Tirilazad
Tirilazad is a drug that has been proposed to treat acute ischaemic stroke. When tested on animal models, tirilazad protects brain tissue, and reduces brain damage. However, the drug fails to treat, and even worsens a stroke when studied on a human being.
Tirilazad is a 21-aminosteroid and belongs to the "Lazaroid" family of agents. The metabolite of tirilazad is called U-89678 . Other known lazaroids found in the data base include the following list of agents: U-74389G, U-74500, U-75412E & U-87999 . The name comes from Lazarus — the biblical figure raised from the dead — because these compounds were thought to “bring cells back to life” after oxidative injury.
More recently Tirilazad has shown some promising results in treating traumatic brain inhury.
Synthesis
The chemical synthesis has been reported:Patent : Precursor patent:
- The starting material is called 21-Hydroxypregna-1,4,9,16-tetraene-3,20-dione 21-acetate . Soft addition of methylmagnesium chloride in the presence copper propionate, followed by saponification of the ester group furnished 21-Hydroxy-16alpha-methylpregna-1,4,9-triene-3,20-dione . FGI of the hydroxy group to the tosyl leaving group, followed by displacement with sodium iodide led to 21-Iodo-16alphamethylpregna-1,4,9-triene-3,20-dione, PC14878745.
- The reaction of 2,4,6-Trichloropyrimidine with 2 equivalents of Pyrrolidine gave 4-chloro-2,6-dipyrimidine . Further reaction of the remaining halogen with piperidine yielded 4--2,6-dipyrimidine .
- Convergent synthesis between 3 and 8 completed the synthesis of tirilazad.