Patent ID: 6787652
Filing Date: 2004-09-07
Classification: A61P,C07D

Abstract:
A compound of Formula I or a pharmaceutically acceptable salt of said compound; wherein W is (a) â€”Oâ€”, (b) â€”S(O)mâ€”, (c) â€”NR30â€”, (d) â€”C(O)â€”, (e) â€”HC&boxH;CHâ€”, (f) â€”CH2â€”, (g) â€”CHFâ€”, (h) â€”CF2â€” or (i) â€”CH(OH)â€”; R1 and R2 are independently (a) hydrogen, (b) halogen, (c) â€”(C1-C6)alkyl, (d) â€”CN, (e) â€”OR12 or (f) -trifluorornethyl; R3 is (a) hydrogen, (b) halogen, (c) â€”(C1-C6)alkyl optionally substituted with one to three substituents independently selected from the group consisting of halogen, â€”OCF3 and â€”CF3, (d) â€”CN, (e) â€”OR12, (f) -trifluoromethyl, (g) â€”NO2, (h) â€”SO2â€”R13, (i) â€”C(O)2R9, (j) â€”C(O)NR19R20, (k) â€”C(O)R16, (l) â€”NR21C(O)â€”NR21R22, (m) â€”NR19â€”C(O)R20 or (n) â€”NR17R18; R4 is (a) â€”C(R14)(R15)(R16), (b) â€”(C0-C3)alkyl-NR17R18, (c) â€”C(O)NR19R20, (d) â€”NR19â€”C(O)â€”R20(c) â€”(C0-C3)alkyl-NR21â€”C(O)â€”NR21R22, (f) â€”S(O)mâ€”R22, (g) â€”S(O)2â€”NR21R22, (h) â€”NR21â€”S(O)2â€”R22, (i) -aryl, (j) -het, (k) â€”OR33 or (l) halogen; provided that in substituents (f) and (h), R22 is other than â€”OR34; and provided that when substituent (b) is â€”(C0)alkyl-NR17R18, R18 is other than â€”(O)â€”R28 or â€”S(O)2â€”R29; or R3 and R4 may be taken together to form a carbocyclic ring of Formulaâ€”(CH2)bâ€” or a heterocyclic ring selected from the group consisting of â€”Qâ€”(CH2)câ€” and â€”(CH2)jâ€”Qâ€”(CH2)kâ€” wherein Q is O, S or NR25; wherein said carbocyclic ring is optionally substituted with one or more substituents independently selected from Group V; and wherein said heterocyclic ring is optionally substituted with one or more substituents independently selected from Group Z; R5 is hydroxy or methoxy; or R4 and R5 may be taken together to form a heterocyclic ring selected from the group consisting of â€”CR31&boxH;CR32â€”NHâ€”, â€”N&boxH;CR31â€”NHâ€”, â€”CR31&boxH;CR32â€”Oâ€” and â€”CR31&boxH;CR32â€”Sâ€”; R6 is (a) hydrogen, (b) halogen, (c) â€”(C1-C6)alkyl optionally substituted with one to three substituents independently selected from the group consisting of halogen, â€”OCF3 and â€”CF3, (d) â€”CN, (e) â€”OR12, (f) -trifluoromethyl, (g) â€”NO2, (h) â€”SO2â€”R13, (i) â€”C(O)2R9, (j) â€”C(O)NR19R20, (k) â€”C(O)R16, (l) â€”NR21C(O)NR21R22, (m) â€”NR19â€”C(O)R20 or (n) â€”NR17R18; R7 is (a) hydrogen, (b) â€”(C1-C4)alkyl wherein each carbon atom is optionally substituted with 1 to 3 halo atoms or (c) â€”(CH2)nCOOR9; R8 is (a) hydrogen, (b) â€”(C1-C6)alkyl, (c) â€”C(O)â€”OR9, (d) â€”C(O)NR10R11 or (e) â€”CN; provided that in substituent (c), R9 is other than methyl or ethyl; and provided that in substitutent (d), R10 and R11 are not both hydrogen; R9 is (a) â€”(C1-C12)alkyl optionally substituted with one or more substitutents independently selected from Group V, (b) â€”(C2-C12)alkenyl optionally substituted with phenyl, (c) â€”(C2-C12)dialkenyl, (d) â€”(C3-C10)cycloalkyl, (e) -aryl or (f) -het; R10 and R11 are independently (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C3-C10)cycloalkyl optionally substituted with one or more substituents independently selected from Group V, (d) â€”(C2-C12)alkenyl or (e) -het; or R10 and R11 for any occurrence may be taken together with the nitrogen atom to which are they attached to form het; R12 is (a) hydrogen or (b) â€”(C1-C6)alkyl wherein each carbon atom is optionally substituted with 1 to 3 fluoro atoms; R13 is (a) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (b) â€”(C2-C12)alkenyl, (c) â€”(C3-C10)cycloalkyl, (d) â€”NR17R18, (e) -aryl or (f) -het; R14 is (a) hydrogen, (b) â€”(C1-C6)alkyl or (c) â€”Oâ€”R34; R15 is (a) hydrogen or (b) â€”(C1-C6)alkyl; or R14 and R15 are taken together with the carbon atom to which they are attached to form a carbonyl group; R16 is (a) hydrogen, (b) â€”(C1-C6)alkyl, (c) â€”(C0-C6)alkyl-(C3-C10)cycloalkyl, (d) â€”(C0-C6)alkyl-aryl or (e) â€”(C0-C6)alkyl-het; R17 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) -aryl, (d) -het, (e) â€”OR34 or (f) â€”(C3-C10)cycloalkyl; R18 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) -aryl, (d) -het, (e) â€”C(O)â€”R28, (f) â€”S(O)2â€”R29, (g) â€”OR34 or (h) â€”(C3-C10)cycloalkyl; or R17 and R18 for any occurrence are taken together with the nitrogen atom to which they are attached to form het; R19 and R20 for each occurrence are independently (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C0-C6)alkyl-aryl, (d) â€”(C0-C6)alkyl-het, (e) â€”C(O)â€”NR26R27, (f) â€”C(O)â€”R28, (g) â€”S(O)2â€”R29, (h) â€”OR34 (i) â€”(C3-C10)cycloalkyl; or R19 and R20 for any occurrence are taken together with the nitrogen atom to which they are attached to form het; R21 and R22 for each occurrence are independently (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one to three substituents independently selected from Group V, (c)-aryl, (d) -het, (e) â€”(C3-C10)cycloalkyl or (f) â€”OR34; or R21 and R22 are taken together with the nitrogen atom to which they are attached to form het; R25 for each occurrence is independently (a) hydrogen, (b) â€”(C1-C6)alkyl, (c) â€”COR29 or (d) â€”SO2R29; R26 and R27 for each occurrence are independently (a) hydrogen, (b) â€”(C1-C6)alkyl, (c) â€”(C3-C10)cycloalkyl, (d) â€”(C0-C6)alkyl-aryl, or (e) â€”(C0-C6)alkyl-het, R28 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C2-C12)alkenyl, (d) â€”(C3-C10)cycloalkyl, (e) -aryl or (f) -het; R29 is (a) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (b) â€”(C2-C12)alkenyl, (c) â€”(C3-C10)cycloalkyl, (d) -aryl or (e) -het; R30 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C1-C12)alkenyl, (d) â€”(C3-C10)cycloalkyl, (e) â€”C(O)â€”R31 or (f) â€”S(O)mâ€”R32; R31 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C2-C12)alkenyl, (d) â€”(C3-C10)cycloalkyl, (e) -aryl, (f) -het or (g) â€”OR34; R32 is (a) hydrogen, (b) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (c) â€”(C2-C12)alkenyl, (d) â€”(C3-C10)cycloalkyl, (e) -aryl or (f) -het; R33 is (a) â€”(C0-C6)alkyl-aryl, (b) â€”(C0-C6)allyl-het, (c) â€”(C7-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (d) â€”(C1-C6)alkyl wherein at least one carbon atom is substituted with 1 to 3 fluoro atoms, (e) â€”(C2-C12)alkenyl or (f) â€”(C3-C10)cycloalkyl; R34 is (a) -aryl, (b) -het, (c) â€”(C1-C12)alkyl optionally substituted with one or more substituents independently selected from Group V, (d) â€”(C2-C12)alkenyl or (e) â€”(C3-C10)cycloalkyl; â€”(C3-C10)cycloalkyl for each occurrence is a fully or partially saturated mono-, bi- or tricyclic ring containing three to ten carbon atoms; wherein in the bicyclic ring, a monocyclic cycloalkyl ring is spiro fused to another cycloalkyl ring or is fused via two carbon atoms to a benzene ring or another cycloalkyl ring; and wherein in the tricyclic ring, a bicyclic ring is spiro fused to a cycloalkyl ring or is fused via two atoms to a benzene ring or another cycloalkyl ring; said â€”(C3-C10)cycloalkyl optionally contains one to three bridging atoms independently selected from carbon, oxygen, sulfur and nitrogen; said bridging atoms are attached to two carbon atoms in the ring; and said bridging atoms are optionally substituted with one to three groups independently selected from â€”(C1-C6)alkyl and hydroxy; said cycloalkyl ring is optionally substituted on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings if the moiety is tricyclic, with one or more substitutents independently selected from Group V; Group V is (a) â€”C1-C6)alkyl optionally substituted with one or two hydroxy, (b) â€”(C2-C5)alkynyl, (c) -halogen, (d) â€”NR35R36, (e) â€”NO2, (f) â€”OCF3, (g) â€”OR37, (h) -SR37, (i) â€”oxo, (j) -trifluoromethyl, (k) â€”CN, (l) â€”C(O)NR35â€”OH, (m) â€”COOR35, (n) â€”Oâ€”C(O)â€”(C1-C6)alkyl, (o) â€”(C3-C10)cycloalkyl optionally substituted with CN, (p) â€”(C0-C6)alkyl-aryl, (q) â€”(C0-C6)alkyl-het, (r) â€”C(O)â€”(C1-C6)alkyl or (s) â€”C(O)-aryl; R35 and R36 for each occurrence are independently (a) hydrogen, (b) â€”(C1-C6)alkyl or (c) â€”(C0-C6)alkyl-aryl; R37 is (a) hydrogen, (b) â€”(C1-C6)alkyl optionally substituted with one or