ABSTRACT
The steroid scaffold was explored as a molecular framework capable of providing useful ligands for receptors or enzymes. When combining this idea with the fact that heterocyclic rings are frequently found in many drug categories, the synthesis of some steroid mimics with heterocyclic rings, such as pyridine and pyrazole at each end of the scaffold, were synthesized from decalin-1,5-dione. A new bis-pyrazole analogue (LC-6) proved to be an effective antiallergic agent as an inhibitor passive cutaneous anaphylaxis (PCA) following oral administration. LC-6 did not inhibit skin reactions due to the release of histamine or other chemical mediators from mast cells; rather, it inhibited the release of histamine and other inflammatory chemicals from mast cells by stabilizing the cells. This mechanism was identical to the one postulated for disodium cromoglycate (DSCG), which is not orally active. LC-6 is orally active and protective for as long as 6 h after oral administration. Preclinical work that included preliminary toxicological and teratological studies were completed, but the drug was never investigated clinically.
