EP0512865A2 — Novel cholesterol lowering compounds

Claim 1

Independent Claim 2679 words

A compound of structural formula (I): wherein a is 0 or 1; A is -C(O)-, -NR 3- C(O)-, or -OC(O)-; R 1 is selected from the group consisting of: (1) C 1-20 alkyl, (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 ocycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(0)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n- ; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the -carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3 C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (11) C 3-10 cycloalkyl; and (12) substituted C 3-10 cycloalkyl in which one or more of the substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) C 1-10 alkylS(O)n-, (p) C 1-10 alkyl, (q) -CO 2 H, (r) -vinylidene, (s) R 3- C(O)-, (t) R 2 O-C(O)-O-, (u) R 3 R 3 N-C(O)-O-, and (v) R 2 0-C(O)-NR 3- ; Each R 2 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloaIkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; and (9) C 3-10 alkynyl; Each R 3 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloaIkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; (9) C 3-10 alkynyl; (10) hydrogen; and (11) C 1-5 alkyl substituted with X 1 ; R 4 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3 -, -O-, or -S(O)n-; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R20-C(O)-NR 3- ; and (11) C 3-10 cycloalkyl; (12) substituted C 3-10 cycloalkyl in which one or more of the substituents is selected from: (a) halogen, (b) hydroxy, (c) R 3 R3 N -, (d) R 2 0-, (e) R 2 0-C(0)-, (f) R 3 -C(O)-O-, (g) OXO, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (13) hydrogen; R 5 is selected from the group consisting of: (1) hydrogen; (2) C 1-10 alkyl; (3) aryl substituted with X and Y; (4) arylC 1-4 alkyl, wherein aryl is substituted with X and Y; (5) R 2 0-C(O)-; (6) C 3-10 cycloalkyl; ( 7 ) R 3- C(O)-; and (8) R 3 R 3 N-C(O)-; R 6 and R 6 a are each independently selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0-, (e) R 2 0-C(0)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 NOC(O)-O-, and (t) R 2 0-C(O)-NR3-; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R 3 R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, ( f ) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (6) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the carbons is substituted with: (a) halogen (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (7) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkynyl wherein alkynyl contains one or more triple bonds; (10) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0 -, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (11) C 2 - 20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n -; (12) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (13) aryl substituted with X and Y; (14) Heteroaryl substituted with X and Y; (15) C 3-5 cycloalkyl; (16) substituted C 3-5 cycloalkyl in which one or more of the substituents is selected from: (a) R 3 0-, and (b) R 3 R3N-; and (17) hydrogen; aryl including X, Y substitution is: heteroaryl including X, Y substitution is selected from: wherein: Q is -NR 3 , -O- or -S-; heterocycloalkyl is: wherein: M is -NR 3 , -O-, -S- or -CH 2 - X and Y are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-10 alkyl; (6) aryl substituted with X 1 and Y 1 ; (7) R 2 0-; (8) arylcarbonyloxy-, wherein aryl is substituted with X 1 and Y 1 ; (9) R 3 -C(O)-O-; (10) -CO 2 R 2 ; (11) -CO 2 H; (12) nitro; and (13) -NR 3 R 3 ; X 1 and Y 1 are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-4 alkyl; (6) R20-; (7) R 3- C(O)-O-; (8) -CO 2 R 2 ; (9) -CO 2 H; and (10) nitro; n is 0, 1 or 2; Z 1 , Z 2 and Z 3 are each independently selected from: (1) -OR6a; (2) -SR 6a ; and (3) -NR 6a R 6a ; provided that when R 5 and R 6 are H and Z 1 , Z 2 and Z 3 are each OH or OCH 3 , then R 1 and R 4- (A) a - are not both respectively and or or or and or a pharmaceutically acceptable salt of formula (I).

