22888-57-9Relevant academic research and scientific papers
An activated building block for the introduction of the histidine side chain in aliphatic oligourea foldamers
Nelli, Yella-Reddy,Douat-Casassus, Céline,Claudon, Paul,Kauffmann, Brice,Didierjean, Claude,Guichard, Gilles
experimental part, p. 4492 - 4500 (2012/07/27)
A new N-Boc-protected monomer for the synthesis of oligourea foldamers containing the (1H-imidazolyl-4yl)methyl side chain of histidine, has been prepared in seven steps from Trt-His(τ-Trt)-OMe. This protecting group combination on histidine was found to
Hit to lead studies on (hetero)arylpyrimidines-Agonists of the canonical Wnt-β-catenin cellular messaging system
Gilbert, Adam M.,Bursavich, Matthew G.,Alon, Nippa,Bhat, Bheem M.,Bex, Frederick J.,Cain, Michael,Coleburn, Valerie,Gironda, Virginia,Green, Paula,Hauze, Diane B.,Kharode, Yogendra,Krishnamurthy, Girija,Kirisits, Matthew,Lam, Ho-Sun,Liu, Yao-Bin,Lombardi, Sabrina,Matteo, Jeanne,Murrills, Richard,Robinson, John A.,Selim, Sally,Sharp, Michael,Unwalla, Raymond,Varadarajan, Usha,Zhao, Weiguang,Yaworsky, Paul J.
scheme or table, p. 366 - 370 (2010/04/06)
A series of (hetero)arylpyrimidines agonists of the Wnt-β-catenin cellular messaging system have been prepared. These compounds show activity in U2OS cells transfected with Wnt-3a, TCF-luciferase, Dkk-1 and tk-Renilla. Selected compounds show minimal GSK-3β inhibition indicating that the Wnt-β-catenin agonism activity most likely comes from interaction at Wnt-3a/Dkk-1. Two examples 1 and 25 show in vivo osteogenic activity in a mouse calvaria model. One example 1 is shown to activate non-phosphorylated β-catenin formation in bone.
Synthesis and x-ray absorption spectroscopy structural studies of Cu(I) complexes of HistidylHistidine peptides: The predominance of linear 2-coordinate geometry
Himes, Richard A.,Ga, Young Park,Barry, Amanda N.,Blackburn, Ninian J.,Karlin, Kenneth D.
, p. 5352 - 5353 (2008/02/05)
Modified His-His dipeptides have been reacted with copper(I) salts to model active-site Cu ions bound by contiguous His residues in certain oxygen-activating copper proteins, as well as amyloid β-peptide. Chelation of copper(I) by these ligands affords linear, two-coordinate complexes as studied structurally by X-ray absorption spectroscopy. The complexes are robust toward oxidation, showing limited to no reactivity with O2, and they bind CO weakly. Reaction with a third ligand (N-methylimidazole) affords complexes with a markedly different structure (distorted T-shaped) and reactivity, binding CO and oxidizing rapidly upon exposure to dioxygen. Copyright
Synthesis and in vitro pharmacology of a series of new chiral histamine H3-receptor ligands: 2-(R and S)-amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives
Kovalainen, Jari T.,Christiaans, Johannes A. M.,Kotisaari, Sanna,Laitinen, Jarmo T.,M?nnist?, Pekka T.,Tuomisto, Leena,Gynther, Jukka
, p. 1193 - 1202 (2007/10/03)
To investigate stereospecificity and the mechanism of activation of the histamine H3-receptor, a series of 2-(R and S)-amino-3-(1H-imidazol-4(5)- yl)propyl ether derivatives were synthesized. In these compounds, the structures of the well-known antagonist iodoproxyfan and the full agonists R- or S-(α)-methylhistamine were combined in one molecule. The obtained 'hybrid' molecules were tested for H3-receptor affinity on rat cerebral cortex. Some selected compounds were further screened for H3-receptor functional activity with GTPγ[35S] autoradiography studies using rat brain tissue sections. The affinity of all the synthesized compounds (-log K(i) = 5.9-7.9) was lower than that found for iodoproxyfan or two of its analogues; however, the compounds showed stereospecificity. The S-configuration of the series of 2-amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives, which resembles the stereochemistry of R-(α)-methylhistamine, was more favorable. Incorporation of an amino group in the propyl chain of iodoproxyfan and analogues did not alter the antagonistic behavior for compounds with an aromatic side chain. However, when also the aromatic moiety was replaced by a cyclohexyl group, the compounds behaved as agonists. This indicates that an interaction between the side chain amino group and the H3-receptor protein is involved in H3-receptor activation. The 2-(S)-amino-3-(1H-imidazol-4(5)- yl)propyl cyclohexylmethyl ether (23) has H3-receptor agonistic properties with high affinity for the histamine H3-receptor (-log K(i) = 7.9 ± 0.2) and might serve as a useful tool for further studies concerning drug design and receptor-ligand interactions.
Facile Preparation of the 1-Hydroxybenzotriazolyl Ester of N-Tritylpyroglutamic Acid and its Application to the Synthesis of TRH, 2>TRH and Analogues Incorporating cis- and trans-4-Hydroxy-L-proline
Papaioannou, Dionissios,Athanassopoulos, Constantinos,Magafa, Vassiliki,Karigiannis, George,Karamanos, Nikos,et al.
, p. 103 - 114 (2007/10/02)
One-pot treatment of N-trityl-L-glutamic acid with DCC followed by DCC-HOBt provided a high yielding synthesis of the 1-hydroxybenzotriazolyl ester of N-trityl-L-pyroglutamic acid (Trt-Glp). Coupling of this active ester with the methyl esters of Nim-tritylated L- and D-histidine provided the corresponding dipeptides which upon saponification and coupling with the methyl esters of L-proline and trans-4-hydroxy-L-proline (Hyp) gave the protected tripeptides Trt-Glp-L and D-His-(Nim-Trt)-Pro-OMe and Trt-Glp-L and D-His(Nim-Trt)-Hyp-OMe. Some 10percent of the epimeric (at the His residue) products were formed during this procedure. Sequential saponification and one-pot Mitsunobu-type intramolecular esterification of the latter tripeptides, followed by transesterification with MeOH, provided the corresponding tripeptides Trt-Glp-L and D-His(Nim-Trt)-cHyp-OMe with inversion of configuration at C-4 of the Hyp ring. The observed conformer ratios about the His-Pro amide for all of these tripeptides are discussed in terms of structural features. Detritylation with trifluoroacetic acid followed by ammonolysis completed the synthesis of TRH and its analogues Glp-D-His-Pro-NH2, Glp-L- and D-His-Hyp-NH2 and Glp-L- and -D-His-cHyp-NH2.
