The present invention relates to the medicinal use of small organic compounds, in particular amide and urea derivatives, for the treatment of congenital disorders of glycosylation, and in particular PMM2 congenital disorder of glycosylation.
1. Compound of formula (I) <img class="EMIRef" id="495200330-ib0049" /> wherein R<1> is - a phenyl ring, or a 6- or 5-membered heterocyclic ring containing one or more heteroatoms selected from O, N and S; wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, phenyl, C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or =NH; - a fused ring group consisting of 2 or 3 rings, wherein each ring is independently a phenyl ring or a 6- or 5-membered heterocyclic ring containing one or more heteroatoms selected from O, N and S; and wherein each ring is independently unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, phenyl, C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or =NH; - NHR<4> , wherein R<4> is a phenyl ring, or a 6- or 5-membered heterocyclic ring containing one or more heteroatoms selected from O, N and S; and wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, phenyl, C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or =NH; or - -CH<2> -R<5> , wherein R<5> is -CN, or a phenyl ring, or a 6- or 5-membered heterocyclic ring containing one or more heteroatoms selected from O, N and S; and wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, phenyl, C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or =NH; R<2> is -(CH<2> )<n> -X, wherein n is 0, 1, 2 or 3, and X is - a phenyl ring, or a 6- or 5-membered heteroaromatic ring containing one or more heteroatoms selected from O, N and S; and wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, CF<3> , C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or -NHC(O)Me; or - a fused ring group consisting of 2 rings, wherein each ring is independently a phenyl ring or a 6- or 5-membered heteroaromatic ring containing one or more heteroatoms selected from O, N and S; and wherein each ring is independently unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen, CF<3> , C<1> -C<6> alkyl (preferably methyl), -O-C<1> -C<6> alkyl (preferably OMe), =O, or -NHC(O)Me; R<3> is H or -(CH<2> )<n> -X, wherein X and n are as defined for R<2> ; or R<2> and R<3> , together to the nitrogen atom to which they are bound, form a pyrrolidine or piperidine ring; or a pharmaceutically acceptable salt or solvate thereof; for use as a medicament. 2. Compound, salt or solvate for use according to claim 1, wherein R<1> is - a phenyl ring, or a 6- or 5-membered heteroaromatic ring containing one or two heteroatoms selected from O and N; and wherein the rings are unsubstituted or substituted at one or more available positions with halogen, -O-C<1> -C<6> alkyl (preferably OMe) or C<1> -C<6> alkyl, (preferably Me); or - NHR<4> , wherein R<4> is a phenyl ring, or a 6- or 5-membered heteroaromatic ring containing one or two heteroatoms selected from O and N; and wherein the rings are unsubstituted or substituted at one or more available positions with halogen, -O-C<1> -C<6> alkyl (preferably OMe) or C<1> -C<6> alkyl, (preferably Me). 3. Compound, salt or solvate for use according to any preceding claim, wherein R<1> is a phenyl ring, or a 6-membered heteroaromatic ring containing one or two N heteroatoms; and wherein the rings are unsubstituted or substituted at one or more available positions with halogen. 4. Compound, salt or solvate for use according to any preceding claim, wherein R<1> is a phenyl ring; wherein the ring is unsubstituted or substituted at one or more available positions with halogen. 5. Compound, salt or solvate for use according to claims 1 or 2, wherein R<1> is NHR<4> , wherein R<4> is a phenyl ring, or a 6-membered heteroaromatic ring containing one or two N heteroatoms; and wherein the rings are unsubstituted or substituted at one or more available positions with halogen. 6. Compound, salt or solvate for use according to claims 1-2 or 5, wherein R<1> is NHR<4> , wherein R<4> is a phenyl ring; wherein the ring is unsubstituted or substituted at one or more available positions with halogen. 7. Compound, salt or solvate for use according to any preceding claim, wherein R<2> is a phenyl ring, or a 6- or 5-membered heteroaromatic ring containing one or more N heteroatoms; and wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen or C<1> -C<6> alkyl. 8. Compound, salt or solvate for use according to any preceding claim wherein R<2> is phenyl or pyridyl; wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , halogen or C<1> -C<6> alkyl. 9. Compound, salt or solvate for use according to any preceding claim, wherein R<3> is H or a phenyl ring, or a 6- or 5-membered heteroaromatic ring containing one or more N heteroatoms; and wherein the ring is unsubstituted or substituted at one or more available positions with NH<2> , OH, halogen or C<1> -C<6> alkyl. 10. Compound, salt or solvate for use according to any preceding claim, wherein R<3> is H, or phenyl or pyridyl; wherein the rings are unsubstituted or substituted at one or more available positions with NH<2> , halogen or C<1> -C<6> alkyl. 11. Compound for use according to claim 1, wherein the compound is: <img class="EMIRef" id="495200330-ib0050" /> <img class="EMIRef" id="495200330-ib0051" /> <img class="EMIRef" id="495200330-ib0052" /> <img class="EMIRef" id="495200330-ib0053" /> <img class="EMIRef" id="495200330-ib0054" /> <img class="EMIRef" id="495200330-ib0055" /> <img class="EMIRef" id="495200330-ib0056" /> <img class="EMIRef" id="495200330-ib0057" /> <img class="EMIRef" id="495200330-ib0058" /> <img class="EMIRef" id="495200330-ib0059" /> <img class="EMIRef" id="495200330-ib0060" /> or <img class="EMIRef" id="495200330-ib0061" /> or a pharmaceutically acceptable salt or solvate thereof. 12. Compound for use according to claim 1, wherein the compound is: <img class="EMIRef" id="495200330-ib0062" /> <img class="EMIRef" id="495200330-ib0063" /> <img class="EMIRef" id="495200330-ib0064" /> <img class="EMIRef" id="495200330-ib0065" /> or a pharmaceutically acceptable salt or solvate thereof. 13. Compound for use according to claim 1, wherein the compound is: <img class="EMIRef" id="495200330-ib0066" /> or a pharmaceutically acceptable salt or solvate thereof. 14. Compound, salt or solvate for use according to any preceding claim, for use in the treatment of a congenital disorder of glycosylation, preferably PMM2-CDG. 15. Pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as defined in any of claims 1-13, and a pharmaceutically acceptable excipient.