- 2-AMINO-1,3,4-THIADIAZINE AND 2-AMINO-1,3,4-OXADIAZINE BASED ANTIFUNGAL AGENTS
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The invention provides a compound which is a diazine of formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt thereof, for use as an antifungal agent: (I) wherein X, N', C', A and E are as defined herein. The invention also provides a compound of Formula (I) as defined herein.
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- Metal-Free Synthesis of N-Aryl Amides using Organocatalytic Ring-Opening Aminolysis of Lactones
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Catalytic ring-opening of bio-sourced non-strained lactones with aromatic amines can offer a straightforward, 100 % atom-economical, and sustainable pathway towards relevant N-aryl amide scaffolds. Herein, the first general, metal-free, and highly efficient N-aryl amide formation is reported from poorly reactive aromatic amines and non-strained lactones under mild operating conditions using an organic bicyclic guanidine catalyst. This protocol has high application potential as exemplified by the formal syntheses of drug-relevant molecules.
- Guo, Wusheng,Gómez, José Enrique,Martínez-Rodríguez, Luis,Bandeira, Nuno A. G.,Bo, Carles,Kleij, Arjan W.
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p. 1969 - 1975
(2017/05/16)
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- Beyond the five and six: Evaluation of seven-membered cyclic anhydrides in the castagnoli-cushman reaction
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The Castagnoli-Cushman reaction with benzo[d]- oxepine-2,4(1H,5H)-dione as an anhydride component allowed for preparation of 2,3-disubstituted 4-oxo-2,3,4,5-tetrahydro-1H-benzo[d]- azepine-1-carboxylic acids in 21-75% yields and with good trans diastereoselectivity. The method worked with imines generated from aromatic or a-branched aliphatic aldehydes and is amenable for both parallel synthesis and scale-up. The procedure for epimerization of the resulting trans-disubstituted tetrahydrobenzo[d]azepines to their cis isomers was also developed.
- Adamovskyi, Mykhailo I.,Ryabukhin, Sergey V.,Sibgatulin, Dmitriy A.,Rusanov, Eduard,Grygorenko, Oleksandr O.
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supporting information
p. 130 - 133
(2017/09/08)
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- HISTONE DEACETYLASE INHIBITORS AS THERAPEUTICS FOR NEUROLOGICAL DISEASES
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The invention provides HDAC inhibitors that may be used as therapeutics for the treatment of a neurodegenerative or neuromuscular condition. The invention provides compounds of formula I. The invention also provides pharmaceutical compositions and articles of manufacture that include these compounds, as well as methods of treating and methods of preventing or delaying the onset of a neurodegenerative or neuromuscular condition.
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Page/Page column 38; 39
(2008/06/13)
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- Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors
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Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. A mercaptoamide functionality was designed as a bidentate zinc chelator and incorporated into the hydroxamic acid based SAHA (1) scaffold in order to identify non-hydroxamate compounds as potential inhibitors of histone deacetylases. Two sets of mercaptoamides 2 and 3 with varying spacer length were synthesized and their HDAC inhibitory activity was evaluated. Low micromolar inhibition was observed for mercaptoamides 2e, 3b, and 3d.
- Anandan, Sampath-Kumar,Ward, John S.,Brokx, Richard D.,Bray, Mark R.,Patel, Dinesh V.,Xiao, Xiao-Xi
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p. 1969 - 1972
(2007/10/03)
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- Identification of a potent non-hydroxamate histone deacetylase inhibitor by mechanism-based drug design
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In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, mercaptoacetamide 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling are also reported. In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling suggested that the mercaptoacetamide moiety of 5b interacts with the zinc in the active site of HDACs and removes a water molecule from the reactive site of the deacetylation.
- Suzuki, Takayoshi,Matsuura, Azusa,Kouketsu, Akiyasu,Nakagawa, Hidehiko,Miyata, Naoki
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p. 331 - 335
(2007/10/03)
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- Novel histone deacetylase inhibitors: Design, synthesis, enzyme inhibition, and binding mode study of SAHA-Based non-hydroxamates
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In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i) substrate (acetyl lysine) analogues (compounds 3-7), (ii) analogu
- Suzuki, Takayoshi,Nagano, Yuki,Matsuura, Azusa,Kohara, Arihiro,Ninomiya, Shin-Ichi,Kohda, Kohfuku,Miyata, Naoki
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p. 4321 - 4326
(2007/10/03)
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- Structural biasing elements for in-cell histone deacetylase paralog selectivity
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We use the structural dissection of two 1,3-dioxanes with in-cell histone deacetylase (HDAC) paralog selectivity to identify key elements for selective HDAC inhibitors. We demonstrate that o-aminoanilides are inactive toward HDAC6 while apparently inhibit
- Wong, Jason C.,Hong, Roger,Schreiber, Stuart L.
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p. 5586 - 5587
(2007/10/03)
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- Biaryl acids: Novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2
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A series of biaryl acids has been found to show micromolar inhibition of the HIV reverse transcriptase (RT) from types 1 and 2 with IC50s in the micromolar range. The series was discovered by consideration of the polymerase active site and sub-structure searching of the company compound collection. Synthesis of analogues to investigate the SAR is described. Two of these compounds have shown inhibition of HIV-2 RT only.
- Milton,Slater,Bird,Spinks,Scott,Price,Downing,Green,Madar,Bethell,Stammers
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p. 2623 - 2628
(2007/10/03)
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- Intramolecular Vilsmeier processes: a new route to cyclopenta- and cyclohexa-fused quinolines by cyclisation of adipic and pimelic bis-amides
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Symmetrical and unsymmetrical bis-amides derived from adipic and pimelic acid and secondary amines react in POCl3 solution to give the title compounds by way of a Vilsmeier reagent-α-chloro enamine interaction.Adipanilide and pimelanilide only cyclise with added PCl5.However the bis-N-substituted derivatives (N-methyl or N-phenyl) of adipanilide and pimelanilide give quinolinium salts in good yield.Unsymmetrical amides with an N-substituted anilide at one end and an aliphatic unit at the other only proceed as far as the intermediate stage, giving 1,2-disubstituted cyclo-pentanes or -hexanes.Analogous amides derived from suberic and sebacic acid do not give quinolinium salts but instead give complex mixtures.
- Meth-Cohn, Otto,Goon, Simon
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