42840-02-8Relevant articles and documents
Metal-free C-H Activation over Graphene Oxide toward Direct Syntheses of Structurally Different Amines and Amides in Water
Shukla, Prashant,Asati, Ambika,Bhardiya, Smita R.,Singh, Manorama,Rai, Vijai K.,Rai, Ankita
, p. 15552 - 15561 (2020/12/02)
Unprecedented metal-free synthesis of a variety of amines and amides is reported via amination of C(sp3)-H and C(sp2)-H bonds. The strategy involves graphene-oxide/I2-catalyzed nitrene insertion using PhINTs as a nitrene (NT) source in water at room temperature. A wide range of structurally different substrates, viz., cyclohexane, cyclic ethers, arenes, alkyl aromatic systems, and aldehydes/ketones, having an α-phenyl ring have been employed successfully to afford the corresponding nitrene insertion product in good yield, albeit low in few cases. The envisaged method has superiority over others in terms of its operational simplicity, metal-free catalysis, use of water as a solvent, ambient reaction conditions, and reusability of the catalyst.
Synthesis and thrombin, factor Xa and U46619 inhibitory effects of non-amidino and amidino N2-thiophenecarbonyl- and N2-tosylanthranilamides
Lee, Soo Hyun,Lee, Wonhwa,Nguyen, ThiHa,Um, Il Soo,Bae, Jong-Sup,Ma, Eunsook
, (2017/06/08)
Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N2-thiophencarbonyl- and N2-tosyl anthranilamides 1-20 and six amidino N2-thiophencarbonyl- and N2-tosylanthranilamides 21-26 were synthesized to evaluate their activated partial thromboplastin time (aPTT) and prothrombin time (PT) using human plasma at a concentration of 30 μg/mL in vitro. As a result, compounds 5, 9, and 21-23 were selected to study the further antithrombotic activity. The anticoagulant properties of 5, 9, and 21-23 significantly exhibited a concentration-dependent prolongation of in vitro PT and aPTT, in vivo bleeding time, and ex vivo clotting time. These compounds concentration-dependently inhibited the activities of thrombin and FXa and inhibited the generation of thrombin and FXa in human endothelial cells. In addition, data showed that 5, 9, and 21-23 significantly inhibited thrombin catalyzed fibrin polymerization and mouse platelet aggregation and inhibited platelet aggregation induced by U46619 in vitro and ex vivo. Among the derivatives evaluated, N-(30-amidinophenyl)-2-((thiophen-200-yl)carbonylamino)benzamide (21) was the most active compound.
Synthesis and Caco-2 cell permeability of N-substituted anthranilamide esters as ADP inhibitor in platelets
Kim, Sohee,Shin, Beom Soo,Ma, Eunsook
, p. 1147 - 1156 (2015/02/19)
Twelve N-substituted anthranilamide esters (1-5, 8, 9, 12, 13, and 15-17) were synthesized and evaluated for their ability to inhibit the in vitro aggregation by washed human platelets induced by adenosine 5′-diphosphate (10 μM). The antiplatelet activity of DL-n-butyl 5-hydroxy-N-(2-phenoxypropionyl)anthranilate (9, IC50 = 10.5 μM) was most active among the tested compounds and ethyl ester 8 (IC50 = 11.2 μM) showed the second most activity. DL-Ethyl and DL-n-butyl 5-(p-toluenesulfonyloxy)-N-(2-phenoxypropionyl)anthranilate (12, IC50 = 13.1 μM and 13, IC50 = 14.0 μM), DL-methyl N-(2-phenoxybutyryl)anthranilate (2, IC50 = 12.7 μM), DL-N-(2-phenoxypropionyl)anthranilic acid (5, IC50 = 13.7 μM) displayed lower antiplatelet activity than 8 and 9. Compound 5 was more active than methyl ester prodrug 1. n-Butyl 5-hydroxy-N-(4′-acetoxybenzoyl)anthranilate (15, IC50 = 28.3 μM) showed moderate activity. Compounds 1 (IC50 = 42.8 μM), 4 (IC50 = 56.7 μM), 16 (IC50 = 51.0 μM), and 17 (IC50 = 49.8 μM) exhibited low antiplatelet activity. Methyl N-phenoxyacetylanthranilate (3, IC50 = 78.0 μM) showed the lowest antiplatelet activity. The compounds with branched alkyl chain (2 and 5) were more active than compounds with straight chain (3 and 4). The apparent permeability coefficient (Papp, cm/s) values of compounds 2 and 9 were determined as 45.34 ± 4.67 and 33.17 ± 5.15 × 10-6 cm/s by Caco-2 cell permeability assay.