Claim 2

Dependent Claim 2679 words

A compound of structural formula (I): wherein a is 0 or 1; A is -C(O)-, -NR 3- C(O)-, or -OC(O)-; R 1 is selected from the group consisting of: (1) C 1-20 alkyl, (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 ocycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(0)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n- ; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the -carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3 C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (11) C 3-10 cycloalkyl; and (12) substituted C 3-10 cycloalkyl in which one or more of the substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) C 1-10 alkylS(O)n-, (p) C 1-10 alkyl, (q) -CO 2 H, (r) -vinylidene, (s) R 3- C(O)-, (t) R 2 O-C(O)-O-, (u) R 3 R 3 N-C(O)-O-, and (v) R 2 0-C(O)-NR 3- ; Each R 2 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloaIkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; and (9) C 3-10 alkynyl; Each R 3 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloaIkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; (9) C 3-10 alkynyl; (10) hydrogen; and (11) C 1-5 alkyl substituted with X 1 ; R 4 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3 -, -O-, or -S(O)n-; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R3R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R20-C(O)-NR 3- ; and (11) C 3-10 cycloalkyl; (12) substituted C 3-10 cycloalkyl in which one or more of the substituents is selected from: (a) halogen, (b) hydroxy, (c) R 3 R3 N -, (d) R 2 0-, (e) R 2 0-C(0)-, (f) R 3 -C(O)-O-, (g) OXO, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (13) hydrogen; R 5 is selected from the group consisting of: (1) hydrogen; (2) C 1-10 alkyl; (3) aryl substituted with X and Y; (4) arylC 1-4 alkyl, wherein aryl is substituted with X and Y; (5) R 2 0-C(O)-; (6) C 3-10 cycloalkyl; ( 7 ) R 3- C(O)-; and (8) R 3 R 3 N-C(O)-; R 6 and R 6 a are each independently selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0-, (e) R 2 0-C(0)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 NOC(O)-O-, and (t) R 2 0-C(O)-NR3-; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R 3 R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, ( f ) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (6) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the carbons is substituted with: (a) halogen (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (7) C 2 - 20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n -; (8) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkynyl wherein alkynyl contains one or more triple bonds; (10) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0 -, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (11) C 2 - 20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n -; (12) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (13) aryl substituted with X and Y; (14) Heteroaryl substituted with X and Y; (15) C 3-5 cycloalkyl; (16) substituted C 3-5 cycloalkyl in which one or more of the substituents is selected from: (a) R 3 0-, and (b) R 3 R3N-; and (17) hydrogen; aryl including X, Y substitution is: heteroaryl including X, Y substitution is selected from: wherein: Q is -NR 3 , -O- or -S-; heterocycloalkyl is: wherein: M is -NR 3 , -O-, -S- or -CH 2 - X and Y are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-10 alkyl; (6) aryl substituted with X 1 and Y 1 ; (7) R 2 0-; (8) arylcarbonyloxy-, wherein aryl is substituted with X 1 and Y 1 ; (9) R 3 -C(O)-O-; (10) -CO 2 R 2 ; (11) -CO 2 H; (12) nitro; and (13) -NR 3 R 3 ; X 1 and Y 1 are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-4 alkyl; (6) R20-; (7) R 3- C(O)-O-; (8) -CO 2 R 2 ; (9) -CO 2 H; and (10) nitro; n is 0, 1 or 2; Z 1 , Z 2 and Z 3 are each independently selected from: (1) -OR6a; (2) -SR 6a ; and (3) -NR 6a R 6a ; provided that when R 5 and R 6 are H and Z 1 , Z 2 and Z 3 are each OH or OCH 3 , then R 1 and R 4- (A) a - are not both respectively and or or or and or a pharmaceutically acceptable salt of formula (I).

