Method of locking 1alpha-OH of vitamin D compounds in axial orientation

摘要

A method of altering the conformational equilibrium of the A-ring of a 1a-hydroxylated vitamin D compound to lock the chair conformation of the A-ring in a geometry having an axially oriented 1a-hydroxyl, in order to increase its biological activity is disclosed, wherein the step of locking comprises: (1) adding a bond system to the A-ring, which is an anchoring bond system, a flattening bond system or a bridged bond system, or (2) modifying the A-ring by adding one or more substituents which interact with other substituents on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1a-hydroxyl in the axial orientation. These compounds may be suitable for treating diseases such as metabolic bone disease, diseases characterised by abnormal cell proliferation cell differentiation and disorders that are characterised by an imbalance in the immune system.