PSEUDOURIDIMYCIN (PUM) AND ITS DERIVATIVES
The present invention relates to novel compounds of formula (I) and pharmaceutically acceptable salts thereof, a process for the preparation thereof, as well as pharmaceutical compositions containing them and the use thereof as drugs, particularly for the treatment of infectious diseases.
1 . A compound of formula (I)
where R is independently selected from the croup consisting of:
H;
a straight, branched, cyclic C 1 -C 20 alkyl group, or a combination thereof;
a straight, branched, cyclic C 2 -C 20 alkenyl group, or a combination thereof;
a straight, branched, cyclic C 2 -C 20 alkynyl group, or a combination thereof;
a benzylic group; and
a naphthylic group;
X is independently selected from H, OH, or NH 2 ; and
Y is independently selected from one of the following heterocyclic groups:
2 . The compound according to claim 1 , characterized in that said R is H, said X is OH and said Y is
and the compound is represented by the formula (II)
3 . The compound according to claim 1 , characterized in that said X is selected to be equal to OH, said R is selected to be equal to PhCH 2 —, said Y is selected to be equal to
and the compound is represented by the formula (III)
4 . The compound according to claim 1 , characterized in that said X is selected to be equal to H, said R is selected to be equal to H, said Y is selected to be equal to
and the compound is represented by the formula (IV)
5 . A compound of formula (V)
6 . Micro-organism Streptomyces sp. NAI38640, deposited as number DSM26212 on Jul. 20, 2012, in the Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH (DSMZ).
7 . A method of using the compound of formula (I) according to claim 1 as a medicament, characterized in that it comprises administering said compound in its pharmaceutically-acceptable form.
8 . A method of using the compound of formula (I) according to claim 1 in the treatment of infectious disease, characterized in that it comprises said compound in its pharmaceutically-acceptable form.
9 . A process for preparing the compound of formula (I) of claim 1 , characterized in that it comprises culturing the Streptomyces spp. NAI38640, deposited as number DSM26212 on Jul. 20, 2012 in the Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH (DSMZ), or a variant thereof, or a mutant thereof, able to produce a compound of formula (II)
collecting the product of formula (II) from the mycelium and/or fermentation broth, isolating the pure compound of formula (II) through chromatographic techniques, lengthening the glutamine chain of compound (II) through hydrolysis of the primary amide and subsequent amidation with a suitable R—NH 2 group, and removing the N-hydroxylic group through reduction with suitable reducing agents.
10 . A process for preparing the compound of formula (I) of claim 1 , characterized in that it comprises condensing a suitably protected or a modified dipeptide with a properly protected aminonucleoside, subsequently removing the protecting groups, and guanylating.
11 . A pharmaceutical composition comprising the compound of formula (I) of claim 1 as an active ingredient in admixture with a pharmaceutically acceptable vehicle.
12 . A method of using the pharmaceutical composition according to claim 11 as a medicament, characterized in that it comprises administering said pharmaceutical composition.
13 . A method of using the pharmaceutical composition according to claim 11 in the treatment of infectious disease, characterized in that it comprises administering said pharmaceutical composition.