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. 0074 Informula I, SS represents a solid surface including I0083. When the hydroxyl group is attached to a silicon polymeric molecules that has been modified by covalent atom on the Solid Surface, the material comprising the Solid attachment of the following moiety: Surface is typically silica, e.g. glass. The glass modified in accordance with the present invention may, for example, be a mirror or part of a medical instrument. I0084. In formula I, in represents an integer from 2-8. For example, n can be 2, 3, 4, 5, 6, 7, or 8. I0085 Y represents - NR = NR, PR, PR, OH, -SH, SR, SR —SO —SO, OR, —OR, 0075 Preferably, the solid surface is a macro surface. A —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane deriva macro Surface is a surface of an object that is significantly tive selected from: larger than a powder. Some examples of macro Surfaces are fabrics or threads for making clothing or protective garments, plastic objects, medical devices, and wooden objects. 0076. The solid surface can also be a micro surface. Micro Surfaces include powders and nanoparticles. As defined in this specification, powders do not include C.-cyclodextrin and B-cyclodextrin. In a preferred embodiment, Y represents one of the diazabi 0077. In its unmodified state, the solid surface comprises cyclo2.2.2]octane derivatives shown above. In another pre polymeric molecules having more than one primary hydroxyl ferred embodiment, Y represents —NR —NR, or —OH. group attached to a carbon or to a siliconatom. An unmodified Surface can be a natural Surface or a synthetic Surface, and I0086 Rindependently represents H. Calkyl, or phenyl. may, if necessary, be altered to comprise multiple hydroxyl C. alkyl represents hydrocarbon groups of 1, 2, 3, or 4 groups. For example, polyesters can be altered in accordance carbonatoms in length. A hydrocarbon group is bonded at one with international PCT application US06/040587 to have pri end to another chemical moiety, e.g. an atom. For example, if mary hydroxyl groups. Y represents —NR wherein one R represents Hand the other 0078. An unmodified surface is made into a modified sur R represents C alkyl, then Y is —NHCHs. face by converting the hydroxyl groups into electrophilic I0087) R' independently represents H, C, alkyl, phenyl, leaving groups, then treating the activated Surface with an NR, PR, PR -OH, -SH, -SR, "SR, appropriate tertiary amine under conditions that cause the - SO = OR, C(O)R, C(O)OR, or -SO, OR. leaving group to be replaced by a nitrogenatom of the tertiary 0088 In a preferred embodiment, Y represents amine. 0079. When the hydroxyl group is attached to a carbon atom in the unmodified Solid Surface, the Surface will gener ally comprise natural polymers such as carbohydrates or pro teins, or synthetic polymers, or mixtures thereof. 0080. In this specification, carbohydrates refer to all poly mers of (+)-glucose except C.-cyclodextrin or B-cyclodextrin. Although carbohydrates include starch and glycogen, the car R" is C, alkyl. bohydrate of primary interest in the present specification is 0089. The letters aB in formula I, and elsewhere in this cellulose. The cellulose may, for example, be in the form of application, represent the number and identity of anions nec bulk cellulose, or in the form of cotton, linen, rayon, or essary to maintain a charge-neutral compound. B represents cellulose acetate. The cotton may, for example, be cotton any anion having a valence (c) of 1-3. Some examples of cloth, cotton gauze or bulk cotton. The carbohydrates may anions include monovalent anions such as halides (e.g., F. also be in the form of wood or paper. Cl, Br, and I), OH, and H divalent anions such as S, 0081. Other types of material wherein a surface hydroxyl CO', SO’, and trivalent anions such as PO. group is attached to a carbon atom include proteinacious 0090 The letter a represents an integer such that the over materials. Materials comprising proteins include wool and all charge of the compound is neutral. For example, when the silk. compound contains a divalent cation and B is Cl, thena is 2 0082 Each of the materials described above may exist by and c is 1. In another example, when the compound contains itself, or as blends with one or more other materials. For a divalent cation and B is S, thena is 1 and c is 2. US 2008/0299070 A1 Dec. 4, 2008

0091. In another embodiment, the invention relates to 0100. An example of an antiviral compound that is embed novel antiviral surfaces having the formula III: ded in a polymeric material or is coated on a Surface is represented by formula II: Y—(CH2), X-Z-X—(CH2), YaB (II) (III) 0101 Z in formula II 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. The unmodified polyol can be any molecule having more than one primary hydroxyl group. The unmodified polyol may, for example, be 0092. In formula III, the letters SS, n, Y. a, B, and c are as an alkane polyol, a polyether, a carbohydrate, or a protein. described above for formula I. n1 represents either 0 or 1. In 0102) An alkane polyol of the present invention is an this embodiment, the Solid Surface is preferably silica, e.g. alkane with a minimum of two carbonatoms and a maximum glass. of twelve carbon atoms, and at least two primary hydroxyl 0093. The group UT in formula III is an optional linker. groups. Some examples of alkane polyols include glycerol; When UT is present (i.e. n1 =1), Useparates the solid surface mannitol; ethylene glycol, 1.5-pentanediol: 1,2,3,4,5,6,7,8- (SS) and the positively charged nitrogen atom. When the octaneoctol; 1,6,12-dodecanetriol; and 3-methanolyl-1,6- group UT is absent (i.e. n1 =0), the solid surface SS is bonded hexanehexyl. directly to the positively charged nitrogen atom. 0103) The unmodified polyol can be a polyether. In this specification, polyether refers to molecules having at least 0094 For stability, the linking group UT is preferably two primary hydroxyl groups and having a minimum of one, present (i.e. n1 =1) when the hydroxyl group on the unmodi and a maximum of about 10,000, preferably about 1,000, fied Solid Surface is attached to a silicon atom, as, for example, more preferably about 100, and most preferably about 10 in the case of silica, e.g. glass. Modified silica Surfaces are ether groups. Some examples of polyethers include polyeth more stable when the positively charged nitrogen atom in ylene glycol and polypropylene glycol. formula III is bonded to a carbon atom than when the posi 0104 Carbohydrates include Saccharides, e.g., monosac tively charged nitrogenatom is bonded to a silicon atom. The charides, oligosaccharides, and polysaccharides. The mini carbon atom, e.g., a hydrocarbon chain, in turn, is covalently mum number of saccharide units in an oligosaccharide is two. bonded to the oxygen atom of the hydroxyl group on the The maximum number of saccharide units in an oligosaccha surface of the silica. ride is typically twelve, preferably ten. 0095. The letter III in formula III represents - O , 0105 Polysaccharides have more than twelve saccharide —S , NQ- or - SiR . T represents a hydrocarbon units, and may have up to several thousand units, e.g. up to a chain comprising a minimum of 1 carbon atom and a maxi maximum of about 10,000. In this specification, polysaccha mum of 24 carbon atoms. Q represents H, a hydrocarbon rides refer to polymers of (+)-glucose, and include cellulose, group comprising a minimum of 1 carbon atom and a maxi starch and glycogen. The Saccharides can be in either the D or mum of 24 carbon atoms, phenyl, or benzyl. Preferably, Q L configuration. Saccharide units can be either aldoses or represents hydrogen, methyl, or ethyl. R represents a hydro ketoses. carbon group comprising a minimum of 1 carbonatom and a 0106. The number of carbons in a saccharide unit can be maximum of 24 carbon atoms, phenyl, or benzyl. from three carbons to about six carbons. An example of a 0096. In this specification, a distinction is made between three carbon Sugar is glyceraldehyde. Examples of four car hydrocarbon groups and hydrocarbon chains. A hydrocarbon bon Sugars include erythrose and threose. Examples of five group is bonded at only one end to another chemical moiety. carbon Sugars include ribose, arabinose, Xylose and lyxose. A hydrocarbon chain is bonded independently at each end to Examples of six carbon Sugars include allose, altrose, glu another chemical moiety, e.g., to a group, or to an atom. cose, mannose, gulose, idose, galactose and talose. All of 0097. The carbon atoms of a group or chain can all be these saccharides further include the corresponding 2'-deoxy saturated, or can all be unsaturated. Alternatively, a chain can derivatives. comprise a mixture of Saturated and unsaturated carbon 0107 The polyol can be a polyamino acid having at least atoms. The unsaturated hydrocarbon chains contain one or two amino acids with primary hydroxyl groups. Polyamino more double and/or triple bonds. acids include oligopeptides and proteins. An oligopeptide has 0098. In another embodiment, the invention relates to two to twelve amino acid residues. Typically, proteins have Solid antiviral compositions consisting of a polymeric mate more than twelve amino acid residues and up to about 1,000 rial and, embedded therein, an antiviral compound. amino acid residues. 0099. Any polymeric material that is solid at room tem 0108. The letter X informula II represents 1,4-diazoniabi perature, and that is molten and stable at temperatures up to cyclo2.2.2. octane, as shown below. about 400° C. may be used in the invention. Preferably, the polymeric material is molten and stable attemperatures up to about 500°F. Examples of polymeric materials include, but are not limited to, polyvinyl chloride, polyester, polyethyl ene, polypropylene, polystyrene, polymethacrylate, poly acrylate, polyacrylaminde, nylon, and rayon. Other poly meric materials include natural and synthetic rubber. US 2008/0299070 A1 Dec. 4, 2008

