Scriptgen Pharmaceuticals, Inc.

Boston University

Other

Mark A Wuonola

Gary R Gustafson

Jennifer V Schaus

James S Panek

Tao Hu

Zhe Li

David G Powers

Tau Hu

The present invention provides convergent processes for preparing myxopyronins and corallopyronins, compounds useful as antibacterial therapeutics. The present invention also provides novel compositions of matter which are useful for the preparation of pyronin antibiotics.

Pyronin antibacterials, process and novel intermediates thereto

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

Disclosed is a method for the inhibition of binding of a ligand to an RNA, the inhibition being mediated by a small organic molecule that binds to the RNA, thereby inhibiting ligand binding. A preferred class of small organic molecules are compounds exemplified by 2,5-Bis[3-(2-N,N-dimethylaminopropylamidino)phenyl]furan.

Small molecule inhibition of RNA/ligand binding

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.

Growing community of inventors

Waltham, MA, United States of America

Mark A Wuonola