Patent ID: 6306873
Filing Date: 2001-10-23
Classification: A61P,C07C,C07D

Abstract:
A compound of general formula (I): ##STR35##whereinR.sup.1 and R.sup.3 may be the same or different and each independently represents a group --L.sup.1 --R.sup.5, where L.sup.1 is a direct bond, a straight or branched C.sub.1-6 alkylene chain, a straight or branched C.sub.2-6 alkenylene chain, a straight or branched C.sub.2-6 alkylylene chain or a straight or branched C.sub.1-6 alkylene chain containing an oxygen or sulfur atom, a phenylene, imino (--NH--) or alkylimino linkage, or a sulfinyl or sulfonyl group, in which each of the alkylene, alkenylene and alkynylene chains may be optionally substituted, the substituents selected from alkoxy, aryl, carboxy, cyano, cycloalkyl, halogen, heteroaryl, hydroxyl, or oxo; and R.sup.5 represents hydrogen, aryl, aroyl, carboxy or an acid bioisostere, cyano, cycloalkyl, cycloalkenyl, heterocyceloalkyl, heteroaryl, arylalkoxycarbonyl, --NH--C(.dbd.O)--NH.sub.2, --C.dbd.N--O--C(.dbd.O)--NH.sub.2, --C.dbd.(O)--NY.sup.1 Y.sup.2, (where Y.sup.1 and Y.sup.2 are independently selected from hydrogen, alkyl, arylalkyl, and aryl, or the group NY.sup.1 Y.sup.2 may form a 4-6 membered cyclic amine {which may optionally contain a further heteroatom selected from O, S, or NR.sup.6 in which R.sup.6 is hydrogen, alkyl, aryl or arylalkyl, or which may be fused to an additional aromatic ring}), --NY.sup.1 SO.sub.2 aryl, --NHR.sup.6, --SR.sup.6, or --OR.sup.6 ;R.sup.2 and R.sup.4 may be the same or different and are each independently hydrogen or alkyl; orR.sup.2 and R.sup.4 together form a bond; orR.sup.1 and R.sup.2, or R.sup.1 and R.sup.3, or R.sup.3 and R.sup.4 together with the carbon atom(s) to which they are attached form a 3 to 8 membered cycloalkyl or cycloalkenyl ring, optionally substituted by alkyl, arylalkyl, or heteroarylalkyl, and which may optionally contain a heteroatom selected from O, S or NR.sup.6 ; orR.sup.1 and R.sup.3 together with the carbon atoms to which they are attached form a heteroaryl ring;Y represents carboxy or an acid bioisostere;A.sup.1 represents a direct bond, a straight or branched C.sub.1-4 alkylene chain or a NR.sup.6 group;Ar is a group selected from: ##STR36##where the dotted lines indicate optional bonds between B--C, and/or C--D, and/or D--E;R.sup.7 represents a straight- or branched-chain alkyl group of 1 to about 6 carbon atoms, optionally substituted by one or more halogen atoms, or when Z.sup.1 represents a direct bond R.sup.7 may also represent a hydrogen atom or a lower alkenyl or lower alkynyl group;R.sup.8 represents an optionally substituted cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl, heteroaryl or partially saturated bicycloaryl group;R.sup.9 represents R.sup.10, --OR.sup.10, --SR.sup.10, --SOR.sup.12, --SO.sub.2 R.sup.12, --SO.sub.2 NR.sup.10 R.sup.11, --NR.sup.10 SO.sub.2 R.sup.12, --NR.sup.10 R.sup.11, --O(C--O)NR.sup.10 R.sup.11, --NR.sup.10 C(.dbd.O)R.sup.12, --N(OH)C(.dbd.O)R.sup.12, or --C(.dbd.O)N(OH)R.sup.12 (where R.sup.10 and R.sup.11, which may be the same or different, each represent a hydrogen atom, or an alkyl, alkenyl, heterocycloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl group, or the group NR.sup.10 R.sup.11 may also represents a 3 to 7 membered cyclic amine optionally containing one or more additional heteroatom selected from O, NR.sup.6, or S, andR.sup.12 represents an alkyl, alkenyl, heterocycloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl group);A.sup.2 represents a direct bond; and Z.sup.2 represents an oxygen or sulfur atom; orA.sup.2 represents a straight- or branched C.sub.1-6 alkylene chain optionally substituted by halogen, hydroxyl, alkoxy, oxo, cycloalkyl, aryl or heteroaryl; and Z.sup.2 represents an oxygen or sulfur atom or a direct bond; orA.sup.2 represents a straight- or branched-carbon chain comprising from 2 to about 6 carbon atoms which contains a double or triple carbon-carbon bond, or is interrupted by an oxygen or sulfur atom, a phenylene, imino (--NH--) or alkylimino linkage, or a sulfinyl or sulfonyl group; and Z.sup.2 represents an oxygen or sulfur atom or a direct bond;B, C, D, and E independently represent a carbon atom or a heteroatom selected from O, S, N, NOR.sup.13 or NR.sup.13 (where R.sup.13 is hydrogen or a C.sub.1-4 straight- or branched-chain alkyl, aryl, arylC.sub.1-4 alkyl, heteroaryl or heteroarylC.sub.1-4 alkyl group), or three of B, C, D or E represent a carbon atom or a heteroatom as defined above and the other represents a direct bond; but excluding compounds where two O or S atoms are in adjacent positions;Q.sup.1, Q.sup.2 and Q.sup.3, which may be the same or different, each represents a CH or CX.sup.1 linkage or a nitrogen atom (where X.sup.1 represents a halogen atom); andn is 0, 1 or 2, (with the proviso that when A.sup.1 is NR.sup.6 n is 2);and N-oxides thereof, and their prodrugs, pharmaceutically acceptable salts, and solvates (e.g. hydrates), thereof, but excluding the compound 3-[3-(4-fluorophenyl)phenylthio]propionic acid.