340165-30-2Relevant articles and documents
Structure-Activity Studies of Truncated Latrunculin Analogues with Antimalarial Activity
Varghese, Swapna,Rahmani, Rapha?l,Drew, Damien R.,Beeson, James G.,Baum, Jake,Smith, Brian J.,Baell, Jonathan B.
, p. 679 - 693 (2020/11/30)
Malarial parasites employ actin dynamics for motility, and any disruption to these dynamics renders the parasites unable to effectively establish infection. Therefore, actin presents a potential target for malarial drug discovery, and naturally occurring actin inhibitors such as latrunculins are a promising starting point. However, the limited availability of the natural product and the laborious route for synthesis of latrunculins have hindered their potential development as drug candidates. In this regard, we recently described novel truncated latrunculins, with superior actin binding potency and selectivity towards P. falciparum actin than the canonical latrunculin B. In this paper, we further explore the truncated latrunculin core to summarize the SAR for inhibition of malaria motility. This study helps further understand the binding pattern of these analogues in order to develop them as drug candidates for malaria.
BICYCLIC KETONE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 53; 54, (2019/02/02)
The invention provides novel compounds having the general formula (I): (I) wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.
BICYCLIC COMPOUNDS FOR USE AS RIP1 KINASE INHIBITORS
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Page/Page column 43, (2019/05/07)
The invention provides novel compounds having the general formula (I) or pharmaceutically acceptable salts thereof, wherein RA, RB1, RB2, the A ring and the B ring are as described herein, pharmaceutical compositions inclu
N-[4-OXO-2,3-DIHYDRO-1,5-BENZOXAZEPIN-3-YL]-5,6-DIHYDRO-4H-PYRROLO[1,2-B]PYRAZOL E-2-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS RIP1 KINASE INHIBITORS FOR TREATING E.G. IRRITABLE BOWEL SYNDROME (IBS)
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Page/Page column 37; 41, (2019/11/12)
The invention provides compounds having the general formula (I): or pharmaceutically acceptable salts thereof, wherein X, Y, R1, R2, R7a, R7b, X, RB1, RB2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and the compounds for use as receptor-interacting protein-1 (RIP1) kinase inhibitors in methods of treating e.g. Parkinson's or Alzheimer's disease, irritable bowel disorders (IBD), Crohn's disease, respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD). An exemplary compound is e.g. (4S,6S)-4-fluoro-6-phenyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-l,5- benzoxazepin-3-yl]-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-2- carboxamide (example 11) with a Ki (uM) in a RIP1 assay of 0.0044 uM..
Z -selective alkene isomerization by high-spin cobalt(II) complexes
Chen, Chi,Dugan, Thomas R.,Brennessel, William W.,Weix, Daniel J.,Holland, Patrick L.
supporting information, p. 945 - 955 (2014/02/14)
The isomerization of simple terminal alkenes to internal isomers with Z-stereochemistry is rare, because the more stable E-isomers are typically formed. We show here that cobalt(II) catalysts supported by bulky β-diketiminate ligands have the appropriate kinetic selectivity to catalyze the isomerization of some simple 1-alkenes specifically to the 2-alkene as the less stable Z-isomer. The catalysis proceeds via an "alkyl" mechanism, with a three-coordinate cobalt(II) alkyl complex as the resting state. β-Hydride elimination and [1,2]-insertion steps are both rapid, as shown by isotopic labeling experiments. A steric model explains the selectivity through a square-planar geometry at cobalt(II) in the transition state for β-hydride elimination. The catalyst works not only with simple alkenes, but also with homoallyl silanes, ketals, and silyl ethers. Isolation of cobalt(I) or cobalt(II) products from reactions with poor substrates suggests that the key catalyst decomposition pathways are bimolecular, and lowering the catalyst concentration often improves the selectivity. In addition to a potentially useful, selective transformation, these studies provide a mechanistic understanding for catalytic alkene isomerization by high-spin cobalt complexes, and demonstrate the effectiveness of steric bulk in controlling the stereoselectivity of alkene formation.
An approach to aliphatic 1,8-stereocontrol: Diastereoselective syntheses of (±)-patulolide C and (±)-epipatulolide C
Hoegenauer, E. Kate,Thomas, Eric J.
, p. 6995 - 7014,20 (2012/12/12)
The tin(iv) bromide promoted reaction of 7-hydroxy-7-phenylhept-2- enyl(tributyl)stannane 11 with benzaldehyde gave a mixture of the epimeric 1,8-diphenyloct-3-ene-1,8-diols 12 and so indirect methods were developed for aliphatic 1,8-stereocontrol to comp
Mesoporous aluminosilicate-catalyzed allylation of carbonyl compounds and acetals
Ito, Suguru,Hayashi, Akira,Komai, Hirotomo,Yamaguchi, Hitoshi,Kubota, Yoshihiro,Asami, Masatoshi
, p. 2081 - 2089 (2011/04/19)
A mesoporous aluminosilicate (Al-MCM-41) was found to be an effective heterogeneous catalyst for the reaction of both carbonyl compounds and acetals with allylsilanes to afford the corresponding homoallyl silyl ethers and homoallyl alkyl ethers, respectively. Both the mesoporous structure and the presence of aluminum moiety were indispensable for the high catalytic activity of Al-MCM-41. Moreover, Al-MCM-41 could catalyze the reaction of acetals chemoselectively in the presence of the corresponding carbonyl compounds. The solid acid catalyst Al-MCM-41 could be recovered easily by filtration and could be reused three times without a significant loss of catalytic activity.
Expeditious syntheses of (±)-allo-sedamine and (±)-allo- lobeline via a combination of aza-Sakurai-Hosomi and hydroformylation reactions
Spangenberg, Thomas,Airiau, Etienne,Thuong, Mathieu Bui The,Donnard, Morgan,Billet, Manuella,Mann, André
scheme or table, p. 2859 - 2863 (2009/05/07)
The expeditious preparation of allo-sedamine and allo-lobeline via 1,3-diastereoselective aza-Sakurai-Hosomi reaction followed by hydroformylation is reported. Georg Thieme Verlag Stuttgart.
Total synthesis of (+/-)-diospongin A via Prins reaction
Hiebel, Marie-Aude,Pelotier, Béatrice,Piva, Olivier
, p. 7874 - 7878 (2008/02/08)
A straightforward synthesis of (+/-)-diospongin A starting from benzaldehyde is described. A Prins cyclization reaction to control the relative configuration of the three stereogenic centers and a Mitsunobu inversion represent the key steps of the approac
Crucial role of the ligand of silyl Lewis acid in the Mukaiyama aldol reaction
Ishihara, Kazuaki,Hiraiwa, Yukihiro,Yamamoto, Hisashi
, p. 1564 - 1565 (2007/10/03)
The Me3SiX-induced Mukaiyama aldol reaction proceeds through each catalytic cycle under the influence of X-: the silyl group of Me3SiNTf2 does not release from -NTf2 and that of silyl enol ether intermolecularly transfers to the product, while the silyl group of Me3SiOTf remains in the product and that of the silyl enol ether becomes the catalyst for the next catalytic cycle.