Claim 3

Dependent Claim 2456 words

The compound of Claim 1 wherein: R 1 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 0alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, ( n ) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, , (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (9) C 2 - 20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; and (10) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3 , -O- or -S(O) n - and wherein one or more carbons substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; Each R 2 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; and (9) C 3-10 alkynyl; Each R 3 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; (9) C 3-10 alkynyl; (10) hydrogen; and (11) C 1-5 alkyl substituted with X 1 ; R 4 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-; (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- , (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(0)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; and (11) hydrogen; R 5 is selected from the group consisting of: (1) hydrogen; (2) C 1-10 alkyl; (3) aryl substituted with X and Y; (4) arylC 1-4 alkyl, wherein aryl is substituted with X and Y; (5) R 2 0-C(O)-; (6) C 3-10 cycloalkyl; (7) R 2- C(O)-; and (8) R 3 R 3 N-C(O)-; R 6 and R 6 a are each independently selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3NC(O)-O-, and (t) R 2 0-C(O)-NR3-; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (6) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen (b) hydroxy, (c) R3 R 3 N -, (d) R 2 0 -, (e) R 2 0-C(O)-, (f) R 3- C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (7) C 2 - 20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, ( s ) R3R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (9) C 2 - 20 alkynyl wherein alkynyl contains one or more triple bonds; (10) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3- C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, ( s ) R3R 3 N-C(O)-O-, and (t) R 2 O-C(O)-NR 3 -; (11) C 2 - 20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n -; (12) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substitutents is selected from: a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, ( s ) R3R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (13) aryl substituted with X and Y; (14) Heteroaryl substituted with X and Y; (15) C 3-5 cycloalkyl; (16) substituted C 3-5 cycloalkyl in which one or more of the substituents is selected from: (a) R 3 0-, and (b) R 3 R 3 N-; and (17) hydrogen; aryl including X, Y substitution is heteroaryl including X, Y substitution is selected from: wherein: heterocycloalkyl is selected from: wherein: X and Y are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-10 alkyl; (6) aryl substituted with X 1 and Y 1 ; (7) R 2 0-; (8) arylcarbonyloxy-, wherein aryl is substituted with X 1 and Y 1 ; (9) R 3 -C(O)-O-; (10) -CO 2 R 2 ; (11) -CO 2 H; (12) nitro; and (13) -NR 3 R 3 ; X 1 and Y 1 are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-4 alkyl; (6) R20-; (7) R 3 -C(O)-O-; (8) -CO 2 R 2 ; (9) -CO 2 H; and (10) nitro; n is 0, 1 or 2; Z 1 , Z 2 and Z 3 are each independently selected from: (1) -OR6a; (2) -SR 6a ; and (3) -NR 6a R 6a ; provided that when R 5 and R 6 are H and Z 1 , Z 2 and Z 3 are each OH or OCH 3 , then R 1 and R 4- (A) a - are not both respectively and or or or or a pharmaceutically acceptable salt of formula (I).

Claim 4

Dependent Claim 2471 words

The compound of Claim 1 wherein: R 1 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1 - 20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; and (10) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3 , -O- or -S(O) n - and wherein one or more carbons substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; Each R 2 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; and (9) C 3-10 alkynyl; Each R 3 is independently selected from: (1) C 1-10 alkyl; (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; (9) C 3-10 alkynyl; (10) hydrogen; and (11) C 1-5 alkyl substituted with X 1 ; R 4 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-; (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- , (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) aryl substituted with X and Y; (6) heteroaryl substituted with X and Y; (7) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; (10) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substitutents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; and (11) hydrogen; R 5 is selected from the group consisting of: (1) hydrogen; (2) C 1-10 alkyl; (3) aryl substituted with X and Y; (4) arylC 1-4 alkyl, wherein aryl is substituted with X and Y; (5) R 2 0-C(O)-; (6) C 3-10 cycloalkyl; ( 7 ) R 2- C(O)-; and (8) R 3 R 3 N-C(O)-; R 6 and R 6 a are each independently selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3 R 3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 NOC(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3- C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R3R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (5) C 2 - 20 alkenyl wherein alkenyl contains one, two or three double bonds; (6) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-O, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3 -C(O)-NR 3 -,' (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (7) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; (8) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) aryl S(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (9) C 2-20 alkynyl wherein alkynyl contains one, two or three triple bonds; (10) substituted C 2-20 alkynyl wherein alkynyl contains one, two or three triple bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, ( n ) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 0-C(0)-0-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (11) C 2 - 20 alkynyl wherein alkynyl contains one, two or three triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n -; (12) substituted C 2-20 alkynyl wherein alkynyl contains one, two or three triple bonds and one or more of the saturated carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substitutents is selected from: a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl-, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n -, wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, ( n ) R3R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (13) aryl substituted with X and Y; (14) Heteroaryl substituted with X and Y; (15) C 3-5 cycloalkyl; (16) substituted C 3-5 cycloalkyl in which one or more of the substituents is selected from: (a) R 3 0-, and (b) R3R3N-; and (17)hydrogen; aryl is phenyl with X and Y substitution heteroaryl including X, Y substitution is selected from: and wherein: heterocycloalkyl is selected from: and wherein: X and Y are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-10 alkyl; (6) aryl substituted with X 1 and Y 1 ; (7) R 2 0-; (8) arylcarbonyloxy-, wherein aryl is substituted with X 1 and Y 1 ; (9) R 3 -C(O)-O-; (10) -CO 2 R 2 ; (11) -CO 2 H; (12) nitro; and (13) -NR 3 R 3 ; X 1 and Y 1 are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-4 alkyl; (6) R20-; (7) R 3 -C(O)-O-; (8) -CO 2 R 2 ; (9) -CO 2 H; and (10) nitro; n is 0, 1 or 2; Z 1 , Z 2 and Z 3 are each independently selected from: (1) -OR 6a ; (2) -SR 6a ; and (3) -NR 6a R 6a ; provided that when R 5 and R 6 are H and Z 1 , Z 2 and Z 3 are each OH or OCH 3 , then R 1 and R 4- (A) a - are not both respectively and or or or or a pharmaceutically acceptable salt of formula (I).

