Patent ID: 6436986
Filing Date: 2002-08-20
Classification: C07D

Abstract:
A compound of formula I or a pharmaceutically acceptable salt or prodrug thereof, wherein:R1 is L1â€”RA, R2, R3, R4, R7, R8, and R9 are independently selected from H, OH, OG where G is an OH protecting group, alkoxy of 1-4 carbons, haloalkoxy of 1 to 4 carbons, halogen or C1-C12 alkyl, L1 is selected from: (1) a covalent bond, (2) â€”Oâ€”, (3) â€”S(O)tâ€”, where t is 0, 1, or 2, (4) â€”C(X)â€”, where X is O or S, (5) â€”NR12â€”, where R12 is selected from (a) hydrogen, (b) C1-C6[C12]cycloalkyl, (c) C1-C6[C12]alkyl, (7) â€”Xâ€²C(X)â€”, wherein X is as previously defined and Xâ€² is O or S, (8) â€”C(X)Xâ€²â€”, wherein X and Xâ€² are as previously defined, (9) â€”Xâ€²C(X)Xâ€³â€”, wherein X and Xâ€² are as previously defined, and Xâ€³ is O or S, provided that when X is O, at least one of Xâ€² or Xâ€³ is O, (10) â€”NR13C(X)â€”, (11) â€”C(X)NR13â€”, (12) â€”NR13C(X)Xâ€²â€”, (13) â€”Xâ€²C(X)NR13â€”, (14) â€”SO2NR13â€”, (15) â€”NR13SO2â€”, and (16) â€”NR13SO2NR14â€”, wherein (6)-(16) are drawn with their right ends attached to RA;RA is selected from (1) â€”OH, (2) â€”OG where G is a â€”OH protecting group, (3) â€”SH, (4) â€”CN, (5) halo, (6) haloalkoxy of one to twelve carbons, (7) perfluoroalkoxy of one to twelve carbons, (8) â€”CHO, (9) â€”NR12R12â€² where R7 is defined previously and R12â€² is selected from (a) hydrogen, (b) C1-C12 alkyl substituted with 1 or 2 substituents independently selected from aryl or C3-C12 cycloalkyl, (c) C3-C12 alkenyl, provided that a carbon of a carbon-carbon double bond is not attached directly to nitrogen, (d) C3-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not attached directly to nitrogen, (b) C1-C12 alkyl, and (c) C1-C12 perfluoroalkyl, provided that when RA is (1) to (11), L1 is a covalent bond, (12) C1-C12 alkyl, (13) C2-C12 alkenyl, provided that a carbon of a carbon-carbon double bond is not attached directly to L1 when L1 is other than a covalent bond, (14) C2-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not attached directly to L1 when L1 is other than a covalent bond, where (12), (13), and (14) can be optionally substituted with 1, 2, or 3 substituents independently selected from (a) C1-C12 alkoxy, (b) â€”OH, provided that no two â€”OH groups are attached to the same carbon, (c) â€”SH, provided that no two â€”SH groups are attached to the same carbon, (d) â€”CN, (e) halo, (f) â€”CHO, (g) â€”NO2, (h) C1-C12 haloalkoxy, (i) C1-C12 perluoroalkoxy, (n) â€”C(X)NR13R14, (o) &boxH;Nâ€”OR16, (p) &boxH;NR16, (q) â€”S(O)tR16, (r) â€”Xâ€²C(X)R16, (s) (&boxH;X), and (t) â€”OSO2R16, (15) C3-C12 cycloalkyl, (16) C4-C12 cycloalkenyl, provided that a carbon of a carbon-carbon double bond is not attached directly to L1 when L1 is other than a covalent bond, where (15) and (16) can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from (a) C1-C12 alkyl, (b) aryl, (c) C1-C12 alkoxy, (d) halo, and (e) â€”OH, provided that no two â€”OH groups arc attached to the same carbon, (17) C1-C12 perfluoroalkyl, R1 and R2 together are oX*â€”Y*â€”Z*â€” where X* is â€”Oâ€” or â€”CH2â€”, Y* is â€”C(O)â€” or â€”(C(R17)(R18))vâ€” where R17 and R18 are independently hydrogen or C1-C12 alkyl and v is 1, 2, or 3, and Z* is selected from â€”CH2â€”, â€”CH2S(O)tâ€”, â€”CH2Oâ€”, â€”CH2NR12â€”, â€”NR12â€”, and â€”Oâ€”; L2 is selected from (1) a covalent bond, (2) C1-C12 alkylene, (3) C1-C12 alkylene substituted with 1 or 2 substituents independently selected