Organosulfur compounds

Abstract

To provide organosulfur compounds of formula (I), and pharmaceutical compositions comprising these organosulfur compounds.SOLUTION: The invention provides organosulfur compounds of formula (I), where R1 and R2 are as defined herein, and pharmaceutical compositions comprising these organosulfur compounds. The organosulfur compounds and the pharmaceutical compositions are used for treating infection and / or for treating inflammation and / or for reducing the formation of blood clots.SELECTED DRAWING: None

Description

[Technical field]

[0001] Technical Field The present invention generally relates to organosulfur compounds of formula (I) and pharmaceutical compositions comprising one or more organosulfur compounds of formula (I).The present invention also relates to a method for preparing the organosulfur compounds of formula (I).The present invention further relates to various uses of the organosulfur compounds of formula (I), for example, as antibacterial agents, as anti-inflammatory agents, as antithrombotic agents, for wound treatment and / or for cystic fibrosis treatment and / or for epidermolysis bullosa treatment. [Background technology]

[0002] background Many organosulfur compounds are known to have physiological effects. For example, ajoene, an organosulfur compound found in garlic extract, is known to have antibacterial, anti-inflammatory and antithrombotic effects. Therefore, it is desirable to have new alternative or improved organosulfur compounds that may have one or more beneficial physiological effects. Summary of the Invention

[0003] Abstract According to a first aspect of the present invention there is provided a compound of formula (I):

[0004] [ka] Formula (I) (In the above formula, R 1 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl or substituted heterocyclyl, and R 2 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl or alkenyl.

[0005] The compounds of formula (I) can have an E or Z configuration. Thus, in certain embodiments, the compounds can be according to formula (IA) or formula (IB). [ka] (In the above formula, R 1 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl or substituted heterocyclyl, and R 2 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, or alkenyl.

[0006] Also provided herein are compositions comprising mixtures of E and Z stereoisomers of compounds of Formula (I).

[0007] According to a second aspect of the invention there is provided a pharmaceutical composition comprising a compound of the first aspect of the invention and a pharma- ceutically acceptable excipient and / or carrier and / or diluent.

[0008] According to a third aspect of the invention there is provided a compound or pharmaceutical composition according to any aspect of the invention (including all embodiments thereof) for use in a method of treatment for treating a microbial infection, and / or for treating inflammation, and / or for reducing blood clot formation, and / or for treating wounds, and / or for treating cystic fibrosis, and / or for treating epidermolysis bullosa.

[0009] According to a fourth aspect of the invention there is provided use of a compound or pharmaceutical composition according to any aspect of the invention (including all embodiments thereof) in the manufacture of a medicament for treating a microbial infection, and / or for treating inflammation, and / or for reducing blood clot formation, and / or for treating a wound, and / or for treating cystic fibrosis, and / or for treating epidermolysis bullosa.

[0010] According to a fifth aspect of the present invention there is provided a method of treatment for treating a microbial infection, and / or for treating inflammation, and / or for reducing blood clot formation, and / or for treating wounds, and / or for treating cystic fibrosis, and / or for treating epidermolysis bullosa, comprising administering to a subject a compound or pharmaceutical composition according to any aspect of the present invention (including all embodiments thereof).

[0011] According to a sixth aspect of the invention there is provided a non-therapeutic use of a compound or pharmaceutical composition according to any aspect of the invention (including all embodiments thereof) as an antibacterial and / or anti-inflammatory and / or anti-thrombotic agent. For example, there is provided herein an in vitro use of a compound or pharmaceutical composition according to any aspect of the invention (including all embodiments thereof) as an antibacterial and / or anti-inflammatory and / or anti-thrombotic agent.

[0012] According to a seventh aspect of the present invention, there is provided a process for producing a compound of the first aspect of the present invention, which process may, for example, proceed via the following reaction scheme:

[0013] [ka]

[0014] The details, examples and preferences provided with respect to any particular one or more of the described aspects of the invention are described further herein and apply equally to all aspects of the invention. Any combination of the embodiments, examples and preferences described herein in all possible variations thereof is encompassed by the present invention unless otherwise indicated herein or otherwise clearly contradicted by context. [Brief description of the drawings]

[0015] Brief explanation of the figure The invention may be described with reference to the following non-limiting drawings.

[0016] [Figure 1] FIG. 1 shows a plot of concentration versus % S. aureus biofilm mass for the compounds of formula (I) tested in Example 4 compared to ajoene and DMSO. [Diagram 2] FIG. 2 shows a plot of concentration versus % P. aeruginosa biofilm mass for the compounds of formula (I) tested in Example 4 compared to ajoene and DMSO. [Diagram 3] FIG. 3 shows a plot of concentration versus % P. aeruginosa biofilm mass for the compounds of formula (I) tested in Example 6 compared to ajoene, HDMF, cysteamine, gallium nitrate and C-30. [Figure 4] FIG. 4 shows a plot of concentration versus % S. aureus biofilm mass for the compounds of formula (I) tested in Example 6 compared to ajoene, HDMF, cysteamine, gallium nitrate and C-30. [Diagram 5] FIG. 5 shows a microscope image of a sample from the scratch test described in Example 7. [Figure 6] FIG. 6 shows a plot of scratch area versus time (h) for the compound of formula (I) tested in Example 7 compared to a vehicle control, sulforaphane, an EGF positive control, and a BAY 61-3606 hydrochloride hydrate negative control. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Detailed Description Compounds and Pharmaceutical Compositions The present invention is based, at least in part, on the surprising discovery that compounds of formula (I) have advantageous antibacterial and / or wound healing activity. For example, embodiments of the present invention are based on the surprising discovery that compounds of formula (I) provide improved antibacterial and / or wound healing activity compared to other organosulfur compounds.

[0018] Hereinafter, the present invention will be described according to the preferred embodiment of the present invention by referring to the accompanying description. However, it should be understood that the description is limited to the preferred embodiment of the present invention only to facilitate the discussion of the present invention, and it is considered that those skilled in the art can devise various modifications without departing from the scope of the appended claims.

[0019] Terms generally used hereinbefore and hereinafter, unless otherwise indicated, preferably have the meanings given below, the more specific meanings of which may be used independently of one another in preferred embodiments of the invention instead of the general definition, and these more specific meanings describe particularly preferred embodiments of the invention.

[0020] When the term "at least one" or "one or more" appears hereinbefore and hereinafter, this means 1 to 10, preferably 1 to 3, in particular 1 or even 2 of the listed features, e.g. components. When giving ranges, such as mass percent ranges, these are inclusive of the limits given. Thus, for example, "from X to Y" means "from X (inclusive) to Y (inclusive)."

[0021] The compounds of the present invention are according to formula (I). [ka] Formula (I) (In the above formula, R 1 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl or substituted heterocyclyl, and R 2 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, or alkenyl.

[0022] The compounds of the invention may be according to formula (IA) and / or formula (IB). [ka] (In the above formula, R 1 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl or substituted heterocyclyl, and R 2 is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, or alkenyl.

[0023] The term "phenyl" as used herein refers to a phenyl group of formula C derived from benzene by removal of a hydrogen atom. 6 H 5 It refers to a group having the formula:

[0024] The term "substituted phenyl" as used herein refers to a group derived from benzene by removal of a hydrogen atom, where one or more of the remaining hydrogen atoms on the benzene ring are replaced with a functional group. The substituted phenyl can contain, for example, one, two, three, four or five functional groups. The substituted phenyl can contain, for example, one or two functional groups. The substituted phenyl can contain, for example, only one functional group. The substitution can occur, for example, at the meta, ortho or para position of the phenyl ring.

[0025] Each functional group can be independently selected from, for example, an alkyl group, a haloalkyl group, an ester group, an alkoxy group, a halogen group, an alkylsulfone group, a haloalkoxy group, or an amine group. Thus, a substituted phenyl can be, for example, an alkylphenyl, a haloalkylphenyl, an alkylbenzoate, an alkoxyphenyl, a halophenyl, an alkylphenylsulfone, a haloalkoxyphenyl, or an aminophenyl.

[0026] The term "alkyl" as used herein refers to a group derived from a saturated straight or branched chain hydrocarbon by removal of a hydrogen atom. Alkyl can contain, for example, 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms.

[0027] The term "haloalkyl" as used herein refers to a group derived from a saturated straight or branched hydrocarbon by removal of a hydrogen atom, where one or more of the remaining hydrogen atoms of the alkyl group are replaced with a halogen. A haloalkyl can contain, for example, 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms. A haloalkyl can contain, for example, 1 to 8 halogen atoms, or 1 to 5 halogen atoms, or 1 to 4 halogen atoms, or 1 to 3 halogen atoms. The halogen atoms can each be independently selected from iodine, chlorine, bromine, and fluorine. A haloalkyl can be, for example, a halomethyl. For example, a haloalkyl can be a trihalomethyl. For example, a haloalkyl can be a trifluoromethyl. Thus, a haloalkylphenyl can be, for example, a halomethylphenyl. A haloalkylphenyl can be, for example, a trihalomethylphenyl. A haloalkylphenyl can be, for example, a trifluoromethylphenyl. A trifluoromethyl group can be, for example, at the para position of a phenyl ring.

[0028] The term "ester" as used herein refers to a group having the formula -C(=O)OR, where R is an alkyl group. The alkyl is a saturated straight or branched chain hydrocarbon. The alkyl can contain, for example, 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms. The alkyl can contain one carbon atom (a methyl group), such as, for example, an alkyl benzoate is methyl benzoate. The ester group can be, for example, in the para position of a phenyl ring.

[0029] The term "alkoxy" as used herein refers to a group having the formula -OR, where R is an alkyl group. The alkyl is a saturated straight or branched chain hydrocarbon. The alkyl can contain, for example, 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms. The alkyl can contain one carbon atom (a methyl group), such as, for example, an alkoxyphenyl being a methoxyphenyl. The alkoxy can be, for example, at the meta, ortho, or para position of the phenyl ring.

[0030] The term "haloalkoxy" as used herein refers to a group having the formula -OR, where R is an alkyl group, one or more hydrogen atoms of the alkyl group being replaced with a halogen. A haloalkoxy can, for example, contain 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms. A haloalkoxy can, for example, contain 1 to 8 halogen atoms, or 1 to 5 halogen atoms, or 1 to 4 halogen atoms, or 1 to 3 halogen atoms. The halogen atoms can each be independently selected from iodine, chlorine, bromine, and fluorine. A haloalkoxy group can, for example, be in the para position of a phenyl ring. A haloalkoxy can, for example, be a fluoroalkoxy. A haloalkoxy can, for example, be a halomethoxy. For example, a haloalkoxy can be a trihalomethoxy. For example, a haloalkoxy can be a trifluoromethoxy. Thus, a haloalkoxyphenyl can, for example, be a halomethoxyphenyl. A haloalkoxyphenyl can, for example, be a trihalomethoxyphenyl. A haloalkoxyphenyl can, for example, be a trifluoromethoxyphenyl. A trifluoromethoxy group can be, for example, at the para position of a phenyl ring.

[0031] The term "halo" or "halogen" as used herein refers to any of fluorine, chlorine, bromine, iodine and astatine. In certain embodiments, the halogen is selected from fluorine, chlorine, bromine and iodine. In certain embodiments, the halogen is selected from fluorine, chlorine and bromine. In certain embodiments, the halogen is fluorine or chlorine. In certain embodiments, the halogen is fluorine. Thus, the substituted phenyl can be a fluorophenyl. The halogen can be, for example, in the para position of the phenyl ring.

[0032] The term "alkylsulfone" as used herein refers to a group having the formula -S(O)(O)R, where R is an alkyl group. The alkyl group can contain, for example, 1 to 8 carbon atoms, or 1 to 4 carbon atoms, or 1 to 2 carbon atoms. The alkyl can contain, for example, one carbon atom (a methyl group), such that the alkylsulfone is a methylsulfone (thus, a substituted phenyl is a methylphenylsulfone). The alkylsulfone can be, for example, in the para position of the phenyl ring.

[0033] The term "amine" as used herein refers to a group having the formula -NRR', where R and R' are each independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, carbonyl (-C(O)R''), where R'' is an alkyl group, ester, or alkylsulfone. Thus, the term "aminophenyl" as used herein refers to a group derived from benzene by removal of a hydrogen atom, where one or more of the remaining hydrogen atoms on the benzene ring are replaced by an amine group, as defined herein. In certain embodiments, R and R' of an amino group are each independently selected from hydrogen and alkyl. In certain embodiments, both R and R' are alkyl groups, e.g., both R and R' can be alkyl groups containing 1 to 4 carbon atoms. In certain embodiments, both R and R' are methyl. Thus, the substituted phenyl can be dimethylaminophenyl. In certain embodiments, both R and R' can be hydrogen.

[0034] R 1 When is a substituted phenyl, the substituted phenyl can preferably be halophenyl, haloalkylphenyl, alkoxyphenyl or alkylphenylsulfone. Halophenyl can be, for example, iodophenyl, chlorophenyl, bromophenyl or fluorophenyl, preferably fluorophenyl. Haloalkylphenyl can be, for example, halomethylphenyl, for example, trihalomethylphenyl, for example, trifluoromethylphenyl. Alkoxyphenyl can be, for example, methoxyphenyl, ethoxyphenyl or propoxyphenyl, preferably methoxyphenyl. Alkylphenylsulfone can be, for example, methylphenylsulfone, ethylphenylsulfone or propylphenylsulfone, preferably methylphenylsulfone.

