61389-68-2Relevant academic research and scientific papers
Synthesis of pharmaceutical drugs from cardanol derived from cashew nut shell liquid
Shi, Yiping,Kamer, Paul C. J.,Cole-Hamilton, David J.
, p. 1043 - 1053 (2019/03/12)
Cardanol from cashew nut shell liquid extracted from cashew nut shells was successfully converted into various useful pharmaceutical drugs, such as norfenefrine, rac-phenylephrine, etilefrine and fenoprofene. 3-Vinylphenol, the key intermediate for the synthesis of these drugs, was synthesised from cardanol by ethenolysis to 3-non-8-enylphenol followed by isomerising ethenolysis. The metathesis reaction worked very well using DCM, but the greener solvent, 2-methyl tetrahydrofuran, also gave very similar results. Hydroxyamination of 3-vinylphenol with an iron porphyrin catalyst afforded norfenefrine in over 70% yield. Methylation and ethylation of norfenefrine afforded rac-phenylephrine and etilefrine respectively. A sequence of C-O coupling, isomerising metathesis and selective methoxycarbonylation afforded fenoprofene in good yield. A comparison of the routes described in this paper with some standard literature syntheses of 3-vinylphenol and of the drug molecules shows significant environmental advantages in terms of precursors, yields, number of steps, conditions and the use of catalysts. The Atom Economy of our processes is generally similar or significantly superior to those of the literature processes mainly because the side products produced during synthesis of 3-vinylphenol (1-octeme, 1,4-cyclohexadiene and propene) are easily separable and of commercial value, especially as they are bio-derived. The E Factor for the production of 2-vinylphenol by our process is also very low compared with those of previously reported syntheses.
Structure Guided Lead Generation toward Nonchiral M. tuberculosis Thymidylate Kinase Inhibitors
Song, Lijun,Merceron, Romain,Gracia, Bego?a,Quintana, Ainhoa Lucía,Risseeuw, Martijn D. P.,Hulpia, Fabian,Cos, Paul,Aínsa, José A.,Munier-Lehmann, Hélène,Savvides, Savvas N.,Van Calenbergh, Serge
, p. 2753 - 2775 (2018/04/23)
In recent years, thymidylate kinase (TMPK), an enzyme indispensable for bacterial DNA biosynthesis, has been pursued for the development of new antibacterial agents including against Mycobacterium tuberculosis, the causative agent for the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous efforts toward the exploration of novel and potent Mycobacterium tuberculosis TMPK (MtTMPK) inhibitors, and reported here the design of a novel series of non-nucleoside inhibitors of MtTMPK. The inhibitors display hitherto unexplored interactions in the active site of MtTMPK, offering new insights into structure-activity relationships. To investigate the discrepancy between enzyme inhibitory activity and the whole-cell activity, experiments with efflux pump inhibitors and efflux pump knockout mutants were performed. The minimum inhibitory concentrations of particular inhibitors increased significantly when determined for the efflux pump mmr knockout mutant, which partly explains the observed dissonance.
COMPOUND EXHIBITING REGULATORY ACTIVITY ON LYSOPHOSPHATIDYLSERINE RECEPTOR FUNCTION
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Paragraph 0217, (2015/12/19)
The object of the present invention is to provide a compound having a lysophosphatidylserine receptor function modulation activity or a salt thereof. A compound having a lysophosphatidylserine receptor function modulation activity or a salt thereof, or a pharmaceutical composition or a lysophosphatidylserine receptor function moderator containing such compound or salt is provided by the present invention.
Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174
Ikubo, Masaya,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Sayama, Misa,Otani, Yuko,Uwamizu, Akiharu,Suzuki, Keisuke,Kishi, Takayuki,Shuto, Akira,Ishiguro, Jun,Okudaira, Michiyo,Kano, Kuniyuki,Makide, Kumiko,Aoki, Junken,Ohwada, Tomohiko
supporting information, p. 4204 - 4219 (2015/06/08)
Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS-specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-activity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and l-serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysoPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174.
Design of CID-cleavable protein cross-linkers: Identical mass modifications for simpler sequence analysis
Kandur, Wynne V.,Kao, Athit,Vellucci, Danielle,Huang, Lan,Rychnovsky, Scott D.
, p. 9793 - 9807 (2015/10/05)
The cross-linking Mass Spectrometry (XL-MS) technique has enormous potential for studying the interactions between proteins, and it can provide detailed structural information about the interaction interfaces in large protein complexes. Such information h
AROMATIC RING COMPOUND
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Paragraph 0452, (2015/01/18)
Provided is an aromatic ring compound having a GPR40 agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has a GPR40 agonist activity, and is useful as an agent for the prophylaxis or treatment of diabetes and the like.
Ti/Ni-mediated inter- and intramolecular conjugate addition of aryl and alkenyl halides and triflates
Marquez, Irene R.,Miguel, Delia,Millan, Alba,Marcos, M. Luisa,De Cienfuegos, Luis Alvarez,Campana, Araceli G.,Cuerva, Juan M.
, p. 1529 - 1541 (2014/03/21)
In this work, we show that the unique combination of a nickel catalyst and Cp2TiCl allows the direct conjugate addition of aryl and alkenyl iodides, bromides, and to a lesser extent, chlorides and triflates to α,β-unsaturated carbonyls at room temperature, without requiring the previous formation of an organometallic nucleophile. The reaction proceeds inter- and intramolecularly with good functional group compatibility, which is key for the development of free protecting group methodologies. Carbo- and heterocycles of five- and six-membered rings are obtained in good yields. Moreover, some insights about the mechanism involved have been obtained from cyclic voltammetry, UV-vis, and HRTEM measurements.
Discovery of azetidinone acids as conformationally-constrained dual PPARα/γ agonists
Wang, Wei,Devasthale, Pratik,Farrelly, Dennis,Gu, Liqun,Harrity, Thomas,Cap, Michael,Chu, Cuixia,Kunselman, Lori,Morgan, Nathan,Ponticiello, Randy,Zebo, Rachel,Zhang, Litao,Locke, Kenneth,Lippy, Jonathan,O'Malley, Kevin,Hosagrahara, Vinayak,Zhang, Lisa,Kadiyala, Pathanjali,Chang, Chiehying,Muckelbauer, Jodi,Doweyko, Arthur M.,Zahler, Robert,Ryono, Denis,Hariharan, Narayanan,Cheng, Peter T.W.
, p. 1939 - 1944 (2008/09/20)
A novel class of azetidinone acid-derived dual PPARα/γ agonists has been synthesized for the treatment of diabetes and dyslipidemia. The preferred stereochemistry in this series for binding and functional agonist activity against both PPARα and PPARγ receptors was shown to be 3S,4S. Synthesis, in vitro and in vivo activities of compounds in this series are described. A high-yielding method for N-arylation of azetidinone esters is also described.
Novel Compounds
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Page/Page column 76-77; 87, (2008/06/13)
There is provided a compound of formula (I): processes for the manufacture thereof, pharmaceutical compositions thereof and uses in therapy.
A short route to the macrocyclic core of biaryl ether-based cyclopeptides
Chattopadhyay, Shital K.,Bandyopadhyay, Ayan,Pal, Benoy K.
, p. 3655 - 3659 (2008/02/03)
A new route based on an intramolecular Horner-Wadsworth-Emmons type olefination of amidophosphonates has been developed for the construction of a 17-membered macrocyclic scaffold related to some biologically important biaryl ether-based cyclic peptides.
