Abstract: A high-throughput screening methods for identifying candidate anticancer medicinal agents is described herein. The candidate anticancer medicinal agents are arylfluorosulfate compounds derived from phenolic compounds. The method involves in situ generation of the arylfluorosulfate compounds in multi-well plates by reaction of phenolic compounds in DMSO with a saturated solution of SO2F2 dissolved in a solvent such as acetonitrile, in the presence of an organic base, followed by reaction of generated fluoride ion with trimethylsilanol to form volatile trimethylsilyl fluoride. Solvents, organic base, and silyl compounds are then removed, in vacuo, to afford the arylfluorosulfate compounds suitable for biological screening in cancer cell lines without further purification.

Abstract: Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X1—S(O)(X2)F)m groups attached thereto, wherein Z is O, NR, or N; X1 is a covalent bond or CH2CH2; m can be 1 or 2 depending on the identity of Z; and X2 is O or NR. In some embodiments, the core group is an amino acid or a protein. In some embodiments the core group is a compound that has therapeutic activity toward a therapeutic target.

Abstract: In alternative embodiments, the provided are therapeutic combinations comprising: nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nervous system (CNS); and, a brain efflux transporter inhibitor, or an inhibitor of renal tubular secretion, wherein optionally the brain efflux transporter inhibitor or the inhibitor of renal tubular secretion comprises a P-glycoprotein inhibitor, an organic anion transporter (OAT) inhibitor and/or an organic cation (OCT) transporter inhibitor.

Abstract: Thionyl tetrafluoride gas reacts efficiently with primary amines to form reactive iminosulfur oxydifluoride compounds. These dual SVI—F loaded iminosulfur oxydifluoride compounds, in turn, readily react with secondary amines or aryloxy silyl ethers (ArO—SiR3), yielding the corresponding fused heteroatom-linked substrates. Iminosulfur oxyfluoride polymers also are provided by disclosed methods.

Abstract: This application describes modified amino acids and polypeptides comprising a SO2F or CH2CH2SO2F group bound to the side chain of an amono acid or amino acid residue of a polypeptide in place of a hydrogen of a hydroxyl or amino substituent thereof. Methods of covalently binding the polypeptides to receptot sites of receptor proteins are also described herein.

Abstract: This application describes a compound represented by Formula (I): wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: This application describes a compound represented by Formula (I): wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: This application describes a compound represented by Formula (I): YZX1—S(O)(X2)F)m]n??(I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: A high-throughput screening methods for identifying candidate anticancer medicinal agents is described herein. The candidate anticancer medicinal agents are arylfluorosulfate compounds derived from phenolic compounds. The method involves in situ generation of the arylfluorosulfate compounds in multi-well plates by reaction of phenolic compounds in DMSO with a saturated solution of SO2F2 dissolved in a solvent such as acetonitrile, in the presence of an organic base, followed by reaction of generated fluoride ion with trimethylsilyl chloride to form volatile trimethylsilyl fluoride. Solvents, organic base, and silyl compounds are then removed, in vacuo, to afford the arylfluorosulfate compounds suitable for biological screening in cancer cell lines without further purification.

Abstract: Condensation of fluoro-substituted and silyl-substituted monomers provides polymers suitable for use, e.g., as engineering polymers. A monomer composition is condensed in the presence of a bifluoride or poly(hydrogen fluoride) fluoride salt. The monomer composition contains a compound of formula F-X-F and a compound of formula (R1)3Si—Z—Si(R1)3, and forms an alternating X-Z polymer chain and a silyl fluoride byproduct. X has the formula -A(-R2-A)n-; each A is SO2, C(?O), or Het; R2 is an organic moiety; n is 0 or 1; Het is an aromatic nitrogen heterocycle; Z has the formula -L-R3-L-; each L is O, S, or N(R4); and each R3 is an organic moiety, and R4 comprises H or an organic moiety.