[0035] R 1When is a substituted phenyl, the substituted phenyl can preferably be a haloalkylphenyl. The halogen can be, for example, one or more of iodine, chlorine, bromine or fluorine. The halogen can be, for example, fluorine. When more than one halogen atom is present, all the halogen atoms can be the same. The haloalkylphenyl can be, for example, a halomethylphenyl. The halomethylphenyl can be, for example, a trihalomethylphenyl. The trihalomethylphenyl can be, for example, a trifluoromethylphenyl.

[0036] R 2 When is a substituted phenyl, the substituted phenyl can be a haloalkylphenyl, an alkyl benzoate, or an alkoxyphenyl. In the haloalkylphenyl, the halogen can be, for example, one or more of iodine, chlorine, bromine, or fluorine. When more than one halogen atom is present, all the halogen atoms can be the same. The haloalkylphenyl can be, for example, a halomethylphenyl. The halomethylphenyl can be, for example, a trihalomethylphenyl. The trihalomethylphenyl can be, for example, a trifluoromethylphenyl. The alkyl benzoate can be, for example, a methyl benzoate, an ethyl benzoate, or a propyl benzoate. The alkyl benzoate can be, for example, a methyl benzoate. The alkoxyphenyl can be, for example, a methoxyphenyl, an ethoxyphenyl, or a propoxyphenyl. The alkoxyphenyl can be, for example, a methoxyphenyl.

[0037] The term "cycloalkyl" as used herein refers to a group derived from a monocyclic saturated hydrocarbon by removal of a hydrogen atom. Cycloalkyl can contain, for example, 3 to 10 carbon atoms, or 3 to 8 carbon atoms, or 3 to 6 carbon atoms, or 3 to 5 carbon atoms, or 3 to 4 carbon atoms. Cycloalkyl can be, for example, cyclopropyl or cyclobutyl or cyclopentyl. Cycloalkyl can be, for example, cyclopropyl.

[0038] The term "substituted cycloalkyl" as used herein refers to a group derived from a monocyclic saturated hydrocarbon by removal of a hydrogen atom, where one or more of the remaining hydrogen atoms on the monocyclic saturated hydrocarbon are replaced by a functional group. The substituted cycloalkyl can include, for example, one, two, three, four or five functional groups. The substituted cycloalkyl can include, for example, one or two functional groups. The substituted cycloalkyl can include, for example, only one functional group. The substitution can be, for example, at the meta, ortho or para position of the phenyl ring. Each functional group can be independently selected from, for example, an alkyl group, a haloalkyl group, an ester group, an alkoxy group, a halogen group, an alkylsulfone group, a haloalkoxy group or an amino group, as described above.

[0039] The term "heterocyclyl" as used herein refers to a group derived from a saturated or unsaturated ring structure having atoms of at least two different elements as ring members by removing a hydrogen atom. A heterocyclyl can be, for example, a heteroaryl. A heterocyclyl can have, for example, one or more carbon atoms and one or more atoms selected from nitrogen, oxygen, and sulfur as ring members. A heterocyclyl can be, for example, an isoxazole, a furan, a pyrimidine, or a thiophene. For example, a heterocyclyl can be a furan or a thiophene.

[0040] The term "substituted heterocyclyl" as used herein refers to a group derived from a saturated or unsaturated ring structure having atoms of at least two different elements as ring members, where one or more of the remaining hydrogen atoms on the heterocyclyl are replaced by a functional group. A substituted heterocyclyl can be, for example, a substituted heteroaryl. A substituted heterocyclyl can include, for example, one, two, three, four or five functional groups. A substituted heterocyclyl can include, for example, one or two functional groups. A substituted heterocyclyl can include, for example, only one functional group. Each functional group can be, for example, an alkyl group (e.g., methyl) or an alkoxy group (e.g., methoxy). Substitution can occur, for example, on a carbon atom. A heterocyclyl can include, for example, an oxazole ring, an isoxazole ring, a furan ring, a pyrimidine ring or a thiophene ring. A substituted heterocyclyl can be, for example, a substituted furan ring or a substituted thiophene ring. Each functional group can be independently selected from, for example, an alkyl group, a haloalkyl group, an ester group, an alkoxy group, a halogen group, a sulfonyl group (eg, alkylsulfonyl), a haloalkoxy group, or an amine group.

[0041] The term "alkenyl" as used herein refers to a group derived from an unsaturated straight or branched hydrocarbon. An alkenyl group can, for example, contain 1, 2 or 3 carbon-carbon double bonds. For example, an alkenyl group can contain one carbon-carbon double bond. An alkenyl can, for example, contain 2 to 8 carbon atoms, or 2 to 4 carbon atoms, or 2 to 3 carbon atoms. An alkenyl can, for example, be ethenyl.

[0042] R 1 may be selected from, for example, phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, and substituted cycloalkyl. For example, R 1may be selected from phenyl, halophenyl, halomethylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, and substituted cycloalkyl. For example, R 1 may be selected from phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone, cycloalkyl and substituted cycloalkyl. The alkyl group of the haloalkylphenyl may, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl or cycloalkyl moiety of the substituted cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl or substituted cycloalkyl may, for example, be cyclopropyl or substituted cyclopropyl.

[0043] R 1 may be selected from, for example, phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl. For example, R 1 may be selected from phenyl, halophenyl, halomethylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl. For example, R 1may be selected from phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone, cycloalkyl, substituted cycloalkyl, heterocyclyl and substituted heterocyclyl. The alkyl group of the haloalkylphenyl may, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl or cycloalkyl moiety of the substituted cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl or substituted cycloalkyl may, for example, be cyclopropyl or substituted cyclopropyl. The heterocyclyl or heterocyclyl moiety of the substituted heterocyclyl may, for example, contain 3 to 6 carbon atoms and 1 or 2 heteroatoms (for example, oxygen or sulfur). For example, the heterocyclyl or heterocyclyl moiety of the substituted heterocyclyl may, for example, contain 4 or 5 carbon atoms and 1 heteroatom (for example, oxygen or sulfur). The heterocyclyl or substituted heterocyclyl may, for example, be furan, thiophene, substituted furan or substituted thiophene.

[0044] R 1 R may be selected, for example, from phenyl, substituted phenyl, and cycloalkyl. 1 may be selected from, for example, phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, and cycloalkyl. For example, R 1 may be selected from phenyl, halophenyl, halomethylphenyl, alkoxyphenyl, alkylphenylsulfone, and cycloalkyl. For example, R 1 may be selected from phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone and cycloalkyl. The alkyl group of the haloalkylphenyl may, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl may, for example, be cyclopropyl.

[0045] R1 R may be selected, for example, from phenyl, substituted phenyl, and cycloalkyl. 1 may be selected from, for example, phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, and heterocyclyl. For example, R 1 may be selected from phenyl, halophenyl, halomethylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, and heterocyclyl. For example, R 1 may be selected from phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone and cycloalkyl. The alkyl group of the haloalkylphenyl may, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl may, for example, be cyclopropyl. The heterocyclyl may, for example, contain 3 to 6 carbon atoms and 1 or 2 heteroatoms (for example oxygen or sulfur). The heterocyclyl may, for example, contain 4 or 5 carbon atoms and 1 heteroatom (for example oxygen or sulfur). The heterocyclyl may, for example, be furan or thiophene.

[0046] R 1 R can be, for example, phenyl, substituted phenyl, cycloalkyl, or heterocyclyl. 1 R can be, for example, phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl, or heterocyclyl. 1 can be, for example, phenyl or a substituted phenyl, such as phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, or alkylphenylsulfone. For example, R 1 can be phenyl or cycloalkyl. For example, R 1can be a substituted phenyl or cycloalkyl, such as halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl. For example, R 1 can be phenyl. For example, R 1 can be a substituted phenyl. For example, R 1 can be cycloalkyl. For example, R 1 can be a substituted cycloalkyl. For example, R 1 can be heterocyclyl. For example, R 1 can be substituted heterocyclyl. The alkyl group of the haloalkylphenyl can, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl or cycloalkyl portion of the substituted cycloalkyl can, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl or substituted cycloalkyl can, for example, be cyclopropyl or substituted cycloalkyl. The heterocyclyl or heterocyclyl portion of the substituted heterocyclyl can, for example, contain 3 to 6 carbon atoms and 1 or 2 heteroatoms (for example, oxygen or sulfur). For example, the heterocyclyl or heterocyclyl portion of the substituted heterocyclyl can, for example, contain 4 or 5 carbon atoms and 1 heteroatom (for example, oxygen or sulfur). The heterocyclyl or substituted heterocyclyl can, for example, be furan, thiophene, substituted furan or substituted thiophene.

[0047] R 2 may be selected from, for example, phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, substituted cycloalkyl, and alkenyl. For example, R 2 may be selected from phenyl, halomethylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, substituted cycloalkyl, and alkenyl. For example, R 2can be selected from phenyl, trifluoromethylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, substituted cycloalkyl and alkenyl. The alkyl groups of haloalkylphenyl, alkyl benzoate and alkoxyphenyl can, for example, each contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. The cycloalkyl can, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. The cycloalkyl can, for example, be cyclopropyl. The alkenyl can, for example, contain 2 to 4 carbon atoms and one double bond, for example 2 to 3 carbon atoms and one double bond. The alkenyl can, for example, be ethenyl. R 2 R may be selected, for example, from phenyl, substituted phenyl, cycloalkyl, and alkenyl. 2 For example, R may be selected from phenyl, substituted phenyl, cyclopropyl, and alkenyl. 2 may be selected from phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cyclopropyl, and alkenyl. For example, R 2 may be selected from phenyl, halomethylphenyl, alkyl benzoate, alkoxyphenyl, cyclopropyl, and alkenyl. For example, R 2 may be selected from phenyl, trifluoromethylphenyl, alkyl benzoate, alkoxyphenyl, cyclopropyl and alkenyl. The alkyl groups of haloalkylphenyl, alkyl benzoate and alkoxyphenyl may each, for example, contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. Cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. Cycloalkyl may, for example, be cyclopropyl. Alkenyl may, for example, contain 2 to 4 carbon atoms and one double bond, for example 2 to 3 carbon atoms and one double bond. Alkenyl may, for example, be ethenyl.

[0048] R 2R may be selected, for example, from phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, and ethenyl. 2 For example, R may be selected from phenyl, substituted phenyl, cycloalkyl, and ethenyl. 2 may be selected from phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, and ethenyl. For example, R 2 may be selected from phenyl, halomethylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, and ethenyl. For example, R 2 may be selected from phenyl, trifluoromethylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl and ethenyl. The alkyl groups of haloalkylphenyl, alkyl benzoate and alkoxyphenyl may, for example, each contain 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. Cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. Cycloalkyl may, for example, be cyclopropyl.

[0049] R 2 R may be selected, for example, from phenyl, substituted phenyl, cyclopropyl, and ethenyl. 2 R may be selected, for example, from phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, and ethenyl. 2 may be selected from, for example, phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cyclopropyl, and ethenyl. The alkyl groups of haloalkylphenyl, alkyl benzoate, and alkoxyphenyl may, for example, each contain 1 to 4 carbon atoms, for example, 1 or 2 carbon atoms. Cycloalkyl may, for example, contain 3 to 6 carbon atoms or 3 to 4 carbon atoms. Cycloalkyl may, for example, be cyclopropyl.

[0050] In certain embodiments, R 1 is phenyl, substituted phenyl or cycloalkyl; R 2is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, or alkenyl. 1 is phenyl, haloalkylphenyl or cycloalkyl; R 2 is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, haloalkylphenyl or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, or alkenyl. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, substituted phenyl, cycloalkyl or alkenyl; R 1 When R is haloalkylphenyl, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, for example, 1 or 2 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2When is haloalkylphenyl, alkyl benzoate, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, for example 1 or 2 carbon atoms.

[0051] In certain embodiments, R 1 is phenyl, substituted phenyl, cycloalkyl or heterocyclyl; R 2 is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, or alkenyl. 1 is phenyl, haloalkylphenyl, cycloalkyl or heterocyclyl; R 2 is phenyl, substituted phenyl, cycloalkyl, or alkenyl. In certain embodiments, R 1 is phenyl, haloalkylphenyl, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl, or alkenyl. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, substituted phenyl, cycloalkyl or alkenyl; R 1When R is haloalkylphenyl, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When is haloalkylphenyl, alkyl benzoate, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, for example 1 or 2 carbon atoms.

[0052] In certain embodiments, R 1 is phenyl, substituted phenyl or cycloalkyl; R 2 is phenyl, substituted phenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, such as 3 or 4 carbon atoms, for example 3 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms; 1 and / or R 2 When R is haloalkylphenyl, alkyl benzoate, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, for example 1 or 2 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms; 2 When R is alkenyl, the alkenyl contains one double bond and 2 to 6 carbon atoms, e.g., 2 or 3 carbon atoms. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone or cycloalkyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms; 2 When R is alkenyl, the alkenyl contains one double bond and 2 to 6 carbon atoms, for example 2 or 3 carbon atoms; 1 and / or R 2 When is haloalkylphenyl, alkylbenzoate, alkoxyphenyl, or alkylphenylsulfone, the haloalkyl or alkyl group contains 1 to 4 carbon atoms, for example, 1 or 2 carbon atoms.

[0053] In certain embodiments, R 1is phenyl, substituted phenyl, cycloalkyl or heterocyclyl; R 2 is phenyl, substituted phenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms, for example 3 carbon atoms, and / or 1 When R is heterocyclyl, the heterocyclyl contains 3 to 6 carbon atoms and 1 or 2 heteroatoms (e.g., oxygen or sulfur), for example 4 or 5 carbon atoms and 1 heteroatom (e.g., oxygen or sulfur), for example, the heterocyclyl is furan or thiophene. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms, and / or 1 When is heterocyclyl, the heterocyclyl contains 3 to 6 carbon atoms and 1 or 2 heteroatoms (e.g., oxygen or sulfur), for example, 4 or 5 carbon atoms and 1 heteroatom (e.g., oxygen or sulfur), for example, the heterocyclyl is furan or thiophene.

