132101-95-2Relevant academic research and scientific papers
Pd/C(en)-catalyzed chemoselective hydrogenation with retention of the N-Cbz protective group and its scope and limitations
Hattori, Kazuyuki,Sajiki, Hironao,Hirota, Kosaku
, p. 8433 - 8441 (2007/10/03)
A chemoselective method for the hydrogenation of acetylene, olefin, azide, nitro and benzyl ester functionalities with retention of the aliphatic N-Cbz group was established. The chemoselectivity was accomplished by using a combination of 5% Pd/C-ethylenediamine [5% Pd/C(en)] and THF (or 1,4-dioxane) as a solvent, and the scope and limitations of this methodology were investigated. These results reinforce the utility of N-Cbz protective groups in synthetic chemistry, especially in peptide synthesis. (C) 2000 Elsevier Science Ltd.
Synthesis and activity of 6-substituted purine linker amino acid immunostimulants
Zacharie, Boulos,Gagnon, Lyne,Attardo, Giorgio,Connolly, Timothy P.,St-Denis, Yves,Penney, Christopher L.
, p. 2883 - 2894 (2007/10/03)
A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,V-dimethylamino)purin-9- yl]pentoxy]carbonyl]D-arginine (BCH-1393, 4a), displayed an in vitro stimulation of CTLs comparable to interleukin 2 (IL 2). BCH-1393 increased the CTL response between 10-9 M and 10-5 M. Further, this potent in vitroactivity was reflected as a significant increase in CTL cell number in vivo. However, immunophenotyping of some of the other equipotent compounds did not reveal a parallel relative increase in CTLs in vivo. It was difficult to formulate a rigorous structure-activity relationship based on in vitro CTL activity. Nevertheless, the activity was dependent upon the nature of the 6- substituent on the purine, the type and stereochemistry of the amino acid, and the distance and spatial freedom between the purine and amino acid as defined by the length and rigidity of the linker. These compounds were generally nontoxic, as exemplified by BCH-1393. BCH-1393 is a promising immunostimulant which may be targeted for those disease states which require an increased CTL or TH1 type response.
New Inhibitors of Human Renin That Contain Novel Replacements at the P2 Site
Doherty, Annette M.,Kaltenbronn, James S.,Hudspeth, James P.,Repine, Joseph T.,Roark, William H.,et al.
, p. 1258 - 1271 (2007/10/02)
A series of renin inhibitors with novel modifications at the P2 site has been prepared.Structure-activity relationships reveal that for a particular P2 fragment the in vitro potency is highly dependent on the nature of the P2' portion in addition to the P1-P1' group.The length of the P2 side chain and choice of ε-N P2 substitution have been found to be important for in vitro potency although the degree of unsaturation in the P2 side chain is not particularly significant.Molecular modeling studies have shown that it is possible for the P2 side chain to interact unfavorably with the P2' bi nding site.It has been possible to control the specificity for renin over cathepsin D by correct modification at the P2' and P1-P1' sites.Variations at the P4 site have been utilized to lower the log P values of these renin inhibitors while maintaining high potency.Compound 42, which exhibited an IC50 of 3.70 nM, log P of 2.3, and showed high specificity for renin, was selected for further studies.It was found to be very stable under neutral, acidic, and basic conditions.In simulated intestinal juice, compound 42 had a half-life of 37 min while it was virtually unaffected by simulated gastric juice after 4 h.Compound 42 produced a significant hypotensive response upon intravenous administration to the salt-depleted normotensive cynomolgus monkey.
