- Microwave-Assisted Ruthenium- and Rhodium-Catalyzed Couplings of α-Amino Acid Ester-Derived Phosphinamides with Alkynes
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Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C?H functionalization under microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.
- Li, Xue-Hong,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
(2021/12/23)
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- ANTIVIRAL PRODRUGS OF TENOFOVIR
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Compounds of Formula I: and pharmaceutically acceptable salts and co-crystals thereof are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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Page/Page column 29; 30; 33
(2018/09/26)
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- New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy
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There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (ΔaX) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α′-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α′)-C?H bond. In buffer, the three main hfs (aN, aH, and aP) of their EPR spectra vary reversibly with pH and, from aP or aH titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pKa ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers.
- Thétiot-Laurent, Sophie,Gosset, Ga?lle,Clément, Jean-Louis,Cassien, Mathieu,Mercier, Anne,Siri, Didier,Gaudel-Siri, Anouk,Rockenbauer, Antal,Culcasi, Marcel,Pietri, Sylvia
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p. 300 - 315
(2017/02/15)
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- METHODS FOR TREATING ARENAVIRIDAE AND CORONAVIRIDAE VIRUS INFECTIONS
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Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.
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Paragraph 0638-0639
(2017/04/04)
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- METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS
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Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae vims infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula (IV): The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.
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Paragraph 0236
(2016/05/19)
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- PROCESS FOR THE PREPARATION OF ANAGRELIDE AND ANALOGUES THEREOF
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The present invention relates to a novel process for producing anagrelide, 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin 2(3H)-one, or certain analogues thereof. The process of the invention also provides improved processes for producing key intermedia
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Paragraph 0094; 0095
(2013/08/28)
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- PROCESS FOR THE PREPARATION OF ANAGRELIDE AND ANALOGUES THEREOF
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The present invention relates to a novel process for producing anagrelide, 6,7-dichloro-1,5- dihydroimidazo [2,1-b] quinazolin 2 (3H)-one, or certain analogues thereof. The process of the invention also provides improved processes for producing key interm
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Page/Page column 23-24; 30-31
(2012/05/05)
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- Microwave-assisted, zinc-mediated peptide coupling of N-benzyl-α,α-disubstituted amino acids
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Incorporation of the extremely hindered amino acid N-benzylaminoisobutyric acid into dipeptides under microwave irradiation with commercial zinc dust is described. A comparative survey of various methodologies for hindered peptide couplings was undertaken
- Cianci, Julia,Baell, Jonathan B.,Harvey, Andrew J.
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p. 5973 - 5975
(2008/02/10)
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- Antiviral phosphoramidates
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The invention provides novel nucleoside compounds of formula I wherein R1, R2a, R2b, R3, R4, R5, R6, R8a, R9 and R10 are as defined herein which are useful for the treatment of Hepatitis C Virus (HCV) mediated diseases. The invention further provides methods for treatment or prophylaxis of HCV mediated diseases with compounds of formula I and pharmaceutical compositions comprising these compounds,
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Page/Page column 18; 22
(2008/06/13)
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- CHEMICAL COMPOUNDS
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Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an α-amino acid moiety. The α-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.
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Page/Page column 22
(2010/02/10)
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- 1,3-oxazin-4-one derivatives as herbicides
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PCT No. PCT/EP96/02616 Sec. 371 Date Apr. 13, 1998 Sec. 102(e) Date Apr. 13, 1998 PCT Filed Jun. 18, 1996 PCT Pub. No. WO97/00865 PCT Pub. Date Jan. 9, 19971,3-oxazin-4-ones of formula (I), wherein R1 represents phenyl optionally substituted; R2 represents: a straight- or branched-chain alkyl having from one to ten carbon atoms which is substituted by one or more groups R8 which may be the same or different; a straight- or branched-chain optionally halogenated alkenyl or alkynyl group having up to ten carbon atoms; or a group selected from cyano, -CHO, -COR7, -CO2H, -CO2R7, -COSR7, -CONR9R10, -CH=NOH, -CH=NOR7, -CH=NOCOR7, -CH=NNR9R10, -CH2CN, -CH2NO2 and oxiranyl; R3 represents phenyl optionally substituted or R3 represents a first five to seven membered heteroaromatic ring; said first ring being optionally fused and said first ring being linked to the nitrogen atom of the group NR6 via one of the ring carbon atoms; R4 and R5 independently represent lower alkyl; W represents -NR6-; R6 represents hydrogen, lower alkyl, haloalkyl, alkenyl, alkynyl, -COR7 or -CO2R7; and their use as herbicides.