[0054] In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms;1 and / or R 2 is haloalkylphenyl, alkyl benzoate, alkoxyphenyl, or alkylphenylsulfone, the alkyl group contains 1 to 4 carbon atoms, e.g., 1 or 2 carbon atoms, and / or R 1 When is heterocyclyl, the heterocyclyl contains 3 to 6 carbon atoms and 1 or 2 heteroatoms (e.g., oxygen or sulfur), for example, 4 or 5 carbon atoms and 1 heteroatom (e.g., oxygen or sulfur), for example, the heterocyclyl is furan or thiophene.

[0055] In certain embodiments, R 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2 When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms, and / or 2 When R is alkenyl, the alkenyl contains one double bond and 2 to 6 carbon atoms, e.g., 2 or 3 carbon atoms, and / or 1 When R is heterocyclyl, the heterocyclyl contains 3 to 6 carbon atoms and 1 or 2 heteroatoms (e.g., oxygen or sulfur), for example, 4 or 5 carbon atoms and 1 heteroatom (e.g., oxygen or sulfur), for example, the heterocyclyl is furan or thiophene. 1 is phenyl, halophenyl, haloalkylphenyl, alkoxyphenyl, alkylphenylsulfone, cycloalkyl or heterocyclyl; R 2 is phenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, cycloalkyl or alkenyl; R 1 and / or R 2When R is cycloalkyl, the cycloalkyl contains 3 to 6 carbon atoms, for example 3 or 4 carbon atoms; 2 When R is alkenyl, the alkenyl contains one double bond and 2 to 6 carbon atoms, for example 2 or 3 carbon atoms; 1 and / or R 2 is haloalkylphenyl, alkyl benzoate, alkoxyphenyl, or alkylphenylsulfone, the haloalkyl or alkyl group contains 1 to 4 carbon atoms, e.g., 1 or 2 carbon atoms, and / or R 1 When is heterocyclyl, the heterocyclyl contains 3 to 6 carbon atoms and 1 or 2 heteroatoms (e.g., oxygen or sulfur), for example, 4 or 5 carbon atoms and 1 heteroatom (e.g., oxygen or sulfur), for example, the heterocyclyl is furan or thiophene.

[0056] In certain embodiments, R 1 is phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone or cyclopropyl; R 2 is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl, cyclopropyl, or ethenyl. 1 is phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl or methylphenylsulfone; R 2 is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl, or ethenyl. 1 is phenyl or trifluoromethylphenyl, R 2 is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl or ethenyl.

[0057] In certain embodiments, R 1 is phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone, cyclopropyl, furan or thiophene; R 2is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl, cyclopropyl, or ethenyl. 1 is phenyl, fluorophenyl, trifluoromethylphenyl, methoxyphenyl, methylphenylsulfone, furan or thiophene; R 2 is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl, or ethenyl. 1 is phenyl, trifluoromethylphenyl, furan or thiophene; R 2 is phenyl, trifluoromethylphenyl, methyl benzoate, methoxyphenyl or ethenyl.

[0058] The carbon-carbon double bond between the sulfone group and the disulfide group of the compound of formula (I) can have E or Z stereochemistry. Thus, formula (I) encompasses both the E and Z stereoisomers.

[0059] In certain embodiments, the process for preparing the compound of formula (I) is stereospecific, such that one stereoisomer is formed preferentially over the other, e.g., only one stereoisomer is formed. In certain embodiments, the E and / or Z stereoisomers can be separated from a mixture of E and Z isomers. Thus, in certain embodiments, the compound of formula (I) has an E configuration. In an alternative embodiment, the compound of formula (I) has a Z configuration.

[0060] In certain embodiments, the process for producing the compound of formula (I) produces a mixture of stereoisomers, e.g., about equal amounts of E and Z stereoisomers (e.g., about 10:90 to about 90:10, or about 30:70 to about 70:30, or about 40:60 to about 60:40, or about 45:55 to about 55:45, or about 50:50 E:Z). Thus, the pharmaceutical compositions described herein can include, for example, a mixture of E and Z stereoisomers of formula (I).

[0061] In certain embodiments, the compound of formula (I) is one of the following compounds: These compounds can have an E or Z configuration. Compositions and pharmaceutical compositions that include one of the following compounds can include, for example, a mixture of the E and Z stereoisomers of that compound.

[0062] [ka] 1-Methoxy-4-{[3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}benzene NMR: δ H (400 MHz, CDCl 3 ) 7.32-7.27 (2H, m), 6.93-6.88 (2H, m), Z-isomer: 6.56 (0.77H, dt, J = 9.5, 1.1 Hz), E-isomer: 6.33 (0.23H, br t, J = 14.8 Hz), 5.93-5.74 (1.23H, m), Z-isomer: 5.69 (0.77H, dt, J = 9.5, 7.7 Hz), 5.21-5.12 (2H, m), 4.13 (2H, s), E-isomer: 3.80 (s) Overlapping Z-isomer: 3.80 (s) (total 3H), Z-isomer: 3.72 (1.54H, br d, J = 8.2), E-isomer: 3.59 (0.46H, d, J = 7.6 Hz)

[0063] [ka] 1-Methanesulfonyl-4-{[3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}benzene NMR: δH (400 MHz, CDCl 3) 7.99-7.94 (2H, m), 7.63-7.58 (2H, m), Z-isomer: 6.62 (0.66H, doublet of unresolved triplets, J = 9.5 Hz), E-isomer: 6.41 (0.34H, br d, J = 14.8 Hz), E-isomer: 5.90 (0.34H, dt, J = 14.8Hz) 5.87-5.75 (1H, m) overlapping Z-isomers: 5.73 (0.66H, dt, J = 9.5, 7.8 Hz), 5.21-5.13 (2H, m), 4.26 (2H, s), Z-isomer: 3.84 (1.32H, br d, J = 8.4 Hz), E-isomer: 3.72 (0.68H, br d, J = 7.9Hz), Z-isomer: 3.38 (1.32H, br d, J = 7.4Hz) Overlapping E-isomer: 3.35 (0.68H, br d, J = 7.4 Hz), E-isomer: 3.06 (s)Overlapping Z-isomer: 3.05 (s) (all 3H)

[0064] [ka] 1-Fluoro-4-{[3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}benzene NMR: δH (400 MHz, CDCl 3) 7.40-7.33 (2H, m), 7.13-7.04 (2H, m), Z-isomers: 6.58 (0.71H, dt, J = 9.5, 1.1 Hz), E-isomers: 6.35 (0.29H, doublet of unresolved triplets, J = 14.8 Hz), E-isomers: 5.89 (dt, J = 14.8, 7.6 Hz) overlapping 5.86-7.74 (m) total (1.29H), Z-isomers: 5.70 (0.71H, dt, J = 9.5, 7.7 Hz), 5.21-5.12 (2H, m), 4.15 (2H, s), Z-isomers: 3.76 (1.42H, br d, J = 7.7 Hz), E-isomer: 3.62 (0.58H, br d, J = 7.6 Hz), 3.38-3.33 (2H, m)

[0065] [ka] {[(3-phenylmethanesulfonylprop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δ H (400 MHz, CDCl 3 ) 7.42-7.21 (10H, m) Overlapping residual CHCl 3 Signals, Z-isomer: 6.21 (0.68H, dt, J = 9.5, 1.1 Hz), E-isomer: 6.12 (0.32H, doublet of unresolved triplets, J = 14.8 Hz), E-isomer: 5.78 (0.32H, dt, J = 14.9, 7.6 Hz), Z-isomer: 5.55 (0.68H, dt, J = 9.5, 7.7 Hz), Z-isomer: 4.14 (1.36H, s), E-isomer: 4.13 (0.64H, s), Z-isomer: 3.92 (1.36H, s), E-isomer: 3.91 (0.64H, s), Z-isomer: 3.67 (1.36H, d, J = 7.8 Hz), E-isomer: 3.49 (0.64H, d, J = 7.6Hz)

[0066] [ka] 1-Methoxy-3-{[(3-phenylmethanesulfonylprop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.42-7.33 (5H, m), 7.28-7.15 (2H, m), 6.89-6.83 (2H, m), Z-isomer: 6.26 (0.7H, doublet of unresolved triplets, J = 9.5 Hz), E-isomer: 6.15 (0.3H, doublet of unresolved triplets, J=14.8 Hz), E-isomer: 5.82 (0.3H, dt, J=14.8, 7.6 Hz), Z-isomer: 5.56 (0.7H, dt, J=9.54, 7.70 Hz), Z-isomer: 4.15 (1.4H, s), E-isomer: 4.12 (0.6H, s), Z-isomer: 3.97 (1.4H, s), E-isomer: 3.95 (0.6H, s), E-isomer: 3.86 (0.9H, s), Z-isomer: 3.83 (2.1H, s), Z-isomer: 3.69 (1.4H, d, J = 8.2 Hz), E-isomer: 3.49 (0.6H, d, J = 7.6 Hz)

[0067] [ka] 1-Methoxy-3-({[-3-{[4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl]disulfanyl}methyl)benzene NMR: 1 H-nmr ​​(600Hz, CDCl 3 ): 3.77 (d, J.= 7.8 Hz, 2H, CH 2 -CH=), 3.81 (s, 3H, OCH 3 ), 3.95 (s, 2H, CH 2 -SS), 4.22(s, 2H, CH 2 SO 2), 5.60 - 5.65 (m, 1H, CH 2 -CH=), 6.31 (d, J.= 9.6 Hz, 2H, =CH-SS), 6.85 (d, J = 7.2 Hz, 1H, CH-Ar), 6.91 (d, J = 7.2 Hz, 1H, CH-Ar), 7.25 (t, J = 7.8 Hz, 2H, CH-Ar), 7.54 (d, J = 7.8 Hz, 2H, CH-Ar), 7.69 (d, J = 7.8 Hz, 2H, CH-Ar)

[0068] [ka] 1-Methoxy-2-{[(3-phenylmethanesulfonylprop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.42-7.33 (5H, m), 7.28-7.15 (2H, m), 6.89-6.83 (2H, m), Z-isomer: 6.26 (0.7H, doublet of unresolved triplets, J = 9.5 Hz), E-isomer: 6.15 (0.3H, doublet of unresolved triplets, J=14.8 Hz), E-isomer: 5.82 (0.3H, dt, J=14.8, 7.6 Hz), Z-isomer: 5.56 (0.7H, dt, J=9.54, 7.70 Hz), Z-isomer: 4.15 (1.4H, s), E-isomer: 4.12 (0.6H, s), Z-isomer: 3.97 (1.4H, s), E-isomer: 3.95 (0.6H, s), E-isomer: 3.86 (0.9H, s), Z-isomer: 3.83 (2.1H, s), Z-isomer: 3.69 (1.4H, d, J = 8.2 Hz), E-isomer: 3.49 (0.6H, d, J = 7.6 Hz)

[0069] [ka] 1-Methoxy-4-{[(3-phenylmethanesulfonylprop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.41-7.33 (5H, m), 7.24-7.16 (2H, m), 6.85-6.79 (2H, m), Z-isomer: 6.25 (0.6H, dt, J= 9.5, 1.1 Hz), E-isomer: (0.4H, doublet of non-separable triplets, J = 14.9Hz), E-isomer: 5.79 (0.4H, dt, J = 14.8, 7.7 Hz), Z-isomer: 5.58 (0.6H, dt, J = 9.5, 7.7 Hz), Z-isomer: 4.15 (1.2H, s),E-isomer: 4.13 (0.8H, s), Z-isomer: 3.89 (1.2H, s), E-isomer: 3.87 (0.8H, s), Z-isomer: 3.77 (1.8H, s), E-isomer: 3.74 (1.2H, s), Z-isomer 3.69 (1.2H, d, J = 8.2 Hz), E-isomer: 3.51 (0.8H, d, J = 7.6 Hz)

[0070] [ka] {[3-(prop-2-en-1-yldisulfanyl)prop-2-en-1-sulfonyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.40-7.38 (5H, m), Z-isomer: 6.57 (0.72H, dt, J = 9.5, 1.1 Hz), E-isomer: 6.34 (0.28H doublet of non-separated triplets, J = 14.9 Hz), E-isomer: 5.88 (0.28H, dt, J = 14.8, 7.7Hz) overlapping 5.85-5.74 (1H, m), Z-isomer: 5.70 (0.72H, dt, J = 9.5, 7.7Hz), 5.22-5.12 (2H, m), 4.19 (2H, s), E-isomer: 3.74 (1.54H, dd, J = 7.7, 0.5Hz), Z-isomer: 3.60 (0.54H, d, 7.6 Hz), 3.38-3.33 (2H, m)

[0071] [ka] 1-Methoxy-4-({[-3-{[4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl]disulfanyl}methyl)benzene NMR: 1 H-nmr ​​(600Hz, CDCl 3 ): 3.59 (d, J.= 7.8 Hz, 2H, CH 2 -SO 2 ), 3.78 (s, 3H, OCH 3 ), 3.92 (s, 2H, CH 2 -SS), 4.20 (s, 2H, CH 2 -C-Ar), 5.78-5.88 (m, 1H, CH=), 6.21 (d, J = 15 Hz, 1H, CH-SS), 6.87 (d, J= 8.4 Hz, 2H, CH-Ar), 7.26 (d, J = 8.4 Hz, 2H, CH-Ar), 7.53 (d, J = 7.8 Hz, 2H, CH-Ar), 7.70 (d, J = 7.8Hz, 2H, CH-Ar)