0109 The letters n, Y. R. R. B., a, and c informula II areas for example, carbohydrate and protein Surfaces, activation of described above for formula I. Surface hydroxyl groups may be accomplished by converting 0110. The letter m in formula II represents the number of the hydroxyl group to an active ester. hydroxyl groups that have been replaced by X-(CH2), Y. I0120 Hydroxyl groups may be converted to active esters and may be any number greater than Zero and up to m'-1 by reacting the hydroxyl groups with an esterification reagent wherein m' represents the number of primary hydroxyl in a suitable medium. Suitable reagents include, for example, groups in the unmodified polyol. Z. The minimum values for benzenesulfonyl chloride, p-toluenesulfonyl chloride, thio m" are two, four, and six. The maximum number for m' nyl chloride, and phosphorus tribromide. Suitable media for depends upon the type of polyol. the reaction include, but are not limited to, pyridine, hexane, heptane, ether, toluene, ethyl acetate, and mixtures thereof. 0111 Carbohydrates can contain several thousand saccha The amount of reagent and Volume of Suitable medium are ride units. Each saccharide unit typically contains one pri known to those in the art. mary hydroxyl group. Typically, for a carbohydrate, m' I0121 Equation 1 below depicts an example of the activa should not be greater than 10,000. tion of hydroxyl groups on one of multiple units of a carbo 0112 Proteins may contain up to 1,000 amino acid resi hydrate by reaction with p-toluenesulfonyl chloride: dues and sometimes more. A typical protein contains about 300 amino acid residues. Of the twenty naturally occurring amino acids, only serine contains a primary hydroxyl group. Equation 1 Typically, m' is not greater than 200 for a protein. OH 0113 Preferably, alkane polyols of the present invention contain a minimum of two carbon atoms and a maximum of O TSC twelve carbon atoms, and at least two primary hydroxyl He groups. Typically, m' is not greater than eight for an alkane O HO O pyridine polyol of the present invention. OH 0114. An unmodified polyol is made into a modified polyol by converting the hydroxyl groups into electrophilic leaving groups, then treating the activated polyol with an OTs appropriate tertiary amine under conditions that cause the leaving group to be replaced by a nitrogenatom of the tertiary O O amine. HO O 0115. It is not necessary to activate all of the available OH primary hydroxyl sites present on the Surface of a material. For example, less than about 10% of the available hydroxyl groups on a Surface may be activated to Subsequently provide sufficient antiviral activity. Preferably, about 25% of the 0.122 The activation reaction requires a proton-sink. available hydroxyl groups may be activated, more preferably When pyridine is used as the medium, pyridine functions as about 50%, and most preferably about 75% of the available its own proton-sink. The use of pyridine may be avoided, for hydroxyl groups may be activated. example, by using one of the other, inert Solvent systems 0116 For example, when Z is a carbohydrate comprising disclosed above, and adding an alkaline compound. Such as 2,000 glucose units, m' is 2,000, andmmay be any numberup an insoluble polymeric tertiary amine, to act as the proton to 1999. An antiviral composition for a 2,000 unit carbohy sink. The insoluble polymeric tertiary amine, may be, for drate may, for instance, have a value form of 1,500. example, DEAE-cellulose. 0117. In another example, when Z is a protein comprising I0123 Hydroxyl groups attached to silicon atoms can be 300 amino acid residues, fifteen of which are serine, m' is modified in the same way as chromatographic media, as is fifteen, and m may be any number up to fourteen. An antiviral known in the art. For example, such hydroxyl groups may be composition for a 300 residue protein may, for instance, have treated with various substituted halosilanes, such as chlorosi a value form of seven. lanes or bromosilanes, in a non-reactive (i.e., non-hydroxylic, 0118. In yet another example, when Z is 2,3-hydroxym non-acidic) solvent. The halosilane may have the following ethyl-1,4-butanediol, the alkane polyol contains four primary Structure: hydroxyl groups. The value of m' is four and m may be any number up to three. An antiviral composition for 2.3-hy droxymethyl-1,4-butanediol may, for instance, have a value form of two. R

C1-S-T-X Modification of Surfaces R Activation of Hydroxyl Groups for Covalent Attach ment of Tertiary Amines 0119 Surfaces can be modified in accordance with the where X" is Cl, Br, or I, and T and Rare as described above. invention by methods known in the art. In the case of surfaces 0.124 Treatment of the hydroxyl group with, for example, that have primary hydroxyl groups attached to carbon atoms, chlorosilane results in binding of the Siatom to the oxygen of US 2008/0299070 A1 Dec. 4, 2008 the surface hydroxyl group, thus liberating HC1. This reaction provides a linker which can be used for the attachment of a -continued positively charged moiety. -- -CH3)3CH, 0.125 Equation 2 below depicts an example of the activa N tion of hydroxyl groups on silica with a chlorosilane:

