US 20080299070A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0299070 A1 Engel et al. (43) Pub. Date: Dec. 4, 2008 (54) ANTIVIRAL COMPOUNDS Publication Classification (76) Inventors: Robert Engel, Carle Place, NY (51) Int. Cl. (US); JaimeLee Iolani Rizzo, Glen A 6LX 3L/785 (2006.01) Cove, NY (US); Karin Melkonian A6IP3L/2 (2006.01) Fincher, Garden City, NY (US) Correspondence Address: (52) U.S. Cl. ..................................................... 424/78.36 HOFFMANN & BARON, LLP 6900 UERCHO TURNPIKE SYOSSET, NY 11791 (US) (57) ABSTRACT (21) Appl. No.: 12/130,303 The present invention relates to novel antiviral compounds (22) Filed: May 30, 2008 which are covalently attached to Solid, macro Surfaces. In another embodiment, the invention relates to novel antiviral Related U.S. Application Data compositions including a polymeric material and, embedded (60) Provisional application No. 60/940,839, filed on May therein, an antiviral compound. In other embodiments, the 30, 2007, provisional application No. 60/942,037, invention relates to making a surface antiviral and making a filed on Jun. 5, 2007. polymeric material antiviral. US 2008/0299070 A1 Dec. 4, 2008 ANTIVIRAL COMPOUNDS 0016 wherein: 0017 SS represents a modified solid, macro surface CROSS-REFERENCE TO RELATED comprising polymeric molecules having more than one APPLICATIONS primary hydroxyl group in the unmodified State; 0001. This application claims the benefit of U.S. Provi 0.018 U represents —O— —S —NQ- or sional Application Ser. Nos. 60/940,839 filed May 30, 2007 —SiR : and 60/942,037 filed Jun. 5, 2007, which are incorporated 0.019 Q represents H, a hydrocarbon group comprising herein by reference. a minimum of 1 carbon atom and a maximum of 24 carbon atoms, phenyl, or benzyl; SUMMARY OF THE INVENTION I0020 R represents a hydrocarbon group comprising a minimum of 1 carbonatom and a maximum of 24 carbon 0002 The present invention relates to an antiviral surface atoms, phenyl, or benzyl; having the formula (I): 0021 T represents a hydrocarbon chain comprising a minimum of 1 carbonatom and a maximum of 24 carbon atoms; (I) 0022 n1 represents 0 or 1; 0023 n represents an integer from 2-8; 0024 Y represents - NR, "NR, PR - "PR, OH, -SH, SR, SR —SO —SO, OR, —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2 0003 wherein: octane derivative selected from: 0004 SS represents a modified solid, macro surface comprising polymeric molecules having more than one primary hydroxyl group in the unmodified State; 0005 in represents an integer from 2-8; 0006 Y represents - NR = NR, PR - "PR, OH, -SH, —SR, SR —SO —SO, OR, —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2 octane derivative selected from: 0.025 Rindependently represents H. C. alkyl, orphe nyl: I0026) R' represents H, C, alkyl, phenyl, - NR, PR, PR -OH, -SH, -SR, SR, -SO, —OR, C(O)R, C(O)OR, or -SO, OR; 0027 B represents an anion; 0028 a represents an integer: 0007 Rindependently represents H. C. alkyl, orphe 0029 crepresents the valence of B, and is equal to 1-3: nyl: 0030 wherein a X c represents a number such that the 10008) R' represents H, C, alkyl, phenyl, - NR, compound is charge balanced; and PR, PR-OH, -SH, -SR, "SR, -SO , 0.031 with the proviso that the macro surface is not —OR, C(O)R, C(O)OR, or -SO, OR; C-cyclodextrin or B-cyclodextrin. 0009 B represents an anion; 0032. The invention also relates to a solid antiviral com 0010 a represents an integer: position comprising 0011 c represents the valence of B, and is equal to 1-3: 0033 a) a polymeric material that is solid at room tem 0012 wherein a X c represents a number such that the perature and molten at elevated temperatures and, embedded compound is charge balanced; and therein; 0013 with the proviso that the macro surface is not C-cyclodextrin or B-cyclodextrin. 0034 b) a compound of formula (II): 0014. In a preferred embodiment, Y represents Y—(CH2), X-Z-X—(CH2), YaB (II) wherein: 0035 Z represents a modified polyol having more than one primary hydroxyl group in the unmodified State, wherein at least two of the primary hydroxyl groups have been replaced by X-(CH2), Y groups; 0.036 X represents 0.015 The invention also relates to an antiviral surface having the formula (III): (III) SS-(UT) -NN 1\-N-(CH-Y 17 aB 0037 n independently represents an integer from 2-8; 0038 Y represents - NR = NR, PR, PR, OH, -SH, -SR, "SR, -SO, -SO, OR, US 2008/0299070 A1 Dec. 4, 2008 —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2 0059 a) a polymeric material that is solid at room tem octane derivative selected from: perature and molten at elevated temperatures