Patent NZ-501714-A (NZ)
Title: Imidazolyl-cyclic acetal derivatives, resins and intermediates thereof and use as TNF inhibitors
Inventor: BAMBOROUGH PAUL LINDSAY
IPC: C07D233/54
Filed: 1998-06-12
Abstract: The compounds of formula (I) are TNF inhibitors and may be used in medicaments to treat asthma or joint inflammation. In formula (I): R1 is optionally substituted heteroaryl; R2 is optionally substituted aryl or heteroaryl; R3 is a group -L1R7 or -L2R8, where L1 is an optionally substituted alkylene linkage; R7 is H, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, nitro, S(O)nR9, NHSO2R9, C(=Z)OR10, C(=Z)R10, OR10, N(R11)C(=Z)R9, NY1Y2, SO2NY1Y2, C(=Z)-NY1Y2, N(R11)C(=Z)NY1Y2, N(OR10)C(=Z)NY1Y2, N(OR10)C(=Z)R10, C(=NOR10)R10, C(=Z)NR10OR12, N(R11)C(=NR13)NY1Y2 or N(R11)C(=Z)OR11; L2 is a direct bond or a straight- or branched-carbon chain comprising from 2 to 6 carbon atoms and contains a double or triple carbon-carbon bond; and R8 is H, aryl, cycloalkenyl, cycloalkyl, heteroaryl or heterocycloalkyl; where R9 is alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl, heteroarylalkyl, or heterocycloalkyl; n is 0-2; Z is O or S; R10 is H or R9; R11 is H or alkyl; Y1 and Y2 are H, alkenyl, alkyl, alkynyl, aryl, arylalkyl, cycloalkenyl, cycloalkyl, heteroaryl or heteroarylalkyl, or the group NY1Y2 may form a 5-7 membered cyclic amine which may optionally contain a further heteroatom selected from O, S, or NY3 (where Y3 is H, alkyl, aryl, arylalkyl, CHO, C(=Z)R9 or SO2R9), or which may also be fused to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclic ring system); R12 is H, alkyl, aryl or arylalkyl; and R13 is H, cyano, alkyl, cycloalkyl or aryl; R4 is a group L3R14, where L3 is a direct bond or an optionally substituted alkylene linkage and R14 is H, alkyl, azido, hydroxy, alkoxy, aryl, arylalkyloxy, aryloxy, carboxy (or an acid bioisostere) cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy, heterocycloalkyl, heterocycloalkyloxy, nitro, NY4Y5, N(R10)C(=Z)R15; N(R10)C(=Z)L4R16, NHC(=Z)NHR15, NHC(=Z)NHL4R16, N(R10)SO2R15, N(R10)SO2L4R16, S(O)nR9, C(=Z)NY4Y5 or C(=Z)OR9); where Y4 and Y5 are H, aryl, cycloalkyl, heterocycloalkyl, heteroaryl or alkyl optionally substituted, or the group NY4Y5 may form an optionally substituted 5-7 membered cyclic amine which may also contain a further heteroatom selected from O, S, SO2 or NY6 (where Y6 is H, alkyl, aryl, arylalkyl, C(=Z)R9, C(=Z)OR9 or S02R9) and may also be fused to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclic ring system); R15 is alkyl, alkoxy, aryl, arylalkyloxy, cycloalkyl, heteroaryl, heteroarylalkoxy or heterocycloalkyl; R16 is alkoxy, aryl, arylalkyloxy, arylalkyloxycarbonylamino, carboxy (or an acid bioisostere), cycloalkyl, cyano, halo, heteroaryl, heteroarylalkoxy, heterocycloalkyl, hydroxy or NY1Y2; and L4 is a straight- or branched-chain alkylene linkage containing from 1 to about 6 carbon atoms; R5 is H, alkyl or hydroxyalkyl; or R4 and R5, when attached to the same carbon atom, may form with the carbon atom a cycloalkyl, cycloalkenyl or heterocycloalkyl ring or a group C=CH2; R6 is H or alkyl; and m is 0-2.