[0072] [ka] Methyl-4-({[-3-{[4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl]disulfanyl}methyl)benzoate NMR: δ H (400 MHz, CDCl 3 ) 7.97 (2H, AA'BB'), 7.68-7.61 (2H, m), 7.52-7.45 (2H, m), 7.39-7.32 (2H, m), 6.14 (0.16H, dt, J = 14.9, 1.1 Hz), 5.77 (0.16H, dt, J = 14.9, 7.7 Hz), 4.15 (0.32H, s), 3.93 (0.32H, s), 3.86 (0.48H, s), 3.53 (0.32H, d, J = 7.5 Hz)

[0073] [ka] 1-{[-3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}-4-(trifluoromethyl)benzene NMR: 1 H-nmr ​​(600Hz, CDCl 3 ): 3.39 (d, J.= 7.2 Hz, 2H, CH 2 -SS), 3.70 (d, J.= 7.8 Hz, 2H, CH 2 -CH=), 4.28 (s, 2H, CH 2 ), 5.22 (dd, J.= 9, 15 Hz, 2H, CH 2 =), 5.86 - 5.96 (m, 2H, -CH=), 6.42 (d, J = 15 Hz, 1H, =CHS-S), 7.57 (d, J = 7.8 Hz, 2H, CH-Ar), 7.71 (d, J = 7.8 Hz, 2H, CH-Ar)

[0074] [ka] 1-Methoxy-2-{[(3-{[4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.64 (2H, d, J = 8.1 Hz), 7.52-7.46 (2H, m), 7.29-7.15 (2H, m) overlapping CHCl3 signal, 6.89-6.83 (2H, m), Z-isomer: 6.27 (0.58H, dt, J = 8.4, 1.1 Hz), E-isomer: 6.17 (0.42H, dt, J = 14.8, 1.1 Hz), E-isomer: 5.82 (0.42H, dt, J =14.8, 7.6 Hz), Z-isomer: 5.57 (0.58H, dt, J = 9.5, 7.8 Hz), Z-isomer: 4.18 (1.16H, s), E-isomer: 4.14 (0.84H, s), Z-isomer: 3.98 (1.16H, s), E-isomer: 3.96 (0.84H, s), E-isomer: 3.86 (1.26H, s), Z-isomer: 3.83 (1.74H, s), Z-isomer: 3.74 (1.16H, dd, J = 7.8, 0.7 Hz), E-isomer: 3.53 (0.84H, d, J = 7.5 Hz)

[0075] [ka] 1-(Trifluoromethyl)-4-{[(3-{[4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl)disulfanyl]methyl}benzene NMR: δH (400 MHz,CDCl3) 7.68-7.62 (2H, m), 7.56 (2H, d, J = 8.0 Hz), 7.49 (2H, d, J = 8.1 Hz), 7.43-7.37 (2H, m), Z-isomer: 6.25 (0.72H, d, J = 9.5 Hz), E-isomer: 6.13 (0.28H, d, J = 14.9 Hz),E-isomer: 5.75 (0.28H, dt, J = 14.9, 7.5 Hz), Z-isomer: 5.58 (0.72H, dt, J = 9.5, 7.8 Hz), 4.19 (2H, s), Z-isomer: 3.96 (1.44H, s), Z-isomer: 3.92 (0.56H, s), Z-isomer: 3.70 (1.44H, d, J = 7.9 Hz), E-isomer: 3.52 (0.56H, d, J = 7.7 Hz)

[0076] [ka] {[3-(prop-2-en-1-yldisulfanyl)prop-2-en-1-sulfonyl]methyl}cyclopropane NMR: δH (400 MHz,CDCl3) Z-isomer: 6.56 (0.58H, dt, J = 9.5, 1.2 Hz), E-isomer: 6.40 (0.42H, dt, J = 14.8, 1.0 Hz), E-isomer: 5.92 (0.42H, dt, J = 14.9, 7.6 Hz), 5.87-5.75 (1H, m) Overlapping Z-isomer: 5.72 (0.58H, dt, J = 9.5, 7.8 Hz), 5.21-5.13 (2H, m), Z-isomer: 3.88 (1.16H, d, J = 7.8 Hz), E-isomer: 3.79 (0.84H, d, J = 7.6 Hz), Z-isomer: 3.37 (1.16H, d, J = 7.3), overlapping E-isomer: 3.34 (0.84H, d, J = 7.4 Hz), Z-isomer:2.87 (1.16H, d, J = 7.2 Hz) overlapping E-isomer: 2.87 (0.84H, d, J = 7.2 Hz), 1.23-1.10 (1H, m), 0.79-0.72 (2H, m), 0.43-0.35 (2H, m)

[0077] [ka] {[(3-cyclopropylmethanesulfonylprop-1-en-1-yl)disulfanyl]methyl}cyclopropane NMR: δH (400 MHz,CDCl3) Z-isomer: 6.65 (0.62H, dt, J = 9.5, 1.1 Hz), E-isomer: 6.47 (0.38H, dt, J = 14.8, 1.1 Hz), E-isomer: 5.96 (0.38H, dt, J = 14.8, 7.7 Hz), Z-isomer: 5.72 (0.62H, dt, J = 9.5, 7.8 Hz), Z-isomer: 3.88 (1.24H, d, J = 7.7 Hz), E-isomer: 3.80 (0.76H, d, J = 7.6 Hz), 2.90-2.84 (2H, overlapping doublet), Z-isomer: 2.70 (1.24H, d, J = 7.2 Hz), E-isomer: 2.67 (0.76H, d, J = 7.2 Hz), 1.23-1.00 (2H, m), 0.78-0.72 (2H, m), 0.64-0.57 (2H, m), 0.43-0.35 (2H, m), 0.30-0.24 (2H, m)

[0078] [ka] 2-{[3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}furan NMR: δ H (400 MHz, CDCl 3 ): 7.41-7.42 (1H, m), 6.55 (0.64 H, dt, J = 9.5, 1.1 Hz), 6.48 (0.64 H, dd, J = 3.3, 0.7 Hz), 6.47 (0.34 Hz, dd, J = 3.4, 0.6 Hz), 6.36-6.40 (1.34 H, m), 5.64 (0.66 H, dt, J = 9.5, 7.7 Hz), 5.08-5.16 (2 H, m), 4.23 (d, 2H, J = 7.5 Hz), 3.79 (1.28 H, d, J = 7.8 Hz), 3.64 (0.68 H, d, J = 7.8 Hz), 3.32. 3.30 (4H, pair of non-separating doublets)

[0079] [ka] 2-{[3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}thiophene NMR: δ H (400 MHz, CDCl 3 ): 7.37 (1H, dd, J = 5.2, 1.2 Hz), 7.14-7.18 (1H m), 7.05 (1H, dt, J = 5.2, 3.6 Hz), 6.58 (0.56 H, dt, J = 9.5, 1.1 Hz), 6.39 (0.34 H, dt, J = 14.8, 0.5 Hz), 5.95-5.74 (1.34 H, m), 5.68 (0.56 H, dt, J = 9.5, 7.8 Hz), 5.19 (0.68 H, dq, J = 8.9, 1.3 Hz), 5.15 (1.32 H, dt, J = 8.7, 0.9 Hz), 4.40 (2H, d, J = 5.4 Hz), 3.80 (1H, d, J = 7.8 Hz), 3.36 (1.22 H, d, J = 7.3 Hz), 3.34 (0.68 H, d, J = 7.4 Hz)

[0080] In certain embodiments, the compound of formula (I) is one of the following compounds having the E configuration (a compound according to formula (IA)). [ka] [ka]

[0081] In certain embodiments, the compound of formula (I) is one of the following compounds having a Z configuration (a compound according to formula (IB)). [ka]

[0082] In certain embodiments, the compound of formula (I) is [ka] This compound can have an E or Z configuration. A composition or pharmaceutical composition comprising this compound can, for example, contain a mixture of the E and Z stereoisomers of this compound.

[0083] Further provided herein is a pharmaceutical composition comprising a compound of formula (I) and a pharma- ceutically acceptable carrier and / or excipient and / or diluent. In the context of the present invention, the term "pharmaceutical composition" or "medicament" means a composition comprising a (pharmaceutical effective amount of) compound of formula (I), further comprising one or more pharma- ceutically acceptable carriers and / or excipients and / or diluents.

[0084] The pharmaceutical compositions may further comprise components selected from, for example, adjuvants, vehicles, preservatives, fillers, binders, disintegrating agents, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents, perfuming agents, lubricants, coating agents, encapsulating agents, aerosolizing agents, and dispersing agents, depending on the mode of administration and the nature of the dosage form.

[0085] The pharmaceutical compositions may take the form of, for example, solid preparations including tablets, capsules, caplets, dragees, troches, granules, powders, pellets, beads, dressings, bandages, patches, surgical patches, catheters, pastes and cachets, semi-solid preparations including gels, balms, creams, ointments, gums, foams, liniments, adhesives and lotions, liquid preparations including elixirs, syrups, suspensions, sprays, emulsions, lotions, soaps, shakes, collodions, paints, washes, irrigants and solutions, aerosol preparations using solutions, aqueous systems, suspensions or dispersion systems, foam systems and / or utilizing liquefied gas propellants, compressed gases, dry powders and sprays. Techniques and formulations are generally described in Remington, The Science and Practice of Pharmacy, Mack Publishing Co., Easton, PA, latest edition.

[0086] The pharmaceutical composition (medicament) can be, for example, suitable for oral, nasal, topical, suppository, intravenous or intradermal administration. Alternatively, the composition can be a nutraceutical composition, such as a food, food supplement, dietary supplement, dietary supplement, meal replacement product, beverage, beverage supplement, food additive, animal feed or feed additive.

[0087] The compounds of formula (I) can be administered, for example, in combination with one or more other biologically active agents. Thus, the pharmaceutical composition can include one or more other biologically active agents. The one or more biologically active agents may be, for example, debridement agents, soaps, antibiotics such as penicillins (e.g., penicillin, amoxicillin), cephalosporins (e.g., cephalexin), macrolides (e.g., erythromycin, clarithromycin, azithromycin), fluoroquinolones (e.g., ciprofloxacin, levoflacin, ofloxacin), sulfonamides (e.g., cotrimoxazole, trimethoprim), tetracyclines (e.g., tetracycline, doxycycline) and aminoglycosides (e.g., gentamicin, tobramycin), preservatives such as taurolidine, potassium permanganate, boric acid, surfactants (e.g., octenidine dihydrochloride, octenidine dihydrochloride / phenoxyethanol), alcohols (e.g., ethanol, isopropyl alcohol, n-propanol), anilides (e.g., triclocarban), biguanides (e.g., chlorhexidine, polyhexadine, polyhexamethylene, polyhexanide), bisphenols (e.g., diphenyl ether-triclosan, chlorinated phenols-hexachlorophene), chlorine compounds (e.g., sodium hypochlorite), halophenols (e.g., chloroxylenol), iodine compounds (e.g., Lugol's solution, tincture of iodine, iodophors including polyvinylpyrrolidone iodine, povidone iodine, cadexomer-iodine), silver compounds (e.g., silver sulfadiazine, silver nitrate, (silver released from solutions, cream ointments or nanocrystalline silver, regardless of source), peroxygen (e.g., hydrogen peroxide) and oxygen treatment (in the form of radical oxygen species and gaseous O 2(e.g., hyperbaric chambers, nitrox / natrox), anti-inflammatory drugs (e.g., non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and naproxen), anti-thrombotic drugs such as anticoagulants (e.g., heparin or warfarin), antiplatelet drugs (e.g., aspirin) and thrombolytic drugs (e.g., streptokinase), antimicrobial light sources in the ultraviolet, visible, violet, blue, green, yellow, red and infrared regions (alone or in combination), wound healing devices and photodynamic therapy source treatments, e.g., deep penetrating light therapy, low level light / laser therapy, utilizing light from light sources such as lasers, long or short range polarized and unpolarized and incoherent light sources, e.g., light emitting diodes (LEDs).

[0088] The compound of formula (I) can be administered in combination with one or more other biologically active agents used to treat, for example, cystic fibrosis.Accordingly, the pharmaceutical composition can include one or more other biologically active agents used to treat cystic fibrosis.Examples of biologically active agents used to treat cystic fibrosis include, for example, cystic fibrosis transmembrane conductance regulator (CFTR) modulators (e.g., ivacaftor, lumacaftor, tezacaftor), antibiotics, mucolytics (e.g., dolmase alpha, hypertonic sodium chloride, mannitol), immunomodulators (e.g., azithromycin), bronchodilators and steroids.

[0089] In certain embodiments, the one or more other biologically active agents are present in the composition or pharmaceutical composition in an amount ranging from about 0.00001 wt% to about 99 wt%, based on the total weight of the composition, e.g., from about 0.0001 wt% to about 80 wt%, or from about 0.001 wt% to about 50 wt%, or from about 0.1 wt% to about 15 wt%, or from about 0.5 wt% to about 10 wt%, or from about 0.5 wt% to about 5 wt%, or about 0.1 wt% to about 3 wt%, or about 0.1 wt% to about 2 wt%, or about 0.1 wt% to about 1 wt%, or about 0.001 wt% to about 5 wt%, or about 0.001 wt% to about 2 wt%, or about 0.001 wt% to about 1 wt%, or about 0.001 wt% to 0.5 wt%, or about 0.001 wt% to about 0.1 wt%, or about 0.001 wt% to about 0.01 wt%.