Abstract: Thionyl tetrafluoride gas reacts efficiently with primary amines to form reactive iminosulfur oxydifluoride compounds. These dual SVI—F loaded iminosulfur oxydifluoride compounds, in turn, readily react with secondary amines or aryloxy silyl ethers (ArO—SiR3), yielding the corresponding fused heteroatom-linked substrates. Iminosulfur oxyfluoride polymers also are provided by disclosed methods.

Abstract: Arylfluorosulfate compounds derived from anticancer drugs are disclosed herein, which exhibit improved anti-cancer cell proliferation activities compared to their phenolic drug precursors. Among these compounds, the fluorosulfate derivative of fulvestrant showed significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER+ breast cancer cell line MCF-7, and oral availability in vivo; the fluorosulfate derivative of combretastatin A4 exhibited a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29; and the fluorosulfate derivative of ABT-751 showed enhanced activity relative to ABT-751.

Abstract: This application describes a compound represented by Formula (I): Y?Z?X1—S(O)(X2)F)m]n??(I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: Condensation of fluoro-substituted and silyl-substituted monomers provides polymers suitable for use, e.g., as engineering polymers. A monomer composition is condensed in the presence of a bifluoride or poly(hydrogen fluoride) fluoride salt. The monomer composition contains a compound of formula F-X-F and a compound of formula (R1)3Si—Z—Si(R1)3, and forms an alternating X-Z polymer chain and a silyl fluoride byproduct. X has the formula -A(-R2-A)n-; each A is SO2, C(?O), or Het; R2 is an organic moiety; n is 0 or 1; Het is an aromatic nitrogen heterocycle; Z has the formula -L-R3-L-; each L is O, S, or N(R4); and each R3 is an organic moiety, and R4 comprises H or an organic moiety.

Abstract: Condensation of fluoro-substituted and silyl-substituted monomers provides polymers suitable for use, e.g., as engineering polymers. A monomer composition is condensed in the presence of a basic catalyst. The monomer composition contains a compound of formula F—X—F and a compound of formula (R1)3Si—Z—Si(R1)3, and forms an alternating X—Z polymer chain and a silyl fluoride byproduct. X has the formula -A(—R2-A)n-; each A is SO2, C(?O), or Het; R2 is an organic moiety; n is 0 or 1; Het is an aromatic nitrogen heterocycle; Z has the formula -L-R3-L; each L is O, S, or N(R4); and each R3 is an organic moiety, and R4 comprises H or an organic moiety.

Abstract: Condensation of fluoro-substituted and silyl-substituted monomers provides polymers suitable for use, e.g., as engineering polymers. A monomer composition is condensed in the presence of a basic catalyst. The monomer composition contains a compound of formula F—X—F and a compound of formula (R1)3Si—Z—Si(R1)3, and forms an alternating X—Z polymer chain and a silyl fluoride byproduct. X has the formula -A(—R2-A)n-; each A is SO2, C(?O), or Het; R2 is an organic moiety; n is 0 or 1; Het is an aromatic nitrogen heterocycle; Z has the formula -L-R3-L; each L is O, S, or N(R4); and each R3 is an organic moiety, and R4 comprises H or an organic moiety.

Abstract: This application describes a compound represented by Formula (I): (I) wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X1 is a covalent bond or —CH2CH2—, X2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

Abstract: Condensation of fluoro-substituted and silyl-substituted monomers provides polymers suitable for use, e.g., as engineering polymers. A monomer composition is condensed in the presence of a basic catalyst. The monomer composition contains a compound of formula F—X—F and a compound of formula (R1)3Si—Z—Si(R1)3, and forms an alternating X—Z polymer chain and a silyl fluoride byproduct. X has the formula -A(-R2-A)n-; each A is SO2, C(?O) or Het; R2 is an organic moiety; n is 0 or 1; Het is an aromatic nitrogen heterocycle; Z has the formula -L-R3-L-; each L is O, S, or N(R4); and each R3 is an organic moiety, and R4 comprises H or an organic moiety.