more halo, hydroxy or methoxy, (c) â€”(C0-C6)alkyl-aryl or (d) â€”(C0-C6)alkyl-het; aryl is (a) phenyl optionally substituted with one or more substituents independently selected from Group Z; (b) naphthyl optionally substituted with one or more substituents independently selected from Group Z or (c) biphenyl optionally substituted with one or more substituents independently selected from Group Z; het for each occurrence is a 4-, 5-, 6-, 7- and 8-membered fully saturated, partially saturated or fully unsaturated mono-, bi- or tricyclic heterocyclic ring containing from one to four heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen; wherein in the bicyclic ring, a monocyclic heterocyclic ring is spiro fused to a â€”(C3-C8)cycloalkyl ring or to another heterocyclic ring which is fully or partially saturated; or is fused via two atoms to a benzene ring, a â€”(C3-C8)cycloalkyl ring or another heterocyclic ring; and wherein in the tricyclic ring, a bicyclic ring is spiro fused to a â€”(C3-C8)cycloalkyl ring or to another heterocyclic ring which is fully or partially saturated; or is fused via two atoms to a benzene ring, a (C3-C6)cycloalkyl ring, or another heterocyclic ring; said het optionally contains one to three bridging atoms independently selected from oxygen, sulfur and nitrogen; said bridging atoms are attached to two other atoms in the ring; and said bridging atoms are optionally substituted with one to three groups independently selected from â€”(C1-C16)alkyl and hydroxy; said het optionally has one or two oxo groups substituted on carbon or one or two oxo groups substituted on sulfur; said het is optionally substituted on carbon or nitrogen, on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings if the moiety is tricyclic, with one or more substituents independently selected from Group Z; Group Z for each occurrence is independently (a) hydrogen, (b) halogen, (c) trifluoromethyl, (d) hydroxy, (e) â€”OCF3, (f) â€”CN, (g) â€”NO2, (h) â€”(C1-C6)alkyl optionally substituted with one or more substituents independently selected from the group consisting of hydroxy, halogen, â€”OCF3 and â€”CF3, (i) â€”(C2-C6)alkenyl optionally substituted with phenyl, (j) â€”(C2-C5)alkynyl, (k) â€”(C1-C6)alkoxy, (l) â€”(C0-C6)alkyl-phenyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, â€”OCF3, â€”CF3, â€”(C1-C4)alkyl, â€”(C1-C4)alkoxy and â€”C(O)CH3, (m) â€”(C0-C6)alkyl-naphthyl optionally substituted with one or more substituents independently selected from the group consisting of halogen, â€”OCF3, â€”CF3, â€”(C1-C4)alkyl, â€”(C1-C4)alkoxy and â€”C(O)CH3, (n) â€”C(O)2R35, (o) â€”(C0-C6)alkyl-C(O)NR35R36, (p) â€”(C0-C6)alkyl-C(O)R38, (q) â€”NR35R36, (r) â€”NR35â€”C(O)NR35, (s) â€”NR35â€”C(O)R36, (t) â€”OR37, (u) â€”SR37, (v) â€”(C3-C10)cycloalkyl, (w) â€”(C0-C6)alkyl-pyridinyl optionally substituted with one or more â€”(C1-C6)alkyl which is optionally substituted with one or more substituents independently selected from the group consisting of hydroxy and halo, (x) â€”(C0-C6)alkyl-piperidinyl optionally substituted with one or more â€”(C1-C6)alkyl which is optionally substituted with one or more substituents independently selected from hydroxy and halo, (y) â€”SO2â€”R37, (z) â€”SO2â€”NR35R36 or (al) â€”S-phenyl-CH2OH; R38 is (a) â€”(C1-C6)alkyl, (b) â€”(C0-C6)alkyl-phenyl, (c) â€”(C0-C6)alkyl-phenylethenyl optionally substituted with one to three CF3, (d) â€”(C0-C6)alkyl-pyrrolidinyl or (e) â€”(C0-C6)alkyl-morpholinyl; or any two Z Groups for any occurrence in the same variable may be taken together to form (a) a carbocyclic ring of the formula â€”(CH2)eâ€” or (b) a heterocyclic ring selected from the group consisting of â€”O(CH2)fOâ€”, â€”(CH2)gNHâ€” and â€”CH&boxH;CHNHâ€”; m is 0, 1 or 2; n is 0, 1, 2 or 3; b is 3, 4, 5, 6 or 7; c, f, g, j and k are each independently 2, 3, 4, 5 or 6; and e is 3, 4, 5, 6 or 7; provided that in a compound of Formula I:1) the substituent â€”C(R14)(R15)(R16) in R4 is other than (C1-C4)alkyl; and 2) R4 is halo only when R8 is â€”C(O)â€”OR9 or â€”C(O)NR10OR11.