[0090] In solid dosage forms for oral administration, the compounds of formula (I) may be mixed with one or more pharma- ceutically acceptable carriers, such as dicalcium phosphate or macrolides, and / or any of the following: diluents, fillers or extenders, such as starch, silicon lactose, sucrose, glucose, mannitol, microcrystalline cellulose and / or silicic acid, binders, such as hydroxypropylcellulose, hypromellose, hydroxypropylmethylcellulose, carboxymethylcellulose, gelatin, polyvinylpyrrolidone, polyvinyl acetate, sucrose and and / or acacia, disintegrants such as starches, e.g. potato or tapioca starch, starch derivatives such as sodium starch glycolate, crosspolyvinylpyrrolidone, calcium carbonate, croscarmellose sodium, alginic acid and certain silicates, lubricants such as talc, calcium stearate, magnesium stearate, stearic acid, sodium sulfate, stearyl fumarate, solid polyethylene glycols, solubilizers such as sodium lauryl sulfate, ammonium dodecyl sulfate and sodium dodecyl sulfate, surfactants, For example, nonionic surfactants such as polyglycerol alkyl ethers, glucosyl dialkyl ethers, crown ethers, ester-linked surfactants such as polyoxyethylene alkyl ethers, Brij, Spans (sorbitan esters) and Tweens (polysorbates), anionic surfactants such as sulfonates, phosphates, sulfates and carboxylates, alkyl carboxylates (soaps) such as sodium stearate, dioctyl sodium sulfosuccinate, perfluorooctane sulfonate, linear alkylbenzene sulfonates (LAB) and perfluorobutane sulfonate, alkylaryl ether phosphates, sodium lauroyl sarcosinate and carboxylate-based fluorosurfactants such as perfluorononanoate and perfluorooctanoate, cationic surfactants such as benzalkonium chloride, cetylpyridinium chloride and benzethonium chloride, alkyltrimethylammonium salts such as cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC), zwitterionic surfactants such asSulfonates, sultaine CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), betaines such as cocamidopropyl betaine, flavors and colorants, and mixtures thereof.

[0091] Tablets and other solid dosage forms of pharmaceutical compositions can be optionally prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical formulation art. They can also be formulated to provide slow or controlled release of the active ingredient, for example, using natural and synthetic polymers, such as hydroxypropylmethylcellulose methacrylate, methacrylic acid copolymers (e.g., methyl methacrylate-methacrylic acid copolymer and methyl methacrylate-methacrylic acid copolymer), shellac, ethylcellulose, cellulose acetate phthalate, cellulose acetate trimellitate, polyvinyl acetate phthalate, cellulose acetate succinate, hydroxylpropylmethylcellulose acetate succinate, sodium alginate, waxes, fatty acids, zein, each in various ratios to provide the desired release profile, and other polymer matrices, liposomes and / or microspheres can also be used. These compositions can also optionally contain colorants and / or opacifiers, and can be of such a composition that they release the active ingredient only, or preferentially, in a certain part of the gastrointestinal tract, optionally with a delayed release.

[0092] The pharmaceutical composition may comprise about 50% w / w or less of a pharma- ceutically acceptable carrier and / or excipient and / or diluent, for example about 45% w / w or less of a pharma- ceutically acceptable carrier and / or excipient and / or diluent, or about 40% w / w or less of a pharma- ceutically acceptable carrier and / or excipient and / or diluent, or about 35% w / w or less of a pharma- ceutically acceptable carrier and / or excipient and / or diluent. For example, the pharmaceutical composition may comprise at least about 1% w / w, or at least about 10% w / w, or at least about 15% w / w, or at least about 20% w / w, or about 25% w / w, or at least about 30% w / w of a pharma- ceutically acceptable carrier and / or excipient and / or diluent.

[0093] Liquid form preparations include solutions, suspensions and emulsions, such as water or water-propylene glycol solutions for oral administration.Liquid preparations can also be formulated as solutions in aqueous polyethylene glycol solutions.In certain embodiments, the compound of formula (I) can be mixed with water and / or one or more pharma-ceutically acceptable carriers, such as any of the following: polyethylene glycol, solvents such as alcohol, humectants such as glycerol, sweeteners such as liquid glucose, corn syrup and sucrose, artificial sweeteners such as aspartame, stevia and sucralose, preservatives such as benzoates and parabens, viscosity adjusters / thickeners such as gums and alginates, buffers, flavors and colorants.

[0094] Also included are solid form preparations such as tablets, capsules, granules and powders, which are intended to be converted into liquid form preparations for oral administration immediately before use. Such liquid forms include solutions, suspensions and emulsions. These particular solid form preparations are most conveniently provided in unit dose form, and as such are used to provide a single liquid dosage unit. Alternatively, a spoon or other measuring device can be used to measure a predetermined volume of the solid preparation to provide enough solids to reconstitute multiple individual liquid doses when needed. Solid form preparations intended to be converted into liquid form can contain flavors, colorants, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizers, etc., in addition to the active material. The liquid utilized to prepare liquid form preparations can be water, isotonic water, juice, milk, ethanol, etc., and mixtures thereof.

[0095] The ingredients mentioned above and below are in particular selected from those listed in the appendices of pharmacopoeias, such as the United States Pharmacopoeia National Formulary, the European Pharmacopoeia, the Helvetica Pharmacopoeia, the British Pharmacopoeia, the German Pharmacopoeia, the Chinese Pharmacopoeia, the Japanese Pharmacopoeia or regulatory regulations.

[0096] Uses of compounds of formula (I) and pharmaceutical compositions The compounds and pharmaceutical compositions described herein can be used in a variety of therapeutic and non-therapeutic applications. For example, the compounds and pharmaceutical compositions described herein can be used to provide one or more beneficial effects to a patient. For example, the compounds and pharmaceutical compositions described herein can be used in a variety of cosmetic applications. For example, the compounds and pharmaceutical compositions described herein can be used in in vitro or in vivo methods. The method can include administering a compound or pharmaceutical composition described herein to a subject.

[0097] The term "therapeutic treatment" or "therapeutic method" also includes prevention and alleviation of symptoms of a disease and / or disorder in a subject, but not cosmetic treatments.

[0098] The term "treatment or prevention" and similar terms as used herein refer to any form of health care that aims to eliminate or avoid a disease and / or disorder by common medical practice, or to alleviate its symptoms, including preventive and curative care, as determined according to any of the available tests. Interventions that aim, but do not always aim, with a reasonable expectation of achieving a particular result are encompassed by the term "treatment or prevention". Interventions that are successful in slowing or halting the progression of a disease and / or disorder are encompassed by the term "treat or prevent".

[0099] In certain embodiments, the subject is a human. In other embodiments, the subject is a non-human mammal, such as a non-human primate (e.g., apes, monkeys, and lemurs), companion animals such as cats or dogs, working and sport animals such as dogs, horses and ponies, animals such as pigs, sheep, goats, deer, cows, farm animals, and laboratory animals such as rodents (rabbits, rats, mice, hamsters, gerbils, guinea pigs, etc.).

[0100] The amount of compound or pharmaceutical composition administered can vary depending on the subject or requirements of use. For both therapeutic and non-therapeutic applications, the amount of compound or pharmaceutical composition administered can vary depending on the desired results, the requirements of the subject, and the severity of the condition being treated. Determining the appropriate amount / dosage for a particular situation is within the skill of the art. For example, for therapeutic applications, a physician or veterinarian who is skilled in the art can easily determine and prescribe the effective amount of compound or pharmaceutical composition required. If necessary, the total daily amount / dosage can be divided and administered in portions throughout the day.

[0101] In general, the appropriate daily dose of the active agent (i.e., the compound of formula (I)) is the amount that is the lowest dose effective to produce the desired effect, e.g., therapeutic effect. Due to the non-toxic nature of the composition, it is considered that a wide range of doses can be used. Those skilled in the art will understand that the appropriate dose or dosage will usually vary from subject to subject and will depend on factors such as the severity of the subject's health condition at the time of starting administration. For example, the dose of the active agent in the composition can be up to 15g per day, for example up to about 10g per day, or up to about 5g per day.

[0102] In certain embodiments, the dose of the active agent ranges from 100 mg to about 3 g per day, which may be administered at appropriate intervals throughout the day, optionally as two or more subdoses administered separately in unit dosage form. In certain embodiments, the dose of the active agent in the composition can be from about 200 mg to about 3 g of compound per day, for example, from about 500 mg to about 3 g of compound per day, or from about 750 mg to about 2.5 g of compound per day, or from about 1000 mg to about 2000 mg of compound per day. In certain embodiments, the active agent may be administered two or three times per day. In certain embodiments, each dose of the active agent is about 5 g or less, for example, about 3 g or less, for example, about 2.5 g or less. Each dose of the active agent may be combined with other conventional agents for the desired effect. When the composition is for topical administration, the concentration of the compound is about 100 mg to about 3 g per cm of skin. 2 Approximately 0.01g to 0.5g per cm of skin 2 The amount can be about 0.1 g to about 0.4 g, or about 0.2 g to about 0.3 g per serving.

[0103] The compounds and pharmaceutical compositions described herein can be used, for example, to treat microbial infections, and / or to treat inflammation, and / or to reduce the formation of blood clots, and / or to treat wounds, and / or to treat cystic fibrosis, and / or to treat epidermolysis bullosa. The compounds and pharmaceutical compositions described herein can be used to treat wounds in subjects with epidermolysis bullosa. These uses can be, for example, therapeutic or non-therapeutic.

[0104] The compounds and pharmaceutical compositions described herein can be used as antibacterial agents. As used herein, the term "antibacterial agent" means that the compounds and pharmaceutical compositions described herein can be used to kill microorganisms, inhibit bacterial motility, such as swarming, swimming or convulsions, and / or inhibit the proliferation of microorganisms, and / or reduce the growth of microorganisms.

[0105] The compounds and pharmaceutical compositions described herein can be used to inhibit and / or eradicate bacterial biofilm formation, for example, by inhibiting bacterial signaling, such as quorum sensing, inhibiting bacterial biofilm formation or dispersal, inhibiting or stimulating global regulatory systems (e.g., those that depend on intracellular levels of cyclic dimeric guanosine monophosphate), and inhibiting the formation of functional bacterial cell surface and excretory proteins.

[0106] In certain embodiments, the microorganism may be selected from bacteria, fungi and protozoa. The bacterial strain may be selected from, for example, gram-positive bacteria, gram-negative bacteria and atypical bacteria. The gram-positive bacteria may be selected from, for example, one or more of Clostridium perfringens, Listeria monocytogenes, Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus hemolyticus, Clostridium spp. and Peptostreptococcus spp. Gram-negative bacteria may be selected from, for example, Salmonella typhimurium, Vibrio parahaemolyticus, Enterobacteriaceae, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter, Proteus, Citrobacter, Morganella, Pseudomonas aeruginosa, Acinetobacter baumannii, Campylobacter jejuni, Bacteroides, Prevotella, Helicobacter pylori, and Porphyromonas. Atypical bacteria may be selected from, for example, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, and Mycobacteria. Fungal strains may be selected from, for example, Candida albicans, Candida glabrata, and Aspergillus fumigatus.

[0107] The bacterial strain can be a biofilm-forming bacterium and / or a bacterium capable of forming a biofilm. Biofilm-forming bacteria and / or bacteria capable of forming a biofilm include, for example, Bacillus spp., Listeria monocytogenes, Staphylococcus aureus, Lactobacillus plantarum, Lactococcus lactis, Vibrio fischeri, Aeromonas hydrophila, Aeromonas salmonicida, Agrobacterium tumefaciens, Burkholderia cepacia, Chromobacterium violaceum, Enterobacter agglomerans, Bacillus subtilis ... Stewartii), Escherichia coli, Helicobacter pylori, Pseudomonas aureofaciens, Pseudomonas aeruginosa, Ralstonia solanacearum, Rhizobium etiol, Rhizobium leguminosarum, Rhodobacter sphaeroides, Salmonella typhimurium, Serratia liquefaciens, Sinorhizobium meliloti, Vibrio anguillarum, Vibrio harveyi, Yersinia enterocolitica, and Mycobacterium pseudotuberculosis.

[0108] For example, the compounds and pharmaceutical compositions described herein can be administered to a subject to treat and / or prevent a microbial infection in the subject. For example, the compounds and pharmaceutical compositions described herein can be used to promote healing of damaged wounds on the skin. For example, the compounds and pharmaceutical compositions described herein can be used to prevent a microbial infection in damaged skin. For example, the compounds and pharmaceutical compositions described herein can be used to treat or prevent a microbial infection in the digestive system. For example, the compounds and pharmaceutical compositions described herein can be used to treat or prevent a microbial infection in the nasal or ear cavity of a subject. For example, the compounds and pharmaceutical compositions described herein can be used to treat or prevent a microbial infection in the respiratory tract of a subject. For example, the compounds and pharmaceutical compositions described herein can be used to treat or prevent a microbial infection in the respiratory tract of a cystic fibrosis patient. For example, the compounds and pharmaceutical compositions described herein can be used as a urinary tract rinse or bladder rinse, for example, for urinary implants, indwelling urinary catheters, and kidney dialysis patients.

[0109] Thus, provided herein is a therapeutic use of a compound or pharmaceutical composition described herein as an antibacterial agent. Also provided herein is a compound or pharmaceutical composition described herein for use as an antibacterial agent. Further provided herein is a use of a composition or pharmaceutical composition described herein in the manufacture of an antibacterial medicament. Further provided herein is a therapeutic method for treating and / or preventing a microbial infection in a subject, the method comprising administering to the subject a compound or pharmaceutical composition described herein.

[0110] In certain embodiments, the compounds and pharmaceutical compositions disclosed herein are used for non-therapeutic purposes.

[0111] For example, the compounds described herein can be used as antibacterial agents (e.g., disinfectants) on non-living surfaces. For example, the compounds and pharmaceutical compositions disclosed herein can be used in cosmetic applications, e.g., as antibacterial agents on biological surfaces (e.g., skin). For example, the compounds and pharmaceutical compositions disclosed herein can be used as antibacterial agents in cosmetic skin care compositions or make-up compositions.

