Chemistry: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.[1][2]
Synthesis
The synthesis of SHA-68 was shown in a patent (ref example 1, Ex 1, Ex 2, Ex 16).[3]
The Grignard reaction between Methyl 2-piperazine carboxylate [2758-98-7] (1) and phenylmagnesium bromide [100-58-3] (2) occurs to give alpha,alpha-Diphenyl-2-piperazinemethanol [17532-20-6] (3). {This compound is called Azapipradrol}. Protection of the sterically more accessible piperazine nitrogen with Boc anhydride occurs to give PC23122074 (4). Treatment with ethyl chloroformate [541-41-3] (5) gives the cyclic urethane and hence, PC68420957 (6). Deprotection of the Boc group in the presence of trifluoroacetic acid gave 1,1-Diphenyltetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one [847555-93-5] [847556-28-9] (7). Lastly, treatment with 4-fluorophenyl isocyanate [1195-45-5] (8) gave the substituted urea, thus completing the synthesis of SHA-68 (9).
SAR reveals similarity to RTI-118 & contains the same precursor.
See also
References
- ↑ Fukatsu K, Nakayama Y, Tarui N, Mori M, Matsumoto H, Kurasawa O, Banno H. Bicyclic Piperazine Compound and Use Thereof. PCT Patent WO 2005/021555 A1. Published 26.08.2004
- ↑ "Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-apyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68), a selective antagonist of the neuropeptide S receptor"]. The Journal of Pharmacology and Experimental Therapeutics 325 (3): 893–901. June 2008. doi:10.1124/jpet.107.135103. PMID 18337476.
- ↑ Kohji Fukatsu, et al. WO2005021555 (to Takeda Pharmaceutical Co Ltd).
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