Equation 2

O OH '',O-Si-OH 7 R V p -- C-Si-CHX Her I0129. The synthesis of polyammonium species is known O-Si-O l in the art. For example, see Fabian, et al. “Polycations: Syn theses of Polyammonium Strings as Antibacterial Agents.” Synlett, August 1997. 0.130. An example of the attachment of a positively charged moiety, 1-aza-4-(hexyl)azonia-2.2.2-bicyclooc tane to an active group on silica is shown in equation 4 below, wherein R, X, and X" are as described above:

o-to-i-city Equation 4

R -citx

0126 Examples of non-reactive solvents for use inactiva tion of hydroxyl groups on silica Surfaces, include, but are not limited to, Solvents such as ether, a hydrocarbon, an ester, e.g. ethyl acetate and a simple nitrile, e.g. acetonitrile. Covalent Attachment of Tertiary Amine Group 0127. The surfaces (e.g., carbohydrate, protein, and silica) activated by the process described above are rendered antivi ral by the chemical attachment of a suitable tertiary amine in a Suitable reaction medium. Some examples of suitable reac tion media include, acetonitrile, ethanol, methanol. 2-pro panol, propionitrile, and mixtures thereof. 0128. An example of the attachment of a positively charged moiety, 4-hexyl-1-aza-4-azoniabicyclo2.2.2]octane to an active group on one of multiple units of a carbohydrate is shown in equation 3 below: 0131 Once the modification of a antiviral surface is com plete, the prepared surface may be sequentially washed with a solvent used for the final reaction (e.g., reaction medium Equation 3 used in attachment of positively charged moiety), brine and OTs water, and then dried. Method of Embedding 0.132. The embedded polymeric materials can be made by s HO O methods known in the art. For example, embedding is dis OH cussed in U.S. patent application Ser. No. 12/129,805, the section of which entitled “Method of Embedding is incor porated herein by reference. 0133. In one embodiment, the invention is related to a method of making an antiviral composition by providing a polymeric material. Such as those described above, that is in a Solid state at room temperature; melting the polymeric mate US 2008/0299070 A1 Dec. 4, 2008

