| 摘要 |
<p>This invention relates to compounds of general formula (I), wherein R?1 and R3¿ may be the same or different and each independently represents a group -L1-R5, where L1 is a direct bond, a straight or branched C¿1-6?alkylene chain, a straight or branched C2-6alkenylene chain, a straight or branched C2-6alkynylene chain or a straight or branched C1-6alkylene 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 chosen from alkoxy, aryl, carboxy, cyano, cycloalkyl, halogen, hereroaryl, hydroxyl, or oxo; and R?5¿ represents hydrogen, aryl, aroyl, carboxy or an acid bioisostere, cyano, cycloalkyl, cycloalkenyl, heterocycloalkyl, heteroaryl, arylalkoxycarbonyl, -NH-C(=O)-NH¿2?, -C=N-O-C(=O)-NH2, -C(=O)-NY?1Y2, -NY1SO¿2aryl, -NHR6, -SR6, or -OR?6; R2 and R4¿ may be the same or different and are each independently hydrogen or alkyl; or R?2 and R4¿ together form a bond; or R?1 and R2, or R1 and R3, or R3 and R4¿ 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?6; or R1 and R3¿ together with the carbon atoms to which they are attached form a heteroaryl ring; Y represents carboxy or an acid bioisostere; A1 represents a direct bond, a straight or branched C¿1-4?alkylene chain or a NR?6¿ group; Ar is a group chosen from (i) and (ii) and n is 0, 1 or 2; and N-oxides thereof, and their prodrugs, pharmaceutically acceptable salts, and solvates (e.g. hydrates), thereof. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation. </p> |
