- Design and characterization of a heterocyclic electrophilic fragment library for the discovery of cysteine-targeted covalent inhibitors
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A fragment library of electrophilic small heterocycles was characterized through cysteine-reactivity and aqueous stability tests that suggested their potential as covalent warheads. The analysis of theoretical and experimental descriptors revealed correlations between the electronic properties of the heterocyclic cores and their reactivity against GSH that are helpful in identifying suitable fragments for cysteines with specific nucleophilicity. The most important advantage of these fragments is that they show only minimal structural differences from non-electrophilic counterparts. Therefore, they could be used effectively in the design of targeted covalent inhibitors with minimal influence on key non-covalent interactions.
- Keeley,ábrányi-Balogh,Keseru
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supporting information
p. 263 - 267
(2019/03/05)
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- Convenient preparation of halo-1,3-thiazoles: Important building blocks for materials and pharmaceutical synthesis
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Convenient, scalable and high-yielding approaches to 2,5- and 2,4-dibromo-1,3-thiazole are reported that offer significant improvements over previously reported approaches. 2,5-Dibromo-1,3-thiazole was generated in two steps from commercially inexpensive 2-amino-1,3-thiazole, whereas 2,4-dibromo-1,3-thiazole was generated in a single step from commercially inexpensive 1,3-thiazolidine-2,4-dione. As part of this study, convenient approaches to 2-bromo- and 2-iodo-1,3-thiazole were also developed. Georg Thieme Verlag Stuttgart · New York.
- Grubb, Alan M.,Schmidt, Michael J.,Seed, Alexander J.,Sampson, Paul
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experimental part
p. 1026 - 1029
(2012/05/05)
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- Deprotonative metalation of five-membered aromatic heterocycles using mixed lithium-zinc species
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(Equation Presented) Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl2·TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpipe
- L'Helgoual'ch, Jean-Martial,Seggio, Anne,Chevallier, Floris,Yonehara, Mitsuhiro,Jeanneau, Erwann,Uchiyama, Masanobu,Mongin, Florence
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p. 177 - 183
(2008/09/17)
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- Selective metallation of thiophene and thiazole rings with magnesium amide base
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The chemoselective magnesiation of thiophene and thiazole derivatives were reported using magnesium chloride. Organomagnesium compounds were used at relatively higher temperatures. The results showed that hydrogen-magnesium exchange reaction of thiophene derivatives with iPr2NMgCl proceeded selectively.
- Shilai, Manabu,Kondo, Yoshinori,Sakamoto, Takao
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p. 442 - 444
(2007/10/03)
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- Synthesis of High Carbon Materials from Acetylenic Precursors. Preparation of Aromatic Monomers Bearing Multiple Ethynyl Groups
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The synthesis of polyethynyl aromatics as starting materials for the preparation of highly cross-linked organic solids containing high atom fractions of carbon is described.Treatment of bromo- and iodoaromatic compounds with (trimethylsilyl)acetylene (TMSA) in the presence of palladium(O) and copper(I) in amine solvents yields (trimethylsilyl)ethynyl-substituted aromatics.The TMS protecting groups can be removed by hydrolysis with mild base.Compounds prepared by using this technique include 1,3-diethynylbenzene, 2,5-diethynylthiophene, 1,3-diethynyltetrafluorobenzene, 1,4-diethynyltetrafluorobenzene, 2-ethynylthiazole, 2,4-diethynylthiazole, 2,7-diethynylnaphthalene, hexakis((trimethylsilyl)ethynyl)benzene, tetraethynylthiophene, 2,5-bis((trimethylsilyl)ethynyl)-3,4-bis(3-hydroxy-3-methyl-1-butynyl)thiophene, 2,5-diethynyl-3,4-bis(3-hydroxy-3-methyl-1-butynyl)thiophene, 2,5-bis(4-(2-thienyl)butadiynyl)-3,4-bis(3-hydroxy-3-methyl-1-butynyl)thiophene, and 2,5-bis-(4-(2-thienyl)butadiynyl)-3,4-diethynylthiophene.
- Neenan, Thomas X.,Whitesides, George M.
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p. 2489 - 2496
(2007/10/02)
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- Synthesis of Stannylthiazoles and Mixed Stannylsilylthiazoles and their Use for a Convenient Preparation of Mono- and Bis-halothiazoles
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Stannylthiazoles and stannyl-silylthiazoles have been prepared and employed as thiazolyl carbanion equivalents in reactions with halogens to give mono- and mixed bis-halothiazoles in good yields.
- Dondoni, A.,Mastellari, A. R.,Medici, A.,Negrini, E.,Pedrini, P.
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p. 757 - 760
(2007/10/02)
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