rial at temperatures up to about 400° C. to form a molten cosmetics (e.g., lipsticks, chapped lip treatments, ointments polymeric material; adding an antiviral compound described and creams, mascaras, etc.) brushes, clothing, dressing and above to the molten polymeric material to form a mixture of bandages. the compound embedded in the polymeric material; and cool ing the mixture until it solidifies. Preferably, the polymeric Antiviral Activity material is heated up to temperatures of about 500°F. The antiviral compound may be added to the molten polymeric 0140. The embedded polymeric materials according to the material by any suitable method. For example, the antiviral invention demonstrate antiviral properties against any . compound may be applied to the Surface of the polymeric In this specification, antiviral properties refer to the ability to material before or after melting the polymeric material, or by reduce the number of viral particles on a surface. injecting the antiviral compound into the molten polymeric 0.141. Some examples of susceptible to the com material. All other steps are as described above. pounds of the present invention include: Abelson leukemia 0134. The polymeric material may be heated by any virus, Abelson murine leukemia virus, Abelson's virus, acute known method. Preferred methods include convection heat laryngotracheobronchitis virus, Adelaide River virus, adeno ing, microwave heating, and contact heating. associated virus group, Adenovirus, African horse sickness 0135 The polymeric material and embedded compound virus, African Swine fever virus, AIDS virus, Aleutian mink are as described above. A polymeric material is molten when disease parvovirus, alfalfa mosaic virus, alpharetrovirus, it is sufficiently fluid that a chemical compound can be dis , ALV related virus, Amapari virus, Andean potato persed within it. mottle virus, Aphthovirus, Aquareovirus, , arbovi 0136. The compound may be evenly dispersed within the rus C. arbovirus group A, arbovirus group B, polymeric material. Alternatively, the compound may be con group, Argentine hemorrhagic fever virus, Argentinian hem centrated within the area Surrounding the Surface of the poly orrhagic fever virus, Arterivirus, Astrovirus, Ateline herpes meric material. virus group, Aujezky's disease virus, Aura virus, Ausduk 0.137 For example, the heating of the solid polymeric disease virus, Australian bat lyssavirus, Aviadenovirus, avian material may be controlled, e.g. in an oven, so that only up to erythroblastosis virus, avian infectious bronchitis virus, avian 5%, 10%, 25%, or 50% of the outer portion of the material leukemia virus, avian leukosis virus, avian lymphomatosis becomes molten. Then the antiviral compound is added to the virus, avian myeloblastosis virus, avian paramyxovirus, molten material. Once, the polymeric material is cooled and avian pneumoencephalitis virus, avian reticuloendotheliosis solidifies, the area surrounding the surface of the material will virus, avian sarcoma virus, avian type C group, be antiviral. Avihepadnavirus, Avipoxvirus, , B19 virus, Babanki 0.138. The antiviral compound may be applied to the poly virus, baboon herpesvirus, bacterial virus, baculovirus, bar meric material before or after it is made molten by any ley yellow dwarf virus, Barmah Forest virus, bean pod mottle method known in the art. For example, the antiviral com virus, bean rugose mosaic virus, Bebaru virus, Berrimah pound may be in a solution that is applied to the polymeric virus, betaretrovirus, Birnavirus, Bittner virus, BK virus, material. The solution may be applied to the polymeric mate Black Creek Canal virus, bluetongue virus, Bolivian hemor rial by known methods such as coating, spraying, paddling, rhagic fever virus, Boma disease virus, border disease of application by laundry equipment, exhausting on dyeing sheep virus, borna virus, bovine alphaherpesvirus 1, bovine machinery, or dipping. alphaherpesvirus 2, bovine coronavirus, bovine ephemeral fever virus, bovine immunodeficiency virus, bovine leukemia Antiviral Compositions virus, bovine leukosis virus, bovine mammillitis virus, , bovine papular stomatitis virus, 0.139. The polymeric materials of the invention may be bovine parvovirus, bovine syncytial virus, bovine type Con used to make numerous products that may benefit from anti covirus, bovine viral diarrhea virus, bracovirus, broad bean viral activity. For example, antiviral compounds of the inven mottle virus, broad bean stain virus, brome mosaic virus, tion are advantageously embedded in or applied to working Bromovirus, Buggy Creek virus, bullet shaped virus group, Surfaces in vehicles, public and private facilities, places of Bunyamwera virus Supergroup, Bunyavirus, Burkitt's lym commerce, homes, factories, offices and establishments, phoma virus, Bwamba Fever Bwattany hetero virus, CA including walls, floors, furniture, as well as HVAC, plumbing virus, Calicivirus, California encephalitis virus, camelpox and other equipment; in textiles and fabrics, building prod virus, canarypox virus, canid herpesvirus, canine coronavi ucts, cellulose and paper goods; and also in medical articles rus, canine distemper virus, canine herpesvirus, canine and personal articles, including but not limited to those for minute virus, canine parvovirus, Cano Delgadito virus, Cap protection and treatment, for personal care, and for various illovirus, caprine arthritis virus, caprine encephalitis virus, articles of wear, and for other uses. Additional examples of Caprine Herpes Virus—Capripox virus, Cardiovirus, Car products made from polymeric material in which antiviral lavirus, Carmovirus, carrot mottle virus, Cassia yellow blotch compounds may be embedded in or applied to include, but are virus, Caulimovirus, Cauliflower mosaic virus—caviid herp not limited to, furniture, Petri dishes, clothing, countertops, esvirus 1, Cercopithecine herpesvirus 1, Cercopithecine her condoms, tents, shower curtains, brushes, toys, flooring cov pesvirus 2, cereal yellow dwarf virus, Chandipura virus, ers, gymnastic equipment (including mats), hot tubs, food and Changuinola virus, channel catfish virus, Charleville virus, beverage containers, plastic bags, cutting boards, toilet seats, virus, virus, chimpanzee herpesvi animal carriers, litter boxes, door mats, pool liners, adhesive rus, chub reovirus, chum salmon virus, Closterovirus, Cocal bandages, telephones, keyboards, shoes, and insoles. Further virus, Coho Salmon reovirus, coital exanthema virus, Colo examples of products made from the polymeric materials of rado tick fever virus, Coltivirus, Columbia SK virus, Com the invention include plastic syringes, plastic tubing, and any melina yellow mottle virus, common cold virus, Comovirus, other plastic devices used in hospitals. Some additional congenital , contagious eethyma virus, con examples of products include, but are not limited to, paints, tagious pustular dermatitis virus, Coronavirus, Corriparta US 2008/0299070 A1 Dec. 4, 2008 virus, coryza virus, cowpea chlorotic mottle virus, cowpea virus, human immunodeficiency virus 1, human immunode mosaic virus, cowpea virus, virus, coxsackie Virus, ficiency virus 2, human papillomavirus, human T cell leuke CPV (cytoplasmic polyhedrosis virus), cricket paralysis mia virus, human T cell leukemia virus I, human T cell leu virus, Crimean-Congo hemorrhagic fever virus, croup asso kemia virus II, human T cell leukemia virus III, human T cell ciated virus, Crypotovirus, Cucumovirus, Cypovirus, lymphoma virus I, human T cell lymphoma virus II, human T cytomegalovirus, cytomegalovirus group, cytoplasmic poly cell lymphotropic virus type 1, human T cell lymphotropic hedrosis virus, deer papillomavirus, defective virus, deltaret virus type 2, human T lymphotropic virus I, human T lym rovirus, , Densovirus, Dependovirus, Dhori photropic virus II, human T lymphotropic virus III, ichnovi virus, Dianthovirus, diploma virus, DNA virus, Drosophila C rus, Ilarvirus, infantile gastroenteritis virus, infectious bovine virus, duck hepatitis B virus, duck hepatitis virus 1, duck rhinotracheitis virus, infectious haematopoietic necrosis hepatitis virus 2, duovirus, Duvenhage virus, Deformed wing virus, infectious pancreatic necrosis virus, influenza A virus, virus DWV, eastern equine encephalitis virus, eastern equine influenza B virus, influenza virus (unspecified), influenzavi encephalomyelitis virus, EB virus, virus, Ebola-like rus (unspecified), influenzavirus A, influenzavirus B, influ virus, echo virus, echovirus, echovirus 10, echovirus 28, enzavirus C, influenzavirus D, influenzavirus pr8, insect iri echovirus 9, ectromelia virus, EEE virus, EIA virus, EMC descent virus, insect virus, interfering virus, iridovirus, virus, Emiliania huxleyi virus 86, encephalitis virus, Japanese B virus, virus, JC virus, Junin encephalomyocarditis group virus, encephalomyocarditis virus, Kaposi's sarcoma-associated herpesvirus, Kemerovo virus, Enterovirus, enzyme elevating virus, enzyme elevating virus, Kilham's rat virus, Klamath virus, Kolongo virus, virus (LDH), epidemic hemorrhagic fever virus, epizootic Korean hemorrhagic fever virus, kumba virus, Kysanur forest hemorrhagic disease virus, Epstein-Barr virus, equid alpha disease virus, Kyzylagach virus, La Crosse virus, lactic dehy herpesvirus 1, equid alphaherpesvirus 4, equid herpesvirus 2, drogenase elevating virus, lactic dehydrogenase virus, Lagos equine abortion virus, equine arteritis virus, equine encepha bat virus, Lambda phage, Langur virus, lapine parvovirus, losis virus, equine infectious anemia virus, equine morbillivi virus, Lassa virus, latent rat virus, LCM virus, rus, equine rhinopneumonitis virus, equine rhinovirus, Leaky virus, Lentivirus, Leporipoxvirus, leukemia virus, leu Eubenangu virus, European elk papillomavirus, European kovirus, lumpy skin disease virus, Luteovirus, lymphaden swine fever virus, Everglades virus, Eyach virus, Fabavirus, opathy associated virus, , lymphocytic felid herpesvirus 1, feline calicivirus, feline fibrosarcoma choriomeningitis virus, lymphoproliferative virus group, virus, feline herpesvirus, feline immunodeficiency virus, Lyssavirus, Machupo virus, mad itch virus, maize chlorotic feline infectious peritonitis virus, feline leukemia? sarcoma dwarf virus, maize rough dwarf virus, mammalian type B virus, feline leukemia virus, feline panleukopenia virus, oncovirus group, mammalian type B , mamma feline parvovirus, feline sarcoma virus, feline syncytial virus, lian type Cretrovirus group, mammalian type D retroviruses, Fijivirus, Filovirus, Flanders virus, Flavivirus, foot and mammary tumor virus, Mapuera virus, Marafivirus, Marburg mouth disease virus, Fort Morgan virus, Four Corners han virus, Marburg-like virus, Mason Pfizer monkey virus, Mas tavirus, fowl adenovirus 1, fowlpox virus, Friend virus, tadenovirus, Mayaro virus, ME virus, virus, Melan Furovirus, gammaretrovirus, GB hepatitis virus, GB virus, drium yellow fleck virus—Menangle virus, Mengo virus, Geminivirus, German measles virus, Getah virus, gibbon ape Mengovirus, Middelburg virus, milkers nodule virus, mink leukemia virus, glandular fever virus, goatpox virus, golden enteritis virus, minute virus of mice, MLV related virus, MM shinner virus, Gonometa virus, goose parvovirus, granulosis virus, Mokola virus, Molluscipoxvirus, Molluscum contagio virus, Gross virus, ground squirrel hepatitis B virus, group A Sum virus, monkey B virus, virus, Mononegavi arbovirus, Guanarito virus, guinea pig cytomegalovirus, rales, Morbillivirus, Mount Elgon bat virus, mouse cytome guinea pig type C virus, Gay elephant tycomabanucleoid galovirus, mouse encephalomyelitis virus, mouse hepatitis virus, Hantaan virus, Hantavirus, hard clam reovirus, hare virus, mouse K virus, mouse leukemia virus, mouse mam fibroma virus, HCMV (human cytomegalovirus), helper mary tumor virus, mouse minute virus, mouse pneumonia virus, hemadsorption virus 2, hemagglutinating virus of virus, mouse poliomyelitis virus, mouse polyomavirus, Japan, hemorrhagic fever virus, , , mouse sarcoma virus, mousepox virus, Mozambique virus, Hepadnavirus, hepatitis A virus, hepatitis B virus group, Mucambo virus, mucosal disease virus, mumps virus, murid hepatitis C virus, hepatitis D virus, hepatitis delta virus, hepa betaherpesvirus 1, murid cytomegalovirus 2, murine cytome titis E virus, hepatitis F virus, hepatitis G. virus, hepatitis galovirus group, murine encephalomyelitis virus, murine nonA nonB virus, hepatitis virus, hepatitis virus (nonhuman), hepatitis virus, murine leukemia virus, murine nodule induc hepatoencephalomyelitis reovirus 3, Hepatovirus, heron ing virus, murine polyomavirus, murine sarcoma virus, hepatitis B virus, herpes B virus, virus, herpes , Murray Valley encephalitis virus, simplex virus 1, 2, herpesvirus, herpes myxoma virus, Myxovirus, Myxovirus multiforme, Myxovii virus 7. Herpesvirus ateles, Herpesvirus hominis, Herpesvi rus parotitidis, Nairobi sheep disease virus, Nairovirus, rus infection, Herpesvirus Saimiri, Herpesvirus Suis, Herpes Nanirnavirus, Narivavirus, Ndumo virus, Necrovirus, Neeth virus varicellae, , Hirame rhabdovirus, hog ling virus, Nelson Bay virus, Neopvirus, neurotropic virus, cholera virus, Hordeivirus, human adenovirus 2, human New World Arenavirus, newborn pneumonitis virus, New alphaherpesvirus 1, human alphaherpesvirus 2, human alpha castle disease virus, , noncytopathogenic virus, herpesvirus 3, human B lymphotropic virus, human betaher Noravirus, Norwalk virus, nuclear polyhedrosis virus (NPV)- pesvirus 5, human coronavirus, human cytomegalovirus nipple neck virus, Onyongnyong virus, oat sterile dwarf group, human foamy virus, human gammaherpesvirus 4. virus, Ockelbo virus, oncogenic virus, oncogenic viruslike human gammaherpesvirus 6, human hepatitis A virus, human particle, oncornavirus, Orbivirus, virus, Oropouche virus, herpesvirus 1 group, human herpesvirus 2 group, human her Orthohepadnavirus, orthomyxovirus, , pesvirus 3 group, human herpesvirus 4 group, human herp Orthoreovirus, Orungo, Ovine papillomavirus, Ovine esvirus 6, human herpesvirus 8, human immunodeficiency catarrhal fever virus, owl monkey herpesvirus, Palyam virus, US 2008/0299070 A1 Dec. 4, 2008

