26825-92-3Relevant academic research and scientific papers
SYNTHESIS OF DODEC-10E-EN-1-YL ACETATE - THE SEX PHEROMONE OF Lithocolletis blancardella
Plugar', N. Ya.,Verba, G. G.,Abduvakhabov, A. A.,Kamaev, F. G.
, p. 455 - 457 (1990)
Dodec-10E-en-1-yl acetate - the sex pheromone of the apple leaf miner moth - has been obtained by a four-stage synthesis from monomethyl azelate and crotyl acetate.Its IR, PMR, and mass spectra are given.
Identification and total synthesis of a novel dimethylated fatty acid from the caribbean sponge Calyx podatypa
Carballeira, Nestor M.,Pagan, Mayra
, p. 666 - 669 (2000)
The dimethylated fatty acid 9,13-dimethyltetradecanoic acid was identified for the first time in nature in the Caribbean sponge Calyx podatypa where it occurs together with the rare 10,13-dimethyltetradecanoic acid. The characterization of the novel compound was accomplished using GC- MS, pyrrolidide derivatization, and a five-step total synthesis starting with 8-bromooctanoic acid. The first racemic total synthesis for the rare 10,13- dimethyltetradecanoic acid is also described.
Lipoic acid metabolism in Trypanosoma cruzi as putative target for chemotherapy
Vacchina, Paola,Lambruschi, Daniel A.,Uttaro, Antonio D.
, p. 17 - 23 (2018)
Lipoic acid (LA) is a cofactor of relevant enzymatic complexes including the glycine cleave system and 2-ketoacid dehydrogenases. Intervention on LA de novo synthesis or salvage could have pleiotropic deleterious effect in cells, making both pathways attractive for chemotherapy. We show that Trypanosoma cruzi was susceptible to treatment with LA analogues. 8-Bromo-octanic acid (BrO) inhibited the growth of epimastigote forms of both Dm28c and CL Brener strains, although only at high (chemotherapeutically irrelevant) concentrations. The methyl ester derivative MBrO, was much more effective, with EC50 values one order of magnitude lower (62–66 μM). LA did not bypass the toxic effect of its analogues. Small monocarboxylic acids appear to be poorly internalized by T. cruzi: [14C]-octanoic acid was taken up 12 fold less efficiently than [14C]-palmitic acid. Western blot analysis of lipoylated proteins allowed the detection of the E2 subunits of pyruvate dehydrogenase (PDH), branched chain 2-ketoacid dehydrogenase and 2-ketoglutarate dehydrogenase complexes. Growth of parasites in medium with 10 fold lower glucose content, notably increased PDH activity and the level of its lipoylated E2 subunit. Treatment with BrO (1 mM) and MBrO (0.1 mM) completely inhibited E2 lipoylation and all three dehydrogenases activities. These observations indicate the lack of specific transporters for octanoic acid and most probably also for BrO and LA, which is in agreement with the lack of a LA salvage pathway, as previously suggested for T. brucei. They also indicate that the LA synthesis/protein lipoylation pathway could be a valid target for drug intervention. Moreover, the free LA available in the host would not interfere with such chemotherapeutic treatments.
A short synthesis of enantiomeric phytoprostanes b1 type i
Perlikowska, Wiesawa,Mikoajczyk, Marian
, p. 2715 - 2718 (2009)
The synthesis of both enantiomers of phytoprostane B1 type I from 3-[(dimethoxyphosphoryl)methyl]cyclopent-2-enone is reported. It consists of three steps including regioselective alkylation of the substrate at C(2) with methyl 8-bromooctanoate, subsequen
4-Acyl Pyrrole Capped HDAC Inhibitors: A New Scaffold for Hybrid Inhibitors of BET Proteins and Histone Deacetylases as Antileukemia Drug Leads
Ahlert, Heinz,Bhatia, Sanil,Borkhardt, Arndt,Breit, Bernhard,Gunther, Stefan,Hansen, Finn K.,Hugle, Martin,Kraft, Fabian B.,Mishra, Pankaj,Schaker-Hubner, Linda,Schliehe-Diecks, Julian,Scholer, Andrea,Warstat, Robin
, p. 14620 - 14646 (2021/10/20)
Multitarget drugs are an emerging alternative to combination therapies. In three iterative cycles of design, synthesis, and biological evaluation, we developed a novel type of potent hybrid inhibitors of bromodomain, and extra-terminal (BET) proteins and histone deacetylases (HDACs) based on the BET inhibitor XD14 and well-established HDAC inhibitors. The most promising new hybrids, 49 and 61, displayed submicromolar inhibitory activity against HDAC1-3 and 6, and BRD4(1), and possess potent antileukemia activity. 49 induced apoptosis more effectively than the combination of ricolinostat and birabresib (1:1). The most balanced dual inhibitor, 61, induced significantly more apoptosis than the related control compounds 62 (no BRD4(1) affinity) and 63 (no HDAC inhibition) as well as the 1:1 combination of both. Additionally, 61 was well tolerated in an in vivo zebrafish toxicity model. Overall, our data suggest an advantage of dual HDAC/BET inhibitors over the combination of two single targeted compounds.
