公开(公告)号：EP1047703A1

公开(公告)日：2000-11-02

申请号：EP98960228.9

申请日：1998-11-17

申请人： Incara Pharmaceutical Corp.

发明人： ALLANSON, Nigel, Mark ,  CHAN, Tin, Yau ,  HATZENBUHLER, Nicole, T. ,  JAIN, Rakesh, K. ,  KAKARLA, Ramesh ,  LIANG, Rui ,  LIU, Dashan ,  SILVA, Domingos ,  SOFIA, Michael

IPC分类号： C07H1/00 ,  C07H5/00 ,  C07H15/00

CPC分类号： C07H15/04 ,  C07H15/203 ,  C40B40/00

摘要： A combinatorial chemical library of compounds structurally related to the moenomycin class of antibiotics has formula (I) wherein D is a donor mono- or disaccharide, A is an acceptor monosaccharide, and P-R is a lipophosphoglycerate mimetic group. Members of the library have a glycosidic linkage between the anomeric carbon of D and the C2 carbon of A, and the D-A moiety is in turn covalently linked through the anomeric carbon of A to the P-R group. Members of the library exhibit their greatest structural diversity in terms of substitutions occurring at the C3 position of the A residue, substitutions at the C2 position of the D residue, and different P-R groups used in assembling the compounds. Members of the library are preferably synthesized by solid phase techniques involving stepwise coupling of the respective units to a support, functionalizing the A and/or D saccharides either before or after immobilizing them on the support, and cleaving the assembled compounds from the support. Preferred functionalities attached to the sugar residues are amides, carbamates, ureas, sulfonamides, substituted amines, esters, carbonates, and sulfates. Exemplary P-R groups are derivatives of homoserine, glyceric acid, salicylates and mandelic acid. Members of the library can be screened for anti-microbial activity by contacting them with a culture of microbes and monitoring the growth rate of the microbes.