Papillomavirus, Papillomavirus Sylvilagi, Papovavirus, tomato bushy stunt virus, Tomato spotted wilt virus, Tombus parainfluenza virus, parainfluenza virus type 1, parainfluenza virus, Torovirus, Tospovirus, transforming virus, tumor virus, virus type 2, parainfluenza virus type 3, parainfluenza virus Tupaia virus, turkey rhinotracheitis virus, turkeypox virus, type 4, Paramyxovirus, , paravaccinia virus, turnip yellow mosaic virus, Tymovirus, type C retroviruses, parsnip yellow fleck virus, Parvovirus, , par type D oncovirus, type D retrovirus group, ulcerative disease vovirus group, pea enation mosaic virus, Pestivirus, Phlebo rhabdovirus, Una virus, Uukuniemi virus group, virus, phocine distemper virus, Phytoreovirus, Picodnavirus, virus, vacuolating virus, , , , pig cytomegalovirus, pigeonpox virus, Piry Varicola virus, variola major virus, variola virus, Vasin Gishu virus, Pixuna virus, plant rhabdovirus group, plant virus, disease virus, VEE virus, Venezuelan equine encephalitis pneumonia virus of mice, Pneumovirus, poliomyelitis virus, virus, Venezuelan equine encephalomyelitis virus, Venezu poliovirus, Polydnavirus, polyhedral virus, polyoma virus, elan hemorrhagic fever virus, Vesicular stomatitis virus, Vesiculovirus, Vilyuisk virus, viper retrovirus, viral haemor Polyomavirus, Polyomavirus bovis, Polyomavirus cercopith rhagic septicemia virus, Template:VIRUS76 viruslike par eci, Polyomavirus hominis 2, Polyomavirus maccacae 1, ticle, Visna Maedi virus, Visna virus, volepox virus, VSV Polyomavirus muris 1, Polyomavirus muris 2, Polyomavirus (vesicular stomatitis virus), Wallal virus, Warrego virus, papionis 1, Polyomavirus papionis 2, Polyomavirus Sylvilagi, virus, WEE virus, , western equine encepha Pongine herpesvirus 1, porcine epidemic diarrhea virus, por litis virus, western equine encephalomyelitis virus, Whataroa cine hemagglutinating encephalomyelitis virus, porcine par virus, Winter Vomiting Virus, woodchuck hepatitis B virus, vovirus, porcine transmissible gastroenteritis virus, porcine woolly monkey sarcoma virus, wound tumor virus, WRSV type C virus, Potato leaf roll virus, Potato mop top virus, virus, Yaba monkey tumor virus, Yaba virus, , Potato virus Y. Potexvirus, Potyvirus, pox virus, poxvirus, virus, Yug Bogdanovac virus, and ZYMV (Zuc poxvirus variolae, Prospect Hill virus, provirus, pseudocow chini yellow mosaic virus). pox virus, virus, psittacinepox virus, Puumala 0142. In this specification, groups of various parameters virus, quailpox virus, rabbit fibroma virus, rabbit kidney containing multiple members are described. Within a group Vaculolating virus, rabbit papillomavirus, virus, rac of parameters, each member may be combined with any one coon parvovirus, raccoonpox virus, radish mosaic virus, or more of the other members to make additional Sub-groups. Ranikhet virus, rat cytomegalovirus, rat parvovirus, rat virus, For example, if the members of a group area, b, c, d, and e, Rauscher's virus, recombinant vaccinia virus, recombinant additional Sub-groups specifically contemplated include any virus, reovirus, reovirus 1, reovirus 2, reovirus 3, reptilian two, three, or four of the members, e.g., a and c; a, d, and e, b, type C virus, respiratory infection virus, respiratory syncytial c, d, and e, etc. virus, respiratory virus, reticuloendotheliosis virus, Retrovi 0143. In some cases, the members of a first group of rus, Rhabdovirus, Rhabdovirus carpia, , rhi parameters, e.g., a, b, c, d, and e, may be combined with the novirus, Rhizidiovirus, rice dwarf virus, rice gall dwarf virus, members of a second group of parameters, e.g., A, B, C, D, rice ragged stunt virus, virus, Riley's virus, and E. Any member of the first group or of a sub-group thereof rinderpest virus, RNA tumor virus, RNA virus, Ross River may be combined with any member of the second group or of virus, Rotavirus, rougeole virus, Rous sarcoma virus, a Sub-group thereof to form additional groups, i.e., b with C: virus, rubeola virus, Rubivirus, Russian autumn encephalitis a and c with B, D, and E, etc. virus, SA 11 simian virus, SA2 virus, Sabia virus, Sagiyama 014.4 For example, in the present invention, groups of virus, Saimirine herpesvirus 1, Salivary gland virus, Sandfly various parameters are defined (e.g. R. R', SS, n,Y, B, a, and fever virus group, Sandjimba virus, SARS virus, satellite c). Each group contains multiple members. For example, R virus, SDAV (sialodacryoadenitis virus), virus, Sem independently represents H. C. alkyl, or phenyl. Each mem liki Forest Virus, Sendai virus, Seoul virus, sheeppox virus, ber may be combined with each other member to form addi Shope fibroma virus, Shope papilloma virus, simian foamy tional Sub-groups, e.g., H and phenyl, Hand C alkyl, and C. virus, simian hepatitis. A virus, simian human immunodefi alkyl and phenyl. ciency virus, simian immunodeficiency virus, simian parain 0145 The instant invention further contemplates embodi fluenza virus, simian T cell lymphotrophic virus, simian ments in which each element listed under one group may be virus, simian virus 40, , Sin Nombre virus, Sind combined with each and every element listed under any other bis virus, virus, Sobemovirus, South American group. For example, U is defined above as representing hemorrhagic fever viruses, sparrowpox virus, spring beauty O , —S , NQ- or -SiR . T is defined as repre senting a hydrocarbon chain comprising a minimum of 1 latent virus, Spumavirus, squash mosaic virus, squirrel carbon atom and a maximum of 24 carbon atoms. Each ele fibroma virus, squirrel monkey retrovirus, SSV 1 virus group, ment of U ( O , —S , NQ- or - SiR ) can be STLV (simian T lymphotropic virus) type I, STLV (simian T combined with each and every element of T (a hydrocarbon lymphotropic virus) type II, STLV (simian T lymphotropic chain comprising a minimum of 1 carbon atom and a maxi virus) type III, stomatitis papulosa virus, Submaxillary virus, mum of 24 carbon atoms). For example, in one embodiment, Suid alphaherpesvirus 1, Suid herpesvirus 2, Suipoxvirus, U may be —O— and T may be a 14 carbon chain. Alterna Swamp fever virus, Swinepox virus, Swiss mouse leukemia tively, U may be —S- and T may be a 6 carbon chain, etc. virus, T4 phage, T7 phage, TAC virus, Tacaribe complex Similarly, a third group is n, in which the elements are defined virus, Tacaribe virus, virus, Taterapox virus, Tench as an integer from 2-8. Each of the above embodiments may reovirus, Tenvivirus. Theiler's encephalomyelitis virus, be combined with each and every element of n. For example, Theiler's virus, Thogoto virus, Thottapalayam virus, Tick in the embodiment wherein U is —O— and T is a 14 carbon borne encephalitis virus, Tioman virus, tobacco mosaic virus, chain, n may be 8 (or any other number within the element of tobacco rattle virus, Tobamovirus, Tobravirus, Togavirus, n). US 2008/0299070 A1 Dec. 4, 2008

