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(12) United States Patent (10) Patent No.: US 9,605,014 B2 Woods Et Al USOO9605O14B2 (12) United States Patent (10) Patent No.: US 9,605,014 B2 Woods et al. (45) Date of Patent: Mar. 28, 2017 (54) GLYCOMIMETICS TO INHIBIT C07H 19/01 (2013.01); C07H 19/02 PATHOGEN-HOST INTERACTIONS (2013.01); C07H 19/04 (2013.01); C07H 19/24 (2013.01); G06F 19/10 (2013.01) (71) Applicants: UNIVERSITY OF GEORGIA (58) Field of Classification Search RESEARCH FOUNDATION, INC., None Athens, GA (US); NATIONAL See application file for complete search history. UNIVERSITY OF IRELAND, GALWAY, Galway (IE): (56) References Cited GLYCOSENSORS AND DLAGNOSTICS, LLC., Athens, GA U.S. PATENT DOCUMENTS (US) 5,637,569 A * 6/1997 Magnusson ........ A61K 47/4833 (72) Inventors: Robert J. Woods, Athens, GA (US); 514/25 6,245,902 B1 6/2001 Linhardt et al. Paul V. Murphy, Galway (IE); Loretta 6,664,235 B1 12/2003 Kanie et al. Yang, San Diego, CA (US); Hannah 2006/0173199 A1 8/2006 Hong et al. M. K. Smith, Clare (IE); Jenifer 2011/O257032 A1 10/2011 Sasisekharan et al. Hendel, Alymer (CA) FOREIGN PATENT DOCUMENTS (73) Assignees: University of Georgia Research Foundation, Inc., Athens, GA (US); WO WO 98.31697 A1 6, 1998 National University of Ireland, WO WO 2012, 118928 A2 9, 2012 Galway, Galway (IE); Glycosensors and Diagnostics, LLC., Athens, GA OTHER PUBLICATIONS (US) Itzstein, Mark von, Nature Reviews, “The war against influenza: (*) Notice: Subject to any disclaimer, the term of this discovery and development of sialidase inhibitors', 2007, vol. 6, pp. patent is extended or adjusted under 35 967-974 U.S.C. 154(b) by 112 days. International Patent Application No. PCT/US2013/031238, filed Mar. 14, 2013; Written Opinion, issued May 30, 2013; 8 pages. (21) Appl. No.: 14/385,312 International Patent Application No. PCT/US2013/031238, filed Mar. 14, 2013; International Search Report, issued May 30, 2013; (22) PCT Filed: Mar. 14, 2013 4 pages. International Patent Application No. PCT/US2013/031238, filed (86). PCT No.: PCT/US2O13/031238 Mar. 14, 2013; International Preliminary Report on Patentability, issued Sep. 16, 2014; 10 pages. S 371 (c)(1), Angström et al., “Delineation and comparison of ganglioside (2) Date: Sep. 15, 2014 binding epitopes for the toxins of Vibrio cholerae, Escherichia coli, and Clostridium tetani: evidence for overlapping epitopes' Proc (87) PCT Pub. No.: WO2013/138563 Natl AcadSci USA, 1994; 91(25): 11859-63. Babai et al., “New fimbrial gene cluster of S-fimbrial adhesin PCT Pub. Date: Sep. 19, 2013 family” Infect Immun, 2000; 68(10):5901-7. Backenson, “Borrelia burgdorferi shows specificity of binding to (65) Prior Publication Data glycosphingolipids” Infect Immun, 1995; 63(8):2811-7. US 2015/OO72952 A1 Mar. 12, 2015 Blumenschein et al., “Atomic resolution insight into host cell recognition by Toxoplasma gondii” EMBO.J. 2007; 26(11):2808 20. Related U.S. Application Data Case et al., “The Amber biomolecular simulation programs' J (60) Provisional application No. 61/611,890, filed on Mar. Computat Chem, 2005; 26:1668-88. 16, 2012. (Continued) (51) Int. Cl. Primary Examiner — Layla Berry C07H 17/04 (2006.01) Assistant Examiner — Bahar Craigo C07H 15/20 (2006.01) (74) Attorney, Agent, or Firm — Mueting, Raasch & C07H 17/02 (2006.01) Gebhardt, PA. C07H 19/01 (2006.01) C07H 19/02 (2006.01) (57) ABSTRACT C7H 9/04 (2006.01) The present invention relates to novel glycomimetic com C7H 9/24 (2006.01) pounds that are rationally designed to inhibit the binding of C7H I5/04 (2006.01) various pathogens to cell Surface sialylated galactose and CO7D 455/02 (2006.01) methods of use thereof. Specifically sialic acid glycosides G06F 9/10 (2011.01) and C-glycosides are disclosed that form a lactam ring (52) U.S. Cl. structure or a cyclic etherfamine ring structure with the CPC ........... C07H 17/04 (2013.01); C07D455/02 adjacent monosaccharide residue. (2013.01); C07H 15/04 (2013.01); C07H 15/20 (2013.01); C07H 17/02 (2013.01); 21 Claims, 13 Drawing Sheets US 9,605,014 B2 Page 2 (56) References Cited Biarnes et al., “Substrate distortion in the Michaelis complex of Bacillus 1,3-1,4-beta-glucanase. Insight from first principles molecular dynamics simulations.” J Biol Chem, 2006, 281: 1432-41. 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