Patent ID: 6355620
Filing Date: 2002-03-12
Classification: A61P,C07H

Abstract:
A compound selected from the group consisting ofa compound of formula (I) a compound of formula (II) â€ƒand a compound of formula (III) â€ƒand pharmaceutically acceptable salts, esters, and prodrugs thereof wherein, in formulas (I)-(III), Y and Z together are selected from the group consisting of (1) oxo, (2) &boxH;Nâ€”OH, (3) &boxH;Nâ€”OR1 wherein R1 is selected from the group consisting of (a) â€”C1-C12-alkyl, (b) â€”C1-C12-alkyl substituted with aryl, (c) â€”C1-C12-alkyl substituted with substituted aryl, (d) â€”C1-C12-alkyl substituted with heteroaryl, (e) â€”C1-C12-alkyl substituted with substituted heteroaryl, (f) â€”C3-C12-cycloalkyl, (g) â€”Si(R2)(R3)(R4), wherein R2, R3, and R4, are each independently â€”C1-C12- alkyl or aryl, and (h) â€”(CH2)nNR5R6 wherein n is two to six, and R5 and R6 are independently selected from the group consisting of (i) hydrogen, (ii) â€”C1-C12-alkyl, (iii) â€”C1-C12-alkyl substituted with aryl, (iv) â€”C1-C12-alkyl substituted with substituted aryl, (v) â€”C1-C12-alkyl substituted with heteroaryl, and (vi) â€”C1-C12-alkyl substituted with substituted heteroaryl, â€ƒor â€ƒR5 and R6 taken together with the atom to which they are attached are C3-C12-heterocycloalkyl, â€ƒand (4) &boxH;Nâ€”OC(R7)(R8)(â€”OR1), wherein R1 is defined above, and R7 and R8 are independently selected from the group consisting of (i) hydrogen, (ii) â€”C1-C12-alkyl, (iii) â€”C1-C12-alkyl substituted with aryl, (iv) â€”C1-C12-alkyl substituted with substituted aryl, (v) â€”C1-C12-alkyl substituted with heteroaryl, and (vi) â€”C1-C12-alkyl substituted with substituted heteroaryl, â€ƒor â€ƒR7 and R8 taken together with the atom to which they are attached are C3-C12-cycloalkyl, â€ƒor one of Y and Z is hydrogen, and the other is selected from the group consisting of (1) hydrogen, (2) hydroxy, (3) â€”OR1 wherein R1 is defined above, and (4) â€”NR5R6 wherein R5 and R6 are defined above; T is selected from the group consisting of (1) â€”Oâ€”, (2) â€”NHâ€”, and (3) â€”N(W(Rg))â€” wherein W is absent or selected from the group consisting of (a) â€”Oâ€”, (b) â€”(CH2)pâ€” wherein p is one to six, and (c) â€”NHâ€”, â€ƒand â€ƒRg is selected from the group consisting of (a) hydrogen, (b) â€”C3-C7-cycloalkyl, (c) aryl, (d) substituted aryl, (e) heteroaryl, (f) substituted heteroaryl, (g) â€”C1-C6-alkyl, (h) â€”NR5R6 wherein R5 and R6 are defined above, and (i) â€”C1-C6-alkyl substituted with one or more substituents independently selected from the group consisting of (i) aryl, (ii) substituted aryl, (iii) heteroaryl, (iv) substituted heteroaryl, (v) hydroxy, (vi) â€”OR1, and (vii) â€”NR5R6 wherein R5 and R6 are defined above; Ra is selected from the group consisting of (1) â€”C1-C10-alkyl optionally substituted with one or more substituents independently selected from the group consisting of (a) halogen, (b) hydroxy, (c) â€”OR1, (d) oxo, (e) â€”NR5R6 wherein R5 and R6 are defined above, (f) â€”CO2R1 wherein R1 is defined above, (g) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (h) &boxH;Nâ€”OR1 wherein R1 is defined above, (i) cyano, (j) â€”S(O)qR1 wherein