0146 The compounds of this invention are limited to those p-toluenesulfonyl chloride (0.155 mol) in 150 ml pyridine as that are chemically feasible and stable. Therefore, a combi dispersing medium. The reaction medium is agitated over nation of Substituents or variables in the compounds night. The modified cotton cloth is removed and washed with described above is permissible only if such a combination ice-water. The washed modified cotton cloth is then placed in results in a stable or chemically feasible compound. A stable compound or chemically feasible compound is one in which acetonitrile containing 57.74 g (0.155 mol) of 4-hexyl-1-aza the chemical structure is not substantially altered when kept at 4-azoniabicyclo2.2.2]octane chloride and the reaction mix a temperature of 40°C. or less, in the absence of moisture or ture is agitated overnight. The modified cotton cloth is then other chemically reactive conditions, for at least a week. removed from the reaction medium, washed sequentially 0147 A list following the word “comprising is inclusive with acetonitrile, brine and water, and dried in air. or open-ended, i.e., the list may or may not include additional unrecited elements. A list following the words “consisting of Example 4 is exclusive or closed ended, i.e., the list excludes any element not specified in the list. 0148 All numbers in the specification are approximate Preparation of Antiviral Wood unless indicated otherwise. 014.9 The method of treating a condition, disorder or dis 0153. A 25 g sample of wood (maple) (bearing a maxi ease with a chemical compound or a chemical composition mum of 0.465 equivalents of hydroxyl groups, approximately includes the use of the chemical compound or chemical com 0.155 equivalents of which are primary hydroxyl groups) is position in the manufacture of a medicament for the treatment placed in a solution of 29.5g of the activating agent p-tolu of the condition, disorder or disease. A compound or a group enesulfonyl chloride (0.155 mol) in 150 ml pyridine as dis of compounds said to be effective in treating a condition, persing medium. The reaction medium is agitated overnight. disorder or disease includes the compound or group of com The modified wood is removed and washed with ice-water. pounds for use in treating the condition, disorder or disease. The washed modified wood is then placed in acetonitrile containing 53.40 g (0.155 mol) of 4-hexyl-1-aza-4-azoniabi EXAMPLES cyclo2.2.2]octane chloride and the reaction mixture was agi Example 1 tated overnight. The modified wood is then removed from the Preparation of N-hexyl-N,N-dimethyl-N-(2-thiom reaction medium, washed sequentially with acetonitrile, ethyl)ethylammonium bromide brine and water and dried in air. 0150. The ammonium salt N-hexyl-N,N-dimethyl-N-(2- thiomethyl)ethylammoniumbromide is prepared by adding Example 5 66.1 g (0.210 mol) of 1-bromohexane in 150 ml of ethyl acetate to 25 g (0.210 mol) of N,N-dimethyl-N-(2-thiom Preparation of Antiviral Silk ethyl)ethylamine in 250 ml of ethyl acetate. The solution mixture is stirred. The resultant precipitate is collected by 0154) A 25 g sample of 100% silk (bearing a maximum of suction filtration and washed with ether and dried under 0.057 equivalents of primary hydroxyl groups) is placed in a WaCUU. Solution of 10.8 g of the activating agent p-toluenesulfonyl chloride (0.155 mol) in 150 ml pyridine as dispersing Example 2 medium. The reaction medium is agitated overnight. The Preparation of Antiviral Cotton Cloth with N-hexyl modified silk is removed and washed with ice-water. The N,N-dimethyl-N-(2-thiomethyl)ethylammonium washed modified silk is then placed in a solution of 21.2 g of bromide 4-hexyl-1-aza-4-azoniabicyclo[2.2.2]octane chloride in 100 0151. A 25 g sample of 100% cotton cloth is placed in a ml of acetonitrile and the reaction mixture is agitated over Solution of 29.5 g of the activating agent p-toluenesulfonyl night. The modified silk is then removed from the reaction chloride (0.155 mol) in 150 ml pyridine as dispersing medium, washed sequentially with acetonitrile, brine and medium. The reaction medium is agitated overnight. The water and dried in air. modified cotton cloth is removed and washed with ice-water. The washed modified cotton cloth is then placed with N-hexyl-N,N-dimethyl-N-(2-thiomethyl)ethylammonium Example 6 bromide (62.4 g., 0.155 mol) in acetonitrile and is agitated overnight. The modified cotton cloth is then removed from Preparation of Antiviral Wool with 4-hexyl-1-aza-4- the reaction mixture, washed sequentially with acetonitrile, azoniabicyclo2.2.2]octane chloride brine and water, and dried in air. 0.155. A 25 g sample of 100% wool (bearing a maximum Example 3 of 0.052 equivalents of hydroxyl groups) is placed in a solu tion of 9.90 g of the activating agent p-toluenesulfonyl chlo Preparation of Antiviral Cotton Cloth with 4-hexyl ride (0.155 mol) in 150 ml pyridine as dispersing medium. 1-aza-4-azoniabicyclo2.2.2]octane chloride. The reaction medium is agitated overnight. The modified 0152. A 25 g sample of 100% cotton cloth (bearing a wool is removed and washed with ice-water. The washed maximum of 0.465 equivalents of hydroxyl groups, approxi modified wool is then placed in a solution of 20.82 g (0.052 mately 0.155 equivalents of which are primary hydroxyl mol) of 4-hexyl-1-aza-4-azoniabicyclo2.2.2]octane chloride groups) is placed in a solution of 29.5g of the activating agent in 100 ml of acetonitrile and the reaction mixture is agitated US 2008/0299070 A1 Dec. 4, 2008

