Production of bitter principle derivatives

Patent metadata

Field	Value
Publication number	US-12129222-B2
Application number	US-201716324758-A
Country	US
Kind code	B2
Filing date	Aug 11, 2017
Priority date	Aug 11, 2016
Publication date	Oct 29, 2024
Grant date	Oct 29, 2024

Abstract

It is an object of the present invention to introduce carboxylic acid-functionalities suitable for coupling into the denatonium structure by means of simple synthesis, namely the synthesis of bitter principle derivatives based on the denatonium structure according to formula 1:

For example, according to the invention, lidocaine derivatives may be reacted with carboxylated benzyl halogenides. The carboxylated denatonium derivatives of the present invention are especially applied in medicine, biology, medical engineering as well as cosmetics, the pharmaceutical, chemical, and foodstuff industry.

First claim

The invention claimed is:

1. A compound of general formula 1

wherein:
(i) X − represents halogenide, sulphate, benzoate, acetate, trifluoroacetate, hydroxide, saccharinate, or capsaicinate,
(ii) R1-R10 independently represent:
(a) hydrogen,
(b) halogen,
(c) C1-C5 alkyl,
(d) C1-C4 alkoxy,
(e) C1-C20 alkoxycarbonyl
(f) —NH—P or —O—P, wherein P is a hydrogen
or a residue consisting of 1-30 amino acids selected from the group consisting of D-amino acids, L-amino acids and unnatural amino acids, wherein said amino acids are optionally modified for coupling,
(g) —(Y) n —COOM with M=Na, K, or [N(R12) 4 ] + , or
(h) —(Y) n —C(O)NR14R15, further wherein Y represents an organic residue selected from the group consisting of: —CH 2 , —CH(CH 3 )—, —CH 2 —CH 2 —, —(CH 2 ) 3 —, —CH═CH—, —C≡C—, —O—CH 2 —CH 2 —, —O—CH 2 —CH 2 —O—CH 2 —CH 2 —, and —NH—CH 2 —CH 2 — and n=0 or 1,

(iii) R14 and R15 represent hydrogen, a C1-C12 alkyl, or a residue consisting of 1-30 amino acids selected from the group consisting of D-amino acids, L-amino acids and unnatural amino acids, and
(iv) at least one of the residues R1-R10 is a (a) —(Y) n —COOM or (b) —(Y) n —C(O)NR14R15, wherein Y, M, R14, and R15 are as defined above, and
(v) R11 and R12 independently represent hydrogen or a C1-C10 alkyl residue.

2. The compound according to claim 1 , wherein, in the general formula 1:
(i) residue R11 is an ethyl group,
(ii) residues R9 and R10 are methyl groups,
(iii) residues R1, R4, R5, R6, R7, and R8 represent hydrogen, and
(iv) one of residues R2 and R3 represents hydrogen and the other is selected from the group consisting of;
(a) —(Y) n —COOM with M=Na, K, or [N(R12) 4 ] + , and
(b) —(Y) n —C(O)NR14R15,
or residues R2 and R3 independently represent:
(a) —(Y) n —COOM with M=Na, K, or [N(R12) 4 ] + , or
(b) —(Y) n —C(O)NR14R15, wherein Y, M, R14, and R15 are as defined in claim 1 , further wherein:
a. residues R14 and R15 independently represent hydrogen, a C1-C12 alkyl or a residue consisting of 1-30 amino acids selected from the group consisting of D-amino acids, L-amino acids and unnatural amino acids, residue R12 represents hydrogen or a C1-C10 alkyl residue.

3. A substrate comprising a compound according to claim 1 , bound to a substrate surface fabricated of a metal, ceramic, glass, or polymeric material via one of residues R1-R10 of said compound.

Assignees

• Univ Wuerzburg J Maximilians
• Julius Maximilians Univ

Inventors

• Wyrwa Ralf
• Rode Claudia
• Seemann Thomas
• Meinel Lorenz
• Ritzer Jennifer
• Schnabelrauch Matthias

Classifications

• A61K47/186

  Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide · CPC title

• C07C269/04

  from amines with formation of carbamate groups · CPC title

• A61K47/65 Primary

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• C07C233/07

  having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• A61K47/54

  the modifying agent being an organic compound · CPC title