Patent ID: 6809092
Filing Date: 2004-10-26
Classification: A61K,A61P,C04B,C07D,C07K

Abstract:
A compound of formula (I-X), wherein R is (i) hydrogen, (ii) C1-8 alkyl, (iii) CycA, (iv) C1-8 alkyl substituted with a group selected from halogen atom, CycA, nitro, CF3 and cyano, CycA is mono-, bi- or tri-cyclic C3-15 carboring or mono-, bi- or tri-cyclic 3-15 membered heteroring comprising 1-4 of nitrogen, 1-2 of oxygen and/or 1 of sulfur; R16 is (1) C1-8 alkyl, (2) C2-8 alkenyl, (3) C2-8 alkynyl, (4) CycA or (5) C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted with a group selected from halogen, nitro, CF3, cyano, CycA, NR18R19 and â€”NHC(O)-CycA; R17, R18 and R19 each independently are, hydrogen or C1-4 alkyl, AA1 is (i) a single bond, or wherein R1 and R2 are the same or different and represent (i) hydrogen, (ii) C1-8 alkyl, (iii) CycA or (iv) C1-8 alkyl substituted with 1-5 of group selected from the following (1)-(8): (1) â€”NR21R22, (2) â€”OR23, (3) â€”SR24, (4) â€”COR25, (5) â€”NR26CONR21R22, (6) guanidino, (7) CycA, (8) â€”NR26SO2R21; or R1 and R2 are taken together to form C2-8 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR20â€” and the alkylene may be substituted with â€”NR21R22 or â€”OR23, R20 is hydrogen, C1-4 alkyl, â€”COOâ€”(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl, R21, R22, R23, R24 and R26 are the same or different and represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, R25 is C1-4 alkyl, phenyl, â€”NR21R22, wherein all symbols have the same meanings as above, â€”OR23, wherein R23 is the same meaning as above, or C1-4 alkyl substituted with phenyl, R3 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or R3 is taken together with R1 to form C2-6 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR20â€” and the alkylene may be substituted with â€”NR21R22 or â€”OR23, or when AA1 is AA1 and R may be taken together to form â€ƒis a 5-12 membered mono- or bi-cyclic heteroring and the other symbols have the same meanings as above, AA2 is (i) a single bond, wherein R4 and R5 are the same or different and represent (1) hydrogen, (2) C1-8 alkyl, (3) CycA or (4) C1-8 alkyl substituted with 1-5 of group selected from the following (a)-(h): (a) â€”NR41 R42, (b) â€”OR43, (c) â€”SR44, (d) â€”COR45, (e) â€”NR46CONR41R42, (f) guanidino, (g) CycA, (h) â€”NR46SO2R41; or R4 and R5 are taken together to form C2-8 alkylene wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR40â€” and the alkylene may be substituted with â€”NR41R42 or â€”OR43, R40 is hydrogen, C1-4 alkyl, â€”COOâ€”(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl, R41, R42, R43, R44 and R46 are the same or different and represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, R45 is C1-4 alkyl, phenyl, â€”NR41R42, wherein all symbols have the same meaning as above, â€”OR43, wherein R43 has the same meaning as above, or C1-4 alkyl substituted with phenyl, R6 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or R6 is taken together with R4 to form C2-6 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR40â€” and the alkylene may be substituted with â€”NR41R42 or â€”OR43, R48 is hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl or when AA1 is a single bond, R48 and R may be taken together to form C2-6 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR47â€”, wherein R47 is hydrogen or C1-4 alkyl, CycC is a 3-17 membered mono- or bi-cyclic heteroring, CycD is a C3-14 mono- or bi-cyclic carboring or a 3-14 membered mono- or bi-cyclic heteroring, or AA2 and AA1 are taken together to form wherein CycE is a 4-18 membered mono- or bi-cyclic heteroring, CycF is a 5-8 membered monocyclic heteroring, and the other symbols have the same meanings as above, R7 and R8 are the same or different and represent (i) hydrogen, (ii) C1-8 alkyl, (iii) CycA or (iv) C1-8 alkyl substituted with 1-5 of group selected from the following (1)-(8); (1) â€”NR61R62, (2) â€”OR63, (3) â€”SR64, (4) â€”COR65, (5) â€”NR66CONR61R62, (6) guanidino, (7) CycA, (8)â€”NR66SO2R61, or