R1 is defined above and q is zero to two, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) heterocycloalkyl, (p) substituted heterocycloalkyl, (q) â€”NHC(O)R1 wherein R1 is defined above, (r) â€”NHC(O)NR5R6 wherein R5 and R6 are defined above, (s) &boxH;NNR5R6 wherein R5 and R6 are defined above, (t) &boxH;NNHC(O)R1 wherein R1 is defined above, and (u) &boxH;NNHC(O)NR5R6 wherein R5 and R6 are defined above, (2) â€”C3-alkenyl, (3) â€”C3-alkynyl, wherein (2) and (3) can be optionally substituted with a substituent selected from the group consisting of (a) halogen, (b) carboxaldehyde, (c) â€”CO2R1 wherein R1 is defined above, (d) â€”C(O)R1 wherein R1 is defined above, (e) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (f) cyano, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (4) â€”C4-C10-alkenyl, and (5) â€”C4-C10-alkynyl, wherein (4) and (5) can be optionally substituted with one or more substituents independently selected from the group consisting of (a) halogen, (b) hydroxy, (c) â€”OR1, (d) oxo, (e) â€”NR5R6 wherein R5 and R6 are defined above, (f) â€”CO2R1 wherein R1 is defined above, (g) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (h) &boxH;Nâ€”OR1 wherein R1 is defined above, (i) cyano, (j) â€”S(O)qR1 wherein R1 and q are defined above, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) heterocycloalkyl, (p) substituted heterocycloalkyl, (q) â€”NHC(O)R1 wherein R1 is defined above, (r) â€”NHC(O)NR5R6 wherein R5 and R6 are defined above, (s) &boxH;NNR5R6 wherein R5 and R6 are defined above, (t) &boxH;NNHC(O)R1 wherein R1 is defined above, and (u) &boxH;NNHC(O)NR5R6 wherein R5 and R6 are defined above; Rb is hydrogen or a hydroxy protecting group; R is selected from the group consisting of (1) â€”C1-C10-alkyl optionally substituted with one or more substituents independently selected from the group consisting of (a) halogen, (b) hydroxy, (c) â€”OR1, (d) oxo, (e) â€”NR5R6 wherein R5 and R6 are defined above, (f) â€”CO2R1 wherein R1 is defined above, (g) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (h) &boxH;Nâ€”OR1 wherein R1 is defined above, (i) cyano, (j) â€”S(O)qR1 wherein R1 and q are defined above, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) heterocycloalkyl, (p) substituted heterocycloalkyl, (q) â€”NHC(O)R1 wherein R1 is defined above, (r) â€”NHC(O)NR5R6 wherein R5 and R6 are defined above, (s) &boxH;NNR5R6 wherein R5 and R6 are defined above, (t) &boxH;NNHC(O)R1 wherein R1 is defined above, and (u) &boxH;NNHC(O)NR5R6 wherein R5 and R6 are defined above, (2) â€”C3-alkenyl, (3) â€”C3-alkynyl, wherein (2) and (3) can be optionally substituted with a substituent selected from the group consisting of (a) halogen, (b) carboxaldehyde, (c) â€”CO2R1 wherein R1 is defined above, (d) â€”C(O)R1 wherein R1 is defined above, (e) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (f) cyano, (g) aryl, (h) substituted aryl, (i) heteroaryl, and (j) substituted heteroaryl, (4) â€”C4-C10-alkenyl, (5) â€”C4-C10-alkynyl, wherein (4) and (5) can be optionally substituted with one or more substituents independently selected from the group consisting of (a) halogen, (b) hydroxy, (c) â€”OR1 wherein R1 is