from (a) C3-C8 spiroalkyl, (b) C5-C8 spiroalkenyl, (c) oxo, (d) halo, and (e) â€”OH, provided that no two â€”OH groups arc attached to the same carbon, (4) C1-C12 alkynylene, (5) â€”NR12â€”, (6) â€”C(X)â€”, (7) â€”Oâ€”, and (8) â€”S(O)tâ€”; and R5 is selected from (1) halo, (2) â€”CN, provided that when R5 is (1), (2), or (3), L2 is a covalent bond, (3) C1-C12 alkyl, (4) C2-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not attached directly to L3 when L3 is other than a covalent bond, (5) C3-C12 cycloalkyl, (6) heterocycle, (7) aryl where (3)-(7) can be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from (a) â€”OH, provided that no two â€”OH groups are attached to the same carbon, (b) â€”SH, provided that no two â€”SH groups are attached to the same carbon, (c) â€”CN, (d) halo, (e) â€”CHO, (f) â€”NO2, (g) C1-C12 haloalkoxy, (h) C1-C12 perfluoroalkoxy, (i) â€”NR13â€²R14â€² where R13â€² and R14â€² are selected from (i) hydrogen, (ii) C1-C12 alkanoyl, (iii) C1-C12 alkoxycarbonyl, (iv) C1-C12 alkoxycarbonyl substituted with 1 to 2 phenyl substituents, (v) C3-C12 cycloalkyl, (vi) C1-C12 alkyl, (vii) C1-C12 alkyl substituted with 1, 2, or 3 substituents independently selected from C1-C12 alkoxy, C3-C12 cycloalkyl, and aryl, (viii) C3-C12 alkenyl, provided that a carbon of a carbon-carbon double bond is not directly attached to nitrogen, (ix) C3-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not directly attached to nitrogen, (x) aryl, (xi) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C12 alkyl, C1-C10 alkanoyloxy, C1-C12 alkoxycarbonyl, C1-C12 alkoxy, halo, â€”OH, provided that no two â€”OH groups arc attached to the same carbon, thioalkoxy of one to twelve carbons, perfluoroalkyl of one to twelve carbons, â€”NR12R12â€², â€”CO2R15, â€”OSO2R16, and (&boxH;X), or R13 â€² and R14â€² together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) pyrazine, (vi) morpholine, (vii) thiomorpholine, and (viii) thiomorpholine sulfone where (i)-(viii) can be optionally substituted with 1, 2, or 3 C1-C12 alkyl, (j) CO2R13, (k) â€”C(X)NR13â€²R14â€², (l) &boxH;Nâ€”OR13, (m) â€”Xâ€²C(X)R13, (n) (&boxH;X), (o) â€”Oâ€”(CH2)qâ€”Zâ€”R15 where R15 is as previously defined, q is 1, 2, or 3, and Z is O or â€”S(O)tâ€”, (p) â€”OC(X)NR13â€²R14â€², (q) â€”OSO2R16, (r) C1-C12 alkanoyloxy, (s) â€”LBR30 where LB is selected from (i) a covalent bond, (ii) â€”Oâ€”, (iii) â€”S(O)tâ€”, and (iv) â€”C(X)â€” and R30 is selected from (i) C1-C12 alkyl, (ii) C1-C12 alkenyl, provided that a carbon of a carbon-carbon double bond is not attached directly to LB when LB is other than a covalent bond, (iii) C1-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not attached directly to LB when LB is other than a covalent bond, where (i), (ii), and (iii) can be optionally substituted with C3-C12 cycloalkyl, â€”OH, provided that no two â€”OH groups arc attached to the same carbon, aryl, and heterocycle, (iv) aryl, (v) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C12 alkyl, halo, â€”NO2, and â€”OH, provided that no two â€”OH groups are attached to the same carbon, (vi) heterocycle, and (vii) heterocycle substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C12 alkyl, halo, â€”NO2, and â€”OH, provided that no two â€”OH groups are attached to the same carbon, (x) â€”Xâ€²C(X)Xâ€³R15, (y) â€”C(&boxH;NR7)OR15, and (z) â€”NR7(X)NR13â€²OR14â€², (9) provided that when R5 is (9), L3 is other than â€”NR12â€” or â€”Oâ€”, where the carbon-carbon double bond is in the