Bioinspired catalysis using oligourea helical foldamers

Patent metadata

Field	Value
Publication number	US-10414722-B2
Application number	US-201615189937-A
Country	US
Kind code	B2
Filing date	Jun 22, 2016
Priority date	Jun 22, 2015
Publication date	Sep 17, 2019
Grant date	Sep 17, 2019

Abstract

The present description provides oligourea catalysts, a polar helical oligomeric strands, and methods for catalyzing reactions with polar helical oligomeric strands and oligourea catalysts. In particular, the invention relates to a polar helical oligomeric strand of at least 4 residues selected from the formula (I) and which can be used as a catalyst.

First claim

The invention claimed is:

1. A catalytic foldamer compound consisting of an oligomer of at least 4 urea-containing residues selected from the formula

wherein:
n is≥4;
X and each Y is independently selected from O and S;
R 1 is a fluoroalkyl substituted aryl;
each R 2 is independently selected from the group consisting of hydrogen; side chain of a natural amino acid; fluorine; linear, branched or cyclic C1-C6-alkyl, alkenyl or alkynyl; C1-C6-alkyloxy
each R 3 is independently selected from the group consisting of hydrogen; any side chain of a natural amino acid; fluorine; linear, branched or cyclic C1-C6-alkyl, alkenyl or alkynyl; C1-C6-alkyloxy; and
Z is —NH-alkyl or a short oligomer of at least two residues selected from the group consisting of C-substituted and unsubstituted N-2-aminoethylcarbamoyl residue, C-substituted and unsubstituted N-(2-aminoethyl)carbamothioyl residues, C-substituted and unsubstituted N-(2-aminoethyl) urea residues, C-substituted and unsubstituted γ-amino acid residue, —C-substituted and unsubstituted α-amino acids, and any combination thereof.

2. The compound of claim 1 , wherein the selected compound includes a total number of from 4 to 15 urea-containing residues.

3. The compound of claim 1 , wherein R 1 is 3,5-bis(trifluoromethyl)phenyl.

4. The compound of claim 1 , wherein Z is selected from the group consisting of C-substituted and unsubstituted N-(2-aminoethyl) urea residues, —NH-alkyl, and any combination thereof.

5. The compound of claim 1 , wherein Z is an alpha-peptide.

6. The compound of claim 1 , wherein Z is a gamma-peptide comprising C-substituted and unsubstituted γ-amino acid residues.

7. The compound of claim 1 , wherein Z is an N,N′-linked oligourea comprising C-substituted and unsubstituted N-2-aminoethylcarbamoyl residues and N-2-aminoethyl urea residues.

8. The compound of claim 1 , wherein the compound has the chemical formula:

wherein the absolute configuration of C* is the same (either S or R) for the two adjacent residues.

9. The compound of claim 8 , wherein the compound has the chemical formula:

wherein the absolute configuration of C* is the same (either S or R) for the two adjacent residues.

10. The compound of claim 1 , wherein the compound has the chemical formula:

wherein C* is the same (either S or R) for all n residues and R 4 is an alkyl residue.

11. The compound of claim 1 , wherein the compound has the chemical formula:

C* is the same (either S or R) for all n residues and R 4 is an alkyl residue.

12. The compound of claim 1 , wherein the compound has the chemical formula:

C* is the same (either S or R) for all n residues and R 4 is an alkyl residue.

13. The compound of claim 1 , wherein the Z group is covalently linked to a solid-support, wherein the solid support is further selected from the groups consisting of polystyrene, silica, and polyethylene glycol resins.

14. A catalytic foldamer compound having a structure selected from the structure consisting of:

15. The compound of claim 1 , wherein the foldamer is a pharmaceutically acceptable acid or base salt.

16. The compound of claim 1 , wherein the catalytic foldamer catalyzes at least one reaction selected from the group consisting of: acid catalysis; Michael reaction; 1,2-additions on at least one of C═O, C═N , C═S , C═C, C≡C, C≡N, N═N, N═O, N═S, N≡C, P═O, P═S, and P═N bonds; ring opening of epoxides, aziridines, cyclopropanes, thioepoxides, oxetanes, azetidines, cyclobutanes, or thiooxetanes; addition of nucleophiles; a conjugated addition; a substitution reaction; an elimination reaction; a migration reaction; a Diels alder reactions; electrocyclic reaction; a sigmatropic rearrangement; a dyotropic reaction; a cycloaddition reaction; a reduction reaction; and an oxidation reaction.

17. The compound of claim 1 , wherein the catalytic foldamer compound has a structure selected from the structure consisting of:

18. The compound of claim 1 , wherein Z is a C-substituted and unsubstituted N-(2-aminoethyl) urea residues, C-substituted and unsubstituted γ-amino acid residue, —C-substituted and unsubstituted α-amino acids, —NH-alkyl, and any combination thereof.

19. The compound of claim 3 , wherein Z is a C-substituted and unsubstituted N-(2-aminoethyl) urea residues, C-substituted and unsubstituted γ-amino acid residue, —C-substituted and unsubstituted α-amino acids, —NH-alkyl, and any combination thereof.

20. A therapeutic composition comprising an effective amount of a compound of claim 1 or acid or base salt thereof, and a pharmaceutically acceptable excipient.

21. The composition of claim 20 , wherein the compound comprises at least one chemical modification selected from the group selected from acetylation, phosphorylation, methylation, glycosylation, prenylation, isoprenylation, farnesylation, geranylation, pegylation, a disulfide bond, and a combination thereof.

Assignees

• Centre Nat Rech Scient
• Ureka Sarl

Inventors

• Goudreau Sebastien
• Guichard Gilles
• Fischer Lucile
• Salaun Arnaud
• Diemer Vincent
• Becart Diane

Classifications

• C07D207/09

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title

• C07C335/16

  having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton · CPC title

• C07C275/30 Primary

  being further substituted by halogen atoms, or by nitro or nitroso groups · CPC title

• C07C275/40 Primary

  being further substituted by nitrogen atoms not being part of nitro or nitroso groups · CPC title

• B01J31/0235

  Nitrogen containing compounds · CPC title