Claim 5

Dependent Claim 1556 words

The compound of Claim 1 wherein: R 1 is selected from the group consisting of: (1) C 2-16 alkyl; (2) substituted C 2-16 alkyl in which one or more substituents is selected from: (a) hydroxy, (b) R20-, (c) R 2 0-C(O)-, (d) R 3 -C(O)-O-, (e) oxo, (f) C 3 - 10 cycloalkyl, (g) aryl substituted with X and Y, (h) R 3 R 3 N-C(O)-, (i)-CO 2 H, (j) -vinylidene, (k) R 3- C(O)-, (I) R 2 O-C(O)-O-, and (m) R 3 R 3 N-C(O)-O-; (3) C 2-16 alkyl wherein one of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 2-16 alkyl wherein one of the carbons is replaced by -NR 3- , -O- or-S(O) n - and wherein one or more carbon substituents is selected from: (a) hydroxy, (c) R2 0 -, (c) R 2 0-C(0)-, (d) R 3 -C(O)-O-, (e) oxo, (f) C 3 - 10 cycloalkyl, (g) aryl substituted with X and Y, (h) R 3 R 3 N-C(O)-, (i) -CO 2 H, (j) -vinylidene, (k) R 3- C(O)-, (I) R 2 O-C(O)-O-, and (m) R 3 R 3 N-C(O)-O-; (5) C 2-16 alkenyl wherein alkenyl contains one, two or three double bonds; (6) substituted C 2-16 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) hydroxy, (b) R20-, (c) R 2 0-C(O)-, (d) R 3 -C(O)-O-, (e) oxo, (f) C 3 - 10 cycloalkyl, (g) aryl substituted with X and Y, (h) R 3 R 3 N-C(O)-, (i) -CO 2 H, (j) -vinylidene, (k) R 3- C(O)-, (I) R 2 O-C(O)-O-, and (m) R 3 R 3 N-C(O)-O-; (7) C 2-16 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3- , -O- or-S(O) n -; and (8) substituted C 2-16 alkenyl wherein alkenyl contains one, two or three double bonds and one or more of the nonolefinic carbons is replaced by -NR 3 , -O- or -S(O) n - and wherein one or more carbons substituents is selected from: (a) hydroxy, (b) R20-, (c) R 2 0-C(O)-, (d) R 3 -C(O)-O-, (e) oxo, (f) C 3 - 10 cycloalkyl, (g) aryl substituted with X and Y, (h) R 3 R 3 N-C(O)-, (i) -CO 2 H, (j) -vinylidene, (k) R 3- C(O)-, (I) R 2 O-C(O)-O-, and (m) R 3 R 3 N-C(O)-O-; Each R 2 is independently selected from: (1) C 1-10 alkyl, (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; and (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; Each R 3 is independently selected from: (1) C 1-10 alkyl, (2) aryl substituted with X and Y; (3) arylC 1-4 alkyl wherein aryl is substituted with X and Y; (4) heteroaryl wherein heteroaryl is substituted with X and Y; (5) heteroarylC 1-4 alkyl- wherein heteroaryl is substituted with X and Y; (6) heterocycloalkylC 1-4 alkyl-; (7) C 2-10 alkenyl; (8) arylC 2-10 alkenyl wherein aryl is substituted with X and Y; and (9) hydrogen; R 4 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3 -C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O- or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R 3 N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(0)-, (r) R 2 O-C(O)-O-, (s) R 3 R3N-C(O)-O-, and (t) R 2 0-C(O)-NR3-; (5) aryl substituted with X and Y; (6) C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds; (7) substituted