Patent ID: 6696464
Filing Date: 2004-02-24
Classification: A61P,C07D

Abstract:
A compound of the formula wherein Het is an optionally substituted 5-membered heteroaryl which taken together with (R3)s-phenyl is selected from the group consisting of each R1 is independently selected from hydrogen, (C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic and (C3-C10)cycloalkyl; wherein each of the aforesaid R1 (C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic and (C3-C10)cycloalkyl substituents may optionally be substituted by one to four moieties independently selected from the group consisting of halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C10)heteroaryl-Oâ€”, (C1-C10)heterocyclic-Oâ€”, (C3-C10)cycloalkyl-Oâ€”, (C1-C6)alkyl-Sâ€”, (C1-C6)alkyl-SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6, alkyl]2-amino, (C1-C6)alkyl-SO2â€”N Hâ€”, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N)]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2N(C&boxH;O)â€” (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€” and phenyl-(C&boxH;O)â€”Oâ€”; wherein two R1 (C1-C6)alkyl groups may be taken together with the nitrogen atom to which they are attached to form a five to six membered heterocyclic or heteroaryl ring; R2 is selected from the group consisting of hydrogen, â€”Câ‰¡N, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C10)cycloalkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic and (R1)2â€”Nâ€”; wherein each of the aforesaid (C1-C6)alkyl, (C3-C10)cycloalkyl, phenyl, (C1-C10)heteroaryl and (C1-C10)heterocyclic substituents may optionally be independently substituted by one to four moieties independently selected from the group consisting of halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, phenyl, (C3-C10)cycloalkyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, formyl, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, H2Nâ€”(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-HNâ€”(C&boxH;O)â€”NHâ€”, [(C1-C6)alkyl)]2â€”Nâ€”(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-HNâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C1-C6)alkyl)]2Nâ€”(C&boxH;O)-[((C1-C6)alkyl)-N]â€”, phenyl-HNâ€”(C&boxH;O)â€”NHâ€”, (phenyl-)2Nâ€”(C&boxH;O)â€”NHâ€”, phenyl-HNâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (phenyl-)2Nâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-Oâ€”(C&boxH;O)â€”NHâ€”, phenyl-Oâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (C1-C6)alkyl-SO2NHâ€”, phenyl-SO2NHâ€”, (C1-C6)alkyl-SO2â€”, phenyl-SO2â€”, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, phenyl-(C&boxH;O)â€”Oâ€”, H2Nâ€”(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-HNâ€”(C&boxH;O)â€”Oâ€”, [(C1-C6)alkyl-]2Nâ€”(C&boxH;O)â€”Oâ€”, phenyl-HNâ€”(C&boxH;O)â€”Oâ€”, (phenyl-)2Nâ€”(C&boxH;O)â€”Oâ€”; wherein when said R2 phenyl contains two adjacent substituents, such substituents may optionally be taken together with the carbon atoms to which they are attached to form a five to six membered carbocyclic or heterocyclic ring; wherein each of said moieties containing a phenyl alternative may optionally be substituted by one or two radicals independently selected from the group consisting of (C1-C6)alkyl, halo, (C1-C6)alkoxy, perhalo(C1-C6)alkyl and perhalo(C1-C6)alkoxy; each R3 is independently selected from the group consisting of halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C10)heteroaryl-Oâ€”, (C1-C10)heterocyclic-Oâ€”, (C3-C10)cycloalkyl-Oâ€”, (C1-C6)alkyl-Sâ€”, (C1-C6)alkyl-SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-SO2â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2N(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€” and (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”; wherein two adjacent R3 substituents may be optionally taken together with the carbon atoms to which they are attached to form a five to six membered carbocyclic or heterocyclic ring; s is an integer from zero to five; R4 and R6 are each independently selected from the group consisting of hydrogen, halo or R9-B-(CH2)nâ€”; n is an integer from zero to