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 W and X are independently selected from the group consisting of —OH, —NH 2 and —NHR 3 , where R 3 is lower alkyl, and T is selected from the group consisting of
wherein (W) indicates the point of attachment of T to W; and (X) indicates the point of attachment of T to X, and wherein W and X optionally contain a protecting group.
2. The compound of claim 1 having one or more protecting groups selected from the group consisting of tert-butoxycarbonyl (Boc), dimethyl-3,5-dimethoxybenzyloxycarbonyl (Ddz), 9-fluorenylmethoxycarbonyl (Fmoc), tert-butyldimethylsilyl (TBS or TBDMS), tert-butyldiphenylsilyl (TBDPS), tetrahydropyranyl (THP), acetyl (Ac) and benzyl (Bn).
3. The compound of claim 1 , wherein T is the following:
wherein (W) indicates the point of attachment of T to W; and (X) indicates the point of attachment of T to X.