[0112] For example, the compounds described herein may be used as antimicrobial agents on industrial abiotic surfaces, for example to remove or prevent biofilm formation in pipes used in the water or oil industries, as cleaning agents for water tanks (e.g., in the fishing industry), as anti-fowling agents in industrial processes (e.g., the aquaculture, fishing industry).

[0113] For example, the compounds described herein can be used as food and / or water additives for protection and / or prevention of disease transmission. For example, the compounds described herein can be used to wash plants, fresh fruits and vegetables. The compounds described herein can reduce surface bacteria, extend shelf life, and / or protect surfaces from pest infestation on live crops or produce.

[0114] For example, the compounds described herein can be used as antimicrobial agents in medical devices or compositions, such as cements for bone or dental implants, implants, wound dressings, stitches or threads.

[0115] For example, the compounds described herein can be used as antimicrobial agents on biological surfaces. For example, the compounds described herein can be applied to the skin to kill or inhibit the growth of microorganisms for hygiene reasons (e.g., to prevent the spread of disease). For example, the compounds described herein can be applied to hands as hand sanitizers. For example, the compounds described herein can be used as mouthwashes, for example, to treat or prevent bad breath. For example, the compounds described herein can be used as dental care products, for example, to treat or prevent cavities and disease.

[0116] For example, the compounds described herein can be used for agricultural applications.For example, the compounds described herein can be used to treat or prevent infection of micro-wounds in plants, or to reduce surface pathogens on plants.For example, the compounds described herein can be used as biosecurity disinfectants, for example, for animal farm facilities.For example, the compounds described herein can be used to sterilize animal feed.

[0117] The compounds and pharmaceutical compositions described herein can be used as anti-inflammatory agents. As used herein, the term "anti-inflammatory" means that the compounds and pharmaceutical compositions described herein can be used to reduce inflammation or swelling.

[0118] For example, the compounds and pharmaceutical compositions described herein can be administered to a subject to treat and / or prevent inflammation in the subject. Thus, provided herein is a therapeutic use of a compound or pharmaceutical composition described herein as an anti-inflammatory agent. Also provided herein is a compound or pharmaceutical composition described herein for use as an anti-inflammatory agent. Further provided herein is a use of a composition or pharmaceutical composition described herein in the manufacture of an anti-inflammatory medicament. Further provided herein is a therapeutic method for treating and / or preventing inflammation in a subject, the method comprising administering a compound or pharmaceutical composition described herein to a subject.

[0119] Therefore, the compounds and pharmaceutical compositions described herein can be used to treat or prevent inflammatory diseases or disorders.Examples of inflammatory diseases or disorders include, for example, allergies, cancer, atherosclerosis, ischemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, abdominal diseases, chronic prostatitis, colitis, diverticulitis, glomerulonephritis, hidradenitis suppurativa, hypersensitivity, inflammatory bowel disease, interstitial cystitis, lichen planus, mast cell activation syndrome, mastocytosis, otitis, pelvic inflammatory disease, reperfusion injury, rheumatic fever, rheumatoid arthritis, rhinitis, sarcoidosis, transplant rejection and vasculitis.

[0120] Treatment of inflammation can be determined by measuring the expression levels of one or more inflammatory markers, such as, for example, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). A decrease in CRP and ESR expression indicates a decrease in inflammation.

[0121] The compounds and pharmaceutical compositions described herein can be used as antithrombotic agents.As used herein, the term "antithrombotic" means that the compositions and pharmaceutical compositions described herein can be used to reduce the formation of blood clots, for example, by inhibiting platelet aggregation.Thus, antithrombotic agents can be used to increase the blood flow of a subject.

[0122] For example, the compounds and pharmaceutical compositions described herein can be administered to a subject to reduce the formation of blood clots in the subject. Thus, provided herein is a therapeutic use of the compounds or pharmaceutical compositions described herein as antithrombotic agents. Also provided herein is a compound or pharmaceutical composition described herein for use as an antithrombotic agent. Further provided herein is a use of the compositions or pharmaceutical compositions described herein in the manufacture of antithrombotic agents. Further provided herein is a therapeutic method for reducing the formation of blood clots in a subject, the method comprising administering to a subject a compound or pharmaceutical composition described herein.

[0123] Thus, the compounds and pharmaceutical compositions disclosed herein can be used to treat or prevent disorders associated with blood flow in a subject. The compounds and pharmaceutical compositions disclosed herein can be used to improve (e.g., increase) blood flow in a subject, for example, a subject having a blood flow level outside of what is considered to be a normal or healthy range. For example, the compounds and pharmaceutical compositions disclosed herein can be used to treat or prevent any disease or disorder associated with blood flow (e.g., circulatory system) in a subject. For example, a subject may be susceptible to developing one or more diseases or disorders associated with blood flow.

[0124] Diseases and disorders associated with blood flow and / or platelet aggregation include, for example, cardiovascular diseases, cerebrovascular or brain diseases, immune diseases, bone, joint and / or muscle diseases, and fatigue diseases.

[0125] Cardiovascular diseases and disorders include, for example, coronary artery disease, coronary heart disease, angina, myocardial infarction, hypertensive heart disease, heart failure, pulmonary heart disease, cardiac arrhythmias, inflammatory heart disease, rheumatic heart disease, cardiomyopathy, atrial myopathy, congenital heart disease, endocarditis, inflammatory cardiac hypertrophy, myocarditis, valvular heart disease, aortic aneurysm, venous thrombosis, rheumatic vasculitis, atherosclerosis, peripheral arterial disease, and renal artery stenosis.

[0126] Cerebrovascular and brain diseases include, for example, stroke (eg, mini-stroke, hemorrhagic stroke, ischemic stroke), transient ischemic attack (TIA), subarachnoid hemorrhage, and vascular dementia.

[0127] Immune diseases and disorders include, for example, any disease in which a subject's immune response is lower than that of a normal healthy individual, such as immunodeficiency diseases (e.g., primary, secondary, humoral, T cell, neutropenia, asplenia, and complement deficiencies), hypoimmune responses in subjects with compromised immune systems (e.g., subjects undergoing chemotherapy and / or radiation therapy, subjects infected with HIV, subjects lacking one or more organs associated with immune function, such as the spleen, tonsils, lymph nodes, etc.). For example, immune diseases include ataxia-telangiectasia, Chediak-Higashi syndrome, combined immunodeficiency, complement deficiency, DiGeorge syndrome, hypogammaglobulinemia, Job syndrome, leukocyte adhesion disorder, panhypogammaglobulinemia, Bruton's disease, congenital agammaglobulinemia, selective deficiency of IgA, Wiskott-Aldrich syndrome, and severe combined immunodeficiency (SCID). For example, infections or conditions related to immune health include upper and lower respiratory tract infections, hay fever, sinusitis, and sore throat.

[0128] Joint diseases and disorders include, for example, any disease related to joint, mobility, muscle and bone health, such as arthritis (e.g., osteoarthritis, rheumatoid arthritis, psoriatic arthritis, septic arthritis), bursitis, osteonecrosis, dislocations, Perthes' disease and Paget's disease of bone.

[0129] Fatigue diseases and disorders include, for example, simple fatigue and / or any disease in which fatigue is a symptom, such as chronic fatigue syndrome, anemia, depression, iron deficiency (without anemia), sleep disorders, hypothyroidism, hyperthyroidism, Addison's disease, anorexia nervosa or other eating disorders, autoimmune diseases such as lupus, diabetes, fibromyalgia, kidney disease, liver disease, and malnutrition.

[0130] In certain embodiments, the compounds or pharmaceutical compositions described herein may be used to maintain and / or improve the overall health of the cardiovascular system, for example, to treat or reduce or prevent the onset of one or more cardiovascular related diseases or disorders, and / or to provide a beneficial effect on the metabolic system via maintaining or improving healthy blood flow.

[0131] The compounds and pharmaceutical compositions described herein can be used in a variety of non-therapeutic applications.

[0132] For example, the compounds and pharmaceutical compositions can be used in methods to maintain blood flow in a subject. For example, if a subject is healthy or has normal blood flow levels, and may not be at particular risk of developing, for example, a disease associated with blood flow, the subject can consume a composition disclosed herein to maintain normal blood flow levels. For example, if a subject is healthy and may not be at particular risk of developing, for example, a disease associated with blood flow and / or platelet aggregation, the subject can consume a composition disclosed herein as part of a healthy lifestyle.

[0133] The antithrombotic activity of a compound can be measured by determining the extent of platelet aggregation, for example, using an optical aggregometer.

[0134] The compounds and pharmaceutical compositions described herein can be used as agents to promote wound healing (eg, to cause or accelerate the healing of wounds).

[0135] For example, the compounds and pharmaceutical compositions described herein can be administered to a subject as a wound healing agent. Thus, provided herein is a therapeutic use of the compounds or pharmaceutical compositions described herein for treating a wound. Also provided herein is a compound or pharmaceutical composition described herein for use as a wound healing agent. Further provided herein is a use of the compositions or pharmaceutical compositions described herein in the manufacture of a wound healing agent. Further provided herein is a therapeutic method for healing a wound in a subject, comprising administering to a subject a compound or pharmaceutical composition described herein.

[0136] Thus, the compounds and pharmaceutical compositions disclosed herein can be used to treat or prevent wound-related disorders in a subject. The compounds and pharmaceutical compositions disclosed herein can be used to improve (e.g., enhance) wound healing in a subject, for example, a subject that has an increased number and / or severity of wounds compared to a healthy individual, or a subject that has delayed, incomplete, or atypical wound healing compared to a healthy individual. For example, the compounds and pharmaceutical compositions disclosed herein can be used to treat or prevent any disease or disorder associated with wound healing in a subject. For example, the compounds and pharmaceutical compositions disclosed herein can be used to treat or prevent wounds in a subject that has a disease or disorder that results in delayed, incomplete, or atypical wound healing in the subject. For example, the subject may be susceptible to developing one or more diseases or disorders associated with wound healing.

[0137] Diseases and disorders related to wound healing or that result in delayed, incomplete or atypical wound healing in a subject include, for example, epidermolysis bullosa, diabetes (type 1 or type 2), anemia, circulatory disorders, Ehlers-Danlos syndrome (EDS), eczema and skin ulcers.

[0138] The compounds and pharmaceutical compositions described herein can be used as anti-cancer agents. Thus, the compounds and pharmaceutical compositions described herein can be used to treat or prevent cancer.

[0139] Process for preparing compounds of formula (I) The compounds of formula (I) and pharmaceutical compositions comprising compounds of formula (I) may be prepared by any suitable method.

[0140] In certain embodiments, the pharmaceutical composition is prepared by combining the compound of formula (I) with a pharma- ceutically acceptable carrier and / or excipient and / or diluent. The components are combined in appropriate amounts to obtain a composition having the desired amount and concentration of each component. Each component can be combined with one or more other components in any order and combination suitable to obtain the desired product. For example, each component can be combined by mixing. Such methods are well known in the art, for example, methods known in the pharmaceutical industry. The pharmaceutical composition can be prepared in a dry solid form, for example, in powder form, and can be subjected to further processing steps depending on the type of formulation for the intended final product. This method involves molding, pressing, spray drying, or otherwise processing the mixture into a shape (e.g., bar, ball, pellet, cluster, tablet), preferably a shape having a size and / or texture suitable for consumption by humans or other mammals of the type described herein.

[0141] In certain embodiments, a process for producing a compound of formula (I) may proceed via the following reaction scheme. [ka]

[0142] In certain embodiments, step 1 [ka] With a compound containing propargyl. For example, step 1 can be [ka] With a propargyl halide. For example, step 1 can be [ka] with propargyl bromide.

[0143] The reaction of step 1 can occur in the presence of a hydroxide and an alcohol. The hydroxide can be, for example, potassium hydroxide. The alcohol can be, for example, an organic alcohol such as methanol.

[0144] Step 1 can, for example, include bubbling nitrogen through the reaction mixture. The reaction mixture of step 1 can, for example, have a temperature of about 20° C. or less, e.g., about 10° C. or less, e.g., about 5° C.

[0145] The reaction of step 1 can, for example, form a precipitated product. The reaction mixture can, for example, be allowed to warm to room temperature before the product is purified.

[0146] Purification of the product of step 1 can include, for example, removing the solvent in a vacuum. The residue can then be partitioned between water and an organic compound, such as tert-butyl methyl ether. The aqueous layer can be extracted a second time with more organic compound, such as tert-butyl methyl ether. The organic layer can then be washed with water and brine (e.g., sodium chloride), dried (e.g., with sodium sulfate), filtered, and then concentrated (e.g., under reduced pressure).

[0147] In certain embodiments, step 2 comprises [ka] with thioacetic acid, which may be in an organic solvent, such as, for example, toluene.

[0148] The product of step 1 may be in an organic solvent, such as toluene, which may be degassed, for example, with nitrogen. 2,2'-azobis(2-methylpropionitrile) or 1,1'-azobis(cyanocyclohexane) (ACHN) may be used as the radical initiator for step 2.

[0149] The reaction mixture in step 2 can have a temperature of, for example, about 50° C. or higher, or about 60° C. or higher. For example, the reaction mixture in step 2 can have a temperature in the range of about 50° C. to about 100° C., for example, about 60° C. to about 90° C., for example, about 70° C. to about 80° C.

[0150] After the step 2 product is produced, the reaction mixture can be cooled to room temperature before the product is purified.

[0151] Purification of the product of step 2 can include, for example, removing the solvent in vacuo. The crude residue can be purified (e.g., purified twice) by silica gel flash column chromatography using, for example, heptane:ethyl acetate 10% as the solvent system.

