851028-87-0Relevant academic research and scientific papers
Development of a kilogram-scale synthesis of cis-LC15-0133 tartrate, a potent dipeptidyl peptidase IV inhibitor
Kim, Bong Chan,Kim, Kyu-Young,Lee, Hee Bong,Shin, Hyunik
, p. 626 - 631 (2013/01/03)
(45)-N-Boc-4-fluoro-L-proline methyl ester (4) was prepared from the following sequence of reactions: esterification of trans-4-hydroxy-L-proline (2), Boc protection, and fluorination by DAST. Reaction of 4 with lithiated oxadiazole provided oxadiazolyl ketone 7. Deprotection of the Boc group of 7 and subsequent coupling with bromoacetyl bromide gave bromide 9. Coupling reaction of 9 with excess oxazolidine 16 provided coupled product 17. Unexpectedly, the stereogenic center of 17 was completely epimerized to a virtually 1:1 mixture of cis- and trans-17 at this stage. After the deprotection of the N,O-methylene acetal group of 17 using aqueous ammonium chloride, crystallization induced dynamic resolution (CIDR) of cis- and Awns-mixture of LC15-0133 (1) in the course of tartrate salt formation provided cis-LC15-0133 (1a) tartrate salt in 83% yield (>98% de).
Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: Oxadiazolyl ketones
Koo, Ki Dong,Kim, Min Jung,Kim, Sungsub,Kim, Kyoung-Hee,Hong, Sang Yong,Hur, Gwong-Cheung,Yim, Hyeon Joo,Kim, Geun Tae,Han, Hee Oon,Kwon, O Hwan,Kwon, Tae Sik,Koh, Jong Sung,Lee, Chang-Seok
, p. 4167 - 4172 (2008/02/09)
Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.
