Series Of 2-alkyl Research Articles

Organocatalysts for L-Lactide polymerization: 2-alkyl- and 2-aryl-1,1,3,3-tetramethylguanidines

A series of 2-alkyl- and 2-aryl-1,1,3,3-tetramethylguanidine derivatives were synthesized, and their application in L-Lactide (LA) polymerization was studied. Bn-TMG was the best catalyst in LA polymerization ( [Bn-TMG] = 5 mM, conversion = 94 % after 4 h at 25 °C) compared to other monoguanidine derivatives. In addition, the catalytic activities of C2-dTMG exhibited higher catalytic activity than Bn-TMG, nBu-TMG (monoguanidine derivatives), and C3-dTMG (diguanidine derivative). Density functional theory calculations revealed that Bn-TMG deprotonated benzyl alcohol enhanced benzyl alcohol's initiation ability to LA, and the protonated Bn-TMG activated LA ring-opening process by interacting with the ether oxygen atom of LA. Bn-TMG presented excellent catalytic activity and controllability for LA polymerization at 25 °C.

Non-Aqueous medium titrations of some 3-alkyl(aryl)-4-[3-(2-metylbenzoxy)-4-methoxybenzylideneamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones

A series of 3-alkyl(aryl)-4-[3-(2-metylbenzoxy)-4-methoxybenzylideneamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (1-9) were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide (DMF), and graphs were drawn for all cases. The half-neutralization potential values and the corresponding pKa values were determined by half neutralization method. Thus, the effects of solvents and molecular structure upon acidity were discussed.

Synthesis and antimicrobial screening of 2-alkyl(aryl)-7-chloro-6-fluoro-4-(trifluoromethyl)-quinolines and their phenylacetylene derivatives, promoted by Sonogashira cross-coupling reaction

This paper firstly describes the synthesis of a series of (Z)-4-((3-chloro-4-fluorophenyl)amino)-1,1,1-trifluorobut-3-en-2-ones (3a–f) as well as 1-(1-((3-chloro-4-fluorophenyl)amino)-3,4-dihydronaphthalen-2-yl)-2,2,2-trifluoroethanone (3g), from the O,N-exchange reaction of some 4-methoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones (1) with 3-chloro-4-fluoroaniline (2), at 70–90% yields. Subsequently, in concentrated sulfuric acid, the enaminoketones 3 underwent a successful and regioselective intramolecular cyclocondensation reaction, which furnished a novel series of 2-alkyl(aryl)-7-chloro-6-fluoro-4-(trifluoromethyl)-quinolines (4) at 70–85% yields. To demonstrate synthetic applicability through the Sonogashira coupling reaction for obtaining quinolines with potential antimicrobial activity, the synthesis of a novel series of 2-alkyl(aryl)-6-fluoro-7-(phenylethynyl)-4-(trifluoromethyl)-quinolines (5) was performed, using quinolines 4 and phenylacetylene, via a regioselective Sonogashira coupling reaction (25–50% yield). Unfortunately, the new series of heterocycles 4 and 5 did not produce significant results against bacteria and fungi at the concentrations of 80–0.31μg/mL.

ChemInform Abstract: In(OTf)3‐Catalyzed Chemoselective Alkylation of Tryptamines with 2‐Oxo‐1‐pyrrolidine Derivatives.

The chemoselective alkylation of tryptamine derivatives with 2-oxo-1-pyrrolidine compounds, catalyzed by In(OTf)3, was investigated. A series of 2-alkyl and N-alkyl tryptamine derivatives were synthesized under mild conditions with good total yields (up to 99%) and chemoselectivity (up to 95 : 5).

In(OTf)3-catalyzed chemoselective alkylation of tryptamines with 2-oxo-1-pyrrolidine derivatives

The chemoselective alkylation of tryptamine derivatives with 2-oxo-1-pyrrolidine compounds, catalyzed by In(OTf)3, was investigated. A series of 2-alkyl and N-alkyl tryptamine derivatives were synthesized under mild conditions with good total yields (up to 99%) and chemoselectivity (up to 95 : 5).

Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives

Series of 3-alkyl, 3-aryl-5,5-diphenylimidazolidine-2,4-diones (2–8) and 3-phenacyl-5,5-diphenylimidazolidine-2,4-diones (9–20) were designed, synthesized, and tested for their antitumor activity. The 13 compounds (3–8, 10–15 and 20) were selected by National Cancer Institute (USA) on the basis of degree of the structure variation and computer modeling techniques for evaluation of their antineoplastic activity. A single dose (10 μM) of the tested compounds was used in the National Cancer Institute (NCI) 60 cell lines panel assay selected from different nine organs. The tested compounds possessed selective activity against the renal cancer (A498 and UO-31) cell lines. Interestingly, compound 13 showed moderate selective activities towards A498 and UO-31 cell lines, in addition to strong activity against melanoma (MDA-MB-435) cell line and breast cancer cell lines (MCF7) in 114 and 70 %, respectively. Molecular docking study was performed for the most active compound 13 to identify the structural features required for the antitumor activity. The results achieved can be used as a useful template for future development and further derivatization or modification to obtain more potent and selective antitumor agents. The development of novel molecules containing imidazolidine-2,4-dione pharmacophore have shown promising antitumor activities. Compound 13 exploited broad spectrum and potent antitumor activity with the percentages of inhibition range of 28–114 %.