[0152] In certain embodiments, step 3 [ka] R 2 -Tosylate or R 2 -mesylate. 2 The -tosylate can be present in an organic solvent such as, for example, methanol and / or tetrahydrofuran.

[0153] The product of step 2 can be in an organic solvent, such as, for example, methanol. The reaction of step 1 can occur in the presence of a hydroxide and an alcohol. The hydroxide can be, for example, potassium hydroxide. The alcohol can be, for example, an organic alcohol, such as methanol.

[0154] The temperature of the reaction mixture in step 3 can be, for example, about 0°C or lower, for example, about -10°C or lower, or about -20°C or lower, or about -30°C or lower, or about -40°C or lower, for example, in the range of about -80°C to about -20°C, about -60°C to about -30°C, or about -50°C to about -30°C.

[0155] After the product of step 3 is prepared, the reaction mixture can be allowed to warm to room temperature before the product is purified.

[0156] Purification of the product of step 2 can include, for example, adding an aqueous solution of ammonium chloride to the reaction mixture. The product of step 3 can then be extracted using an organic solvent such as ethyl acetate. The organic layer can then be washed with water and brine (e.g., sodium chloride), dried (e.g., with sodium sulfate), filtered, and then concentrated (e.g., under reduced pressure). The product can then be purified by, for example, silica gel flash column chromatography using 2-3% heptane:ethyl acetate as the solvent system.

[0157] In certain embodiments, step 4 comprises [ka] with 3-chloroperbenzoic acid or other oxidizing agent.

[0158] The product of step 3 can be in an organic solvent such as, for example, dichloromethane.

[0159] The temperature of the reaction mixture in step 4 can be, for example, about -20°C or lower, for example, about -30°C or lower, for example, about -40°C or lower, for example, about -50°C or lower. For example, the temperature of the reaction mixture in step 4 can be about -80°C to about -20°C, or about -70°C to about -40°C, or about -70°C to about -50°C.

[0160] The reaction mixture can be allowed to warm to, for example, room temperature before the product is purified.

[0161] Purification of the product of step 4 can include, for example, partitioning the reaction mixture between a half-saturated aqueous solution of a weak base, such as sodium bicarbonate, and dichloromethane. The aqueous layer can be further extracted using an organic solvent, such as dichloromethane. The organic layer can then be dried (e.g., over magnesium sulfate), filtered, and concentrated (e.g., in vacuo). The product can then be purified by, for example, silica gel flash column chromatography using dichloromethane:ethyl acetate 0-5% as the solvent system.

[0162] In certain embodiments, step 5 comprises: [ka] with a permanganate, such as potassium permanganate, or other oxidizing agent. The permanganate may be in an organic solvent, such as, for example, acetone.

[0163] The reaction mixture can include an organic solvent, such as, for example, acetone. The reaction mixture can include a drying agent, such as, for example, magnesium sulfate.

[0164] The temperature of the reaction mixture in step 5 can be, for example, about 0°C or lower, for example, about -10°C or lower, or about -20°C or lower, or about -30°C or lower, or about -40°C or lower, and can be, for example, in the range of about -80°C to about -20°C, or about -60°C to about -30°C, or about -50°C to about -30°C.

[0165] The reaction mixture can be, for example, filtered (e.g., through a pad of Celite) and washed with an organic solvent (e.g., acetone). The filtrate can be concentrated under reduced pressure. The product can be purified, for example, via silica gel flash column chromatography using, for example, hexane:ethyl acetate 10-30% as a solvent system. EXAMPLES

[0166] Working Example Example 1 - Method for the preparation of 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane

[0167] [ka]

[0168] Step 1 - Preparation of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane A solution of potassium hydroxide (7.02 g, 125.00 mmol) in methanol (240 mL) was stirred in a three-necked round-bottom flask with bubbling nitrogen for 20 minutes and the solution was cooled to 5° C. in an ice-salt bath. (4-(trifluoromethyl)phenyl)methanethiol (20.02 g, 104.30 mmol) was then added dropwise over 15 minutes using a pressure equalizing dropping funnel and the resulting reaction mixture was stirred for an additional 20 minutes. Propargyl bromide (17.4 mL, 156.00 mmol) was then added dropwise via syringe to the mixture over 20 minutes and a precipitate was observed. The reaction mixture was allowed to warm to room temperature and stirred for an additional 2 hours.

[0169] The solvent was removed under reduced pressure and the residue was partitioned between water (300 mL) and tert-butyl methyl ether (200 mL). The aqueous layer was further extracted again with tert-butyl methyl ether (2x200 mL). The organic layers were combined, washed with water (2x200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the desired product prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane as a pale yellow oil (23.09 g, 96% yield).

[0170] Step 2 - Preparation of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate A solution of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane (23.09 g, 100.40 mmol) in toluene (400 mL) was degassed with nitrogen for 20 min. 2,2'-azobis(2-methylpropionitrile) (824 mg, 5.02 mmol) was added to the previous solution and degassing was continued while heating the reaction mixture to 75 °C (internal temperature). Then, a solution of thioacetic acid (7.6 mL, 105.70 mmol) in toluene (100 mL) was added dropwise to the reaction mixture over a period of 2 h. The mixture was stirred under these conditions for 18 h.

[0171] The reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The crude residue was purified twice by silica gel flash column chromatography using heptane:ethyl acetate 10% as the solvent system to give the desired product S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (6.4 g).

[0172] Step 3 - Preparation of 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane A solution of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (3.16 g, 10.33 mmol) in methanol (60 mL) was cooled to −30° C. under nitrogen in an acetonitrile / dry ice bath. A solution of 1 M potassium hydroxide in methanol (12.4 mL, 12.40 mmol) was added dropwise to the previous solution over 15 min. The reaction mixture was stirred for 30 min. The mixture was then further cooled to −65° C. and it was stirred for 15 min, followed by the dropwise addition of a solution of S-allyl tosylate (2.83 g, 12.4 mmol) in methanol (40 mL) over 30 min. The mixture was stirred for an additional 1.5 h. LCMS analysis indicated the reaction was complete.

[0173] A saturated aqueous solution of ammonium chloride (10 mL) was added dropwise to the reaction mixture and allowed to warm to room temperature. The mixture was poured into a saturated aqueous solution of ammonium chloride (400 mL) and extracted with ethyl acetate (3x200 mL). The organic layers were combined, washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel using heptane:ethyl acetate 2-5% as the solvent system to give the desired product 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (3.1 g).

[0174] Step 4 - Preparation of 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane 3-Chloroperbenzoic acid (77%) (2.17 g, 9.67 mmol) was added in four portions to a stirred solution of 1-allyl-2-(3-(((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (3.10 g, 9.21 mmol) in dichloromethane (75 mL) at −78° C. The reaction mixture was allowed to warm slowly to −20° C. over 1.5 h and stirred at this temperature for 1 h and at room temperature for an additional 1 h. LCMS analysis indicated the reaction had reached completion.

[0175] The reaction mixture was quenched with a saturated aqueous solution of sodium bicarbonate (50 mL) and extracted with dichloromethane (3x100 mL). The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by silica gel flash column chromatography using heptane:dichloromethane 50% and heptane:ethyl acetate 5% as the solvent system to give the desired product 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane (2.67 g).

[0176] Step 5 - Preparation of 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane 1-Allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane (2.65 g, 7.52 mmol) was dissolved in acetone (75 mL) at room temperature in a three-necked round-bottom flask equipped with a thermometer and a nitrogen inlet. Magnesium sulfate (9.96 g, 8.27 mmol) was added to the above solution, which was cooled to -40°C. A solution of potassium permanganate (2.67 g, 16.92 mmol) in acetone (100 mL) was added dropwise over 50 min, maintaining the temperature at -30°C. Additional acetone (25 mL) was used to wash in undissolved potassium permanganate. The reaction mixture was stirred at -25°C overnight.

[0177] LCMS analysis indicated the reaction was complete. The reaction mixture was allowed to warm to room temperature and filtered through a pad of Celite, which was washed several times with acetone. The filtrate was concentrated under reduced pressure to provide 1.9 g of crude material. Due to slightly low recovery, the Celite pad was further washed multiple times with acetone and dichloromethane, but this did not yield any significant amount of product. The previously isolated crude material was purified by silica gel flash column chromatography using hexane:ethyl acetate 20% as the solvent system to give the desired product, 1-allyl-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane, as a white solid in a (66:34) (Z:E) ratio (1.50 g).

[0178] Example 2 - Method for the preparation of 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane

[0179] [ka]

[0180] Step 1 - Preparation of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane A solution of potassium hydroxide (7.02 g, 125.00 mmol) in methanol (240 mL) was stirred in a three-necked round-bottom flask with bubbling nitrogen for 20 minutes and the solution was cooled to 5° C. in an ice / salt bath. (4-(trifluoromethyl)phenyl)methanethiol (20.02 g, 104.30 mmol) was then added dropwise over 15 minutes using a pressure equalizing dropping funnel and the resulting reaction mixture was stirred for an additional 20 minutes. Propargyl bromide (17.4 mL, 156.00 mmol) was then added dropwise via syringe to the mixture over 20 minutes and a precipitate was observed. The reaction mixture was allowed to warm to room temperature and stirred for an additional 2 hours.

[0181] The solvent was removed under reduced pressure and the residue was partitioned between water (300 mL) and tert-butyl methyl ether (200 mL). The aqueous layer was further extracted again with tert-butyl methyl ether (2x200 mL). The organic layers were combined, washed with water (2x200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the desired product prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane as a pale yellow oil (23.09 g, 96% yield).

[0182] Step 2 - Preparation of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate A solution of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane (23.09 g, 100.40 mmol) in toluene (400 mL) was degassed with nitrogen for 20 minutes, 2,2'-azobis(2-methylpropionitrile) (824 mg, 5.02 mmol) was added to the previous solution, and degassing was continued while the reaction mixture was heated to 75° C. (internal temperature). A solution of thioacetic acid (7.6 mL, 105.70 mmol) in toluene (100 mL) was then added dropwise to the reaction mixture over a period of 2 hours. The mixture was stirred under these conditions for 18 hours.

[0183] The reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The crude residue was purified twice by silica gel flash column chromatography using heptane:ethyl acetate 10% as the solvent system to provide the desired product S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (6.4 g).

[0184] Step 3-Preparation of 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane A solution of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (3.06 g, 10.00 mmol) in methanol (100 mL) was cooled to −44° C. under nitrogen in an acetonitrile / dry ice bath. A 1 M solution of potassium hydroxide in methanol (12 mL, 12.00 mmol) was added dropwise to the previous solution while maintaining the internal temperature at −37° C. The reaction mixture was stirred for 30 minutes. The mixture was then further cooled to −70° C. in an acetone / dry ice bath. A solution of S-(4-methoxybenzyl) 4-methylbenzenesulfonothioate (4.63 g, 15.00 mmol) in tetrahydrofuran (100 mL) was added dropwise using a dropping funnel while keeping the temperature below −65° C. The mixture was stirred at that temperature for an additional 2 hours and at room temperature for an additional 2 hours.

[0185] The reaction mixture was partitioned between tert-butyl methyl ether (500 mL) and a half-saturated aqueous solution of ammonium chloride (500 mL). The aqueous layer was further extracted with tert-butyl methyl ether (2x200 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on silica gel using hexane:ethyl acetate 2% as the solvent system to give the desired product 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (4.02 g).

[0186] Step 4 - Preparation of 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane 3-Chloroperbenzoic acid (77%) (2.67 g, 11.50 mmol) was added in portions to a stirred solution of 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (4.02 g, 9.60 mmol) in dichloromethane (60 mL) at -70° C. The temperature rose by 5° C. The reaction mixture was allowed to warm slowly to room temperature overnight.

[0187] The reaction mixture was partitioned between dichloromethane (50 mL) and a half-saturated aqueous solution of sodium bicarbonate (100 mL). The aqueous layer was further extracted with dichloromethane (2x50 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel flash column chromatography using dichloromethane:ethyl acetate 3-5% as the solvent system to provide the desired product, 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane (4.05 g).

[0188] Step 5 - Preparation of 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane 1-(4-Methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane (4.05 g, 9.36 mmol) was dissolved in acetone (35 mL) at room temperature in a three-necked round-bottom flask equipped with a thermometer and a nitrogen inlet. Magnesium sulfate (12.61 g, 105.00 mmol) was added to the previous solution and cooled to -35°C. A solution of potassium permanganate (3.35 g, 21.20 mmol) in acetone (350 mL) was added dropwise over 40 min via dropping funnel, keeping the internal temperature below -25°C. The reaction mixture was stirred at -24°C overnight.

[0189] The reaction mixture was allowed to warm to room temperature and was filtered through a pad of Celite, which was washed several times with acetone (500 mL). The filtrate was concentrated under reduced pressure. The crude material was purified by silica gel flash column chromatography (using a 120 g cartridge) using toluene (40 mL) and a small amount of dichloromethane to load the material onto the column and hexane:ethyl acetate 10-20% as the solvent to provide the desired product, 1-(4-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane, as a colorless solid (3:1) (Z:E) ratio (1.70 g).

[0190] Example 3 - Method for the preparation of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane

[0191] [ka]

[0192] Step 1 - Preparation of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane A solution of potassium hydroxide (7.02 g, 125.00 mmol) in methanol (240 mL) was stirred in a three-neck round bottom flask with nitrogen bubbling for 20 minutes and the solution was cooled to 5° C. in an ice / salt bath. (4-(triphenylmethyl)phenyl)methanethiol (20.02 g, 104.30 mmol) was then added dropwise over 15 minutes using a pressure equalizing dropping funnel and the resulting reaction mixture was stirred for an additional 20 minutes. Afterwards, propargyl bromide (17.4 mL, 156.00 mmol) was added dropwise via syringe to the mixture over 20 minutes and a precipitate was observed. The reaction mixture was allowed to warm to room temperature and stirred for an additional 2 hours.