six; each B is independently a bond, â€”(CHR10)â€”, â€”Oâ€”, â€”Sâ€”, â€”(SO2)â€”, â€”(C&boxH;O)â€”, â€”Oâ€”(C&boxH;O)â€”, â€”(C&boxH;O)â€”Oâ€”, â€”(C&boxH;O)â€”NR10â€”, â€”(R10â€”N)â€”, â€”(R10â€”N)â€”SO2â€”, â€”(R10â€”N)â€”(C&boxH;O)â€”, â€”SO2â€”(NR10)â€”, â€”(R10â€”N)â€”(C&boxH;O)â€”(NR11)â€”, â€”(O)â€”(C&boxH;O)â€”(NR10)â€” or â€”(R10â€”N)â€”(C&boxH;O)â€”Oâ€”; R5 and R7 are each independently selected from the group consisting of hydrogen, R14â€”(CR15H)pâ€”, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, (C1-C6)alkyl-(SO2)â€”, phenyl-(SO2)â€”, H2Nâ€”(SO2)â€”, (C1-C6)alkyl-NHâ€”(SO2)â€”, [(C1-C6)alkyl-]2Nâ€”(SO2)â€”, phenyl-NHâ€”(SO2)â€”, (phenyl-)2Nâ€”(SO2)â€”, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-Oâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl-]2Nâ€”(C&boxH;O)â€”, (phenyl-)2Nâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heterocyclic-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, and (C3-C10)cycloalkyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”; wherein each of the aforesaid phenyl, heterocyclic, heteroaryl or cycloalkyl R5 and R7 substituents may optionally be independently substituted by one to four moieties independently selected from the group consisting of halo, R16â€”(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, (C3-C10)cycloalkyl phenyl, benzyl, (C1-C10)heterocyclic, (C1-C10)heteroaryl, (C1-C6)alkyl-SO2â€”, formyl, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-Oâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-Oâ€”(C&boxH;O)â€”, (C1-C5)alkyl-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, (C3-C10)cycloalkyl-Oâ€”, phenoxy, (C1-C10)heterocyclic-Oâ€”, (C1-C10)heteroaryl-Oâ€”, (C1-C6)alkyl-(C&boxH;O)â€”, â€”(C3-C10)cycloalkyl-(C&boxH;O)â€”Oâ€”, phenyl-(C&boxH;O)â€”Oâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”Oâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”Oâ€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, formamidyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-(C&boxH;)â€”NHâ€”, phenyl-(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”NHâ€”, (C1-C10))heteroaryl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”[(C1-C6)alkyl-N]â€”, (C1-C6)alkyl-SO2NHâ€”, (C3-C10)cycloalkyl-SO2NHâ€”, phenyl-SO2NHâ€”, (C1-C10)heterocyclic-SO2NHâ€” and (C1-C10)heteroaryl-SO2NHâ€”; wherein each of said phenyl and heteroaryl moieties may optionally be substituted by one or two radicals independently selected from halo, (C1-C6)alkyl, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl and perfluoro(C1-C6)alkoxy; p is an integer from one to six; R9 is selected from the group consisting of hydrogen, â€”CF3, â€”Câ‰¡N, R13â€”(R12CH)mâ€”, phenyl, (C1-C10)heterocyclic, (C1-C10)heteroaryl, and (C3-C10)cycloalkyl; wherein each of the aforesaid R9 phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic and (C3-C10)cycloalkyl substituents may optionally be substituted by one to four moieties independently selected from the group consisting of halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C10)heteroaryl-Oâ€”, (C1-C10)heterocyclic-Oâ€”, (C3-C10)cycloalkyl-Oâ€”, (C1-C6)alkyl-Sâ€”, (C1-C6)alkyl-SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-SO2â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2N(C&boxH;O)â€” (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2â€”Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€” and phenyl-(C&boxH;O)â€”Oâ€”; wherein two adjacent R9 substituents of said phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic and (C3-C10)cycloalkyl may optionally be taken together with the carbon or heteroatom to which they are attached to form a five or six membered carbocyclic or heterocyclic ring; m is an integer from one to six; R10 is hydrogen, (C1-C6)alkyl-SO2â€” or (C1-C6)alkyl; R11 is hydrogen or (C1-C6)alkyl; each R12 is independently selected from the group consisting of hydrogen, amino, (C1-C6)alkoxy and (C1-C6)alkyl; R13 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, phenoxy, (C1-C10)heteroaryl-Oâ€”, (C1-C10)heterocyclic-Oâ€”, (C3-C10)cycloalkyl-Oâ€”, (C1-C6)alkyl-Sâ€”, (C1-C6)alkyl-SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, â€”NO2, amino (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, (C1-C6)alkyl-SO2â€”NHâ€”, phenyl-SO2â€”NHâ€”, (C1-C6)alkyl-SO2â€”[((C1-C6)alkyl)-N]â€”, phenyl-SO2â€”[((C1-C6)alkyl)-N]â€”, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2N(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€” and phenyl-(C&boxH;O)â€”Oâ€”; R14 is selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, (C3-C10)cycloalkyl, phenyl, (C1-C10)heterocyclic, (C1-C10)heteroaryl, phenyl-(S=O)â€”, (C1-C6)alkyl-SO2â€”, phenyl-SO2â€”, H2Nâ€”SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, phenyl-NHâ€”SO2â€”, [(C1-C6)alkyl-]2Nâ€”SO2â€”, (phenyl-)2Nâ€”SO2â€”, formyl, â€”CN, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, R16â€”(C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-Oâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, R16â€”(C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heterocyclic-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C3-C10)cycloalkyl[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, hydroxy, R16â€”(C1-C6)alkoxy, perhalo(C1-C6)alkoxy, (C3-C10)cycloalkyl-Oâ€”, phenoxy, (C1-C10)heterocyclic-Oâ€”, (C1-C10)heteroaryl-Oâ€”, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”Oâ€”, phenyl-(C&boxH;O)â€”Oâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”Oâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”Oâ€”, â€”NO2, amino, R16â€”(C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, formamidyl, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-(C&boxH;C)â€”NHâ€”, phenyl-(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”NHâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”NHâ€”, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, R16â€”(C1-C6)alkyl-SO2NHâ€”, (C3-C10)cycloalkyl-SO2NHâ€”, phenyl-SO2NHâ€”, (C1-C10)heterocyclic-SO2NHâ€” and (C1-C10)heteroaryl-SO2NHâ€”; wherein each of the aforesaid phenyl, heterocyclic, heteroaryl or cycloalkyl R14 substituents may optionally be independently substituted by one to four moieties independently selected from the group consisting of halo, R16â€”(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, (C3-C10)cycloalkyl, phenyl, benzyl, (C1-C10)heterocyclic, (C1-C10)heteroaryl, (C1-C6)alkyl-SO2â€”, formyl, â€”CN, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-Oâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-Oâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, R16â€”(C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, hydroxy, R16â€”(C1-C6)alkoxy, perhalo(C1-C6)alkoxy, (C3â€”C10)cycloalkyl-Oâ€”, phenoxy, (C1-C10)heterocyclic-Oâ€”, (C1-C10)heteroaryl-Oâ€”, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”Oâ€”, phenyl-(C&boxH;O)â€”Oâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”Oâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”Oâ€”, â€”NO2, amino, R16â€”(C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, formamidyl, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”NHâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”NHâ€”, R16â€”(C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;Oâ€”[((C1-C10)alkyl)-N]â€”, R16â€”(C1-C6)alkyl-SO2NHâ€”, (C3-C10)cycloalkyl-SO2NHâ€”, phenyl-SO2NHâ€”, (C1-C10)heterocyclic-SO2NHâ€” and (C1-C10)heteroaryl-SO2NHâ€”; wherein each of said phenyl and heteroaryl moieties may optionally be substituted by one or two radicals independently selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy, perfluoro(C1-C6)alkyl and perfluoro(C1-C6)alkoxy; each R15 is independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, (C2-C6)alkenyl, perhalo(C1-C6)alkyl, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, hydroxy, (C1-C6)alkoxy, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, formamidyl and (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”; each R16 is independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, perhalo(C1-C6)alkyl, (C1-C10)heterocyclic, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, hydroxy, (C1-C6)alkoxy, perhalo(C1-C6)alkoxy, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, â€”NO2, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2-amino, formamidyl