186371-25-5Relevant academic research and scientific papers
Design, synthesis, and pharmacological characterization of novel endomorphin-1 analogues as extremely potent μ-opioid agonists
Liu, Xin,Wang, Yuan,Xing, Yanhong,Yu, Jing,Ji, Hong,Kai, Ming,Wang, Zilong,Wang, Dan,Zhang, Yixin,Zhao, Depeng,Wang, Rui
, p. 3102 - 3114 (2013/06/04)
Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural α-methylene- β-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt1, (R/S)-βPro2, and (ph)Map4/(2-furyl)Map4. All of the analogues showed a high affinity for the μ-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt1-(R)-βPro 2-Trp3-(2-furyl)Map4 (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki μ = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.
A new class of highly potent and selective endomorphin-1 analogues containing α-methylene-β-aminopropanoic acids (map)
Wang, Yuan,Xing, Yanhong,Liu, Xin,Ji, Hong,Kai, Ming,Chen, Zongyao,Yu, Jing,Zhao, Depeng,Ren, Hui,Wang, Rui
, p. 6224 - 6236 (2012/09/05)
A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural α-methylene-β-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the μ-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (Kiμ = 0.221 nM) and efficacy (EC 50 = 0.0334 nM, Emax = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the μ-opioid receptor.
Effective enantioselective approach to α-aminoalkylacrylic acid derivatives via a synthetic equivalent of an asymmetric Baylis-Hillman reaction: Application to the synthesis of two C-2′ hydroxymethyl analogues of docetaxel
Genisson, Yves,Massardier, Christine,Gautier-Luneau, Isabelle,Greene, Andrew E.
, p. 2869 - 2872 (2007/10/03)
Two C-2′ hydroxymethyl analogues of docetaxel have been synthesized from 10-desacetyl baccatin III and enantiopure (3S)-3-(N-tert-butoxycarbonylamino)-2-methylene-3-phenylpropanoic acid; the latter was prepared via the use of a new method, which is discus
