- A Unified Strategy for the Synthesis of Difluoromethyl- And Vinylfluoride-Containing Scaffolds
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Here, we report a general method for the synthesis of quaternary and tertiary difluoromethylated compounds and their vinylfluoride analogues. The strategy, which relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and either a palladium-catalyzed decarboxylative protonation or a Krapcho decarboxylation, is practical, scalable, and high yielding. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.
- Duchemin, Nicolas,Buccafusca, Roberto,Daumas, Marc,Ferey, Vincent,Arseniyadis, Stellios
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p. 8205 - 8210
(2019/10/16)
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- BACTERIAL EFFLUX PUMP INHIBITORS
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Disclosed herein are compounds of formula I and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.
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- INDOLE DERIVATIVES AS EFFLUX PUMP INHIBITORS
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Disclosed herein are compounds of formula (I): and salts thereof. Also disclosed are compositions comprising compounds of formula I and compounds of formula I for use in treating or preventing bacterial infections.
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- BACTERIAL EFFLUX PUMP INHIBITORS
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Disclosed herein are compounds of formula I: and salts thereof. Also disclosed are compositions comprising compounds of formula I and methods using compounds of formula I.
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- Structural Properties and Stereochemically Distinct Folding Preferences of 4,5-cis and trans-Methano- L -Proline Oligomers: The Shortest Crystalline PPII-Type Helical Proline-Derived Tetramer
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The synthesis, structural properties, and folding patterns of a series of L-proline methanologues represented by cis- and trans-4,5-methano-L-proline amides and their oligomers are reported as revealed by X-ray crystallography, circular dichroism measurements, and DFT calculations. We disclose the first example of a crystalline tetrameric proline congener to exhibit a polyproline II helical conformation. Experimental evidence of PPII-type helical arrangement (both in solution and in the solid state) of cis-4,5-methano-L-proline oligomers is supported by theoretical calculations reflecting the extent of n→π? stabilization of the trans-amide conformation.
- Berger, Gilles,Vilchis-Reyes, Miguel,Hanessian, Stephen
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supporting information
p. 13268 - 13272
(2015/11/09)
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- SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS
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The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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- Methanesulfonic acid mediated cyclization and meyer-schuster rearrangement of γ-amino-ynones: Access to enantiopure pyrrolidine exocyclic vinylogous amides
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α- and β-Amino-ynones have been largely used to prepare heterocyclic rings in the presence of various electrophiles such as protic acids or gold(I). Herein we disclose the unprecedented formation of pyrrolidine exocyclic vinylogous amides, in place of the expected azepinones or piperidinones, starting from γ-amino-ynones derived from amino acids. The process involves a tandem 1,2-addition of the protected nitrogen to the carbonyl group followed by a Meyer-Schuster rearrangement, which efficiently afforded enantiopure pyrrolidine exocyclic vinylogous amides. The sequence is poorly catalyzed by gold salts, but proved to be very efficient in the presence of methanesulfonic acid. Copyright
- Vu, Huy-Dinh,Renault, Jacques,Roisnel, Thierry,Gouault, Nicolas,Uriac, Philippe
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p. 4506 - 4514
(2014/08/05)
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- HEPATITIS C INHIBITOR COMPOUNDS
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Compounds of Formula (I) and (II) wherein R1, R2, R3, R6, A and A' are defined herein. The compounds are useful as inhibitors of the function of NS5A protein encoded by HCV for the treatment of hepatitis C viral infection.
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- HEPATITIS C VIRUS INHIBITORS
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The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds
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- STRUCTURAL MIMETICS OF PROLINE-RICH PEPTIDES AND THE PHARMACEUTICAL USE THEREOF
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The invention relates to compounds of general formula (I), which can be used particularly as structural mimetics of proline-rich peptides and are therefore capable of binding PRM binding domains (proline-rich motif binding domains) of proteins. The invention also relates to the use of said compounds as pharmaceutical active agents and the use of these pharmaceutical active agents for treating bacterial diseases, neurodegenerative diseases and tumours.
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- HEPATITIS C VIRUS INHIBITORS
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The present disclosure relates to methods for making compounds useful in the treatment of Hepatitis C virus (HCV) infection.
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
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- Addressing protein-protein interactions with small molecules: A pro-pro dipeptide mimic with a PPII helix conformation as a module for the synthesis of PRD-binding ligands
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X marks the spot: The synthetic tricyclic amino acid X (see structure; C gray, H cyan, N blue, O red, double bond yellow) can be incorporated, without loss of binding ability, as a Pro-Pro substitute into two peptides that bind to the proline-rich motif-recognizing domains Fyn-SH3. The dipeptide analogue X, which is locked in a polyproline type II helix conformation, is created by stereoselective introduction of a vinylidene bridge into a diproline unit.
- Zaminer, Jan,Brockmann, Christoph,Huy, Peter,Opitz, Robert,Reuter, Cedric,Beyermann, Michael,Freund, Christian,Mueller, Matthias,Oschkinat, Hartmut,Schmalz, Hans-Guenther,Kuehne, Ronald
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supporting information; experimental part
p. 7111 - 7115
(2010/12/18)
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- BI-1H-BENZIMIDAZOLES AS HEPATITIS C VIRUS INHIBITORS
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The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
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Page/Page column 68
(2010/04/03)
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- Diastereoselective synthesis of 4,5′-bis-proline compounds via reductive dimerization of N-acyloxyiminium ions
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A short, practical synthesis of novel, unsymmetrical 4,5′-bis-proline compounds has been achieved, highlighted by the application of an unprecedented samarium diiodide-driven regio- and diastereocontrolled reductive dimerization of N-acyloxyiminium ions generated from readily available 2-methoxy-5- silyloxymethyl-N-Boc pyrrolidines. The title proline dimers proved to be pertinent metal-free catalysts in aldol and Mannich reactions.
- Zanardi, Franca,Sartori, Andrea,Curti, Claudio,Battistini, Lucia,Rassu, Gloria,Nicastro, Giuseppe,Casiraghi, Giovanni
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p. 1814 - 1817
(2007/10/03)
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- Stereoselective synthesis of 2,5-di- and 2,2,5-trisubstituted pyrrolidines by allylation reacton of acyliminium ion
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-Allylation reactions of allytrimethylsilane and an allylcopper reagent to acyliminium ions derived from several 2-monosubstituted and 2,2-disubstituted pyrrolidinones were examined. These reactions proceeded in a stereoselective manner to give the corresponding allylated adducts. The stereochemical outcomes of these reactions were dependent upon the allylating reagents or the structures of the acyliminium ions.
- Shinada, Tetsuro,Hamada, Makoto,Kawasaki, Masanori,Ohfune, Yasufumi
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p. 511 - 525
(2007/10/03)
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- Stereoselective synthesis of trans-threo-trans-oligopyrrolidines: Potential agents for RNA cleavage
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The 2,5-trans-substituted oligopyrrolidines constitute a promising class of novel RNA-binding agents as well as potential building blocks for artificial anion channels. A convergent synthesis of terpyrrolidine 1 and pyrrolidino-THF-pyrrolidine 2 is reported, relying upon convergent coupling of 2,5-trans-pyrrolidinecarboxaldehydes through bridging alkyne units under Felkin-Anh control and subsequent closure of the central ring. After complete deprotection, the free polyamine products were isolated in excellent yield and purity. Crystal structure analyses of a terpyrrolidine and a pyrrolidino-THF-pyrrolidine documented their helical privileged conformations. The compounds were then screened for RNA cleavage activity. Unlike the only weakly active simple polyamines, p-nitrosulfonamide 33 was found to induce cleavage at mM concentrations under physiologically relevant conditions.
