SHA-68

SHA-68 is a drug which acts as a selective, non-peptide antagonist at the neuropeptide S receptor NPSR. In animal studies it reduced motor stereotypes, and blocks the stimulant action of neuropeptide S.

Synthesis

The synthesis of SHA-68 was shown in a patent.
The Grignard reaction between Methyl 2-piperazine carboxylate and phenylmagnesium bromide occurs to give alpha,alpha-Diphenyl-2-piperazinemethanol .. Protection of the sterically more accessible piperazine nitrogen with Boc anhydride occurs to give . Treatment with ethyl chloroformate gives the cyclic urethane and hence, . Deprotection of the Boc group in the presence of trifluoroacetic acid gave 1,1-Diphenyltetrahydro-1H-oxazolopyrazin-3-one . Lastly, treatment with 4-fluorophenyl isocyanate gave the substituted urea, thus completing the synthesis of SHA-68.
SAR reveals similarity to RTI-118 and contains the same precursor.