US 5,942,547 A · 2-Deoxystreptamine derivatives, pharmaceutical compositions thereof and therapeutic methods using same

Abstract

This invention provides a compound having the formula: ##STR1## wherein R.sup.1 and R.sup.3 independently are hydrogen, --CHO, --COCH.sub.3, --COR.sup.7, --A--Ar--(Q).sub.z, etc.; wherein D is a C.sub.1-6 linear, C.sub.3-8 branched or cyclic group having from 4 to about 15 atoms, consisting of C, etc.; wherein D is unsubstituted or substituted with one or more groups independently selected from the group consisting of --OH, NH.sub.2, --NHR.sub.7, etc.; wherein each Q is independently --CNH(NHY), --NHCNH(NHY), --SO.sub.2 W, --SOW, etc.; wherein Y is hydrogen, alkyl, alkenyl, --B--NH.sub.2, --B--NHR.sup.8, etc.; wherein W is alkyl, alkenyl, --B--NH.sub.2, etc.; wherein A nd B independently are a bond, or a C.sub.1-6 linear, C.sub.3-8 branched or cyclic linking group having from 1 to about 15 atoms, consisting of C, optionally interrupted by N, S, P and O; wherein A and B independently are unsubstituted or substituted with --OH, NH.sub.2, etc.; wherein R.sup.7 is an alkyl, a branched alkyl, etc.; wherein R.sup.8, R.sup.9, and R.sup.10 are independently represented by hydrogen, alkyl, branched alkyl, etc.; wherein x is 0, 1 or 2; and z is 0, 1, 2, or 4; wherein R.sup.1 ' and R.sup.3 ' are independently selected from the group consisting of hydrogen, alkyl and benzyl, or alternatively, R.sup.1 and R.sup.1 ' or R.sup.3 and R.sup.3 ' with their respective nitrogen atoms independently form a phthalimido, succinimido, etc.; wherein R.sup.4, R.sup.5, and R.sup.6 independently are selected from the group consisting of hydrogen, --CHO, --COCH.sub.3, --COR.sup.7, etc.; therein said saccharides are optionally linked at the one position of said saccharid group; wherein R.sup.4 and R.sup.5, or R.sup.5 and R.sup.6, together comprise a methylidene, ethylidene, isopropylident, cyclohexylidene or benzylidene bridge, or R.sup.3 and R.sup.4, or R.sup.1 and R.sup.6, together independently form an intramolecular carbamate; wherein R.sup.5 is not hydrogen or glycosyl when R.sup.3 and R.sup.4, or R.sup.1 and R.sup.6, together independently form an intramolecular carbamate; with the provisio that at least two of R.sup.1, R.sup.1 ', R.sup.3, R.sup.3 ', R.sup.4, R.sup.5, and R.sup.6 are not hydrogen. Also provided are pharmaceutical compositions comprising the compound and methods of inhibiting binding of human immunodeficiency virus REV protein to RRE.

A compound having the formula:

##STR41## wherein R.sup.1 and R.sup.3 independently are hydrogen, --CHO, --COCH.sub.3, --COR.sup.7, --COCCl.sub.3, --COCF.sub.3, benzyloxycarbonyl, t-butoxycarbonyl, fluorenylmethyloxycarbonyl, a d or l amino acid, --D--(Q).sub.x or --A--Ar--(Q).sub.z ;
wherein D is a C.sub.1-6 linear alkvl, C.sub.3-8 branched alkvl or C.sub.3-6 cycloalkyl, consisting of C with the proviso that D is optionally interrupted by at least one atom independently selected from the group consisting of N, S, P and O;
wherein D is unsubstituted or substituted with one or more groups independently selected from the group consisting of --OH, NH.sub.2, --NHR.sup.7, --NHR.sup.7 R.sup.8, and alkyl;
wherein each Q is independently --CNH(NHY), --NHCNH(NHY), --NHCO(NHY), --CONHY, --COOH, --COOY, --NHCOY, --NHSO.sub.2 Y, halogen, --CN, --SO.sub.2 W, --SOW --OPO.sub.3, imidazolyl, thiazolyl, pyridyl or indolyl;
wherein Y is hydrogen, alkyl, alkenyl, --B--NH.sub.2, --B--NHR.sup.8, --B--NR.sup.8 R.sup.9, --B-aryl, --B-substituted aryl, --B-morpholino or --B-pyridyl;
wherein W is alkyl, alkenyl, --B--NH.sub.2, --B--NHR.sup.8, --B--NR.sup.8 R.sup.9, --B-aryl, --B-substituted aryl, --B-morpholino or --B-pyridyl;
wherein A and B independently are a bond, or a C.sub.1-6 linear alkyl, C.sub.3-8 branched alkyl or C.sub.3-6 cycloalkyl, consisting of C, with the proviso that A and B are optionally interrupted by at least one atom independently selected from the group consisting of N, S, P and O;
wherein A and B independently are unsubstituted or substituted with one or more groups independently selected from the group consisting of --OH, NH.sub.2, --NHR.sup.7, --NHR.sup.7 R.sup.8, and alkyl;
wherein Ar is an aryl or heteroaryl group having from 6-10 ring atoms and 1-2 rings;
wherein R.sup.7 is an alkyl, a branched alkyl, a cycloalkyl or an aryl group;
wherein R.sup.8, R.sup.9, and R.sup.10 are independently represented by hydrogen, alkyl, branched alkyl, cycloalkyl or aryl groups;
wherein x is 0, 1 or 2;
and z is 0, 1, 2, 3 or 4;
wherein R.sup.1 ' and R.sup.3 ' are independently selected from the group consisting of benzyl or alternatively, R.sup.1 and R.sup.1 ' or R.sup.3 and R.sup.3 ' with their respective nitrogen atoms independently form a phthalimido, succinimido, 2,5-dimethylpyrrolo- or N-1,1,4,4-tetramethyldisilylazacyclopentane group;
wherein R.sup.4, R.sup.5, and R.sup.6 independently are selected from the group consisting of hydrogen, --CHO, --COCH.sub.3, --COR.sup.7, --COCCl.sub.3, --COCF.sub.3, a d or l amino acid compounds having a glycosyl group, --D--(Q).sub.x and --A--Ar--(Q).sub.z ;
wherein said saccharides are optionally linked at the one position of said saccharide group;
wherein R.sup.4 and R.sup.5, or R.sup.5 and R.sup.6, together are a methylidene, ethylidene, isopropylidene, cyclohexylidene or benzylidene bridge, or R.sup.3 and R.sup.4, or R.sup.1 and R.sup.6, together independently form an intramolecular carbamate;
with the proviso that at least two of R.sup.1, R.sup.1 ', R.sup.3, R.sup.3 ', R.sup.4, R.sup.5, and R.sup.6 are not hydrogen.

15 more elements

2-Deoxystreptamine derivatives, pharmaceutical compositions thereof and therapeutic methods using same

Life of this patent

2-Deoxystreptamine derivatives, pharmaceutical compositions thereof and therapeutic methods using same

Life of this patent

Abstract

Claims7