174769-71-2Relevant academic research and scientific papers
Bioactivatable Pseudotripeptidization of Cyclic Dipeptides to Increase the Affinity toward Oligopeptide Transporter 1 for Enhanced Oral Absorption: An Application to Cyclo(l -Hyp- l -Ser) (JBP485)
Jiang, Qikun,Zhang, Jiangnan,Tong, Peiyue,Gao, Yan,Lv, Yiqin,Wang, Changyuan,Luo, Meiling,Sun, Mengchi,Wang, Jian,Feng, Yao,Cao, Linlin,Wang, Gang,Wang, Yang,Kan, Qiming,Zhang, Tianhong,Wang, Yongjun,Liu, Kexin,Sun, Jin,He, Zhonggui
, p. 7708 - 7721 (2019)
The cyclic dipeptides generally present lower affinity toward intestinal oligopeptide transporter 1 (PEPT1) than the linear dipeptides. JBP485 (cyclo(l-Hyp-l-Ser)) is a low-affinity substrate of PEPT1 with poor oral bioavailability. However, JBP923 (l-Hyp-l-Ser) is a high-affinity substrate of PEPT1 with high oral absorption. We hypothesize that the bioactivatable pseudo-tripeptidization prodrug strategy is promising to increase the affinity of cyclic dipeptides toward PEPT1. To test our hypothesis, we design five amino acid ester prodrugs of JBP485. Compared with JBP485, the optimal prodrug (JBP485-3-CH2-O-valine, J3V) demonstrates improved affinity of PEPT1, oral bioavailability in rats and beagle dogs. Moreover, J3V can dose-dependently protect against liver injury. Additionally, J3V is stable in the gastrointestinal tract, beneficial to the PEPT1-mediated membrane transport, and is bioactivated in the enterocytes and hepatic cells, essential to elicit its bioactivity. In summary, the bioactivatable pseudo-tripeptidization strategy shows potential in increasing affinity of PEPT1 to enhance oral bioavailability of cyclic dipeptides.
Ring - trans -4-L- hydroxyproline acyl -L- serine -O- amino acid ester and salts thereof (by machine translation)
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Paragraph 0051; 0052; 0058; 0059; 0065; 0066, (2020/05/08)
The invention belongs to the technical field of medicines, and relates to an anti - 4 4 4 4-L-serine - O O-amino acid ester and a preparation method, according to the present invention, wherein the (trans - 4 4 4 4)-L-serine - O O-amino acid ester prodrug and pharmaceutically acceptable salts thereof have the structure (I) shown in the formula (II) or, therein R. 1 And R2 The compound of amino acid residue, is capable of significantly increasing the trans-4-L-hydroxyproline acyl - L L-serine small intestine membrane permeability, improving the bioavailability, of the drug. (by machine translation)
Pyrolidine derivatives useful in treatment of hepatitis C virus infection
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Page 14, (2010/11/30)
The present invention relates to novel hepatitis C virus ("HCV") protease inhibitors or other flavivirus protease inhibitors of formula, pharmaceutical compositions containing one or more such inhibitors, methods for preparing such inhibitors, uses of the