Simultaneous regioselective synthesis of trifluoromethyl-containing 1,7-phenanthrolines and quinolines from cyclocondensation reaction of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines

This paper reports interesting results of the conventional synthesis of a new series of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40% yields, from cyclization reactions of N,N'-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C6H4-(NHCR=CHC(O)CF3)2] in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7-aminoquinolines, in 20-73% yields, simultaneously. The enaminone precursors were obtained from the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF3C(O)CH=C(R)OR¹, where R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl and R¹ = Me, Et] with 1,3-phenylenediamine under mild conditions, in 47-91% yields.

Aromatase inactivation by 2-substituted derivatives of the suicide substrate androsta-1,4-diene-3,17-dione

To gain the structure–activity relationship of Δ 1-androstenediones (Δ 1-ADs) as mechanism-based inactivator of aromatase, series of 2-alkyl- and 2-alkoxy-substitiuted Δ 1-ADs ( 6 and 9) as well as 2-bromo-Δ 1-AD ( 14) were synthesized and tested. All of the inhibitors examined blocked aromatase in human placental microsomes in a competitive manner. In a series of 2-alkyl-Δ 1-ADs ( 6), n-hexyl compound 6f was the most powerful inhibitor with an apparent K i value of 31 nM. The inhibitory activities of 2-alkoxy steroids 9 decreased in relation to length of the alkyl chain up to n-hexyloxy group ( K i: 95 nM for methoxy 9a). All of the alkyl steroids 6 along with the alkoxy steroid 9, except for the ethyl and n-propyl compounds 6b and 6c, caused a time-dependent inactivation of aromatase. The inactivation rates ( k inact: 0.020–0.084 min −1) were comparable to that of the parent compound Δ 1-AD. The inactivation was prevented by the substrate AD, and no significant effect of l-cysteine on the inactivation was observed in each case. The results indicate that the 2-hexyl compound 6f act as the most powerful mechanism-based inactivator of aromatase among Δ 1-AD analogs and may be submitted to the preclinical study in estrogen-dependent breast cancer.

2-Substitiuted Thio- and Amino-5,8-dimethoxy-1,4-naphthoquinones as a Novel Class of Acyl-CoA: Cholestrol Acyltransferase Inhibitors

A series of 2-alkyl or 2-arylthio-5,8-dimethoxy-1,4-naphthoquinones (2-Thio-DMNQ, 5a-s) and 2-alkylamino-5,8- dimethoxy-1,4-naphthoquinones (2-Amino-DMNQ, 6a-k) was synthesized and evaluated for their ACAT inhibitory activities. Among them, the 2-dodecylthio-DMNQ 5l and 2-isobutylamidoundodecylthio-DMNQ 5r showed the most potent ACAT inhibitory activities with <TEX>$IC_{50}$</TEX> value of 22.8 and 24.4 <TEX>${\mu}M$</TEX>, respectively. In a structure-activity relationship study, 2-thio-DMNQs with side chains of carbon number 11 <TEX>$\sim$</TEX> 15 exhibited significant ACAT inhibitory activities.

Microwave‐assisted synthesis of some 1,2,4‐triazol‐5‐one derivatives

AbstractA series of 3‐alkyl(aryl)‐4‐(p‐hydroxy‐phenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 2 were obtained from the reaction of alkyl (aryl) ester ethoxycarbonyl hydrazones 1 with p‐hydroxy aniline. The reaction of 1 with 1,4‐diamino benzene (1:1) to afford 3‐alkyl(aryl)‐4‐(p‐aminophenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 3. The reaction of 3 with benzaldehyde gave 3‐alkyl(aryl)‐4‐(4′‐benzilidenamino)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 4. All of the above reactions occurred under microwave heating and conventional methods. Their structures were confirmed by 1H NMR, 13C NMR, IR, and elemental analyses. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:38–42, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20381

