Patent ID: 6344466
Filing Date: 2002-02-05
Classification: A61P,C07C,C07D

Abstract:
A compound having the Formula I: or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein:L represents â€”C(O)â€” or â€”SO2â€”; R1 represents a group: R2represents a group: or R1 and R2 can be taken together with the nitrogen atom to which they are attached to form a three to seven membered ring, which optionally contains an additional nitrogen or oxygen atom, and which is optionally benzo- or pyrido-fused, said ring being saturated or partially unsaturated, and said ring having one or two optional substituents on either a ring carbon or nitrogen selected from the group consisting of halogen, hydroxy, acyloxy, alkoxy, aryloxy, alky, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroar(C1-4))alkyl, carboxyalkyl, alkoxycarbonylalkyl, hydroxyalkoxyalkyl, cyano(C2-10)alkyl, hydroxy(C2-10)alkyl, alkoxy(C2-10)alkyl, alkoxyalkyl, monoalkylamino(C2-10)alkyl and dialkylamino(C2-10)alkyl, carboxy, alkoxycarbonyl, carboxamido, formyl, alkanoyl, aroyl, aralkanoyl, sulfonyl, alkylsulfonyl, alkoxysulfonyl, and when said optional substituent is present on a ring carbon, NR13R14; R12 represents hydrogen, C3-7 cycloalkyl, C3-7 cycloalkenyl, C3-7heterocycloalkyl, C3-7 heterocycloalkenyl, aryl, or heteroaryl, which groups are optionally substituted with C1-6 alkyl or hydroxy, or R12 represents diarylmethyl, diheteroarylmethyl, dicycloalkylmethyl or (aryl)(heteroaryl)CHâ€”; Z and Zâ€² independently represent a bond, a C1-6 alkyl chain, a C3-4 alkenyl chain, or a C3-6 alkynyl chain, where one or two nitrogen, oxygen, or sulfur atoms may be optionally contained within each chain, and the chains are optionally substituted by one or more groups selected fiom halogen, hydroxy, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy(C1-6)alkyl, C1-6 acyloxy, NR13R14, NHCOR15, NHSO2R16, COR15, CO2R15, CONR13R14, and SO2NR17R18; provided that when one of R1 or R2 is C3-8 alkyl, cycloalkyl, C3-8 alkenyl, C3-8 alkyny aralkyl, or heteroaryl, any of which is optionally substituted, then the other of R1 or R2 is other than hydrogen, alkyl, aralkyl, aryl, hydroxy(C2-10)alkyl, amino(C2-10)alkyl, monoalkylamino(C2-10)alkyl, dialkylamino(C2-10)alkyl or carboxyalkyl; R13-R16 represent hydrogen, C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alknyl, C6-10 aryl, mono- or di-hydroxy(C6-10)aryl, C6-10 ar(C1-4)alkyl, pyridyl, pyridyl(C1-4)alkyl, carboxy(C1-6)-alkyl, C1-4 alkoxycarbonyl(C1-4)alkyl, cyano(C2-6)alkyl, hydroxy(C2-6)alkyl, C1-4 alkoxy(C2-6)alkyl, momo- and di-(C1-4)alkylamino(C2-6)alkyl; or R13 and R14 together with the nitrogen to which they are attached form a C3-7 heterocycloalkyl ring, or R16 additionally may represent trifluoromethyl; R17 and R18 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C6-10 ar(C1-4)alkyl, pyridyl, pyridyl(C1-4)alkyl, carboxy(C1-6)alkyl, C1-4 alkoxycarbonyl-(C1-4)alkyl, cyano(C2-6)alkyl, hydroxy(C2-6)alky alkoxy(C2-6)alkyl, and mono- and di-(C1-4)alkylamino(C2-6)alkyl, or R17 and R18 can be taken together with the nitrogen atom to which they are attached to form a heterocyclic ring selected from the group consisting of N-morpholino; N-piperazinyl, optionally substituted in the 4-position with C1-6 alkyl, C1-6 hydroxyalkyl, C6-10 aryl, C6-10 aryl(C1-6)alkyl, C1-6 alkylsulfonyl, C6-10 arylsulfonyl, C1-6 alkylcarbonyl, morpholino or C6-10 arylcarbonyl; N-pyrrolyl; N-piperidinyl; N-prrolidinyl N-dihydropyridyl; and N-indolyl; wherein any of said heterocyclic rings can be optionally C-substituted; R3, R4, R5 and R6 are each independently hydrogen, alkyl, cycloalkyl, alkenyl, alkyniyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, trifluoromethyl, halogen, hydroxyalkyl, cyano, nitro, carboxamido, â€”CO2Rx, â€”CH2ORx or â€”ORx, or when present on adjacent carbon atoms, R3 and R4 may also be taken together to form â€”CH&boxH;CHâ€”CH&boxH;CHâ€” or â€”(CH2)qâ€”, where q is from 2 to 6, and R5 and R6 are defined as above; Rx is hydrogen, alkyl or cycloalkyl wherein said alkyl or cycloalkyl may optionally have one or more unsaturations; Y is â€”Oâ€”, â€”NR19â€”, â€”Sâ€”, â€”CHR19â€” or a covalent bond; R19, is hydrogen, C1-6 alkyl, benzyl, phenyl, C2-10 hydroxyalkyl, C2-10 arninoalkyl, C1-4 monoalkylamino(C2-8)alkyl, C1-4 dialkylamino(C2-8)alkyl or C2-10 carboxyalkyl; R7 is hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, hydroxy, alkoxy, aralkoxy, aryloxy, heteroaryloxy, or mono- or di- alkylamino, provided that n is other than zero when R7 is hydroxy, alkoxy, aralkoxy, aryloxy, heteroaryloxy, or mono- or di- alkylamino; R8, R9 and R10 are each independently hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl or carboxyalkyl; or R7 and R8 are taken together to form â€”(CH2)yâ€”, where y is zero, 1 or 2, while R9 and R10 are defined as above; or R7 and R10 are taken together to form â€”(CH2)tâ€”, where t is zero, or 1 to 8, while R8 and R9 are defined as above; or R8 and R9 are taken togeth to form â€”(CH2)râ€”, where r is 2-8, while R7 and R10 are defined as above; X is oxygen or NH; R11 is hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylaminco(C2-10)alkyl, dialkylamino(C2-10)alkyl or carboxyalkyl; Ra, Rb and Rc are independently hydrogen, alkyl, hydroxy, alkoxy, aryloxy, aralkoxy, alkoxycarbonyloxy, cyano or â€”CO2Rw; Rw is alkyl, trichloroethyl, cycloalkyl, phenyl, benzyl, where Rd and Re are independently hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, Rf is hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, Rg is hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, and Rh is aralkyl or C1-6 alkyl;n is from zero to 8; and m is from zero to 4.