Synthetic cyclic peptides and methods of preparation and use thereof
AssigneeAuburn University
InventorsMonika Raj, Victor Adebomi
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Abstract
The present invention relates, in part, to novel compounds comprising 4-imidazolidinone-fused cyclic peptides and compositions thereof. The present invention also relates to methods of generating said compounds and compositions thereof as well as methods of inhibiting protein-protein interaction using said compounds or compositions thereof. In another aspect, the present invention relates, in part, to methods of treating or preventing a various diseases or disorders using said compounds or compositions thereof.
Claims20
A compound comprising 4-imidazolidinone-fused cyclic peptide, wherein the compound is a compound having the structure of
- or a derivative, prodrug, pharmaceutically acceptable salt, solvate, isomer, or tautomer thereof,
- wherein each occurrence of R1, R2, R3, R4, R5, R6, R7, R8, and R9 is independently selected from the group consisting of hydrogen, deuterium, halogen, hydroxyl, alkoxy, amino, aminoalkyl, carbonyl, carboxyl, carboxylic acid, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl, alkynyl, cycloalkynyl, heterocycloalkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, acyl, ester, urea, thiourea, thiol, thioalkyl, thioxo, sulfanyl, sulfinyl, sulfonyl, phosphino, ═O, nitrile, isonitrile, cyano, carbamate, guanidine, guanidine alkyl, amino acid, and any combination thereof;
- wherein R1 and R2 are optionally fused or joined to form a ring;
- each occurrence of Xa and Xb is independently selected from the group consisting of C, —CR10, N, P, P═O, S═O, and any combination thereof;
- wherein each occurrence of R10 is independently selected from the group consisting of hydrogen, deuterium, halogen, hydroxyl, hydroxylalkyl, alkoxy, amino, aminoalkyl, carbonyl, carboxyl, carboxylic acid, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl, alkynyl, cycloalkynyl, heterocycloalkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl, arylalkynyl, heteroarylalkynyl, acyl, ester, urea, thiourea, thiol, thioalkyl, thioxo, sulfanyl, sulfinyl, sulfonyl, phosphine, nitrile, isonitrile, cyano, carbamate, guanidine, guanidine alkyl, amino acid, and any combination thereof;
- m is an integer from 1 to 100;
- n is an integer from 1 to 100;
- o is an integer from 0 to 10;
- x is an integer from 0 to 10;
- y is an integer selected from the group consisting of 0 and 1;
- and
- z is an integer from 0 to 10.
A method of preparing a compound comprising 4-imidazolidinone-fused cyclic peptide, or a derivative, prodrug, pharmaceutically acceptable salt, solvate, isomer, or tautomer thereof, wherein the method comprises the steps of:
- a) obtaining a linear peptide;
- b) adding an aldehyde group to the linear peptide to generate an aldehyde functionalized linear peptide;
- c) incubating the aldehyde functionalized linear peptide in a solvent in the presence of a nucleophilic catalyst;
- d) covalently cyclizing the aldehyde functionalized linear peptide to generate at least one compound comprising 4-imidazolidinone-fused cyclic peptide, or a derivative, prodrug, pharmaceutically acceptable salt, solvate, isomer, or tautomer thereof;
- and
- e) isolating the compound comprising d-imidazolidinone-fused cyclic peptide, or a derivative, prodrug, pharmaceutically acceptable salt, solvate, isomer, or tautomer thereof.
A method of generating a library of 4-imidazolidinone-fused cyclic peptides, wherein the method comprises the steps of:
- a) obtaining a mixture of linear peptides;
- b) adding an aldehyde group to the linear peptides to generate aldehyde functionalized linear peptides;
- c) incubating the aldehyde functionalized linear peptides in a solvent in the presence of a nucleophilic catalyst;
- d) covalently cyclizing the aldehyde functionalized linear peptides to generate 4-imidazolidinone-fused cyclic peptides, or derivatives, prodrugs, pharmaceutically acceptable salts, solvates, isomers, or tautomers thereof;
- and
- e) isolating the 4-imidazolidinone-fused cyclic peptides, or derivatives, prodrugs, pharmaceutically acceptable salts, solvates, isomers, or tautomers thereof.
Dependencies are inferred from the claim text.