| 摘要 |
Substituted saccharin compounds that inhibit elastase-like and chymotrypsin-like serine proteases are disclosed. The compounds inhibit the proteolytic activity of these proteases. The compounds have the following General structural formula (see fig. I) wherein L is -O-,(see fig.II), -S-, (see fig. III), or (see fig. IV) n is 0 or 1; R1 is a C1-C6 alkyl; substituted C1-C6 alkyl with a substituent selected from an ester, amino, amide, oxy, thio, sulfonyl, or sulfinyl group; aryl selected from phenyl, napthyl, biphenylyl, anthracenyl, quinolyl, or pyrimidinyl: heterocyclyl selected from fused or unfused cyclic organic groups that contain one or more heteratoms chosen from N, S or O in the ring structure; or halo group; or substituted aryl or heterocyclyl with a substituent selected from the group consisting of C1-C6 alkyl, cycloalkyl selected from C3 to C6 carbocyclic ring groups, aryl selected from phenyl, naphthyl, biphenylyl, anthracenyl, quinolyl, or pyrimidinyl, halo, nitro, arylamino and alkylamidoaryl; R2 is hydrogen; aryl selected from phenyl, naphthyl, biphenylyl, anthracenyl, quinolyl, or pyrimidinyl; or an electron-withdrawing group selected from substituent groups that will manifest greater inductive effect to draw electrons to themselves than would a hydrogen atom if it occupied the same position on the molecule; and R3 and R4 are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, amino, amido and a straight, cyclic or branched-chain carbon-containing group having from 1 to 20 carbon atoms or more heteroatoms chosen from N, S or O; wherein the - CHR2- group is always appended to a heteroatom on L or on R1; with the provisos that (i) when n is 0 and R2, R3 and R4 are all hydrogen, R1 cannot be halo, phthalimidyl or phenyl; (ii) when n is 1, L is -S- and R2, R3 and R4 are each hydrogen, R1 cannot be 1-phenyl-1H-(5-tetrazolyl) or lower alkyl; (iii) when n is 1, L is -O- or -S-, and R2, R3 and R4 are all hydrogen, R1 cannot be lower-alkanoyl; (iv) when n is 1, L is -O-, -S- or -SO- and R2, R3 and R4 are all hydrogen, or when n is 1, L is -S-, R2 and R4 are hydrogen and R3 is halo, or when n is 1, L is -SO- or - SO2-, R2 is lower-alkoxycarbonyl and R3 and R4 are both hydrogen, R1 cannot be phenyl or substituted phenyl.
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