C 2-20 alkenyl wherein alkenyl contains one, two or three double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R 2 0-, (e) R 2 0-C(0)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) arylS(O) n , wherein aryl is substituted with X and Y, (m) R 3- C(O)-NR3-, (n) R 3 R3N-C(O)-, (o) -CO 2 H, (p) -vinylidene, (q) R 3- C(O)-, (r) R 2 O-C(O)-O-, (s) R 3 R 3 N-C(O)-O-, and (t) R 2 0-C(O)-NR 3- ; and (8) hydrogen; R 5 is selected from the group consisting of: (1) hydrogen; (2) C 1-3 alkyl; and (3) R 2- C(O)-; R 6 is selected from the group consisting of: (1) C 1-20 alkyl; (2) substituted C 1-20 alkyl in which one or more substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) R 3- C(O)-NR 3- , (m) R3R3N-C(O)-, (n) -CO 2 H, and (o) R 2 0-C(O)-NR3-; (3) C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n -; (4) substituted C 1-20 alkyl wherein one or more of the carbons is replaced by -NR 3- , -O-, or -S(O) n - and wherein one or more carbon substituents is selected from: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3- C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) R 3- C(O)-NR 3- , (m) R3R3N-C(O)-, (n) -CO 2 H, and (o) R 2 0-C(O)-NR3-; (5) C 2-20 alkenyl wherein alkenyl contains one or more double bonds; (6) substituted C 2-20 alkenyl wherein alkenyl contains one or more double bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) R 3- C(O)-NR 3- , (m) R3R3N-C(O)-, (n) -CO 2 H, and (o) R 2 0-C(O)-NR3-; (7) C 2-20 alkynyl wherein alkynyl contains one or more triple bonds; (8) substituted C 2-20 alkynyl wherein alkynyl contains one or more triple bonds and wherein one or more of the carbons is substituted with: (a) halogen, (b) hydroxy, (c) R3R3 N -, (d) R20-, (e) R 2 0-C(O)-, (f) R 3 -C(O)-O-, (g) oxo, (h) C 3-10 cycloalkyl, (i) aryl substituted with X and Y, (j) heteroaryl substituted with X and Y, (k) heterocycloalkyl, (I) R 3- C(O)-NR 3- , (m) R3R3N-C(O)-, (n) -CO 2 H, and (o) R 2 0-C(O)-NR3-; (9) aryl substituted with X and Y (10) Heteroaryl substituted with X and Y (11) C 3-5 cycloalkyl (12) substituted C 3-5 cycloalkyl in which one or more of the substituents is selected from: (a) R 3 0-, and (b) R 3 R 3 N-; and (13) hydrogen; aryl is phenyl with X and Y substitution; X and Y are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-10 alkyl, (6) aryl substituted with X 1 and Y 1 ; (7) R 2 0-; (8) arylcarbonyloxy-, wherein aryl is substituted with X 1 and Y 1 ; (9) R 3 -C(O)-O-; (10) -C0 2 R 2 ; (11) -C0 2 H; and (12) nitro; X 1 and Y 1 are each independently selected from: (1) hydrogen; (2) hydroxy; (3) halogen; (4) trifluoromethyl; (5) C 1-4 alkyl; (6) R20-; (7) R 3 -C(O)-O-; (8) -CO 2 R 2 ; (10) -C0 2 H; and (11) nitro; n is 0, 1 or 2; Z 1 , Z 2 and Z 3 are each independently selected from: (1) -OR 6 ; (2) -SR 6 ; and (3) -NR 6 R 6 ; or a pharmaceutically acceptable salt.