Intramolecular N-aza-amidoalkylation in association with Witkop-Winterfeldt oxidation as the key step to synthesize Luotonin-A analogues
Pin, Frédéric,Comesse, Sébastien,Da?ch, Adam
experimental part, p. 5564 - 5571 (2011/08/09)
An expedient four-step approach for the synthesis of a short library of original analogues of the Topo-I Luotonin-A inhibitor, substituted at their C8- and N15-positions, was investigated. This consists of Rutaecarpines formation, their Witkop-Winterfeldt oxidation followed ultimately with functional adjustment of the pyrroloquinolone intermediates. In the first step of these investigations, Rutaecarpines including the Topo-I poison Evodiamine were obtained via the new tandem N-acylation/aza-amidoalkylation using a nitrogen atom as an internal nucleophile with or without association with a decarboxylation.
Synthesis of photochromic dithienylethenes having quinoline and Triazolo[4,3-a]quinoline bridges
Krayushkin,Lichitskii,Pashchenko,Antonov,Nabatov,Dudinov
, p. 1357 - 1363 (2008/03/27)
Convenient synthetic approaches to new photochromic dithienylethenes with quinoline and triazolo[4,3-a]quinoline bridging fragments have been developed.
Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel
Peukert, Stefan,Brendel, Joachim,Pirard, Bernard,Struebing, Carsten,Kleemann, Heinz-Werner,Boehme, Thomas,Hemmerle, Horst
, p. 2823 - 2827 (2007/10/03)
The search for novel, potent Kv1.5 blockers based on an anthranilic amide scaffold employing a pharmacophore-based virtual screening approach is described. The synthesis and structure-activity relationships (SAR) with respect to inhibition of the Kv1.5 ch
Synthesis and biological evaluation of substituted 2-sulfonyl-phenyl-3-phenyl-indoles: A new series of selective COX-2 inhibitors
Hu, Wenhui,Guo, Zongru,Chu, Fengming,Bai, Aiping,Yi, Xiang,Cheng, Guifang,Li, Jing
, p. 1153 - 1160 (2007/10/03)
A new series of substituted 2-sulfonyphenyl-3-phenyl-indole derivatives were synthesized and evaluated for their ability to inhibit COX-2 and COX-1enzymes. Most of the compounds synthesized were found to be highly potent and selective inhibitors of COX-2. This work led to the discovery of 2-aminosulfonylphenyl-3-phenyl-indole 5a which possesses higher activity and selectivity for COX-2 than Celecoxib both in vitro and in vivo.
Anthranilamides and methods of their use
-
, (2008/06/13)
The present invention is related to anthranilamides of formula I, in which R(1) to R(7) have the meanings indicated herein, a process for their preparation, their use as medicaments, and pharmaceutical preparations containing them. The compounds act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. The compounds are therefore suitable for use as novel antiarrhythmic agents for the treatment and prophylaxis of atrial arrhythmias (e.g., atrial fibrillation (AF) or atrial flutter).
A NOVEL SYNTHETIC METHOD OF HMG-CoA REDUCTASE INHIBITOR NK-104 VIA HYDROBORATION-CROSS COUPLING SEQUENCE
Miyachi, Nobuhide,Yanagawa, Yoshinobu,Iwasaki, Hiroshi,Ohara, Yoshio,Hiyama, Tamejiro
, p. 8267 - 8270 (2007/10/02)
The regioselective hydroboration of ethyl (3R,5S)-3,5-isopropylidenedioxy-6-heptynoate, followed by the cross-coupling reaction with an aryl halide, provides ethyl (3R,5S,6E)-7-aryl-3,5-isopropylidenedioxy-6-heptenoate, a precursor of a highly potent HMG-
Synthesis and cardiovascular properties of fluorenyl derivatives related to verapamil
Novella Romanelli,Teodori,Scapecchi,Dei,Budriesi,Chiarini
, p. 1121 - 1138 (2007/10/02)
A series of fluorenyl analogues of verapamil were synthesized and their cardiovascular properties on guinea pig isolated atria and isolated perfused heart evaluated. The compounds were also tested for their calcium antagonistic activity on guinea pig aort
