Scriptgen Pharmaceuticals, Inc.

David G Powers

Gary R Gustafson

Mark A Wuonola

Kelvin T Lam

2-Deoxystreptamine is an aminocyclitol whose structural stability and abundant functionality make it an attractive scaffold for the combinatorial generation of small molecules. The ability to selectively functionalize the various positions of 2-deoxystreptamine with an almost infinite number of different groups ensures that the libraries so generated will be both spatially and functionally diverse. These compounds can then be screened for biological activity to afford lead compounds for pharmaceutical programs. Additionally, biological ligand mimics based on 2-deoxystreptamine can be readily appended, either directly or through a tether, to solid surfaces or incorporated covalently into gels to afford novel materials useful in separation science.

Use of 2-deoxystreptamine as a molecular scaffold for the preparation of

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.

2-Deoxystreptamine derivatives, pharmaceutical compositions thereof and

The subject invention, provides arylhydrazone compounds having the Formula 1: ##STR1## wherein A and B are independently aryl or heteroaryl and A and B independently are substituted with at least one group selected from alkyl, halogen, CN, COOR.sup.7, NR.sup.7 R.sup.8, CONR.sup.7 R.sup.8, NO.sub.2, SR.sup.7, SOR.sup.7, SO.sub.2 R.sup.7, NHCOR.sup.7, NHSO.sub.2 R.sup.7, OR.sup.7, hydroxyalkyl, and aminoalkyl. The compounds of this invention are useful for treating a wide variety of bacterial infections, including diseases of the skin, e.g., acne and skin ulcers, gastroenteritis, colitis, meningitis, keratinitis, conjunctivitis, diseases of the urinary and genital tracts, etc.

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Maynard, MA, United States of America

David G Powers