19728-63-3Relevant articles and documents
Incorporation of chlorinated analogues of aliphatic amino acids during cell-free protein synthesis
Stigers, Dannon J.,Watts, Zachary I.,Hennessy, James E.,Kim, Hye-Kyung,Martini, Romeo,Taylor, Matthew C.,Ozawa, Kiyoshi,Keillor, Jeffrey W.,Dixon, Nicholas E.,Easton, Christopher J.
, p. 1839 - 1841 (2011)
3-Chloro-Abu and 4-chloro-Nva are biosynthetically incorporated into E. coli peptidyl-Pro cis-trans isomerase B, as substitutes for Val and Leu, respectively. The extent of incorporation is up to ~90%, and substituted protein is catalytically active. By contrast, 4-chloro-Val is not an effective replacement for Ile.
Synthesis and evaluation of in vivo anti-hypothermic effect of all stereoisomers of the thyrotropin-releasing hormone mimetic: Rovatirelin Hydrate
Kobayashi, Naotake,Sato, Norihito,Sugita, Katsuji,Takahashi, Kouji,Sugawara, Tamio,Tada, Yukio,Yoshikawa, Takayoshi
, (2019/11/20)
We discovered the orally active thyrotropin-releasing hormone (TRH) mimetic: (4S,5S)-5-methyl-N-{(2S)-1-[(2R)-2-methylpyrrolidin-1-yl]-1-oxo-3-(1,3-thiazol-4-yl)propan-2-yl}-2-oxo-1,3-oxazolidine-4-carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100-fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti-hypothermic effect of all stereoisomers of 1, which has the (4S),(5S),(2S),(2R) configuration from the N-terminus to the C-terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)-isomer 16 did not show any anti-hypothermic effect. Only the (4S),(5S),(2S),(2S)-isomer 10, which has the (2S)-2-methylpyrrolidine moiety at the C-terminus showed the anti-hypothermic effect similar to 1. Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N-terminus and the (2R) configuration at the middle-part, showed a much lower anti-hypothermic effect than that of 1. On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N-terminus or the (2S) configuration of the C-terminus, have little influence on the anti-hypothermic effect.
PROCESS AND INTERMEDIATES FOR SYNTHESIS OF PEPTIDE COMPOUNDS
-
Paragraph 0176; 0177, (2019/02/13)
Disclosed is a new process and intermediates for preparing dipyrrolidine peptide compounds such as, for example, rapastinel. Advantageously, the process may be industrially scalable and cost-effective and use less toxic reagents and/or solvents. Further, the process may be used to prepare peptide compounds having improved purity.