- Arndt, Hans-Dieter,Welz, Ruediger,Mueller, Sabine,Ziemer, Burkhart,Koert, Ulrich
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p. 3945 - 3962
(2007/10/03)
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- Unprecedented migration of N-alkoxycarbonyl groups in protected pyroglutaminol.
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[figure: see text] Cleavage of an O-silyl ether in an N-BOC-protected pyroglutaminol using TBAF led to an unprecedented migration of the BOC group. An investigation of the mechanism, based on experimental data and quantum mechanical calculations, is presented. Similar migration was observed for N-Cbz and N-methoxycarbonyl groups.
- Bunch,Norrby,Frydenvang,Krogsgaard-Larsen,Madsen
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p. 433 - 435
(2007/10/03)
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- Lewis acid assisted vinylogous Mannich and Mukaiyama aldol reactions: A route to densely hydroxylated indolizidine alkaloid analogues
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The hydroxymethyl-substituted indolizidines 6 and 7, representative members of a ring-B-expanded alexine-australine subclass, are readily accessible by starting with furan-based silyloxydiene 12 and hydroxymethyl hemiaminal 11, through a synthesis sequence involving a scantily exploited vinylogous version of the Mannich reaction. The key iminium electrophilic acceptor 11 is, in turn, available through a vinylogous intermolecular Mukaiyama aldolization process between pyrrole-based silyloxydiene 8 and (S)- glyceraldehyde 9.
- Rassu, Gloria,Carta, Paola,Pinna, Luigi,Battistini, Lucia,Zanardi, Franca,Acquotti, Domenico,Casiraghi, Giovanni
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p. 1395 - 1400
(2007/10/03)
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- Stereoselective synthesis of a terpyrrolidine unit, a potential building block for anion recognition
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The first stereoselective synthesis of a trans-threo-trans-threo-trans terpyrrolidine was achieved. A bidirectional strategy involving double acetylide coupling of two trans-N-BOC-pyrrolidine-aldehydes 3, epimerisation-free hydrogenation and ring closure via a seven-membered cyclic sulfate gives access to the terpyrrolidine scaffold.
- Arndt, Hans-Dieter,Polborn, Kurt,Koert, Ulrich
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p. 3879 - 3882
(2007/10/03)
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- Syntheses of 2-[(1S,3S)-1-amino-3-carboxy-3-hydroxypropyl]-thiazole-4-carboxylic acid and the tripeptide skeleton of nosiheptide containing the acid
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The stereoselective synthesis of an amino acid component called Fragment D, N,O-diprotected 2-[(1S,3S)-1-amino-3-carboxy-3-hydroxypropyl]thiazole-4-carboxylic acid of a macrobicyclic peptide antibiotic nosiheptide, was achieved by two routes. The dipeptide, Fragment B-C, 2-[(Z)-1-(N,O-isopropylidene-L-threonylamino)-1-propenyl]thiazole-4-ca rboxylic acid was also synthesized by the thiazole ring formation from (Z)-2-(N,O-diprotected L-threonylamino)-2-butenethioamide with ethyl bromopyruvate. The coupling of two components by using a condensing agent gave the expected tripeptide 2, which is an important partial skeleton of the nosiheptide.
- Shin,Nakamura,Yamada,Yonezawa,Umemura,Yoshimura
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p. 3151 - 3160
(2007/10/03)
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- The synthesis of 4'-t-butylcarbamyl- and 4'-p-toluenesulphonamidyl-2',3'- dideoxy pyrimidine nucleoside analogues
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The preparation of 4'-t-butylcarbamyl-2',3'-dideoxy thymidine, uridine and 5-ethyl uridine nucleoside analogues and 4'-p-toluenesulphonamidyl-2',3'- dideoxy thymidine and 5-ethyl uridine nucleoside analogues from L- pyroglutamic acid is reported.
- Pickering,Malhi,Coe,Walker
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p. 1493 - 1506
(2007/10/02)
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