Indane derivatives

A compound of general formula (I):

• 158
• wherein:
• R1 represents aryl, heteroaryl or a group R3-L2-Ar1-L3-;
• R2 represents hydrogen or lower alkyl;
• R3 represents aryl or heteroaryl;
• R4 is alkyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, or alkyl substituted by aryl, an acidic functional group, cycloalkyl, heteroaryl, heterocycloalkyl, —S(O)mR5, —C(═O)—NY3Y4 or —NY3Y4;
• R5 represents alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocycloalkyl or heterocycloalkylalkyl;
• R6 is hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
• R7 is hydrogen, R5 or alkyl substituted with alkoxy, cycloalkyl, hydroxy, mercapto, alkylthio or —NY3Y4;
• R8 is hydrogen or lower alkyl;
• R9 and R11 are each independently selected from hydrogen or a group consisting of amino acid side chains, an acidic functional group, R5, —C(═O)—R5, or —C(═O)—NY3Y4, or alkyl substituted by an acidic functional group or by R5, —NY3Y4, —NH—C(═O)—R5, —C(═O)—R12—NH2, —C(═O)—Ar2-NH2, —C(═O)—R12—CO2H, or —C(═O)—NY3Y4;
• or R7 and R9 together with the atoms to which they attached form a 3- to 6-membered heterocycloalkyl ring;
• R10 represents C1-6 alkylene, optionally substituted by R4;
• R12 is an alkylene chain, an alkenylene chain, or an alkynylene chain;
• R13 is alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl;
• Ar1 represents an optionally substituted saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N;
• Ar2 is arylene or heteroaryldiyl;
• L1 represents
• (i) a direct bond;
• (ii) an alkenylene, alkylene or alkenylene linkage each optionally substituted by (a) an acidic functional group, cyano, oxo, —S(O)mR4, R5, —C(═O)—R5, —C(═O)—OR5, —N(R6)—C(═Z)—R4, —N(R6)—C(═O)—OR4, —N(R6)—SO2—R4, —NY3Y4 or —[C(═O)—N(R7)—C(R8)(R9)]p—C(═O)—NY3Y4, or by (b) alkyl substituted by an acidic functional group, or by S(O)mR4, —C(═Z)—NY3Y4 or —NY3Y4;
• (iii) a —[C(═O)—N(R7)—C(R8)(R9)]p— linkage;
• (iv) a -Z1-R10- linkage;
• (v) a —R10-Z1-R10— linkage;
• (vi) a —C(R8)(R11)—[C(═O)—N(R7)—C(R8)(R9)]p— linkage;
• or
• (vii) a -L4-L5-L6- linkage;
• L2 represents NR8;
• L3 represents an alkylene, alkenylene or alkynylene chain;
• L4 and L6 each independently represent a direct bond or an alkylene chain;
• L5 represents cycloalkylene or indanylene;
• Y is carboxy or an acid bioisostere;
• Y1 and Y2 are independently hydrogen, alkenyl, alkyl, aryl, arylalkyl, cycloalkyl, heteroaryl or heteroarylalkyl;
• or the group —NY1Y2 may form a cyclic amine;
• Y3 and Y4 are independently hydrogen, alkenyl, alkyl, alkynyl, aryl, cycloalkenyl, cycloalkyl, heteroaryl, heterocycloalkyl, or alkyl substituted by alkoxy, aryl, cyano, cycloalkyl, heteroaryl, heterocycloalkyl, hydroxy, oxo, —NY1Y2, or one or more —CO2R6 or —C(═O)—NY1Y2 groups;
• or the group —NY3Y4 may form a 5- to 7-membered cyclic amine which (i) may be optionally substituted with one or more substituents selected from alkoxy, carboxamido, carboxy, hydroxy, oxo (or a 5-, 6- or 7-membered cyclic acetal derivative thereof), R7;
• (ii) may also contain a further heteroatom selected from O, S, SO2, or NY5;
• and (iii) may also be fused to additional aryl, heteroaryl, heterocycloalkyl or cycloalkyl rings to form a bicyclic or tricyclic ring system;
• Y5 is hydrogen, alkyl, aryl, arylalkyl, —C(═O)—R13, —C(═O)—OR13 or —SO2R13;
• Z is O or S;
• Z1 is O, S(O)n, NR8, SO2NR8, C(═O)NR8 or C(═O);
• m is an integer 1 or 2;
• n is zero or an integer 1 or 2;
• p is zero or an integer 1 to 4;
• the group
• 159
• is attached to the benzene ring of the indane system and the group -L1-Y is attached to either ring of the indane system;
• and
• any aryl or heteroaryl moieties present as a group or part of a group may be optionally substituted;
• but excluding compounds where an oxygen, nitrogen or sulfur atom is attached directly to a carbon-carbon multiple bond of an alkenylene, alkynylene or cycloalkenylene residue;
• and the corresponding N-oxides, and their prodrugs;
• and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs.