Sulfur (vi) fluoride compounds and methods for the preparation thereof

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.

We claim: 
     
         1 . A compound represented by Formula (I):
   Y Z X 1 —S(O)(X 2 )F) m ] n   (1)
   wherein:
 Y is a biologically active organic core group comprising one or more unsubstituted or substituted moiety selected from an aryl group, a heteroaryl group, a nonaromatic hydrocarbyl group, a nonaromatic heterocyclic group, to which each Z independently is covalently bonded; 
 n is 1, 2, 3, 4 or 5; 
 each Z independently is O, NR, or N; 
 when Z is O, m is 1, X 1  is a covalent bond, and the Z is covalently bonded to an aryl or heteroaryl moiety of Y; 
 when Z is NR, m is 1, X 1  is a covalent bond or CH 2 CH 2 ; 
 when Z is N, either (a) m is 2, and X 1  is CH 2 CH 2 ; or (b) m is 1, X 1  is a covalent bond or CH 2 CH 2 , and the Z is a nitrogen in an aromatic or nonaromatic heterocyclic ring portion of core group Y; 
 each X 2  independently is O or NR; and 
 each R independently 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. 
   
     
     
         2 . The compound of  claim 1 , wherein each X 2  is O, each Z independently is O, NR, or N; and at least one Z is O. 
     
     
         3 . The compound of  claim 1 , wherein at least one Z is covalently bonded to a moiety selected from: a heteroaryl moiety of Y, an aryl moiety of Y, and a nonaromatic carbon of Y. 
     
     
         4 . The compound of  claim 1 , wherein one or more of the aryl, heteroaryl aryl, nonaromatic hydrocarbyl, or nonaromatic heterocyclic portions of the compounds of Formula (I), include one or more substituent selected from a hydrocarbyl moiety, —OR 4 , —N(R 4 ) 2 , —N + (R 4 ) 3 , —SR 4 , —OC(═O)R 4 , —N(R 4 )C(═O)R 4 , —SC(═O)R 4 , —OC(═O)OR 5 , —N(R 4 )C(═O)OR 5 , —SC(═O)OR 5 , —OC(═O)N(R 4 ) 2 , —N(R 4 )C(═O)N(R 4 ) 2 , —SC(═O)N(R 4 ) 2 , —OC(═O)SR 5 , —N(R 4 )C(═O)SR 5 , —SC(═O)SR 5 , —C(═O)R 4 , —C(═O)OR 4 , —C(═O)N(R 4 ) 2 , —C(═O)SR 4 , —OC(═NR 4 )R 4 , —N(R 4 )C(═NR 4 )R 4 , —SO 2 R 4 , —SO 2 OR 4 , —SO 2 (NR 4 ) 2 , —N(R 4 )SO 2 OR 5 , —N(R 4 )SO 2 N(R 4 ) 2 , —OSO 2 OR 5 , —OSO 2 N(R 4 ) 2 , —P(═O)(OR 4 ) 2 , —OP(═O)(OR 4 ) 2 , —OP(═O)R 5 (OR 4 ), fluoro, chloro, bromo, iodo, —NO 2 , —N 3 , —N═N—Ar 1 , —CN, a heteroaryl moiety (including heteroaryl materials comprising a single aromatic ring, or multiple fused aromatic rings in which at least one of the fused rings include a heteroatom), a nonaromatic heterocyclic moiety, a fused 5-member nonaromatic carbocyclic ring, a fused 5-member heterocyclic ring, a fused 6-member nonaromatic carbocyclic ring, a fused 6-member nonaromatic nitrogen-containing heterocyclic ring, and any combination of two or more thereof, each R 4  independently is H, hydrocarbyl, heteroaryl, or a nonaromatic heterocyclic moiety; each R 5  independently is hydrocarbyl, heteroaryl, or a nonaromatic heterocyclic moiety; and each Ar 1  independently is aryl or heteroaryl. 
     
     
         5 . The compound of  claim 1 , wherein the core group Y comprises a biologically active material selected from an antimicrobial agent, an enzyme inhibitor, a medicinal agent having activity for treating a non-microbial disease, a medicinal agent that targets a pathogen, an antibiotic, an anti-protozoal agent, and a therapeutic agent that targets an active site in a host subject. 
     