and (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”; wherein said (C1-C10)heterocyclic may optionally be substituted by one to three substituents independently selected from the group consisting of halo, (C1-C6)alkyl, (C1-C6)alkoxy, benzyl, amino, (C1-C6)alkylamino and [(C1-C6)alkyl]2-amino; or R4 and R6 or R4 and R7 or R5 and R5 may be taken together with the atoms to which they are attached to form an optionally substituted five to ten membered saturated, unsaturated or aromatic ring optionally containing two to three heteroatoms independently selected from NH, N, O, S, SO or SO2; wherein said ring may be optionally substituted by one to three substituents independently selected from the group consisting of oxo, halo, (C1-C6)alkyl, phenyl, (C1-C10)heteroaryl, (C1-C10)heterocyclic, (C3-C10)cycloalkyl, hydroxy, (C1-C6)alkoxy, phenoxy, (C1-C10)heteroaryl-Oâ€”, (C1-C10)heterocyclic-Oâ€”, (C3-C10)cycloalkyl-Oâ€”, (C1-C6)alkyl-Sâ€”, (C1-C6)alkyl-SO2â€”, phenyl-Sâ€”, phenyl-(S&boxH;O)â€”, phenyl-SO2â€”, (C1-C6)alkyl-NHâ€”SO2â€”, [(C1-C6)alkyl]2-Nâ€”SO2â€”, phenyl-NHâ€”SO2â€”, (phenyl)2-Nâ€”SO2â€”, phenyl-[N(C1-C6)alkyl]-SO2â€”, formyl, (C1-C6)alkyl-(C&boxH;O)â€”, phenyl-(C&boxH;O)â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”, HOâ€”(C&boxH;O)â€”, (C1-C6)alkyl-Oâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-Oâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-Oâ€”(C&boxH;O)â€”, H2Nâ€”(C&boxH;O)â€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”, phenyl-NHâ€”(C&boxH;O)â€”, phenyl-[(C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”, (C1-C10)heteroaryl-[(C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C1-C10)heterocyclic-NHâ€”(C&boxH;O)â€”, (C1-C10)heterocyclic-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”, (C3-C10)cycloalkyl-[((C1-C6)alkyl)-N]â€”(C&boxH;O)â€”, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkyl-SO2â€”NHâ€”, phenyl-SO2â€”NHâ€”, (C1-C6)alkyl-SO2â€”[((C1-C6)alkyl)-N]â€”, phenyl-SO2â€”[((C1-C6)alkyl)-N]â€”, formamidyl, (C1-C6)alkyl-(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-(C&boxH;O)â€”NHâ€”, phenyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (C1-C10)heteroaryl-(C&boxH;O)â€”NHâ€”, (C1-C10)heteroaryl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (C1-C10)heterocyclic-(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, H2N(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-HNâ€”(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-HNâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”NHâ€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, phenyl-HNâ€”(C&boxH;O)â€”NHâ€”, phenyl-HNâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, (phenyl)2-Nâ€”(C&boxH;O)â€”NHâ€”, (phenyl)2-Nâ€”(C&boxH;O)-[((C1-C6)alkyl)-N]â€”, (C1-C10)heteroaryl-HNâ€”(C&boxH;O)â€”NHâ€”, (C1-C10)heteroaryl-HNâ€”(C&boxH;O)-[((C1-C6)alkyl)-N]â€”, [(C1-C10)heteroaryl]2-Nâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C1-C10)heteroaryl]2-Nâ€”(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-HNâ€”(C&boxH;O)â€”NHâ€”, (C1-C10)heterocyclic-HNâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C1-C10)heterocyclic]2-Nâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C1-C10)heterocyclic]2-Nâ€”(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-HNâ€”(C&boxH;O)â€”NHâ€”, (C3-C10)cycloalkyl-HNâ€”(C&boxH;O)-[((C1-C6)alkyl)-N]â€”, [(C3-C10)cycloalkyl]2-Nâ€”(C&boxH;O)â€”[((C1-C6)alkyl)-N]â€”, [(C3-C10)cycloalkyl]2-Nâ€”(C&boxH;O)â€”NHâ€”, (C1-C6)alkyl-(C&boxH;O)â€”Oâ€”, phenyl-(C&boxH;O)â€”Oâ€”, (C1-C10))heteroaryl-(C&boxH;O)â€”Oâ€”, (C1-C10)heterocyclic-(C&boxH;O)â€”Oâ€”, (C3-C10)cycloalkyl-(C&boxH;O)â€”Oâ€”, (C1-C6)alkyl-NHâ€”(C&boxH;O)â€”Oâ€”, [(C1-C6)alkyl]2-Nâ€”(C&boxH;O)â€”Oâ€”, phenyl-NHâ€”(C&boxH;O)â€”Oâ€”, (C1-C10)heteroaryl-NHâ€”(C&boxH;O)â€”Oâ€”, (C1-C10))heterocyclic-NHâ€”(C&boxH;O)â€”Oâ€” and (C3-C10)cycloalkyl-NHâ€”(C&boxH;O)â€”Oâ€”; or a pharmaceutically acceptable salt thereof.