7141-88-0Relevant academic research and scientific papers
Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation
Oda, Tsuneo,Notoya, Kohei,Gotoh, Masayuki,Taketomi, Shigehisa,Fujisawa, Yukio,Makino, Haruhiko,Sohda, Takashi
, p. 751 - 760 (2007/10/03)
In a search for therapeutic agents for the treatment of osteoporosis and bone fracture, we found that 2-benzothiopyran-1-carboxamide derivatives 1, derived from ipriflavone as a lead compound, increase cellular alkaline phosphatase activity in cultures of rat bone marrow stromal cells. Further modification of 1 has led to the discovery of more potent 3-benzothiepin-2- carboxamide derivatives 2. Of these, 3-benzothiepin derivatives bearing a 4- (dialkoxyphosphorylmethyl)phenyl group on the 2-carboxamide moiety such as 2h and 2q exhibited significant improvement of activity compared to ipriflavone. Asymmetric synthesis of 2h and 2q revealed that the (-)-isomers possessed activities superior to those of the (+)-isomers. Further evaluation of these compounds using the mouse osteoblastic cell line MC3T3-E1 revealed that (-)- 2q enhanced the effect of bone morphogenetic protein. In addition, application of a sustained-release agent containing 2q increased the area of newly formed bone in a rat skull defect model. Based on these findings, (-)- 2q was selected for further investigation as a new drug stimulating bone formation. Synthesis and structure-activity relationships for this novel series of 2-benzothiopyran and 3-benzothiepin derivatives are detailed.
Synthesis of heterocycles from products of the anion arylation of unsaturated compounds. 3. 2-Arylimino-5-arylmethyl-4-thiazolidones
Obushak,Matiichuk,Ganushchak,Burlak
, p. 492 - 496 (2007/10/03)
The reaction of esters of 3-aryl-2-bromopropionic acids with N-arylthioureas gives 2-arylimino-5-arylmethyl-4-thiazolidones, which exist in solution as (E) and (Z) isomers of the imino form. 1998 Plenum Publishing Corporation.
Asymmetric catalysis, part 108: Copper catalysts with optically active ligands in the enantioselective Meerwein arylation of activated olefins
Brunner, Henri,Bluechel, Christian,Doyle, Michael P.
, p. 89 - 95 (2007/10/03)
The copper-catalyzed Meerwein reaction of activated olefins with arenediazonium halides leads to a formal addition of aryl halide to the olefinic double bond. Methyl acrylate, p-tolyldiazonium tetrafluoroborate and tetrabutylammonium chloride in anhydrous acetonitrile were used as a model system, the product being methyl a-chloro-β-tolylpropionate. Applying a newly established methodology, the isolated diazonium tetrafluoroborate and an equivalent amount of tetrabutylammonium chloride were added to the olefin and the copper catalyst, containing optically active ligands, such as 2-and 2,6-pyridinyloxazolines and bisoxazolines. The low optical inductions obtained in the room temperature reaction could be raised to 8.7% ee in the low temperature variant at -40 °C. Two phenyl substituents in the neighborhood of the chiral centers in the bisoxazoline ligands of the catalyst and increasing steric bulk in the ester group of the substrate (methyl, ethyl, menthyl) increase the stereoselectivity of the Meerwein arylation. Replacement of the p-tolyldiazonium salt by the mesityldiazonium salt caused the optical induction in the formation of the corresponding mesityl product rise to 19.5% ee. Thus, though considered to be a radical reaction, the Meerwein arylation of activated olefins can be rendered enantioselective by using copper catalysts with optically active ligands.