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- Dihydro-1,2,4-triazin-6(1H)-ones. II synthesis of several methylated 3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-ones
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Novel syntheses of 4,5-dihydro-1,2,4-triazin-6(1H)-ones were developed by use of imidoyl chlorides. The overall yield of 4,5-dihydro-1,2,4-triazin-6(1H)-ones prepared from amino acid imidates and hydrazines was improved by the development of a much more efficient synthesis of the imidates. The new 1,2-, 1,4- and 5,5-dimethyl dihydro-1,2,4-triazin-6(1H)-ones have been synthesized by cyclocondensation/cycloaddition pathways. Base-catalysed methylation of 3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (15) gave the 1-methylated derivative (8); under similar conditions 2-methyl-3-phenyl-2,5-dihydro-1,2,4-triazin-6(1H)-one (9) afforded the 1,2-dimethyl derivative (7).
- Collins, David J.,Hughes, Timothy C.,Johnson, Wynona M.
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p. 379 - 385
(2007/10/03)
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- Synthesis and serotonergic activity of a series of 2-(JV-benzyl)carboxamido-5-substituted-N,N-dimethyltryptamine derivatives: Novel antagonists for the vascular 5-HT1B-like receptors
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The synthesis and vascular 5-HT,B-like receptor activity of a novel series of 2-(Ar-benzyl)carboxamido-5-substitutedA-4W-dimethyltryptamine derivatives is described. Modifications to the 5-ethylene linked heterocycle are explored. Compounds such as N-benzyl-5-[2-(phthalimido)ethyl]-3-[2-(dimethylamino)ethyl]-l//-indole-2- carboxamide 22 (pA'B = 7.33), tfie 2-aminobenzyl analogue 24 (pA1B = 7.19), which both contain a phthalimide group, and A-4-benzyl-S[2-(l-benzyl-2,5-dioxoimidazolidin-4-yl)ethyl]-3-[2-(dimethylamino) ethyl]-l//-indole-2-carboxamide 81 (pATB = 7.05), which incorporates an N-benzylhydantoin moiety, have good 5-HT1B-like affinity and indicate that there may be a hydrophobic binding pocket within the vascular 5-HT1B-like receptor previously not considered. Compounds including N-benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(2,4-dioxo-l,3-thiazolidinyl)ethyl]-l// -indole-2-carboxamide 39 (pA1B = 7.35) and the dimethyl analogue 46 (pA1B = 7.48) which contain a 2,4-thiazolidinedione moiety have good vascular 5-HT1B-like receptor affinity and show that the sulfur atom is well tolerated. Compound 61 which includes a methylsulfonyl substituent on the 1-nitrogen of the hydantoin ring system has the highest recorded 5-HT1B-like affinity for this series (pA1B = 7.54) and it is proposed that this functional group can interact with a secondary hydrogen bonding region within the receptor. Compounds 22, 24,39,46,61 and 81 also exhibited good selectivity over the a,-adrenoceptors. The most selective compound from this series is 46 which contains a 5,5-dimethylthiazolidine-2,4-dione group and which is 66-fold selective over the a,-adrenoceptors. This finding is consistent with the previous discovery that 5,5-dimethyl substitution on the hydantoin group in a related series of compounds afforded superior selectivity for 5-HT1B-like receptors over a,-adrenoceptors and other 5-HT receptors, in particular 5-HT2A receptors, relative to unsubstituted hydantoin analogues. The selectivity of these compounds for the vascular 5-HT1B-like receptor is discussed. Structure-activity relationship indicated a significant steric requirement of the 5-HT1B-like receptor subtype. Potential modes of binding for several of the compounds to a vascular 5-HT1B-like receptor pharmacophore model are also proposed. The Royal Society of Chemistry 1999.
- Moloney, Gerard P.,Martin, Graeme R.,Mathcws, Neil,Hobbs, Heather,Dodsworth, Susan,Sang, Pang Yih,Knight, Cameron,Maxwell, Miles,Glen, Robert C.
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p. 2699 - 2711
(2007/10/03)
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- SYNTHESE VON 2-METHYLALANIN-PEPTIDEN, DIE pH-ABHAENGIGKEIT IHRER 13C-NMR-SPECTREN UND EINE NEUE METHODE ZUR AUSWERTUNG UEBER CS-DIAGRAMME
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The uncommon amino-acid 2-methylalanine (α-aminoisobutiryc acid, Aib) was investigated by 13C-NMR.The chemical shifts of amino- or carboxy-protected derivates of Aib and of protected oligopeptides are discussed with respect to neighbouring groups and amino acids.The pH-dependence of the 13C-NMR spectra of Aib, Aib-Ala, Ala-Aib, Aib-Ala-Aib and Aib-Ala-Aib-Ala-Aib was studied.Using these examples, a new and advantageous method is demonstrated for the first time for the evaluation of NMR titration curves, which uses so-called chemical shift diagrams (CS diagrams).
- Leibfritz, Dieter,Haupt, Erhard,Dubischar, Norbert,Lachmann, Heinrich,Oekonomopulos, Raymond,Jung, Guenther
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p. 2165 - 2182
(2007/10/02)
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