Spatially-defined macrocyclic compounds useful for drug discovery
View Patent ↗Novel spatially-defined macrocyclic compounds containing specific conformational control elements are disclosed. Libraries of these macrocycles are then used to select one or more macrocycle species that exhibit a specific interaction with a particular biological target. In particular, compounds according to the invention are disclosed as agonists or antagonists of a mammalian motilin receptor and a mammalian ghrelin receptor.
1. A compound of formula W-T-X, wherein T is selected from the group consisting of
wherein:
W is selected from the group consisting of —OH, —NH 2 and —NHR 3 , wherein R 3 is unsubstituted methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, n-butyl, isobutyl or sec-butyl, and X is —NH 2 or —NHR 3 , wherein R 3 is unsubstituted methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, n-butyl, isobutyl or sec-butyl;
(W) indicates the point of attachment of T to W; and (X) indicates the point of attachment of T to X, and
W and/or X may be optionally protected by one or more protecting groups.
2. The compound of claim 1 , wherein R 3 is methyl, ethyl, propyl or isopropyl.
3. The compound of claim 1 , wherein W and/or X is protected by one or more protecting groups selected from the group consisting of tert-butoxycarbonyl (Boc), dimethyl-3,5-dimethoxybenzyloxycarbonyl (Ddz), and 9-fluorenylmethoxycarbonyl (Fmoc).
4. The compound of claim 1 , wherein T is the following:
5. The compound of claim 1 , wherein T is the following: