Patent ID: 6620832
Filing Date: 2003-09-16
Classification: A61P,C07D

Abstract:
A compound of general formula (I): wherein:R1 and R2 together with the nitrogen atom to which they are attached form a cyclic amine; R3 represents optionally substituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocycloalkyl or heterocycloalkylalkyl; R4 represents hydrogen or optionally substituted lower alkyl; R5 is a straight or branched alkylene chain, alkenylene chain or alkynylene chain; R6 is cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldyl, â€”C(&boxH;Z1)â€”NR4â€”, â€”NR4â€”C(&boxH;Z1)â€”, â€”Z1â€”, â€”C(&boxH;O)â€”, â€”C(&boxH;NOR4)â€”, â€”NR4â€”, â€”NR4â€”C(&boxH;Z1)â€”NR4â€”, â€”SO2â€”NR4â€”, â€”NR4â€”SO2â€”, â€”Oâ€”C(&boxH;O)â€”, â€”C(&boxH;O)â€”Oâ€”, â€”NR4â€”C(&boxH;O)â€”Oâ€” or â€”Oâ€”C(&boxH;O)â€”NR4â€”; R7 is hydrogen; or optionally substituted alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; R8 is optionally substituted alkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, or alkyl substituted by optionally substituted aryl, an acidic functional group, cycloalkyl, heteroaryl, heterocycloalkyl, â€”Z1H, â€”Z2R3, â€”C(&boxH;O)â€”NY1Y2 or â€”NY1Y2; R9 is hydrogen, R3 or alkyl substituted with alkoxy, cycloalkyl, hydroxy, mercapto, alkylthio or â€”NY1Y2; R10 is hydrogen or a group consisting amino acid side chains, an acidic functional group, R3, â€”Z2R3, â€”C(&boxH;O)â€”R3, or â€”C(&boxH;O)â€”NY1Y2, or alkyl substituted by an acidic functional group or by R3, â€”Z2R3, â€”NY1Y2, â€”NHâ€”(&boxH;O)â€”R3, â€”C(&boxH;O)â€”R5â€”NH2, â€”C(&boxH;O)â€”Ar3â€”NH2, â€”C(&boxH;O)â€”R5â€”CO2H, or â€”C(&boxH;O)â€”NY1Y2; or R9 and R10 together with the atoms to which they attached form a 3- to 6-membered heterocycloalkyl ring; R11 is C1-6alkylene, optionally substituted by R3; R12 is hydrogen, or alkyl optionally substituted by aryl, an acidic functional group, cycloalkyl, heteroaryl, heterocycloalkyl, â€”Z1H, â€”Z2R3, â€”C(&boxH;O)â€”NY1Y2 or â€”NY1Y2; Ar1 is optionally substituted aryldiyl or heteroaryldiyl; Ar2 is heteroaryldiyl, phenylene or phenylene substituted by halogen, lower alkyl or lower alkoxy; Ar3 is aryldiyl or heteroaryldiyl; L1 represents a â€”R5â€”R6â€” linkage; L2 represents: (i) a direct bond; (ii) an alkylene, alkenylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or aryldiyl linkage each optionally substituted by (a) an acidic functional group, R3, â€”Z1H, â€”Z2R8, â€”C(&boxH;O)â€”R3, â€”N(R7)â€”C(&boxH;O)â€”R8, â€”N(R7)â€”C(&boxH;O)â€”OR8, â€”N(R7)â€”C(&boxH;O)â€”NR4R8, â€”N(R7)â€”SO2â€”R8, â€”NY1Y2, or â€”[C(&boxH;O)â€”N(R9)â€”C(R4)(R10)]pâ€”(&boxH;O)â€”NY1Y2, or by (b) alkyl substituted by an acidic functional group, or by â€”Z1H, â€”Z2R3, â€”C(&boxH;O)â€”NY1Y2 or â€”NY1Y2; (iii) a â€”[C(&boxH;O)â€”N(R9)â€”C(R4)(R10)]9â€” linkage; (iv) a â€”Z3â€”R11â€” linkage; (v) a â€”C(&boxH;O)â€”CH2â€”C(&boxH;O)â€” linkage; or (vi) a â€”R11â€”Z3â€”R11â€” linkage; Y is carboxy; Y1 and Y2 are independently hydrogen; or optionally substituted alkenyl, alkyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl, or alkyl substituted by alkoxy, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, hydroxy, oxo, â€”NY3Y4, or one or more â€”CO2R7 or â€”C(&boxH;O)â€”NY3Y4 groups; or the group â€”NY1Y2 may form a cyclic amine; Y3 and Y4 are independently hydrogen; or optionally substituted alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl or heteroarylalkyl; or the group â€”NY3Y4 may form a cyclic amine; Z1 is O or S; Z2 is O or S(O)n; Z3 is O, S(O)n, NR12, SO2NR12, NR12C(&boxH;O), C(&boxH;O)NR12 or C(&boxH;O); and n is zero or an integer 1 or 2; p is zero or an integer 1 to 4; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs; but excluding compounds where an oxygen, nitrogen or sulphur atom is attached directly to a carbon carbon multiple bond of an alkenyl or alkynyl residue.