1-benzyl)methyl-N-(phenylacetyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(R)-carboxy-1-benzyl-methyl-N-(phenylacetyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(S)-carbomethoxy-1-benzyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(S)-carboxy-1-benzyl)aminomethylphenyl]methyl-4-chloro-5-hydroxy-methylimidazole;
- 2-Butyl-1-[4-(N-(1(S)-carbomethoxy-1-benzyl)-N-pentanoyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1(S)-carboxy-1-benzyl)methyl-N-pentanoyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-5-t-butyldimethylsilyloxymethyl-1-[4-(1-carbomethoxy-1,1-dibenzyl)methyl)aminomethylphenyl]methyl-4-chlorimidazole;
- 2-Butyl-1-[4-(N-(1-carbomethoxy-1,1-dibenzyl)methyl)aminomethylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(N-(1-carboxy-1,1-dibenzyl)methyl)aminomethylphenyl]phenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 1-[4-(1-(N-benzyl-N-pentanoyl)amino-1-(tetrazol-5-ylmethylphenyl]methyl-2-butyl-5-t-butyldimethylsilyloxymethyl-4-chloroimidazole;
- 2-Butyl-4-chloro-5-hydroxymethyl-3-[4-(1-(1'-hydroxy-1-phenyl-1-tetrazol-5-yl)methylphenyl]methylimidazole;
- 2-Butyl-1-[4-(1-carboxy-1-(2-chloro)phenyl)methoxyphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-1-[4-(1-carboxy-1-phenyl)methoxy-3,5-dipropylphenyl]methyl-4-chloro-5-hydroxymethylimidazole;
- 2-Butyl-4-chloro-5-hydroxymethyl-1-[4-(1-phenyl-1-tetrazol-5-yl))methylphenyl]methylimidazole; and
- 2-Butyl-1-[4-(N-(1-carboxy-1-(2-phenyl)ethyl)aminophenyl]methyl-4-chloro-5-hydroxymethylimidazole.
- 7. 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.
- 8. 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.
Parent Case Info
The present invention is a continuation in part of copending application Ser. No. 671,593 filed on Mar. 19, 1991 now abandoned, which is a continuation in part application of copending Ser. No. 479,780 filed Feb. 13, 1990 (now abandoned).
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671593 |
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|
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|