defined above, (d) oxo, (e) â€”NR5R6 wherein R5 and R6 are defined above, (f) â€”CO2R1 wherein R1 is defined above, (g) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (h) &boxH;Nâ€”OR1 wherein R1 is defined above, (i) cyano, (j) S(O)qRâ€” wherein R1 and q are defined above, (k) aryl, (l) substituted aryl, (m) heteroaryl, (n) substituted heteroaryl, (o) heterocycloalkyl, (p) substituted heterocycloalkyl, (q) â€”NHC(O)R1 wherein R1 is defined above, (r) â€”NHC(O)NR5R6 wherein R5 and R6 are defined above, (s) &boxH;NNR5R6 wherein R5 and R6 are defined above, (t) &boxH;NNHC(O)R1 wherein R1 is defined above, and (u) &boxH;NNHC(O)NR5R6 wherein R5 and R6 are defined above; (6) â€”C(O)R1 wherein R1 is defined above, (7) â€”C(O)OR1 wherein R1 is defined above, (8) â€”C(O)NR5R6 wherein R5 and R6 are defined above, (9) hydroxyl, (10) â€”OR1 wherein R1 is defined above, (11) â€”NR5R6 wherein R5 and R6 are defined above, and (12) â€”SO2R1 wherein R1 is defined above; â€ƒand A, B, D, and E are independently selected from the group consisting of (1) hydrogen, and (2) â€”C1-C6-alkyl optionally substituted with one or more substituents selected from the group consisting of (a) â€”Mâ€”R11 wherein M is selected from the group consisting of (i) a covalent bond, (ii) â€”C(O)NHâ€”, (iii) â€”NHC(O)â€”, (iv) â€”NHâ€”, (v) â€”N(CH3)â€”, (vi) â€”Oâ€”, (vii) â€”S(O)nâ€” wherein n is defined above, (viii) â€”C(&boxH;NH)NHâ€”, (ix) â€”C(O)Oâ€”, (x) â€”OC(O)â€”, (xi) â€”OC(O)NHâ€”, (xii) â€”NHC(O)Oâ€”, and (xiii) â€”NHC(O)NHâ€”, â€ƒand â€ƒR11 is selected from the group consisting of (i) â€”C1-C6-alkyl optionally substituted with a substituent selected from the group consisting of (1â€²) aryl, (2â€²) substituted aryl, (3â€²) heteroaryl, and (4â€²) substituted heteroaryl, (ii) aryl, (iii) substituted aryl, (iv) heteroaryl, (v) substituted heteroaryl and (vi) heterocycloalkyl, (b) aryl, (c) substituted aryl, (d) heteroaryl, (e) substituted heteroaryl, (i) heterocycloalkyl, (g) hydroxy, (h) â€”C1-C6-alkoxy, (i) halo, and (j) â€”NR15R16 wherein R15 and R16, together with the nitrogen atom to which they are attached, are a 3- to 7-membered ring optionally containing therein a moiety selected from the group consisting of (i) â€”Oâ€”, (ii) â€”NHâ€”, (iii) â€”N(C1-C6-alkyl)â€”, (iv) â€”N(C1-C6-alkyl-substituted with aryl)â€”, (v) â€”N(C1-C6-alkyl substituted with substituted aryl)â€”, (vi) â€”N(C1-C6-alkyl substituted with heteroaryl)â€”, (vii) â€”N(C1-C6-alkyl substituted with substituted heteroaryl)â€”, (viii) â€”Sâ€”, and (ix) â€”S(O)qâ€” wherein q is defined above, â€ƒor any one pair of substituents selected from the group consisting of AB, AD, AE, BD, BE, and DE, taken together with the atom or atoms to which they are attached, are C3-C7-cycloalkyl or a four- to seven-membered ring containing a moiety selected from the group consisting of (1) â€”Oâ€”, (2) â€”NHâ€”, (3) â€”N(C1-C6-alkyl)â€”, (4) â€”N(C1-C6-alkyl substituted with aryl)â€”, (5) â€”N(C1-C6-alkyl substituted with substituted aryl)â€”, (6) â€”N(C1-C6-alkyl substituted with heteroaryl)â€”, (7) â€”N(C1-C6-alkyl substituted with substituted heteroaryl)â€”, and (8) â€”S(O)qâ€” wherein q is defined above.