Claim 6

Dependent Claim 25 words

The compound of Claim 3 of the structural formula (II) wherein: R 4- (A) a and R 6 are selected from the group consisting of

Claim 7

Dependent Claim 23 words

The compound of Claim 3 of the structural formula (III) wherein: R 5 and R 6 are selected from the group consisting of:

Claim 8

Dependent Claim 27 words

The compound of Claim 3 of the structural formula (IV): wherein: Z 1 , Z 2 and Z 3 are selected from the group consisting of: and

Claim 9

Dependent Claim 49 words

The compound of Claim 3 of the structural formula (V): wherein R 1 and R 4- (A) a are selected from the group consisting of: and wherein: The compound of Claim 3 of the structural formula (VII): wherein R 4 -(A) a - and Z 1 are selected from:

Claim 10

Dependent Claim 79 words

The compound of Claim 1 provided that when R 1 and R 4- (A)a- are selected from: and or or or and R 5 and R 6 are H; then Z 1 , Z 2 and Z 3 are not selected from (a) OH; (b) C 1-5 alkyloxy; and (c) C 1-5 alkyloxy substituted with a member of the group consisting of (1) phenyl, and (2) phenyl substituted with methyl, methoxy, halogen or hydroxy or a pharmaceutically acceptable salt.

Claim 11

Dependent Claim 78 words

The compound of Claim 2 wherein when R 1 and R 4- (A)a- are selected from: and or or or and R 5 and R 6 are H; then Z 1 , Z 2 and Z 3 are not selected from (a) OH; (b) C 1-5 alkyloxy; and (c) C 1-5 alkyloxy substituted with a member of the group consisting of (1) phenyl, and (2) phenyl substituted with methyl, methoxy, halogen or hydroxy; or a pharmaceutically acceptable salt.

Claim 12

Dependent Claim 80 words

The compound of Claim 3 wherein when R 1 and R 4 -(A) a - are selected from: and or or or and R 5 and R 6 are H; then Z 1 , Z 2 and Z 3 are not selected from (a) OH; (b) C 1-5 alkyloxy; and (c) C 1-5 alkyloxy substituted with a member of the group consisting of (1) phenyl, and (2) phenyl substituted with methyl, methoxy, halogen or hydroxy or a pharmaceutically acceptable salt.

Claim 13

Dependent Claim 80 words

The compound of Claim 4 wherein when R 1 and R 4 -(A) a - are selected from: and or or or and R 5 and R 6 are H; then Z 1 , Z 2 and Z 3 are not selected from (a) OH; (b) C 1-5 alkyloxy; and (c) C 1-5 alkyloxy substituted with a member of the group consisting of (1) phenyl, and (2) phenyl substituted with methyl, methoxy, halogen or hydroxy or a pharmaceutically acceptable salt.

Claim 14

Dependent Claim 90 words

The compound of Claim 1 wherein when R 1 and R 4- (A)a- are selected from: and or or or and R 5 and R 6 are H; then if Z 1 , Z 2 and Z 3 are identical, then Z 1 , Z 2 and Z 3 are not selected from (a) OH; (b) C 1-5 alkyloxy; and (c) C 1-5 alkyloxy substituted with a member of the group consisting of (1) phenyl, and (2) phenyl substituted with methyl, methoxy, halogen or hydroxy; or a pharmaceutically acceptable salt.