[0193] The solvent was removed in vacuo and the residue was partitioned between water (300 mL) and tert-butyl methyl ether (200 mL). The aqueous layer was further extracted again with tert-butyl methyl ether (2x200 mL). The organic layers were combined, washed with water (2x200 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give the desired product prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane as a pale yellow oil (23.09 g, 96% yield).

[0194] Step 2 - Preparation of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate A solution of prop-2-yn-1-yl(4-(trifluoromethyl)benzyl)sulfane (23.09 g, 100.40 mmol) in toluene (400 mL) was degassed with nitrogen for 20 min. 2,2'-azobis(2-methylpropionitrile) (824 mg, 5.02 mmol) was added to the previous solution and the reaction mixture was heated to 75° C. (internal temperature) while degassing was continued. A solution of thioacetic acid (7.6 mL, 105.70 mmol) in toluene (100 mL) was then added dropwise to the reaction mixture over 2 h. The mixture was stirred under these conditions for 18 h.

[0195] The reaction mixture was cooled to room temperature and the solvent was removed in vacuo. The crude residue was purified twice by silica gel flash column chromatography using heptane:ethyl acetate 10% as the solvent system to give the desired product S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (6.4 g, 21% yield).

[0196] Step 3 - Preparation of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane A solution of S-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)ethanethioate (1.32 g, 4.31 mmol) in methanol (40 mL) was cooled to -40°C (internal temperature) in an acetonitrile / dry ice bath. A solution of 1M potassium hydroxide in methanol (5.2 mL, 5.17 mmol) was added dropwise over 10 min, maintaining the temperature at -40°C. The resulting mixture was stirred at this temperature for an additional 30 min and then cooled to -70°C using an acetone / dry ice bath. A solution of m-methoxybenzyl mercapto tosylate (1.59 g, 5.17 mmol) in methanol (20 mL) and tetrahydrofuran (4 mL) was added to the previous solution, maintaining the temperature at -65°C. The mixture was maintained at this temperature for 30 min, then warmed to room temperature and stirred for 1 h.

[0197] A saturated aqueous solution of ammonium chloride (20 mL) was carefully added to the reaction mixture until cloudiness persisted. The mixture was then poured into a saturated aqueous solution of ammonium chloride (230 mL) and extracted with ethyl acetate (3x100 mL). The organic extracts were combined, washed with water (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a pale yellow oil. The crude oil was purified by silica gel flash column chromatography using 2-3% heptane:ethyl acetate as the solvent system to give the desired product 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (1.57 g, 87% yield) as a colorless oil.

[0198] Step 4 - Preparation of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane A solution of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)thio)prop-1-en-1-yl)disulfane (1.57 g, 3.77 mmol) in dichloromethane (50 mL) was cooled to −65° C. 3-Chloroperbenzoic acid (1.01 g, 4.52 mmol) was added and the resulting reaction mixture was stirred at −65° C. for 15 min and at room temperature for 3 h.

[0199] The reaction mixture was partitioned between a half-saturated aqueous solution of sodium bicarbonate (50 mL) and dichloromethane. The aqueous layer was further extracted with dichloromethane (2x25 mL). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel flash column chromatography using an 80 g silica cartridge with dichloromethane:ethyl acetate 0-5% as the solvent system to give the desired product 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl)disulfane as an off-white solid in Z:E 71:29 (1.43 g, 88% yield).

[0200] Step 5 - Preparation of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane

[0201] A solution of potassium permanganate (1.17 g, 7.40 mmol) in acetone (100 mL) was added dropwise via addition funnel to a pre-cooled mixture of 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfinyl)prop-1-en-1-yl) disulfane (1.41 g, 3.26 mmol) and magnesium sulfate (4.40 g, 36.60 mmol) in acetone (100 mL) over 15 min, maintaining the temperature below -25 °C. Additional acetone (50 mL) was used to dissolve residual potassium permanganate. The resulting mixture was stirred at -28 °C overnight.

[0202] The reaction mixture was filtered through a pad of Celite, which was washed with acetone (3x70mL). The filtrate was concentrated under reduced pressure and the crude material was purified by silica gel flash column chromatography on an 80g silica cartridge using hexanes:ethyl acetate 10-30% as the solvent system to give the desired product 1-(3-methoxybenzyl)-2-(3-((4-(trifluoromethyl)benzyl)sulfonyl)prop-1-en-1-yl)disulfane as a colorless solid in Z:E 86:14 (753mg, 51% yield).

[0203] Example 4 - Minimum Biofilm Inhibitory Concentration (MBIC) of 1-(trifluoromethyl)-4-{((3-{(4-(trifluoromethyl)phenyl]methanesulfonyl}prop-1-en-1-yl)disulfanyl]methyl}benzene

[0204] The inhibitory activity of the following compounds of formula (I) against Staphylococcus aureus and Pseudomonas aeruginosa was compared with ajoene and DMSO (dimethyl sulfoxide).

[0205] [ka] Test compound 1

[0206] Compounds were assayed for their ability to inhibit biofilm formation of S. aureus or P. aeruginosa as follows. All compounds were prepared as 30 mM stocks in DMSO and diluted to 48 μM (S. aureus) or 144 μM (P. aeruginosa) in TSB. Compounds were further serially diluted 2-fold from 48 μM to 0.75 μM (S. aureus) or 144 μM to 2.3 μM (P. aeruginosa) and added to 96-well plates at 100 μl per well. Overnight cultures of bacteria were diluted to OD in fresh TSB. 600 = 0.07 and 100 μl of the diluted bacterial culture was added to the compound-containing wells. The bacteria were incubated overnight at 37°C in the presence of the compounds. After incubation, the planktonic bacteria were incubated in H 2The remaining biofilm was stained with crystal violet and then washed with 3× O. 570 The absorbance, corresponding to the biofilm mass, was plotted against the compound concentration and IC 50 Values ​​were calculated. Reference: O'Toole GA. Microtiter Dish Biofilm Formation Assay. J. Vis. Exp. (2011).

[0207] The results are shown in Figures 1 and 2. It was surprisingly found that the compound of formula (I) (Test Compound 1) had a lower IC50 against Staphylococcus aureus and Pseudomonas aeruginosa than ajoene.

[0208] Example 5 - Minimum Biofilm Inhibitory Concentration (MBIC) Assay with Ajoene Control as Reference The MBIC assay of the compounds is performed together with ajoene for reference and standardization. The IC50 of ajoene against S. aureus and P. aeruginosa is well defined and reproducible, allowing ajoene to be used as a valid control in the experiments. Therefore, the calculated IC50 for the tested compounds is expressed as % ajoene since it is compared to the IC50 of ajoene in all experiments.

[0209] In a given experiment, if a compound's IC50 is 100% ajoene, then the compound is as effective as ajoene. If a compound's IC50 is less than 100% ajoene, then the compound is more effective than ajoene. If a compound's IC50 is more than 100% ajoene, then the compound is less effective than ajoene.

[0210] Table 1 below shows the MBIC results for representative compounds having the structure of formula (I).

[0211] [Table 1]

[0212] [Table 2]

[0213] [Table 3]

[0214] Example 6 - Comparison of the inhibitory activity of 1-{[-3-(prop-2-en-1-yldisulfanyl)prop-2-ene-1-sulfonyl]methyl}-4-(trifluoromethyl)benzene with other biofilm inhibitors The inhibitory activity of the following compounds against Staphylococcus aureus and Pseudomonas aeruginosa was compared with other biofilm inhibitors, namely ajoene, cysteamine, gallium nitrate, HDMF and C-30.

[0215] [ka] Test compound 2

[0216] The structures of HDMF, cysteamine, gallium nitrate and C-30 are shown below.

[0217] [ka]

[0218] Compounds and other biofilm inhibitors were assayed for inhibitory activity using the MBIC method described in Example 4. The absorbance, corresponding to the biofilm mass, was plotted against the concentration of compounds and other biofilm inhibitors.

[0219] The results are shown in Figures 3 and 4. Surprisingly, it was found that the compound of formula (I) (Test Compound 2) has improved inhibitory activity compared to ajoene, cysteamine, gallium nitrate, HDMF and C-30.

[0220] Example 7 - Scratch closure test HaCaT cells (aneuploid immortal keratinocyte cell line) were cultured in a 96-well plate at 5x10 cells per well. 4 Cells were seeded at 1000 dpi at 37°C and incubated at 5% CO. 2 , and incubated overnight at 95% humidity. Test and control compounds were prepared in 1% DMSO and diluted in pre-warmed HaCaT cell medium to a concentration of 5 μM. Cells were washed with pre-warmed PBS and the monolayer was mechanically damaged by introducing a vertical cell-free area in each well and washed again. Test and control compounds were added and all wells were imaged under a microscope for time point 0. Cells were incubated as above and imaged after 20 h. All conditions were tested with an N of 4 replicates. Scratch closure was analyzed using ImageJ software and standard deviations were calculated. Reduction in scratch closure area was plotted using GraphPrism 8 software.

[0221] The compounds of formula (I) that were tested had the following structures: [ka] Test compound 3

[0222] The comparative compounds were E-ajoene, sulforaphane (SFN), 1% DMSO (vehicle control), epidermal growth factor (EGF) (positive control (pos)) and BAY 61-3606 hydrochloride hydrate (negative control (neg)). The results are shown in Figures 5 and 6. Test compound 3, E-ajoene and sulforaphane at 5 μM all demonstrated improved scratch closure compared to the vehicle control (P<0.0001), with complete scratch closure observed at 20 hours consistent with the epidermal growth factor (EGF) positive control.

[0223] The above has broadly described, without limitation, specific embodiments of the present invention. Variations and modifications as would be readily apparent to one skilled in the art are intended to be within the scope of the present invention as defined in the appended claims.

Claims

1. Formula (I) 【Chemistry 1】 Formula (I) (In the above formula, R １ is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, heterocyclyl or substituted heterocyclyl, and R ２ is phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, or alkenyl.

2. R １ The compound of claim 1 , wherein is phenyl, substituted phenyl, cycloalkyl or substituted cycloalkyl.

3. 3. The compound of claim 1 or 2, wherein the substituted phenyl is an alkylphenyl, haloalkylphenyl, alkyl benzoate, alkoxyphenyl, halophenyl, alkylphenylsulfone, haloalkoxyphenyl, or aminophenyl.

4. 4. The compound of claim 3, wherein said haloalkylphenyl is halomethylphenyl, for example, said halomethylphenyl is trifluoromethylphenyl.

5. 2. The compound of any one of the preceding claims, wherein the alkyl benzoate is methyl benzoate.

6. 2. The compound of any one of the preceding claims, wherein said alkoxyphenyl is methoxyphenyl.

7. 2. The compound of any one of the preceding claims, wherein said halophenyl is fluorophenyl.

8. 2. The compound according to any one of the preceding claims, wherein the alkyl phenyl sulfone is methyl phenyl sulfone.

9. 2. The compound of any one of the preceding claims, wherein said haloalkoxyphenyl is fluoromethoxyphenyl.

10. 2. The compound of any one of the preceding claims, wherein said aminophenyl is dimethylaminophenyl.

11. R １ 2. A compound according to any one of the preceding claims, wherein when is substituted phenyl, said substituted phenyl is halophenyl, haloalkylphenyl, alkoxyphenyl or alkylphenylsulfone.

12. R １ 2. A compound according to any one of the preceding claims, wherein when is substituted phenyl, said substituted phenyl is haloalkylphenyl.

13. R ２ 2. A compound according to any one of the preceding claims, wherein when is substituted phenyl, said substituted phenyl is haloalkylphenyl, alkyl benzoate or alkoxyphenyl.

14. 2. The compound of any one of the preceding claims, wherein said cycloalkyl is cyclopropyl.

15. 2. The compound of any one of the preceding claims, wherein said alkenyl is ethenyl.

16. 2. A compound according to any one of the preceding claims, wherein said heterocyclyl is heteroaryl and / or said substituted heterocyclyl is substituted heteroaryl.

17. 2. A compound according to any one of the preceding claims, wherein said heterocyclyl is furan or thiophene and / or said substituted heterocyclyl is substituted furan or substituted thiophene.

18. R １ is phenyl or substituted phenyl, for example, R １ 4. A compound according to any one of the preceding claims, wherein is substituted phenyl.

19. R ２ is phenyl, substituted phenyl or alkenyl, for example, R ２ 4. A compound according to any one of the preceding claims, wherein is alkenyl.

20. The compound is 【Chemistry 2】 2. A compound according to any one of the preceding claims, wherein

21. A pharmaceutical composition comprising a compound according to any one of claims 1 to 20 and a pharma- ceutically acceptable excipient and / or carrier and / or diluent.

22. 13. A compound or pharmaceutical composition according to any one of the preceding claims for use in a therapeutic method for treating a microbial infection and / or for treating inflammation and / or for reducing the formation of blood clots.

23. 13. Use of a compound or a pharmaceutical composition according to any one of the preceding claims in the manufacture of a medicament for treating a microbial infection and / or for treating inflammation and / or for reducing the formation of blood clots.

24. 13. A therapeutic method for treating a microbial infection and / or treating inflammation and / or reducing the formation of blood clots, said method comprising administering to a subject a compound or pharmaceutical composition according to any one of the preceding claims.

25. 10. Non-therapeutic use of a compound or a pharmaceutical composition according to any one of the preceding claims as an antibacterial and / or anti-inflammatory and / or anti-thrombotic agent.

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