Proteomimetic compounds and methods

A method of identifying a compound to be used as a peptidomimetic agent as antagonist or antagonist of an a-helical protein for its binding site, said method comprising

• providing a cylindrical cage or rigid scaffold compound according to the structure:
• W—B—X—B—Y
• Wherein X is selected from the group consisting of:
• W and Y are each independently selected from the group consisting of:
• wherein Rb is selected from the group consisting of hydrogen, hydroxyl, amine, nitro, methoxy, carboxylic acid, ester, amide, hydrocarbon, olefin, alkylcarboxylate and its salts, alkyl linked ester, alkyl cyano, alkyl linked amine and its salts, alkoxycarboxylate and its salts, alkoxy ester, alkoxy cyano, alkoxy amine and its salts and alkoxy aryl;
• and each B is independently a connecting bond or an amide or ester group connecting W to said X and Y groups;
• said method further comprising identifying chemical substituent groups that are sterically and electronically similar to the natural substituents on the a carbon atoms of natural amino acids and attaching said substituents to unbound atoms on the ring structures of said chemical scaffold, said substituents providing similar steric and electrochemical characteristics to substituents at the position of the α carbon atoms of a peptide or protein sequence in an a helical protein.

A compound or its pharmaceutically acceptable salt of the formula:

• W—B—X—B—Y
• Where X is selected from the group consisting of:
• W and Y are each independently selected from the group consisting of:
• Where R1, R2, R3 and R4 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted hydrocarbon groups, unsubstituted or substituted aryl, unsubstituted or substituted alkylene aryl, unsubstituted or substituted alkylaryl, alkoxy, ester, alkanol, alkanoic acid, thioether, thioester, amine, alkylamine, dialkylamine, unsubstituted or substituted amide or alkyleneamide, unsubstituted or substituted alkyleneamine, unsubstituted and substituted alkyleneguanidine;
• Rb is selected from the group consisting of hydrogen, hydroxyl, amine, nitro, methoxy, carboxylic acid, ester, amide, hydrocarbon, olefin, alkylcarboxylate and its salts, alkyl linked ester, alkyl cyano, alkyl linked amine and its salts, alkoxycarboxylate and its salts, alkoxy ester, alkoxy cyano, alkoxy amine and its salts and alkoxy aryl;
• Rn is a C1-C10 alkyl, alkanol, aryl or a
• group, where T is H or a C1-C12 saturated or unsaturated hydrocarbon, amine, alkylamine, dialkylamine, unsubstituted or substituted alkyleneamine or unsubstituted or substituted alkyleneamide;
• Z is O or S;
• and
• B is a single bond between carbon atoms of W—X or X—Y groups or an ester or amide group linking W—X or X—Y groups.

A method of identifying a compound to be used as a peptidomimetic agent as antagonist or antagonist of an α-helical protein for its binding site, said method comprising:

• providing a cylindrical cage or rigid scaffold compound according to the structure:
• W—B—X—B—Y
• Wherein X is selected from the group consisting of:
• W and Y are each independently selected from the group consisting of:
• wherein Rb is selected from the group consisting of hydrogen, hydroxyl, amine, nitro, methoxy, carboxylic acid, ester, amide, hydrocarbon, olefin, alkylcarboxylate and its salts, alkyl linked ester, alkyl cyano, alkyl linked amine and its salts, alkoxycarboxylate and its salts, alkoxy ester, alkoxy cyano, alkoxy amine and its salts and alkoxy aryl;
• and each B is independently a connecting bond or an amide or ester group connecting W to said X and Y groups;
• said method further comprising identifying chemical substituent groups that are sterically and electronically similar to the natural substituents on the α carbon atoms of natural amino acids and attaching said substituents to unbound atoms on the ring structures of said chemical scaffold, said substituents providing similar steric and electrochemical characteristics to substituents at the position of the α carbon atoms of a peptide or protein sequence in an α helical protein.