- Synthesis, binding affinity and structure-activity relationships of novel, selective and dual targeting CCR2 and CCR5 receptor antagonists
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CCR2 and CCR5 receptors play a key role in the development and progression of several inflammatory, cardiovascular and autoimmune diseases. Therefore, dual targeting of both receptors appeals as a promising strategy for the treatment of such complex, mult
- Junker, Anna,Kokornaczyk, Artur K.,Zweemer, Annelien J. M.,Frehland, Bastian,Schepmann, Dirk,Yamaguchi, Junichiro,Itami, Kenichiro,Faust, Andreas,Hermann, Sven,Wagner, Stefan,Sch?fers, Michael,Koch, Michael,Weiss, Christina,Heitman, Laura H.,Kopka, Klaus,Wünsch, Bernhard
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supporting information
p. 2407 - 2422
(2015/03/04)
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- Development of a new synthetic route of a non-peptide CCR5 antagonist, TAK-779, for large-scale preparation
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A new large-scalable preparation of TAK-779 (1), a non-peptide CCR5 antagonist, has been developed. The route selection was focused on in the process research. The selective reduction of commercially available benzonitrile derivative (4) as the starting material with sodium bis(2-methoxyethoxy)aluminum hydride followed by the Wittig reaction, hydrogenation, and intramolecular acylation gave benzocycloheptanone (7) in good yield. The conversion of α,α-unsaturated carboxylic acid (8) led from 7 to benzyl alcohol (9) and shortened the number of steps using non-protected 4-aminobenzyl alcohol. The reductive alkylation of Me2NH and tetrahydro-4H-pyran-4-one (12) smoothly gave a tertiary amine (3). The coupling of 2 chlorinated 9, and 3 successfully led to an ammonium chloride (1). A new inexpensive preparation which did not require a chromatographic method was achieved.
- Ikemoto, Tomomi,Ito, Tatsuya,Hashimoto, Hideo,Kawarasaki, Tadao,Nishiguchi, Atsuko,Mitsudera, Hiroyuki,Wakimasu, Mitsuhiro,Tomimatsu, Kiminori
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p. 520 - 525
(2013/08/07)
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- Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety
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The search for new small-molecule CCR5 antagonists by high-throughput screening (HTS) of the Takeda chemical library using [125I]RANTES and CHO/CCR5 cells led to the discovery of lead compounds (A, B) with a quaternary ammonium or phosphonium m
- Shiraishi, Mitsuru,Aramaki, Yoshio,Seto, Masaki,Imoto, Hiroshi,Nishikawa, Youichi,Kanzaki, Naoyuki,Okamoto, Mika,Sawada, Hidekazu,Nishimura, Osamu,Baba, Masanori,Fujino, Masahiko
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p. 2049 - 2063
(2007/10/03)
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