University of Massachusetts

Glsynthesis Inc.

Neal C Brown

George Edward Wright

Chengxin Zhi

Wei-Chu Xu

Marjorie H Barnes

The invention features compounds of the formula:or a pharmaceutically acceptable salt thereof, wherein A is CRand B is N; wherein n is 0-3; wherein Ris (CH)&#x2014;{(G)&#x2014;(CH)}&#x2014;L, in which G is CH, CH&#x2550;CH, C&#x2261;C, CO, O, S, or NR, where Ris H or Calkyl, CHR, where Ris OH or Calkyl, CH(CRR), where each of Rand Ris, independently, H, halo, or Calkyl, OCO, CONR, NRCO, where each of Rand Ris, independently, H or Calkyl, SONH, or NHSO; in which m is 1-4, o is 0-4, p is 0-4, and q is 0-4. The compounds disclosed herein have potent anti-microbial, e.g., both Gram-positive and Gram-negative anti-bacterial properties. The compounds inhibit DNA polymerase IIIC and DNA polymerase IIIE enzymes and thus act therapeutically by inhibiting the growth of a broad array of bacteria. The compounds can be administered to prevent or to treat Gram-positive or Gram-negative bacterial infections, e.g., in eukaryotic cell cultures, animals, or humans.

Purine and isosteric antibacterial compounds

The invention relates to prodrugs of N-substituted derivatives of 6-aminouracils, 6-aminoisocytosines, guanines, and 2-aminoadenines. The N-linked substituents include an ester group that is cleaved upon administration into a subject to yield a substituent having a terminal hydroxyl group. Pharmaceutical compositions including these compounds, and methods for treating Gram-positive bacterial infections using these compounds, are also disclosed.

Antibiotic prodrugs

The invention relates to antimicrobial compounds which interact with zinc in a zinc finger of a bacterial DNA polymerase, methods of screening for such compounds, and methods of using such compounds to inhibit polymerase activity or bacterial growth.

Zinc finger-reactive antimicrobial compounds

A method of inhibiting replication of mycoplasmal and Gram-positive bacteria is described. Useful new compounds for in vivo and in vitro inhibition and therapy for infections utilize HPUra-like compounds are also provided. These include a number of novel 3-substituted uracil and isocytosine compounds, and 10-substituted guanine and adenine compounds.

Growing community of inventors

Northboro, MA, United States of America

Neal C Brown