Claim 15

Dependent Claim 51 words

The compound of Claim 1 selected from the group consisting of: a) (1 S,3S,4S,5R,6R,7R)-1-[(4)-hydroxy-3,5-d imethyl-8- phenyl]oct-7-enyl-4,6-7-trihydroxy-6-O-(tet- radeca- 6,12-dienoyl)-2,8-dioxabicyclo[3.2.1]-octane-3,4-5-tricarboxylic acid 3-methyl ester; b) (1S,3S,4S,5R,6R,7R)-1-[(4-hydroxy-3,5-dimethyl-8-phenyl)oct-7-enyl]-4,6,7-trihydroxy-6-O-(tetra- deca-6,12-dienoyl)-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid-3-isopentyl ester (45aa); c) (1S,3S,4S,5R,6R,7R)-1-[(4-hydroxy-3,5-dimethyl-8-phenyl)oct-7-enyl]-4,6,7-trihydroxy-6-O-(tetra- deca-6,12-dienoyl)-2,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid-3-isopentyl-4-pivaloyloxymethyl diester (45ab); d) (1S,3S,4S,5R,6R,7R)-1-[(4-hydroxy-3,5-dimethyl-8-phenyl)oct-7-enyl]-4,6,7-trihydroxy-6-O-(isopropylaminocarbonyl)-2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid (5B); e) (1S,3S,4S,5R,6R,7R)-1-[(4)-acetoxy-5-methyl-6-phenyl]hexyl-4,6,7-trihydroxy-6-O-(isopropylaminocarbonyl)-2,8-dioxabicyclo-[3.2.1]octane-3,4,5-tricarboxylic acid (5C); f) (1S,3S,4S,5R,6R,7R)-1-[(4)-acetoxy-5-methyl-6-phenyl]hexyl-4,6,7-trihydroxy-6-O-(6-methyl-9-phenyl-4-nonenoyl)-2,8-dioxabicyclo[3.2.1]octane-4,5-dicarboxylic acid-3-isopentyl ester (55aa); g) (1S,3S,4S,5R,6R,7R)-1-[(4)-acetoxy-5-methyl-6-phenyl]hexyl-4,6,7-trihydroxy-6-O-(6-methyl-9-phenyl-4-nonenoyl)-2,8-dioxabicyclo[3.2.1]octane-5-carboxylic acid-3-isopentyl-4-pivaloyloxymethyl diester (55ab).

Claim 16

Dependent Claim 20 words

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of Claim 1 and a pharmaceutically acceptable carrier.

Claim 17

Dependent Claim 41 words

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of Claim 1 in combination with a pharmaceutically acceptable nontoxic cationic polymer capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract and pharmaceutically acceptable carrier.

Claim 18

Dependent Claim 54 words

A pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of Claim 1 in combination with a nontoxic therapeutically effective amount of a cholesterol lowering agent selected from the group consisting of: (a) HMG-CoA reductase inhibitor; (b) HMG-CoA synthase inhibitor; (c) Squalene expoxidase inhibitor; (d) Probucol; (e) Niacin; (f) Gemfibrozil; (g) Clofibrate.

Claim 19

Dependent Claim 19 words

A composition of Claim 18 wherein the composition comprises a compound of Claim 1 and an HMG-CoA reductase inhibitor.

Claim 20

Dependent Claim 19 words

A composition of Claim 19 wherein the HMG-CoA reductase inhibitor is selected from lovastatin, simvas- tatin, pravastatin and fluvastatin.

Claim 21

Dependent Claim 17 words

The use of a compound of Claim 1 for the manufacture of a medicament for treating hypercholesterolemia.

Claim 22

Dependent Claim 18 words

The use of a compound of Claim 1 for the manufacture of a medicament for inhibiting squalene synthetase.

Claim 23

Dependent Claim 36 words

A method of inhibiting fungal growth in soil or plant parts or in inanimate objects, comprising applying to the area where growth is to be controlled an antifungally effective amount of a compound of Claim 1.

Claim 24

Dependent Claim 22 words

The use of a compound of Claim 1 for the manufacture of a medicament for inhibiting fungal growth in a living organism.

Claim 25

Dependent Claim 25 words

The use of a compound of Claim 1 for the manufacture of a medicament for inhibiting farnesyl-protein transferase and farnesylation of the oncogene protein Ras.

Claim 26

Dependent Claim 17 words

The use of a compound of Claim 1 for the manufacture of a medicament for treating cancer.

Novel cholesterol lowering compounds

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