R7 and R8 are taken together to form C2-8 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR60â€” and the alkylene may be substituted with â€”NR61R62 or â€”OR63, R60 is hydrogen, C1-4 alkyl, â€”COOâ€”(C1-4 alkyl), phenyl or C1-4 alkyl substituted with phenyl, R61, R62, R63, R64 and R66 are the same or different to represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, R65 is C1-4 alkyl, phenyl, â€”NR61R62, wherein all symbols have the same meanings as above, â€”OR63, wherein R63 has the same meaning as above, or C1-4 alkyl substituted with phenyl, R9 is hydrogen, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl or R9 is taken together with R7 to form C2-6 alkylene, wherein one carbon atom may be replaced by oxygen, sulfur or â€”NR60â€” and the alkylene may be substituted with â€”NR61R62 or â€”OR63, q is an integer of 0 or 1 to 5, R10 is (i) C1-8 alkyl, (ii) C2-8 alkenyl, (iii) C2-8 alkynyl, (iv) halogen, (v) CycA, (vi) â€”COR71, (vii) â€”NR72R73, (viii) â€”OR74, or (ix) C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl substituted with 1-5 of group selected from the following <1>-<7>: <1> CycA, <2> guanidino, <3> â€”COR71, <4> â€”NR72R73, <5> â€”OR74, <6> cyano and <7> â€”P(O)(OR82)2, wherein R82 is hydrogen, C1-8 alkyl, C1-4 alkyl substituted with 1-5 of phenyl, cyano or halogen, R71 is (1) C1-8 alkyl, (2) CycA, (3) â€”NR72R73, (4) â€”OR74 or (5) C1-8 alkyl substituted with CycA, R72 and R73 are the same or different and represent (1) hydrogen, (2) C1-8 alkyl, (3) CycA or (4) C1-8 alkyl substituted with 1-5 of group selected from the following (a)-(f): (a) CycA, (b) guanidino, (c) â€”NR77R78, wherein R77 and R78 are the same or different and represent hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, (d) â€”OR77, wherein R77 has the same meaning as above, (e) â€”COR76, wherein R76 is C1-4 alkyl, phenyl, â€”NR77R78, wherein all symbols have the same meanings as above, â€”OR77, wherein R77 has the same meaning as above, or C1-4 alkyl substituted with phenyl, and (f) cyano; R74 is (1) hydrogen, (2) C1-8 alkyl, (3) CycA, or (4) C1-8 alkyl substituted with 1-5 of groups selected from the following (a)-(h), wherein one carbon atom may be replaced by oxygen, sulfur atom or â€”NR84â€”; (a) CycA, (b) guanidino, (c) â€”SiR79R80R81, wherein R79, R80 and R81 are the same or different to represent, C1-8 alkyl, phenyl or C1-8 alkyl substituted with phenyl, (d) â€”NR77R78, wherein all symbols have the same meanings as above, (e) â€”OR77, wherein R77 has the same meaning as above, (f) â€”COR76, wherein R76 has the same meaning as above, (g) cyano, (h) â€”P(O)(OR82)2, wherein all symbols have the same meanings as above; with the proviso that CycA in R, R1, R2, R4, R5, R7, R8, R10, R16, R71, R72, R73, R74, R83 are the same or different, and CycA, CycB, CycC, CycD, CycE and CycF may be, each independently, substituted with 1-5 of R27: R27 is (1) C1-8 alkyl, (2) halogen, (3) â€”NR11R12, (4) â€”OR13, (5) C5-10 mono- or bi-cyclic carboring, (6) nitro, (7) CF3, (8) cyano, (9) 5-10 membered mono- or bi-cyclic heteroring, (10) â€”SR14, (11) â€”COR15, (12) oxo, (13) â€”SO2R15, (14) â€”OCF3 or (15) C1-8 alkyl substituted with 1-5 of group selected from the following (a)-(m): (a) halogen, (b) â€”NR11R12, (c) â€”OR13, (d) C5-10 mono- or bi-cyclic carboring, (e) nitro, (f) CF3, (g) cyano, (h) 5-10 mono- or bi-cyclic heteroring, (j) â€”SR14, (k) â€”COR15, (l) â€”SO2R15, (m) â€”OCF3, wherein R11 and R12 are the same or different and represent, hydrogen, C1-4 alkyl, â€”COOâ€”(C1-4 alkyl), phenyl or C1-4 substituted with phenyl, R13 and R14 are the same or different and represent, hydrogen, C1-4 alkyl, phenyl or C1-4 alkyl substituted with phenyl, R15 is C1-4 alkyl, phenyl, â€”NR11R12, wherein all symbols have the same meanings as above, â€”OR13, wherein R13 has the same meaning as above, or C1-4 alkyl substituted with phenyl, or a non-toxic salt thereof.