The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Nov. 02, 2010

Filed:

Mar. 07, 2007
Applicants:

Robert C. Moschel, Frederick, MD (US);

Matthew Karl Moschel, Legal Representative, Baltimore, MD (US);

Natalia A. Loktionova, Hershey, PA (US);

Anthony E. Pegg, Hershey, PA (US);

Gary T. Pauly, Frederick, MD (US);

Inventors:

Robert C. Moschel, Frederick, MD (US);

Matthew Karl Moschel, legal representative, Baltimore, MD (US);

Natalia A. Loktionova, Hershey, PA (US);

Anthony E. Pegg, Hershey, PA (US);

Gary T. Pauly, Frederick, MD (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A01N 43/04 (2006.01); A61K 31/70 (2006.01);
U.S. Cl.
CPC ...
Abstract

Disclosed are prodrugs of inactivators of O-alkylguanine-DNA alkyltransferase (AGT). The prodrugs are cleavable by the β-glucuronidase enzyme, which is either administered to the patient or produced by necrotic tumor cells. The prodrugs are represented by the formula A-B-C, wherein A is a glucuronosyl residue linked through its 1-oxygen to the phenyl ring of B; B is a benzyloxycarbonyl group, optionally ring-substituted with one or more electron withdrawing groups; and C is an inactivator of AGT, e.g., a substituted or unsubstituted O-benzylguanine or O-benzyl-2'-deoxyguanosine. Also disclosed are additional inactivators of AGT, pharmaceutical compositions comprising an inactivator or prodrug and a pharmaceutically acceptable carrier, and a method of use of the inactivator or prodrug in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the O-position of guanine.


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