Lantipeptide

Patent metadata

Field	Value
Publication number	US-10487124-B2
Application number	US-201214414446-A
Country	US
Kind code	B2
Filing date	Jul 12, 2012
Priority date	Jul 12, 2012
Publication date	Nov 26, 2019
Grant date	Nov 26, 2019

Abstract

The present invention concerns novel lantipeptide (lanthionine-containing peptide) compounds having general formula (I), a process for their preparation, the key intermediates in said processes, their pharmaceutical acceptable salts and pharmaceutical compositions containing them, as well as their use in the treatment of pain.

First claim

The invention claimed is:

1. A peptide compound having general formula (I)

R 1 and R 2 are independently selected among H or a sugar moiety chosen among monosaccharides, disaccharides, trisaccharides, oligosaccharides and their corresponding deoxy derivatives;
R 3 and R 4 are independently selected among OH, NH 2 , NR 6 R 7 wherein R 6 and R 7 independently represent:
hydrogen; or
an alkyl of 1 to 20 carbon atoms wherein said alkyl being linear, branched, cyclic or combinations thereof; or
an alkenyl of 2 to 20 carbon atoms wherein said alkenyl being linear, branched, cyclic or combinations thereof; or
an alkynyl of 2 to 20 carbon atoms wherein said alkynyl being linear, branched, cyclic or combinations thereof; or
a cycloalkyl of 3 to 8 carbon atom optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a phenyl radical optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a benzyl radical optionally substituted on the phenyl ring by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a naphthyl radical optionally substituted by one or two substituents selected from halo, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a group of formula
—(CH 2 ) n OR 8

in which n represents an integer from 2 to 8 and R 8 represents
hydrogen; or
(C 1 -C 4 ) alkyl; or
a cycloalkyl of 3 to 8 carbon atom optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a phenyl radical optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a group of formula
—(CH 2 ) n NR 9 R 10

in which n represents an integer from 2 to 8 and R 9 and R 10 independently represent
hydrogen; or
(C 1 -C 4 ) alkyl; or
a cycloalkyl of 3 to 8 carbon atom optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a phenyl radical optionally substituted by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms; or
a benzyl radical optionally substituted on the phenyl ring by one or two substituents independently selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, phenyl, phenyl-lower alkyl of 1 to 4 carbon atoms, phenoxy, phenoxy-lower alkyl of 1 to 4 carbon atoms wherein the phenyl and the phenyl portion of the phenyl lower-alkyl, phenoxy and phenoxy-lower alkyl group is optionally substituted by one or two substituents selected from halo, cyano, lower alkyl of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms, and lower alkoxy of 1 to 4 carbon atoms optionally substituted by 1 to 3 halogen atoms;
R 9 and R 10 taken together represent a —(CH 2 ) 3 , —(CH 2 ) 4 —, —(CH 2 ) 2 —O—(CH 2 ) 2 , —(CH 2 ) 2 —S—(CH 2 ) 2 ; or
R 9 and R 10 taken together with the adjacent nitrogen atom represent: a piperazine moiety which may be substituted in position 4 with a substituent selected from (C 1 -C 4 ) alkyl, (C 3 -C 8 ) cycloalkyl, pyridyl, benzyl and substituted benzyl wherein the phenyl moiety bears 1 or 2 substituents selected from chloro, bromo, nitro, (C 1 -C 4 ) alkyl and (C 1 -C 4 ) alko

Assignees

• Iorio Marianna
• Maffioli Sonia
• Monciardini Paolo
• Sosio Margherita
• Donadio Stefano
• Bertorelli Rosalia
• Sasso Oscar
• Reggiani Angelo
• Naicons S R L
• Fondazione St Italiano Tecnologia

Inventors

• Iorio Marianna
• Maffioli Sonia
• Monciardini Paolo
• Sosio Margherita
• Donadio Stefano
• Bertorelli Rosalia
• Sasso Oscar
• Reggiani Angelo

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07K14/365 Primary

  from Actinoplanes (G) · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12R1/045

  Chemistry & Metallurgy · mapped topic

• C12R2001/045

  Actinoplanes · CPC title