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US 9,340,575 B2Granted
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 II receptor (UT) agonists and antagonists are described herein. More specifically, novel derivatives of urotensin II-related peptide (URP) are described herein.
Claims15
A urotensinergic agent or a pharmaceutically acceptable salt thereof having the formula:
- wherein X is a L- or D-amino acid selected from the group consisting of glycine, serine, threonine, cysteine, valine, leucine, isoleucine, methionine, proline, phenylalanine, tyrosine, aspartic acid, glutamic acid, asparagine, glutamine, histidine, lysine, arginine and side-chain conformationally constrained phenylalanines, wherein the conformationally constrained phenylalanines are selected from the group consisting of β-β-diphenylalanine and 4-amino-indolo[2,3-c]azepin-3-one, 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 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-tert-butyloxycarbonyl (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 and 4-ethynyl-1,1′-biphenyl;
- and
- wherein Z is a ligand comprising a radioisotope.
Dependencies are inferred from the claim text.