This application describes modified amino acids and polypeptides comprising a SO.sub.2F or CH.sub.2CH.sub.2SO.sub.2F 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.

This application describes modified amino acids and polypeptides comprising a SO.sub.2F or CH.sub.2CH.sub.2SO.sub.2F 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.

This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) having the structure: (I), pharmaceutical compositions, containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, combination therapies, and processes and intermediates for making such modulators.

##STR00001##

This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) having the structure: (I), pharmaceutical compositions, containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, combination therapies, and processes and intermediates for making such modulators.

##STR00001##

Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X.sup.1—S(O)(X.sup.2)F).sub.m groups attached thereto, wherein Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2; m can be 1 or 2 depending on the identity of Z; and X.sup.2 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.

Described herein are compounds comprising a biologically active organic core group with one to five —Z—(X.sup.1—S(O)(X.sup.2)F).sub.m groups attached thereto, wherein Z is O, NR, or N; X.sup.1 is a covalent bond or CH.sub.2CH.sub.2; m can be 1 or 2 depending on the identity of Z; and X.sup.2 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.

A compound with the following general formula and a general method of making this compound are provided: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are each independently selected from the group that includes hydrogen, halogen, nitro, cyano, amido, pyridyl, alkyl, aryl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl.

##STR00001##

A compound with the following general formula and a general method of making this compound are provided: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are each independently selected from the group that includes hydrogen, halogen, nitro, cyano, amido, pyridyl, alkyl, aryl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl.

##STR00001##

A compound with the following general formula (I) and a general method of making this compound are provided. R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are each independently selected from the group that includes H, halogen, nitro, cyano, amido, pyridyl, alkyl, aryl, acyl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl.

##STR00001##

A compound with the following general formula (I) and a general method of making this compound are provided. R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 are each independently selected from the group that includes H, halogen, nitro, cyano, amido, pyridyl, alkyl, aryl, acyl, alkoxy, cycloalkyl, heteroalkyl, heterocyclyl, aralkyl, heteroaryl and heteroaralkyl.

##STR00001##