and, embedded therein; 0060 b) a compound of formula (II): Y-(CH2), X-Z-X-(CH2), YaB (II) wherein: 0061 Z represents a modified polyol having more than one primary hydroxyl group in the unmodified State, 0039 Rindependently represents H, C alkyl, or phe wherein at least two of the primary hydroxyl groups nyl: have been replaced by X-(CH2), Y groups; I0040) R' represents H. C. alkyl, phenyl, - NR, 0062 X represents PR, PR —OH, -SH, —SR, —SR —SO , —OR, C(O)R, C(O)CR, or -SO, OR; I0041) m represents any number up to m'-1 wherein m' represents the number of primary hydroxyl groups in the polyol in the unmodified state; 0042 B represents an anion; 0043 a represents an integer; and 0044 c represents the valence of B, and is equal to 1-3: 0.063 n independently represents an integer from 2-8; 0045 whereinax crepresents a number such that the (0.064 Y represents - NR, "NR, PR - "PR, compound is charge balanced. OH, -SH, SR, SR —SO —SO, OR, 0046. Another aspect of the invention relates to a method —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2 for protecting a surface from viral contamination, the method octane derivative selected from: comprising converting the Surface to an antiviral Surface hav ing the formula (I): (I) SS-N(1\) N-(CH)-Y aB. 0065 Rindependently represents H. C. alkyl, orphe N 17 nyl: I0066) R' represents H, C, alkyl, phenyl, - NR, 0047 wherein: PR, PR -OH, -SH, -SR, "SR, SO, 0048 SS represents a solid, macro surface comprising —OR, C(O)R, C(O)OR, or -SO, OR; polymeric molecules having more than one primary 0067 m represents any number up to m'-1 wherein m' hydroxyl group; represents the number of primary hydroxyl groups in the 0049 in represents an integer from 2-8; polyol in the unmodified state; 0050 Y represents - NR = NR, PR - "PR, 0068 B represents an anion; OH, -SH, —SR, SR —SO —SO, OR, 0069 a represents an integer; and —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2 0070 c represents the valence of B, and is equal to 1-3: octane derivative selected from: 0071 whereinax crepresents a number such that the compound is charge balanced. DETAILED DESCRIPTION 0072 Various surfaces and polymeric materials may be protected from viral contamination by converting the Surfaces and polymeric materials to antiviral Surfaces and polymeric 0051 Rindependently represents H, C alkyl, or phe materials in accordance with the invention. Antiviral com nyl: pounds of the invention may be applied to various Surfaces I0052) R' represents H, C, alkyl, phenyl, - NR, and polymeric materials by methods known in the art. The PR, PR -OH, -SH, -SR, -SR, SO, antiviral compounds may, for example, be covalently bonded —OR, C(O)R, C(O)OR, or -SO, OR; to a surface, coated on the Surface, e.g. as a modified polyol. 0053 B represents an anion; or embedded in a polymeric material. Such surfaces and 0054 a represents an integer: methods for applying the antiviral compounds to the Surfaces 0055 c represents the valence of B, and is equal to 1-3: are discussed below; are described in exhibits A, B, C, and D 0056 wherein a X c represents a number such that the attached hereto; and are described in PCT/US03/10419, PCT/ compound is charge balanced; and US06/040587, provisional U.S. patent application 60/863, 0057 with the proviso that the macro surface is not 147, and provisional U.S. patent application 60/941,822. The C-cyclodextrin or B-cyclodextrin. discussions of surfaces and methods for applying the antiviral 0058. The invention also relates to a method for protecting compounds to the surfaces in PCT/US03/10419, PCT/US06/ a polymeric material from viral contamination, the method 040587, provisional U.S. patent application 60/863,147, and comprising converting the polymeric material to a solid anti provisional U.S. patent application 60/941,822 are incorpo viral composition comprising rated herein by reference. US 2008/0299070 A1 Dec. 4, 2008 0073. In one embodiment, the invention relates to novel example, any of the forms of cellulose described above may antiviral Surfaces covalently bonded to antiviral compounds be blended with otherforms of cellulose. Similarly, any of the having formula I: forms of proteinacious materials described above may be blended with other forms of proteinacious materials. More over, any of the forms of cellulose described above may be (I) blended with any of the forms of proteinacious materials described above. For example, wool and silk may be blended with cotton. Also, any of the materials and blends described above may be blended with other natural or synthetic mate rials, such as nylon and polyesters.