A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
González-Gil, Inés,Zian, Debora,Vázquez-Villa, Henar,Hernández-Torres, Gloria,Martínez, R. Fernando,Khiar-Fernández, Nora,Rivera, Richard,Kihara, Yasuyuki,Devesa, Isabel,Mathivanan, Sakthikumar,Del Valle, Cristina Rosell,Zambrana-Infantes, Emma,Puigdomenech, María,Cincilla, Giovanni,Sanchez-Martinez, Melchor,Rodríguez De Fonseca, Fernando,Ferrer-Montiel, Antonio V.,Chun, Jerold,López-Vales, Rubén,López-Rodríguez, María L.,Ortega-Gutiérrez, Silvia
supporting information, p. 2372 - 2390 (2020/01/02)
Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.
Lipid nanoparticle formulations of non-viral capsid-free DNA vectors
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Paragraph 0411; 0415-0416, (2020/09/26)
Provided herein are lipid nanoparticle formulations that comprise an ionizable lipid and non-viral, capsid-free DNA vectors with covalently-closed ends.
Decarboxylative Bromination of Sterically Hindered Carboxylic Acids with Hypervalent Iodine(III) Reagents
Kanazawa, Junichiro,Koyamada, Kenta,Miyamoto, Kazunori,Uchiyama, Masanobu,Watanabe, Ayumi
supporting information, p. 1328 - 1334 (2020/08/14)
Sterically hindered three-dimensional (3D) alkyl halides are promising precursors for various reactions; however, they are difficult to synthesize via conventional reactions. We present an efficient and practical method for decarboxylative bromination of sterically hindered 3D aliphatic carboxylic acids using commercially available (diacetoxyiodo)benzene and potassium bromide, one of the most stable and cheapest bromine sources in nature. The present method features a metal-free/Br2-free system, mild reaction conditions, one-pot operation under air at room temperature, wide functional group compatibility, and gram-scale synthetic capability. This highly efficient reaction cleanly converts a broad range of carboxylic acids, the most inexpensive and readily available sources of highly strained/naturally occurring/drug-related scaffolds, into the corresponding alkyl bromides in good to high yields.
Asymmetric syntheses of potential anti-malarial drugs designed from Fieser's 2-hydroxy-3-(2-methyloctyl)naphthalene-1,4-dione
Fisher, Louise M.,Kim, Eliana E.,Moskalev, Nicolai V.,Gribble, Gordon W.
, p. 56 - 66 (2020/10/02)
We describe asymmetric syntheses of the potential anti-malarial drugs (S)-2-(8-fluoro-2-methyloctyl)-3-hydroxynaphthalene-1,4-dione, (S)-2-hydroxy-3-(8-trifluoromethyl-2-methyloctyl)-3-hydroxynaphthalene-1,4-dione, and (S)-2-hydroxy-3-(2-methyloctyl)naphthalene-1,4-dione, which are patterned after Fieser's “10576,” known to be active against the mosquito borne parasite Plasmodium falciparum.
Fenton-Inspired C-H Functionalization: Peroxide-Directed C-H Thioetherification
Groendyke, Brian J.,Modak, Atanu,Cook, Silas P.
, p. 13073 - 13091 (2019/10/10)
Substoichiometric iron mediates the thioetherification of unactivated aliphatic C-H bonds directed by resident silylperoxides. Upon exposure to a catalytic amount of iron(II) triflate, TIPS-protected peroxides bearing primary, secondary, and tertiary C-H sites undergo chemoselective thioetherification of remote C-H bonds with diaryl disulfides. The reaction demonstrates a broad substrate scope and functional group tolerance without the use of any noble metal additives. Mechanistic experiments suggest that the reaction proceeds through 1,5-H atom abstraction by a hydroxyl radical generated with iron.