Z or E configuration, and R19, R20, and R21 are independently selected from (a) hydrogen, (b) halo, (c) C1-C12 alkyl, and (d) C1-C12 alkyl substituted with (i) C1-C12 alkoxy, (ii) â€”OH, provided that no twvo â€”OH groups are attached to the same carbon, (iii) â€”SH, provided that no two â€”SH groups are attached to the same carbon, (iv) â€”CN, (v) halo, (vi) â€”CHO, (vii) â€”NO2, (viii) C1-C12 haloalkoxy, (ix) C1-C12 perfluoroalkoxy, (x) â€”NR13â€²R14â€²(xi) &boxH;NNR13â€²R14â€², (xii) â€”NR12NR13â€²R14â€², (xiii) â€”CO2R15, (xiv) â€”C(X)NR13â€²R14â€², (xv) &boxH;Nâ€”OR15, (xvi) &boxH;NR15, (xvii) â€”S(O)tR15, (xviii) â€”Xâ€²C(X)R15, (xix) (&boxH;X), (xx) â€”Oâ€”(CH2)qâ€”Zâ€”R15, (xxi) â€”OC(X)NR13â€²R14â€², (xxii) â€”LBR30, (xxiii) C1-C12 alkanoyloxy, (xxiv) â€”OSO2R16, and (xxv) â€”NR7(X)NR13â€²R14â€², or R20 and R21 together are selected from (a) C3-C12 cycloalkyl, (b) C4-C12 cycloalkenyl, and (c) â€ƒ(allene) where R22 and R23 are independently hydrogen or C1-C12 alkyl, and (10) C4-C12 cycloalkenyl carbons where the cycloalkenyl group or the ring formed by R20 and R21 together can be optionally substituted with one or two substituents independently selected from (a) C1-C12 alkoxy, (b) â€”OH, provided that no two â€”OH groups are attached to the same carbon, (c) â€”SH, provided that no twvo â€”SH groups are attached to the same carbon, (d) â€”CN, (e) halo, (f) â€”CHO, (g) â€”NO2, (h) C1-C12 haloalkoxy, (i) C1-C12 perfluoroalkoxy, (j) â€”NR13â€²R14â€²(k) &boxH;NNR13â€²R14â€², (l) â€”NR12NR13â€²R14â€², (m) â€”CO2R15, (n) â€”C(X)NR13â€²R14â€², (o) &boxH;Nâ€”OR15, (p) &boxH;NR15, (q) â€”S(O)tR15, (r) â€”Xâ€²C(X)R15, (s) (&boxH;X), (t) â€”Oâ€”(CH2)qâ€”Zâ€”R15, (u) â€”OC(X)NR13â€²R14â€², (v) â€”LBR30, (w) C1-C12 alkanoyloxy, (x) â€”OSO2R16, and (y) â€”NR7(X)NR13â€²R14â€²; R6 is hydrogen or C1-C12 alkyl; or R10 and R11 are independently selected from (i) hydrogen, (ii) C1-C12 alkanoyl; (iii) C1-C12 alkoxycarbonyl; (iv) C1-C12 alkoxycarbonyl and is substituted with 1 or 2 phenyl substituents, (v) C1-C12 cycloalkyl, (vi) C1-C12 alkyl, (vii) C1-C12 alkyl substituted with 1, 2, or 3 substituents independently selected from C1-C12 alkoxy, C3-C12 cycloalkyl, and aryl, (viii) C3-C12 alkenyl, provided that a carbon of a carbon-carbon double bond is not directly attached to nitrogen, (ix) C3-C12 alkynyl, provided that a carbon of a carbon-carbon triple bond is not directly attached to nitrogen, (x) aryl, (xi) aryl substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-C12 alkyl, C1-C12 alkanoyloxy, C1-C12 alkoxycarbonyl, C1-C12 alkoxy, halo, â€”OH, provided that no twvo â€”OH groups are attached to the same carbon, C1-C12 thioalkoxy, C1-C12 perfluoroalkyl, â€ƒâ€”NR12R12â€², â€ƒâ€”CO2R15, â€ƒâ€”OSO2R16, and â€ƒ(&boxH;X), (xii) â€”S(O)tR35, where t is 0, 1, or 2, and R35 is selected from (1) C1-C12 alkyl, (2) C2-C12 alkenyl, (3) C2-C12 alkynyl where (1)-(3) can be optionally substituted, (4) â€”OH, and (5) â€”NR12R12â€²; R10 and R11 together with the nitrogen atom to which they are attached form a ring selected from (i) aziridine, (ii) azetidine, (iii) pyrrolidine, (iv) piperidine, (v) pyrazine, (vi) morpholine, (vii) thiomorpholine, and (viii) thiomorpholine sulfone where (i)-(viii) can be optionally substituted with 1, 2, or 3 C2-C12 alkyl, and R35 and R7 together with the ring that they are attached form a 5-, 6-, or 7-membered ring with 0, 1, or 2 double bonds and 0-4 substituents selected from a group consisting of C1-C12 alkyl, halogen, or oxo.