229006-88-6Relevant articles and documents
Synthesis, binding affinity and structure-activity relationships of novel, selective and dual targeting CCR2 and CCR5 receptor antagonists
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
, p. 2407 - 2422 (2015/03/04)
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
Convenient efficient synthesis of TAK-779, a nonpeptide CCR5 antagonist: Development of preparation of various ammonium salts using trialkylphosphite and N-halogenosuccinimide
Ikemoto, Tomomi,Nishiguchi, Atsuko,Mitsudera, Hiroyuki,Wakimasu, Mitsuhiro,Tomimatsu, Kiminori
, p. 1525 - 1529 (2007/10/03)
A convenient and efficient synthesis of TAK-779 (1a), a nonpeptide CCR5 antagonist, has been achieved. The new methylation of tertiary amine (2) using trimethyl phosphite and N-chlorosuccinimide, followed by the addition of HCl led to ammonium chloride (1a) in 89% isolated yield without requiring a chromatographic method. By this preparation, ammonium methanesulfonate (1e) could be obtained in 75% isolated yield.
Development of a new synthetic route of a non-peptide CCR5 antagonist, TAK-779, for large-scale preparation
Ikemoto, Tomomi,Ito, Tatsuya,Hashimoto, Hideo,Kawarasaki, Tadao,Nishiguchi, Atsuko,Mitsudera, Hiroyuki,Wakimasu, Mitsuhiro,Tomimatsu, Kiminori
, p. 520 - 525 (2013/08/07)
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.