overnight. The modified wool is then removed from the reac at 400°F. for 30 sec. to cause dissolution in the polyester tion medium, washed sequentially with acetonitrile, brine and material, and then cooled to ambient temperature. water and dried in air. Example 11 Example 7 Preparation of DABCO in PVC 0160 To a preparation of PVC prepared for finishing and Preparation of Antiviral Wool with P-Hexyl-PP heated to 350° F is added the agent bis-1',3'-(1-hexyl)-1,4- Diphenylphosphine diazoniabicyclo2.2.2]octane-2-propanol tetrachloride in an amount of 10 g/square meter of finished Surface. After press 0156 A 25 g sample of 100% wool (bearing a maximum ing and cooling samples the Surface is antiviral. of 0.052 equivalents of hydroxyl groups) is placed in a solu tion of 9.90 g of the activating agent p-toluenesulfonyl chlo We claim: ride (0.155 mol) in 150 ml pyridine as dispersing medium. 1. An antiviral surface having the formula (I): The reaction medium is agitated overnight. The modified wool is removed and washed with ice-water. The washed (I) modified wool is then placed in a solution of 13.62 g (0.052 mol) of P-hexyl-PP-diphenylphosphine in 100 ml of aceto nitrile and the reaction mixture is agitated overnight. The modified wool is then removed from the reaction medium, washed sequentially with acetonitrile, brine and water and wherein: dried in air. SS represents a modified solid, macro Surface comprising polymeric molecules having more than one primary Example 8 hydroxyl group in the unmodified State; in represents an integer from 2-8; Preparation of 1-hexyl-1-thionium-4-thiacyclohex Y represents —NR —NR, PR, PR —OH, ane bromide SH, -SR, "SR. —SO. , —SO, OR, —OR, —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane 0157. The sulfonium salt 1-hexyl-1-thionium-4-thiacy derivative selected from: clohexane bromide is prepared by adding 63.3 g (0.201 mol) of 1-bromohexadecane in 150 ml of ethyl acetate to 25 g (0.201 mol) of 1,4-dithiane in 250 ml of ethyl acetate. The solution mixture is stirred. The resultant precipitate is col O lected by suction filtration and washed with ether and dried under vacuum. Rindependently represents H. C. alkyl, or phenyl: Example 9 R" represents H.C. alkyl, phenyl, -NR, PR, PRs. OH, -SH, -SR, SR, -SO, OR, —C(O)R, Preparation of Antiviral Cotton Cloth with 1-hexyl - C(O)OR, or -SO, OR; 1-thionium-4-thiacyclohexane bromide B represents an anion; a represents an integer, 0158. A 25 g sample of 100% cotton cloth is placed in a c represents the Valence of B, and is equal to 1-3: Solution of 29.5 g of the activating agent p-toluenesulfonyl wherein a X c represents a number Such that the compound chloride (0.155 mol) in 150 ml pyridine as dispersing is charge balanced; and medium. The reaction medium is agitated overnight. The with the proviso that the macro Surface is not C.-cyclodex modified cotton cloth is removed and washed with ice-water. trin or f3-cyclodextrin. The washed modified cotton cloth is then placed in acetoni 2. An antiviral Surface according to claim 1, wherein the trile with 1-hexyl-1-thionium-4-thiacyclohexane bromide primary hydroxyl group is attached to a carbon atom on the (62.4g, 0.155 mol) and is agitated overnight. The modified Surface. cotton cloth is then removed from the reaction mixture, 3. An antiviral Surface according to claim 1, wherein the washed sequentially with acetonitrile, brine and water, and surface is a fabric. dried in air. 4. An antiviral Surface according to claim 1, wherein the Surface is thread. Example 10 5. An antiviral surface according to claim 1, wherein the Surface is a powder. Application of modified DABCO detergent to poly 6. An antiviral Surface according to claim 1, wherein the ester fabric Surface is clothing. 7. An antiviral surface according to claim 1, wherein the 0159. The agent, bis-1',3'-(1-hexyl)-1,4-diazoniabicyclo Surface is a protective garment. 2.2.2]octane-2-propanol tetrachloride, is placed in an aque 8. An antiviral Surface according to claim 1, wherein the ous solution (10% of agent by weight) and the polyester to be Surface comprises a carbohydrate. treated is saturated with this solution. The polyester fabric is 9. An antiviral surface according to claim 8, wherein car pressed under a roller to remove excess liquid and then heated bohydrate is a polysaccharide. US 2008/0299070 A1 Dec. 4, 2008

