Patent ID: 6316626
Filing Date: 2001-11-13
Classification: C07D,C12Q,C40B,G01N

Abstract:
A compound having the formula: ##STR19##wherein:R.sub.1 and R.sub.1' are, individually CH.sub.2, CH(R.sub.2), C.dbd.O, C.dbd.S, S(.dbd.O).sub.2, C(.dbd.O)NH, C(.dbd.S)NH or C(.dbd.O)O;R.sub.2 is H, substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 alkenyl, substituted or unsubstituted C.sub.2 -C.sub.20 alkynyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.3 -C.sub.14 cycloalkyl, substituted or unsubstituted C.sub.5 -C.sub.14 fused cycloalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclylalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.4 -C.sub.14 heteroaralkyl, CH(R.sub.7)--NH--R.sub.7' or CH(R.sub.7)--NH--R.sub.1' --R.sub.3 ; wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone sulfonate, sulfonamide, thiol, and thioalkoxy; or R.sub.1 and R.sub.2, together, are H, or an amino protecting group;R.sub.3 is H;R.sub.4 is H, R.sub.1 -R.sub.2 or R.sub.11 -R.sub.12 ;R.sub.5 is, H, substituted or unsubstituted C.sub.1 -C.sub.1 alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 alkenyl, substituted or unsubstituted C.sub.2 -C.sub.20 alkynyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.3 -C.sub.14 cycloalkyl, substituted or unsubstituted C.sub.5 -C.sub.14 fused cycloalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclylalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.4 -C.sub.14 heteroaralkyl, --R.sub.1 -R.sub.2, or N(R.sub.8)(R.sub.9)--C(.dbd.O); wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone, sulfonate, sulfonamide, thiol, and thioalkoxy;R.sub.6 is, H, substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 alkenyl, substituted or unsubstituted C.sub.2 -C.sub.20 alkynyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.3 -C.sub.14 cycloalkyl, substituted or unsubstituted C.sub.5 -C.sub.14 fused cycloalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclylalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.4 -C.sub.14 heteroaralkyl, --R.sub.1 -R.sub.2, or --C(.dbd.O)O--R.sub.3 ; wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone, sulfonate, sulfonamide, thiol, and thioalkoxy; or R.sub.5 and R.sub.6, together, are (CH.sub.2).sub.nd, (CH.sub.2).sub.nd --O--(CH.sub.2).sub.ne, (CH.sub.2).sub.nd --N(R.sub.10)--(CH.sub.2).sub.ne, or (CH.sub.2).sub.nd --S--(CH.sub.2).sub.ne ;R.sub.7 is H, substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 alkenyl, substituted or unsubstituted C.sub.2 -C.sub.20 alkynyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.3 -C.sub.14 cycloalkyl, substituted or unsubstituted C.sub.5 -C.sub.14 fused cycloalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclylalkyl, substituted or unsubstituted C.sub.6 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.6 -C.sub.14 heteroaralkyl, or a group selected from the group consisting of groups attached to the .alpha.-position of amino acids, wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone, sulfonate, sulfonamide, thiol, and thioalkoxy;R.sub.7' is H or an amino protecting group;R.sub.8 and R.sub.9 are each, independently, H, substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, substituted or unsubstituted C.sub.2 -C.sub.10 alkenyl, substituted or unsubstituted C.sub.2 -C.sub.20 alkynyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.3 -C.sub.14 cycloalkyl, substituted or unsubstituted C.sub.5 -C.sub.14 fused cycloalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclyl, substituted or unsubstituted C.sub.4 -C.sub.14 heterocyclylalkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.4 -C.sub.14 heteroaralkyl, wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone, sulfonate, sulfonamide, thiol, and thioalkoxy; or R.sub.8 and R.sub.9, together, are (CH.sub.2).sub.nd, (CH.sub.2).sub.nd --O--(CH.sub.2).sub.ne, (CH.sub.2).sub.nd --N (R.sub.10)--(CH.sub.2).sub.ne, or (CH.sub.2).sub.nd --S--(CH.sub.2).sub.ne ;R.sub.10 is substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, substituted or unsubstituted C.sub.6 -C.sub.14 aryl, or substituted or unsubstituted C.sub.6 -C.sub.14 aralkyl, substituted or unsubstituted C.sub.4 -C.sub.14 heteroaryl; substituted or unsubstituted C.sub.4 -C.sub.14 heteroaralkyl, wherein the substituent groups are selected from the group consisting of acyl, alkoxy, alkoxycarbonyl, alkyl, alkenyl, alkynyl, amino, amido, azido, aryl, heteroaryl, carboxylic acid, cyano, guanidino, halo, haloalkyl, haloalkoxy, hydrazino, hydroxyl, alkylsulfonyl, nitro, sulfide, sulfone, sulfonate, sulfonamide, thiol, and thioalkoxy;R.sub.11 is a linker moiety;R.sub.12 is a solid support; andnd and ne are each, independently, 1 to 4;provided that said compound is not:N-[1-[1,1'-biphenyl]-4-ylsulfonyl)-5-[[[4-[(2,4-dioxo-5-thiazolidinylidene) methyl]bezoy]amino]methyl]-3-pyrrolidinyl]-4-[(3-oxo-2(3H)-isothizolyl)meth yl]-, [3S-[3.alpha.,5.alpha.(E)]]-benzamide; orN-[(4-amino-2-pyrrolidinyl) methyl]-3-methyl-L-valyl-L-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-, (2S-trans)-, tris (trifluoroacetate)-L-glutamine; orN-[[1-[(1,1-dimethylethoxy) carbonyl]-4-[[(1,1-dimethyletyhoxy) carbonyl]amino]-2-pyrrolidinyl]methyl]-3-methyl-L-1,2,3,4-tetrahydor-3-iso quinolinecarbonyl-, (2S-trans)-, tris (trifluoroacetate)- L-glutamine; orN-[(4-amino-2-pyrrolidinyl) methyl]-3-methyl-L-valyl-L-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-, (2S-trans)-trifluoroacetate L-glutamine; orN-[(4-amino-2-pyrrolidinyl) methyl]-3-methyl-L-valyl-L-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-, (2S-trans)- L-glutamine; or3-[[[1-[(4-chlorophenyl) sulfonyl]-4-[[(4-chlorophenyl) sulfonyl]amino]-2-pyrrolidinyl]methyl]amino]-,(2S-trans)-benzoic acid; or4-azido-2-(azidomethyl)-1-(p-tolylsulfonyl)-, (-)-pyrrolidine.