Novel agonists and antagonists of the urotensinergic system
AssigneeInstitut National De La Recherche Scientifique
InventorsDavid Chatenet, Alain Fournier, Myriam Letourneau
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Abstract
Novel urotensin ll receptor (UT) agonists and antagonists are described herein. More specifically, novel derivatives of urotensin ll-related peptide (URP) are described herein.
Claims23
A urotensinergic agent or a pharmaceutically acceptable salt thereof having the formula:
- wherein X is an L- or D-amino acid selected from the group consisting of Glycine, Alanine, Serine, Threonine, Cysteine, Valine, Leucine, Isoleucine, Methionine, Proline, Phenylalanine, Tyrosine, Tryptophan, Aspartic Acid, Glutamic Acid, Asparagine, Glutamine, Histidine, Lysine, Arginine and side-chain conformationally restricted phenylalanines, or a phenylalanine analogue having the formula:
- wherein R is a substituent introduced by metal catalysed reaction using a boronic acid, a boronic acid derivative, a substituted vinyl, or a substituted alkynyl.
A urotensinergic agent or a pharmaceutically acceptable salt thereof, wherein the agent substantially includes the N-terminal segment of a Ull isoform.
A radiolabelled urotensinergic agent having the formula:
- wherein R is a substituent introduced by metal catalysed reaction using a boronic acid or a boronic acid derivative selected from the group consisting of phenylboronic acid, 4-hydroxyphenylboronic acid, 4-methoxycarbonylphenylboronic acid, 4-pyridineboronic acid, 4-cyanophenylboronic acid, 4-(hydroxymethyl)phenylboronic acid, 3-furanboronic acid, 2-furanboronic acid, 3-thiophenboronic acid, 3-nitro-phenylboronic acid, trans-2-chloromethylvinylboronic acid, trans-1-propen-1-ylboronic acid, 2-Boc-indoleboronic acid, acetamidophenylboronic acid, 4-(N-Boc-amino)phenylboronic acid, 4-phenoxyphenylboronic acid, 4-acetylphenylboronic acid and 2,4,6-trifluorophenylboronic acid;
- and
- wherein Z is a ligand comprising a radioisotope.
A radiolabelled urotensinergic agent having the formula:
- wherein the substituted vinyl (R—C═C—) is introduced by metal catalysed reaction using a substituted vinyl selected from the group consisting of vinylbenzene, 1-methyl-4-vinylbenzene, 1-methyl-3-vinylbenzene, 1-methyl-2-vinylbenzene, 1,3,5-trimethyl-2-vinylbenzene, 1-vinylnaphthalene, 2-vinylnaphthalene, 1-isopropyl-4-vinylbenzene, 1-(chloromethyl)-4-vinylbenzene, 1-chloro-4-vinylbenzene, 3-vinylbenzene, 4-vinylbenzoic acid, 1-(trifluoromethyl)-2-vinylbenzene, 1-(trifluoromethyl)-4-vinylbenzene, 1-(trifluoromethyl)-3-vinylbenzene, isopropenylbenzene, 4-nitrostyrene, 4-vinylalanine, 4-vinylanisole, 1-tert-butoxy-4-vinylbenzene, 4-vinylphenyl acetate and 1-ethoxy-4-vinylbenzene;
- and
- wherein Z is a ligand comprising a radioisotope.
A radiolabelled urotensinergic agent having the formula:
- wherein the substituted alkynyl (R—C≡C—) is introduced by metal catalysed reaction using a substituted alkynyl selected from the group consisting of ethynylbenzene, 1-ethynyl-4-fluorobenzene, 1-ethynyl-4-tert-butylbenzene, 1-ethynyl-4-methoxy-2-methylbenzene, ethynylcyclohexane, 1-decyne, 9-ethynylphenanthrene, 1-ethynylnaphthalene, 4-ethynylbenzonitrile, 1-ethynyl-4-(trifluoromethyl)benzene, 4-ethynylaniline, 4-ethynyl-1,1′-biphenyl;
- and
- wherein Z is a ligand comprising a radioisotope.
Dependencies are inferred from the claim text.