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Synthesis 2015; 47(09): 1291-1302
DOI: 10.1055/s-0034-1380345
DOI: 10.1055/s-0034-1380345
paper
Efficient Synthesis of N-[4-(4-Chlorophenyl)butyl]-S-(3-piperidinopropyl)isothiourea (OUP-186) and Its Analogues Using 2-Nitrophenylacetyl Isothiocyanate: Application to Novel Histamine H3R Antagonists
Further Information
Publication History
Received: 27 January 2015
Accepted after revision: 14 February 2015
Publication Date:
19 March 2015 (online)
Abstract
A potent histamine H3 receptor antagonist OUP-186 with an S-alkyl-N-alkylisothiourea structure was synthesized using 3-phenylpropanoyl isothiocyanate (PPI) as an SCN source. The synthetic route was significantly improved by replacing 3-phenylpropanoyl isothiocyanate with 2-nitrophenylacetyl isothiocyanate (NPAI), giving a 74% overall yield in three steps from 4-(4-chlorophenyl)butylamine. In addition, the 2-nitrophenylacetyl isothiocyanate method successfully yielded two fluorine-containing analogues, and a shorter, C2 homologue of OUP-186.
Key words
S-alkyl-N-alkylisothiourea - histamine H3 receptor - non-imidazole - H3 antagonist - cancer growth inhibitionSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1380345.
- Supporting Information
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