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

被引：4

作者：

Yoneyama, Hiroki ^{[1
]}

Magata, Takuji ^{[1
]}

Uemura, Kenji ^{[1
]}

Usami, Yoshihide ^{[1
]}

Tanaka, Satoshi ^{[1
]}

Takaoka, Masanori ^{[1
]}

Harusawa, Shinya ^{[1
]}

机构：

[1] Osaka Univ Pharmaceut Sci, Takatsuki, Osaka 5691094, Japan

来源：

SYNTHESIS-STUTTGART | 2015年 / 47卷 / 09期

关键词：

S-alkyl-N-alkylisothiourea; histamine H-3 receptor; non-imidazole; H-3; antagonist; cancer growth inhibition; H-3 RECEPTOR ANTAGONISTS; THERAPEUTIC TARGETS; MOLECULAR-CLONING; ISOTHIOUREAS; DERIVATIVES; THIOUREA; RELEASE; LIGANDS;

D O I：

10.1055/s-0034-1380345

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A potent histamine H-3 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, C-2 homologue of OUP-186.

引用

页码：1291 / 1302

页数：12

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