70972-98-4Relevant academic research and scientific papers
Dynamic combinatorial evolution within self-replicating supramolecular assemblies
Nguyen, Remi,Allouche, Lionel,Buhler, Eric,Giuseppone, Nicolas
, p. 1093 - 1096 (2009)
(Figure Presented) Survival of the fittest: Self-assemblies made of dynamic block copolymers (dynablocks) can self-replicate by catalyzing the formation of their own building blocks. Moreover, in competition experiments, the differential thermodynamic sta
Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors
Li, Hao,Sibley, Christopher D.,Kharel, Yugesh,Huang, Tao,Brown, Anne M.,Wonilowicz, Laura G.,Bevan, David R.,Lynch, Kevin R.,Santos, Webster L.
, (2021/01/07)
The sphingosine 1-phosphate (S1P) signaling pathway is an attractive target for pharmacological manipulation due to its involvement in cancer progression and immune cell chemotaxis. The synthesis of S1P is catalyzed by the action of sphingosine kinase 1 or 2 (SphK1 or SphK2) on sphingosine and ATP. While potent and selective inhibitors of SphK1 or SphK2 have been reported, development of potent dual SphK1/SphK2 inhibitors are still needed. Towards this end, we report the structure–activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors with 22d being the most potent dual SphK1/SphK2 inhibitor (SphK1 Ki = 0.679 μM, SphK2 Ki = 0.951 μM) reported in this series. 22d inhibited the growth of engineered Saccharomyces cerevisiae and decreased S1P levels in histiocytic lymphoma myeloid cell line (U937 cells), demonstrating inhibition of SphK1 and 2 in vitro. Molecular modeling studies of 22d docked inside the Sph binding pocket of both SphK1 and SphK2 indicate essential hydrogen bond between the 2-(hydroxymethyl)pyrrolidine head to interact with aspartic acid and serine residues near the ATP binding pocket, which provide the basis for dual inhibition. In addition, the dodecyl tail adopts a “J-shape” conformation found in crystal structure of sphingosine bound to SphK1. Collectively, these studies provide insight into the intermolecular interactions in the SphK1 and 2 active sites to achieve maximal dual inhibitory activity.
Potential for minimal self-replicating systems in a dynamic combinatorial library of equilibrating imines
Morrow, Sarah M.,Bissette, Andrew J.,Fletcher, Stephen P.
supporting information, p. 5005 - 5010 (2017/07/27)
The presence of a self-replicator in a dynamic combinatorial library (DCL) offers function above and beyond libraries under thermodynamic control, moving towards out-of-equilibrium systems which mimic biological networks. In this work, we examine a previously reported DCL based on reversible imine formation to give amphiphilic structures. The amphiphilic imines were readily produced in organic solvents, and were found to aggregate to micelles in water as judged by diffusion-ordered NMR spectroscopy, dynamic light scattering and interferometric scattering microscopy. Unfortunately, the autocatalytic formation of products was not observed in water, and preformed imines slowly hydrolysed to aldehyde and amine components at neutral pD.
Bilitrienones from the chemical oxidation of dodecasubstituted porphyrins
Ongayi, Owendi,Vicente, M. Gra?a H.,Ghosh, Brahma,Fronczek, Frank R.,Smith, Kevin M.
experimental part, p. 63 - 67 (2010/03/04)
The structure of the ring-opened product from direct oxidation of meso-tetra-arylporphyrins has been controversial for three decades. Herein we show that bilitrienones 2 are obtained from oxidation of metal-free dodecasubstituted porphyrins 1 in the prese
Novel dicarboxylic acid derivatives
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Page/Page column 17, (2008/06/13)
The present patent application concerns new compounds of formula (I): displaying agonistic activity at sphingosine-1-phosphate (S1P) receptors, their process of preparation and their use as immunosuppressive agents.
Synthesis and characterization of fully conjugated porphyrin tapes
Ikeue, Takahisa,Aratani, Naoki,Osuka, Atsuhiro
, p. 293 - 302 (2007/10/03)
meso-meso, β-β, β-β Triply-linked zinc(II) porphyrin tapes were synthesized by powerful oxidation of meso-meso-linked zinc(II) porphyrin arrays up to tetramers with DDQ-Sc(OTf)3. Coordination of butylamine to zinc(II) ions of porphyrin rings di
USE OF CYSTEINYL LEUKOTRIENE 2 RECEPTOR ANTAGONISTS
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Page/Page column 16-17, (2010/02/13)
The instant invention provides a method for treating and/or reducing the risk for atherosclerosis, pulmonary fibrosis and stroke, comprising administering an effective amount of a cysteinyl leukotriene 2 receptor antagonist, including a selective cysteiny
The discovery of 3-(N-alkyl)aminopropylphosphonic acids as potent S1P receptor agonists
Hale, Jeffrey J.,Doherty, George,Toth, Leslie,Li, Zhen,Mills, Sander G.,Hajdu, Richard,Keohane, Carol Ann,Rosenbach, Mark,Milligan, James,Shei, Gan-Ju,Chrebet, Gary,Bergstrom, James,Card, Deborah,Rosen, Hugh,Mandala, Suzanne
, p. 3495 - 3499 (2007/10/03)
3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes.
Development of novel EDG3 antagonists using a 3D database search and their structure-activity relationships
Koide, Yuuki,Hasegawa, Takeshi,Takahashi, Atsuo,Endo, Akira,Mochizuki, Naoki,Nakagawa, Masako,Nishida, Atsushi
, p. 4629 - 4638 (2007/10/03)
Sphingosine-1-phosphate (S1P) is an intracellular second messenger and an extracellular mediator through endothelial differentiation gene (EDG) receptors, which are a novel class of G-protein-coupled receptors. Although EDG has attracted much attention because of its various roles, no selective agonists or antagonists have yet been developed. This could account for the delay in clarifying the physiological roles of members of the EDG family. Because precise structural information on EDG receptors is not yet available, pharmacophore models were generated based on structural information for S1P using the rational drug design software Catalyst. Novel antagonists, 2-alkylthiazolidine-4-carboxylic acids, were retrieved from a three-dimensional database search using the pharmacophore models, and these showed activity for EDG3. On the basis of their nonphosphoric acid structure, more potent antagonists, 2-(m- or p-heptylphenyl)thiazolidine-4-carboxylic acid, were developed.
Synthesis of Unbranched 4-Alkylbenzaldehydes
Osman, Maged A.
, p. 2448 - 2449 (2007/10/02)
The preparation of unbranched 4-alkylbenzaldehydes free of positional and branched-chain isomers by different methods is described.A one-step preparation of the aldehydes is reported which involves the direct hydrogenation of a Friedel-Craft's complex in the presence of Pd/C catalyst.