     
         6 . The compound of  claim 1 , wherein the core group Y comprises a protein. 
     
     
         7 . The compound of  claim 1 , wherein the core group Y comprises a first compound that has therapeutic activity toward a therapeutic target. 
     
     
         8 . The compound of  claim 1 , wherein the compound comprises tyrosine, 2,6-dimethyltyrosine, or a peptide comprising one or more residues selected from tyrosine and 2,6-dimethyltyrosine, in which the phenolic OH of the tyrosine or 2,6-dimethyltyrosine is substituted by —OSO 2 F. 
     
     
         9 . The compound of  claim 1 , wherein the compound comprises an amino acid comprising a nucleophilic side chain or a peptide comprising one or more amino acid residue comprising a nucleophilic side chain, which includes an —SO 2 F or —CH 2 CH 2 SO 2 F group in place of a hydrogen on a hydroxyl or amino substituent of the nucleophilic side chain. 
     
     
         10 . The compound of  claim 9 , wherein the amino acid or amino acid residue comprising the nucleophilic side chain is selected from the group consisting of lysine, serine, tyrosine, histidine, and arginine. 
     
     
         11 . The compound of  claim 1 , wherein the compound of Formula (I) has a biological activity toward substantially the same target condition as the biologically active core group Y. 
     
     
         12 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically acceptable carrier, vehicle, or diluent. 
     
     
         13 . A compound comprising:
 an amino acid; and   an —SO 2 F group or —OSO 2 F group attached thereto.   
     
     
         14 . The compound of  claim 13 , wherein the —SO 2 F or —OSO 2 F group is attached to the amino acid sidechain. 
     
     
         15 . The compound of  claim 13 , wherein the —SO 2 F or —OSO 2 F group is attached to the amino acid via an aryl group. 
     
     
         16 . The compound of  claim 13 , wherein the compound comprises —CH 2 CH 2 SO 2 F or —OSO 2 F. 
     
     
         17 . The compound of  claim 16  wherein the —CH 2 CH 2 SO 2 F group is attached to the amino acid at a nitrogen substituent thereof. 
     
     
         18 . The compound of  claim 16 , wherein the —CH 2 CH 2 SO 2 F or —OSO 2 F group is attached to the amino acid at the aryl group, and the —CH 2 CH 2 SO 2 F group is attached to the aryl group at a nitrogen substituent thereof. 
     
     
         19 . A compound comprising:
   Y—Z—X 1 —SO 2 -Nu-Protein, or
     Y—SO 2 -Nu-Protein,
   wherein:   Y is a biologically active organic core group comprising one or more unsubstituted or substituted moiety selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded;   Z is O, NR, or N;   when Z is O, X 1  is a covalent bond, and Z is covalently bonded to an aryl or heteroaryl moiety of Y;   when Z is NR, X 1  is a covalent bond or CH 2 CH 2 ;   when Z is N, either (a) X 1  is CH 2 CH 2 ; or (b) X 1  is a covalent bond or CH 2 CH 2 , and the Z is a nitrogen in an aromatic or nonaromatic heterocyclic ring portion of core group Y;   R is 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;   Protein comprises a receptor protein; and   Nu comprises a nucleophilic sidechain of a nucleophilic amino acid residue within a receptor site of the receptor protein.   
     
     
         20 . The compound of  claim 19  wherein the compound comprises: Y—Z—X 1 —SO 2 -Nu-Protein. 
     
     
         21 . The compound of  claim 20 , wherein Z is attached to the biologically active core group Y at an aryl group thereof. 
     
     
         22 . The compound of  claim 19 , wherein the nucleophilic amino acid residue within the receptor site comprises serine, tyrosine, histidine, lysine, cysteine, or arginine. 
     
     
         23 . The compound of  claim 19 , wherein the receptor protein comprises a hormone receptor or a chemokine receptor. 
     
     
         24 . The compound of  claim 19 , wherein the core group Y comprises a first compound that has therapeutic activity toward a therapeutic target.