Synthesis of novel 3,4-diaryl-5-aminopyrazoles as potential kinase inhibitors

Pierce, Larry T.; Cahill, Michael G.; McCarthy, Florence O.

doi:10.1016/j.tet.2011.04.077

Cited by 28 publications

(15 citation statements)

References 41 publications

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“…Purification by flash column chromatography (CHCl 3 /MeOH/NH 4 OH 90:10:1 3 40:10:1) yielded the product as a yellow solid (2.34 g, 13.34 mmol, 79%). Analytical data were in agreement with the literature (38).…”

Section: Synthesis Of Trp-derivatives 7-aza-trp and 5-fluoro-trpsupporting

confidence: 89%

“…A partially related polar network is observed in the structure of LAAO from C. rhodostoma. However, these interactions rely on the conservation of only three residues (Asp 38 , Arg 46 , and Arg 64 VioA numbering) but otherwise make use of a closely related array of polar contacts involving several structurally conserved water molecules that are positioned via equivalent main chain atoms of non-conserved amino acids. As described for most flavoproteins, an Mg 2ϩ ion is involved in ionic bonds to the diphosphate group of FADH 2 .…”

Section: B and G)mentioning

confidence: 99%

“…For this purpose, 5-fluoro-Trp and 7-aza-Trp were synthesized starting from commercially available 5-fluoroindole and 7-azaindole, respectively. First, a Mannich reaction to the corresponding gramines was performed, followed by addition of methyl iodide (38). The resulting tetramethylammonium iodide salts were obtained with very good yields.…”

Section: B and G)mentioning

confidence: 99%

“…7-Azagramine (7A) was synthesized according to the procedure of Pierce et al (38). Purification by flash column chromatography (CHCl 3 /MeOH/NH 4 OH 90:10:1 3 40:10:1) yielded the product as a yellow solid (2.34 g, 13.34 mmol, 79%).…”

Section: Synthesis Of Trp-derivatives 7-aza-trp and 5-fluoro-trpmentioning

confidence: 99%

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Biosynthesis of Violacein, Structure and Function of l-Tryptophan Oxidase VioA from Chromobacterium violaceum

Füller

Röpke

Krausze

et al. 2016

Journal of Biological Chemistry

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Violacein is a natural purple pigment of Chromobacterium violaceum with potential medical applications as antimicrobial, antiviral, and anticancer drugs. The initial step of violacein biosynthesis is the oxidative conversion of L-tryptophan into the corresponding ␣-imine catalyzed by the flavoenzyme L-tryptophan oxidase (VioA). A substrate-related (3-(1H-indol-3-yl)-2-methylpropanoic acid) and a product-related (2-(1H-indol-3-ylmethyl)prop-2-enoic acid) competitive VioA inhibitor was synthesized for subsequent kinetic and x-ray crystallographic investigations. Structures of the binary VioA⅐FADH 2 and of the ternary VioA⅐FADH 2 ⅐2-(1H-indol-3-ylmethyl)prop-2-enoic acid complex were resolved. VioA forms a "loosely associated" homodimer as indicated by small-angle x-ray scattering experiments. VioA belongs to the glutathione reductase family 2 of The amino acid tryptophan (Trp) is a versatile metabolite that is shunted into several microbial secondary pathways. The oxidative dimerization of two Trp scaffolds is an essential step for the synthesis of the natural bisindole compounds violacein, rebeccamycin, and staurosporine. The water-insoluble purple pigment violacein is mainly produced by the bacteria Chromobacterium violaceum and Janthinobacterium lividum in tropical habitats where it might be responsible for the shielding against UV radiation (1-3). Various biological activities of violacein, including antibacterial, antiviral, as well as cytotoxic effects against several tumor cell lines, have been demonstrated (4). The related compounds rebeccamycin and staurosporine show strong antitumorigenic activity because of DNA topoisomerase or protein kinase inhibition (5, 6).Synthesis of violacein, rebeccamycin, or staurosporine is based on a closely related initial pathway in which orthologous enzymes catalyze the oxidation of a Trp moiety into the related indole-3-pyruvic acid (IPA) 2 imine by the enzymes VioA, RebO, or StaO ( Fig. 1) (7-9). Subsequently, oxidative coupling of two imines by VioB, RebD, or StaD results in the formation of a short-lived compound that was proposed to be an IPA imine dimer (7, 10). For the synthesis of rebeccamycin and staurosporine, this reactive intermediate is spontaneously converted into chromopyrrolic acid (11-13). By contrast, violacein biosynthesis requires a key intramolecular rearrangement. The postulated IPA imine dimer is the substrate of VioE, which is catalyzing a [1,2]-shift of the indole ring to produce protodeoxyviolaceinic acid (7,14). Fig. 1 gives a schematic overview about the related pathways as follows: common enzymatic reactions and the involved cofactors are highlighted (gray shading), subsequent steps for the synthesis of violacein (VioE, VioD, VioC, and one autocatalytic step) (3, 7), rebeccamycin (RebP, RebC, RebG, and RebM) (15, 16), and staurosporine (StaP, StaC, StaG, StaN, StaMA, and StaMB) (16) are indicated.Synthesis of violacein starts with the FAD-dependent oxidation of L-Trp to IPA imine catalyzed by VioA. The VioA protein from C. violaceum shares a su...

