161596-47-0Relevant articles and documents
Novel series of highly potent non-peptide growth hormone secretagogues with improved bioavailability
Ishige, Hirohide,Ishiyama, Nobuo,Mimura, Mitsuo,Hayashida, Mitsuo,Okuno, Tadashi,Ukai, Kiyoharu,Kiyofuji, Takeshi,Yoneda, Yasuo,Tauchi, Shinji,Aoyama, Akinori,Inoguchi, Kiyoshi
, p. 561 - 566 (2006)
The discovery and the SAR of acylproline derivatives as highly potent growth hormone secretagogues (GHSs) with good oral bioavailability are described. One representative compound, N-[3-(2,2-dimethylpropylamino)-2-hydroxypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)- carbonylamino]-3-naphthalen-2-ylpropionamide (4e), showed potent GHS activity (ED50=1 nM) and good oral bioavailability (BA=33.2%). Moreover, the optically pure N-[3-(2,2-dimethylpropylamino)-2(S)-hydroypropyl]-2(R)-[1-(2,2-dimethylpropionyl)pyrrolidine-2(S)-carbonylamino]-3-naphthalen-2- ylpropionamide ((2S)-4e) showed a good metabolic stability against in vitro clearance (human liver microsome) with potent GHS activity.
Preparation method of rivaroxaban intermediate
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Paragraph 0057-0065, (2020/05/02)
The invention provides a preparation method of a rivaroxaban intermediate. The preparation method comprises: (1) carrying out a reaction on a compound A and a compound B in an alcohol or an alcohol aqueous solution to obtain a compound C; and (2) reacting the compound C with N,N'-carbonyldiimidazole in a reaction solvent selected from acetonitrile or butyronitrile to obtain a reaction solution containing a compound D, and performing cooling crystallization to obtain a compound D.
Low-cost and high-purity S-glycidyl phthalimide synthesis method
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Paragraph 0062; 0063; 0064; 0065; 0066, (2019/03/10)
The invention relates to a low-cost and high-purity S-glycidyl phthalimide synthesis method, which comprises: carrying out a substitution reaction on potassium phthalimide and R-2,2-disubstituted-4-halomethyl-1,3-dioxolane to generate N-(S-2,2-disubstituted-1,3-dioxolane-4-)methylphthalimide, carrying out a ketone (aldehyde) removing ring-opening reaction to produce N-2-S-hydroxy-3-halogenated n-propyl phthalimide, and finally carrying out an elimination reaction to remove hydrogen halide so as to generate S-glycidyl phthalimide, wherein S-glycidyl phthalimide is the key intermediate for the preparation of rivaroxaban. According to the present invention, the synthesis method has advantages of inexpensive and easily-available raw materials, high stability, high reaction selectivity and highproduction efficiency, and the obtained S-glycidyl phthalimide has advantages of low cost and high purity, and is favorable for the industrial production of high-purity rivaroxaban.