Synthesis of some phenyl N-arylcarbamates

Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA-4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on β-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a–r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of β-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values ≤18 µM and ≥4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.

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“…170–171°C. The melting point, 1 H NMR, 13 C NMR and IR data are in agreement with previous reports [35] . I.R.…”

Section: Methodssupporting

confidence: 92%

Docking, Synthesis and Antiproliferative Activity of N-Acylhydrazone Derivatives Designed as Combretastatin A4 Analogues

et al. 2014

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“…Most isomers (CppOMe, CpoOMe, CmpOMe, CmoOMe, and CopOMe) were synthesized by using condensation reactions of aminopyridines with commercially available p - and o -methoxyphenyl chloroformates in the presence of triethylamine base (Et 3 N) and CH 2 Cl 2 solvent. − The CopOMe isomer was synthesized under solventless conditions (without base) in order to minimize formation of double carbamates where both amino H atoms are substituted by phenyl chloroformates (in an analogous reaction to that used in the synthesis of the trezimide and tennimide macrocycles). , The remainder (CpmOMe, CmmOMe, ComOMe, and CooOMe) were synthesized using the Curtius rearrangement, − performed as a two-step (one pot) reaction with isonicotinic or nicotinic acids as starting materials, diphenylphosphoryl azide as converting agent, and Et 3 N in anhydrous acetonitrile at 70 °C. On formation of the pyridinyl isocyanate, addition of m - or o -methoxyphenol initiates the final condensation to a methoxyphenyl- N -pyridinylcarbamate. − For CooOMe, the reaction was performed at 110 °C in toluene instead of acetonitrile .…”

Section: Experimental Sectionmentioning

confidence: 99%

The First Phenyl-N-pyridinylcarbamate Structures: Structural and Conformational Analysis of Nine Methoxyphenyl-N-pyridinylcarbamates

Mocilac

Gallagher

2013

Crystal Growth & Design

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A 3 × 3 isomer grid of nine methoxyphenyl-N-pyridinylcarbamates (C13H12N2O3) as CxxOMe (x = para-/meta-/ortho-) represents the first phenyl-N-pyridinylcarbamate crystal structures to be reported. Structural relationships have been correlated in all nine crystal structures as derived from ab initio calculations and the solid-state using conformational analysis. N–H···N hydrogen bonds dominate as the primary interaction in all nine isomers. Two isomers (CmmOMe, CmoOMe) form unusual cyclic N–H···N trimer synthons as R3 3(15) with two distinct conformations isolated in the CmoOMe structure, whereas the three CoxOMe isomers form N–H···N hydrogen bonded dimers based on the R2 2(8) motif. For all isomers, C–H···O interactions assist in aggregation, and in most cases the methoxy group augments the hydrogen bonding. The solid state and modeled conformations are mismatched in three isomers where the methoxy groups and meta-methoxyphenyl rings (mOMe) (in the solid state) adopt metastable or unstable conformations compared to their optimized computational models. This is rationalized in terms of preferred solid state conformations and observed interactions as compared to the computational models.

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“…Thermally reversible systems, which are being investigated, are cellulose N-arylcarbamates [4-6, 8, 9], esters [13,14], Michael-addition products [12], and Diels-Alder adduct-containing cross links [ 2, 3 J . Encouraging results for the carbamates and the Michael-addition products are obtained when tertiary amino groups are present in the system [ 8, 12 J . During the course of examination of the cellulose N-pyridyl-carbamate linkages [ 9 ] ; it was observed in thermogravimetric analysis (TGA) that weight losses in excess of those resulting from substituent losses occur at temperatures substantially below cellulose decomposition temperatures. It is, thus, apparent that the basic tertiary amino nitrogen of the pyridyl group is altering the cellulose decomposition [9].…”

Section: Introductionmentioning

confidence: 99%

“…Encouraging results for the carbamates and the Michael-addition products are obtained when tertiary amino groups are present in the system [ 8, 12 J . During the course of examination of the cellulose N-pyridyl-carbamate linkages [ 9 ] ; it was observed in thermogravimetric analysis (TGA) that weight losses in excess of those resulting from substituent losses occur at temperatures substantially below cellulose decomposition temperatures. It is, thus, apparent that the basic tertiary amino nitrogen of the pyridyl group is altering the cellulose decomposition [9]. An investigation of the effects of organic tertiary amino groups on the thermal decomposition of cotton cellulose in the absence of other substituent groups was undertaken.…”

Section: Introductionmentioning

confidence: 99%

Thermal Investigation of Diethylaminoethyl-Substituted Cotton Celluloses

Hobart

Berni

Mack

1970

Textile Research Journal

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The thermal behavior of diethylaminoethyl-substituted cotton celluloses was examined by thermogravimetric analysis, differential thermal analysis, and differential scanning calorimetry. Samples at levels up to 10% substituent content (prepared via an anhydrous sodium cellulosate method) were compared with other samples prepared by the conventional aqueous sodium hydroxide method. All thermal analyses were carried out in purified dry nitrogen or high vacuum at heating rates of 5-40°C/min. Considerable variation was observed when the samples in the base form were compared with those placed in the salt (hydrochloride) form. The effect of basic diethylaminoethyl groups on the cellulosic thermal degradation was shown in altered thermal patterns and Δ H of pyrolysis. In the hydrochloride form, lower Δ H of pyrolysis and decreased decomposition temperature were observed. These observations together with other minor thermal effects which were found to be associated with the decomposition, are compared with recent studies on the effect of inorganic bases on the pyrolysis of cotton cellulose.

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Synthesis of some phenyl N-arylcarbamates

Cited by 12 publications

References 5 publications

Docking, Synthesis and Antiproliferative Activity of N-Acylhydrazone Derivatives Designed as Combretastatin A4 Analogues

Docking, Synthesis and Antiproliferative Activity of N-Acylhydrazone Derivatives Designed as Combretastatin A4 Analogues

The First Phenyl-N-pyridinylcarbamate Structures: Structural and Conformational Analysis of Nine Methoxyphenyl-N-pyridinylcarbamates

Thermal Investigation of Diethylaminoethyl-Substituted Cotton Celluloses

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