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Section: Synthesis Of Trp-derivatives 7-aza-trp and 5-fluoro-trpsupporting

confidence: 89%

Section: B and G)mentioning

confidence: 99%

Section: B and G)mentioning

confidence: 99%

Section: Synthesis Of Trp-derivatives 7-aza-trp and 5-fluoro-trpmentioning

confidence: 99%

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Biosynthesis of Violacein, Structure and Function of l-Tryptophan Oxidase VioA from Chromobacterium violaceum

Füller

Röpke

Krausze

et al. 2016

Journal of Biological Chemistry

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“…Common pathways toward 5‐aza‐9‐deaza‐adenines containing orthoester as a precursor are shown in Scheme .…”

Section: Carbon‐carbon and Carbon‐heteroatom Bond Formation Reactionsmentioning

confidence: 99%

Orthoesters: Multiple Role Players in Organic Synthesis

Nazarian

Dabiri

2020

ChemistrySelect

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Dedicated to the memories of Prof. Abbas Shafiee Orthoesters are characterized by three alkoxy groups attached to a single carbon atom. This functional group is used primarily as a masking group for carboxylic acids, due to its robust stability towards strong nucleophiles and bases. Besides this protection role, orthoesters have further utility as versatile precursors in organic synthesis. This review focuses on the latter role of orthoesters as well as their applications in stereoselective synthesis.

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Eisenporphyrin‐katalysierte C‐H‐Funktionalisierung von Indol mit Diazoacetonitril für die Synthese von Tryptaminen

et al. 2019

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Die Funktionalisierung von C-H-Bindungen mit Nichtedelmetallkatalysatoren ist ein wichtiges Forschungsgebiet fürd ie Entwicklung effizienter und nachhaltiger Synthesemethoden. In diesem Artikel beschreiben wir die Entwicklung Eisenporphyrin-katalysierter Reaktionen von Diazoacetonitril mit N-Heterocyclen um so einen Zugang zu wertvollen Vorläufern zu Tryptaminen zu erhalten. Darüberhinaus berichten wir über experimentelle mechanistischeS tudien sowie über konzeptionelle Studien zu einer enzymatischen Synthese mit dem Enzym YfeX. Mit dem leichtz ugänglichen FeTPPCl-Katalysator konnten wir hoche ffiziente C-H-Funktionalisierungsreaktionen von Indol und Indazol-Heterocyclen zeigen. Diese Reaktionen kçnnen unter milden Reaktionsbedingungen, mit exzellenten Ausbeuten und großer Toleranz funktioneller Gruppen inklusive Anwendungen im Grammmaßstab durchgeführt werden und erçffnen so einen einzigartigen, effizienten Zugang zu Tryptaminen.

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Synthesis of novel 3,4-diaryl-5-aminopyrazoles as potential kinase inhibitors

Cited by 28 publications

References 41 publications

Biosynthesis of Violacein, Structure and Function of l-Tryptophan Oxidase VioA from Chromobacterium violaceum

Biosynthesis of Violacein, Structure and Function of l-Tryptophan Oxidase VioA from Chromobacterium violaceum

Orthoesters: Multiple Role Players in Organic Synthesis

Eisenporphyrin‐katalysierte C‐H‐Funktionalisierung von Indol mit Diazoacetonitril für die Synthese von Tryptaminen

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