10. An antiviral surface according to claim 9, wherein the Y represents —NR —NR, PR, PR —OH, polysaccharide is cellulose. SH, —SR, SR —SO —SO, OR, —OR, 11. An antiviral surface according to claim 10, wherein the —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane cellulose is cellulose acetate. derivative selected from: 12. An antiviral surface according to claim 9, wherein the polysaccharide is cotton. 13. An antiviral surface according to claim 12, wherein the cotton is cotton cloth, cotton gauze, or bulk cotton. N-R O 14. An antiviral surface according to claim 13, wherein the cotton is blended with other fabrics. 15. An antiviral surface according to claim 9, wherein the Rindependently represents H. C. alkyl, or phenyl: polysaccharide is starch. R" represents H, C, alkyl, phenyl, - NR-2, -PR2. 16. An antiviral surface according to claim 9, wherein the "PR-OH, -SH, -SR, SR —SO. , —OR, polysaccharide is glycogen. - C(O)R, C(O)OR, or -SO, OR; 17. An antiviral surface according to claim 1, wherein the B represents an anion; Surface comprises a protein. a represents an integer, 18. An antiviral surface according to claim 17, wherein the c represents the Valence of B, and is equal to 1-3: protein is wool. wherein a X c represents a number Such that the compound is charge balanced; and 19. An antiviral surface according to claim 17, wherein the with the proviso that the macro Surface is not C.-cyclodex protein is silk. trin or f3-cyclodextrin. 20. An antiviral surface according to claim 1, wherein Y 23. An antiviral surface according to claim 22, wherein the represents Surface is silica. 24. An antiviral Surface according to claim 22, wherein the Surface is glass. 25. A Solid antiviral composition comprising a) a polymeric material that is solid at room temperature and molten at elevated temperatures and, embedded therein; 21. An antiviral surface according to claim 20, wherein Y b) a compound of formula (II): represents Y—(CH2), X-Z-X—(CH2), YaB (II) wherein: Z represents a modified polyol having more than one pri mary hydroxyl group in the unmodified State, wherein at least two of the primary hydroxyl groups have been replaced by X-(CH2), Y groups; R" is C. alkyl. X represents 22. An antiviral surface having the formula (III):

(III)

n independently represents an integer from 2-8; Y represents —NR, "NR, PR, "PR —OH, SH, -SR, "SR, -SO, -SO, OR, OR, wherein: —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane SS represents a modified solid, macro Surface comprising derivative selected from: polymeric molecules having more than one primary hydroxyl group in the unmodified State; U represents —O-, -S , —NQ- or -SiR : Q represents H, a hydrocarbon group comprising a mini mum of 1 carbon atom and a maximum of 24 carbon atoms, phenyl, or benzyl; R represents a hydrocarbon group comprising a minimum Rindependently represents H. C. alkyl, or phenyl: of 1 carbon atom and a maximum of 24 carbon atoms, phenyl, or benzyl, R" represents H, C, alkyl, phenyl, - NR-2, -PR2. *PR, -OH, -SH, -SR, "SR, -SO, OR, T represents a hydrocarbon chain comprising a minimum - C(O)R, C(O)OR, or -SO, OR; of 1 carbon atom and a maximum of 24 carbon atoms; m represents any number up to m'-1 wherein m' repre n1 represents 0 or 1; sents the number of primary hydroxyl groups in the in represents an integer from 2-8; polyol in the unmodified state; US 2008/0299070 A1 Dec. 4, 2008 13

B represents an anion; a represents an integer, and c represents the Valence of B, and is equal to 1-3: wherein a X c represents a number Such that the com O pound is charge balanced. 26. An antiviral composition according to claim 25. wherein the polyol is an alkane polyol. 27. An antiviral composition according to claim 26, Rindependently represents H. C. alkyl, or phenyl: wherein the alkane polyol is glycerol, mannitol, ethylene R" represents H, C, alkyl, phenyl, -NR, PR, glycol, or polyethylene glycol. "PR, -OH, -SH, -SR, SR, -SO, OR, 28. An antiviral composition according to claim 25. - C(O)R, C(O)OR, or -SO, OR; wherein the polyol is a carbohydrate. B represents an anion; 29. An antiviral composition according to claim 25, a represents an integer, wherein the polyol is a protein. c represents the Valence of B, and is equal to 1-3: 30. An antiviral composition according to claim 25, wherein a X c represents a number Such that the compound wherein the polymeric material is selected from the group is charge balanced; and consisting of polyvinyl chloride, a polyester, polyethylene, with the proviso that the macro Surface is not C.-cyclodex polypropylene, polystyrene, polymethacrylate, polyacrylate, trin or f3-cyclodextrin. polyacrylamide, nylon, and rayon. 36. A method for protecting a polymeric material from 31. An antiviral composition according to claim 30, viral contamination, the method comprising converting the wherein the polyester is selected from the group consisting of polymeric material to a solid antiviral composition compris polyethylene terephthalate, and poly-1.4, cyclohexylenedim 1ng ethylene terephthalate. a) a polymeric material that is solid at room temperature 32. An antiviral composition according to claim 25. and molten at elevated temperatures and, embedded wherein the polymeric material is natural or synthetic rubber. therein; 33. An antiviral composition according to claim 25, b) a compound of formula (II): wherein Y independently represents Y—(CH2), X-Z-X—(CH2), YaB (II) wherein: Z represents a modified polyol having more than one pri O mary hydroxyl group in the unmodified State, wherein at least two of the primary hydroxyl groups have been replaced by X-(CH2), Y groups; X represents 34. An antiviral composition according to claim 33, wherein Y represents

and n independently represents an integer from 2-8; Y represents —NR —NR, PR, PR —OH, SH, -SR, "SR. —SO. , —SO, OR, —OR, R" is C. alkyl. —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane 35. A method for protecting a surface from viral contami derivative selected from: nation, the method comprising converting the Surface to an antiviral surface having the formula (I): O

(I) Rindependently represents H. C. alkyl, or phenyl: ta w R" represents H.C. alkyl, phenyl, -NR, PR, PRs. OH, -SH, SR, SR—SO ,—OR, —C(O)R, - C(O)OR, or -SO, OR; m represents any number up to m'-1 wherein m' repre wherein: sents the number of primary hydroxyl groups in the SS represents a Solid, macro Surface comprising polymeric polyol in the unmodified state; molecules having more than one primary hydroxyl B represents an anion; group; a represents an integer, and in represents an integer from 2-8; c represents the Valence of B, and is equal to 1-3: Y represents —NR, "NR, PR —"PR, -OH, wherein a X c represents a number Such that the com SH, —SR, SR —SO —SO, OR, —OR, pound is charge balanced. —C(O)R. —C(O)OR, or a diazabicyclo[2.2.2]octane derivative selected from: c c c c c