SYNTHESIS OF NEW 1,2,4-TRIAZOLOQUINAZOLINE DERIVATIVES AS CNS MODULATORS

A series of 1,2,4-triazolo4,3-cJquinazoline-3-thiol was synthesized by reacting isatoic anhydrides (Ia, Ib) with thiosemicarbazide to yield the appropriate 2-acylhydrazinocarbothioamides (IIab ,IIb) which were cyclized to afford 5-(2- substituted aminophenyl)-1,2,4-triazol-3-thiols (IIIab ,IIIb) using sodium hydroxide. The triazol derivatives (IIIab,IIIb) were cyclized to the new 1,2,4-riazolo4,3-cquinazoline-3-thiol (IV) upon condensation with aromatic aldehydes. Whereas, cyclization of (IIIab,IIIb) with formaldehyde unexpectedly afforded 3-hydroxymethyl-1,2,4-triazolo1,5-cquinazolin-2-thione (VIa, VIb). The last reaction is the role-play to the formation of a series of 1,2,4-triazolo 1,5-cquinazoline-2-thiol (VLc, VId, VII) upon boiling of the appropriate 1,2,4-triazolo4,3-cquinazoline-3-thiol in ethanol with acidified formaldehyde. Also, alkylation of 3-thiol derivatives (IV) with the appropriate alkyl halide in alkaline medium afforded a new series of 3-alkyl (or 3-aralkyl) thio-1,2,4-triazolo4,3-cquinazolines (Va-b). Otherwise, alkylation of 5-(2-methylaminophenyl)-1,2,4-triazol-3-thiol (IIIa) was affected firstly and followed by condensation with either carbon disulfide or hydroxybenzaldehyde to produce 3-alkylthio-6- methyl-1,2,4-triazolo(4,3-cquinazolin-5(6H)-thione (IX) or 3-alkylthio-5-(hydroxyphenyl)-6-methyl-1,2,4-triazolo4,3- c]quinazoline (V1-1) respectively. Oxo-desulfuration was the key-procedure for preparation of 3-hydroxy-6-methyl-5-(4- nitrophenyl)-1,2,4-triazolo4,3-cquinazoline (X) from its thione analogue. The new triazoloquinazoline derivatives were subjected to preliminary pharmacological screening, where compounds (VIf, Vb, VIa, VIb, VId, X) produced a moderate to high CNS stimulant effect when tested on mice. Furthermore, compound (VIa) was tested by recording the electroencephalographic changes induced by its intravenous injection in conscious rabbits which gave noticeable results.

New Efficient Approach for the Synthesis of 2‐Alkyl(aryl) Substituted 4H‐Pyrido[1,2‐a]pyrimidin‐4‐ones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Regiospecific One‐Pot Synthesis of New Trifluoromethyl Substituted Heteroaryl Pyrazolyl Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regiospecific one-pot synthesis of new trifluoromethyl substituted heteroaryl pyrazolyl ketones

These 2-pyrazolines showed interesting antimycobacterial activity in vitro. Thus, considering the biological importance of 2-pyrazolines and some ketone derivatives and the fact that the reactions to obtain structurally similar compounds, employing aryl or heteroarylhydrazides and fluorinated βdiketones (CF 3 COCH 2 COCF 3 or CF 3 COCH 2 COR) are rare in the literature [20-25], we have recently reported a new regiospecific synthetic method to obtain a series of six 3-aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1 H-1picolinoylpyrazoles, in a one-step reaction and in good yields from the reaction of β-methoxyvinyl trifluoromethyl ketones with 2-pyridinecarboxamidrazone [26]. However, this work [26] allowed to obtain only picolinoyl derivatives under acid condition. Moreover, the 2pyridinecarboxamidrazone was previously obtained with some experimental difficulty. Although the possibility of preparing trihalomethylated pyrazoles and pyrazolines by a regiospecific cyclocondensation reaction of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoro(chloro)-3-alken-2-ones with hydrazines has long been explored by our research group [27], a general and system atic methodology that allows the synthesis of new interesting trifluoromethyl substituted heteroaryl pyrazolyl ketones (trifluoromethylated heteroaroylpyrazoles) was not yet developed. In view of these observations, we became interested in heterocycles, which may play an important role in the physiological processes of living or ganisms. Thus, on the course of our research program concerning the application of 4-alkoxy-4-alkyl(aryl)-1,1,1-trihalo-3-alken-2-ones to obtain new trihalomethylated heterocycles, we wish to report the regiospecific synthesis of a new series of 3alkyl(aryl)-5-trifluoromethyl-5-hydroxy-1-(heteroaroyl)4,5-dihydro-1H-pyrazoles and some aromatic derivatives which have been obtained from the cyclocondensation reaction of 2-thiophenecarboxylic hydrazide, furoic

Estrogen receptor ligands. Part 3: The SAR of dihydrobenzoxathiin SERMs

A class of dihydrobenzoxathiins 1 exhibiting a high degree of selectivity for ERα over ERβ has been discovered. The SAR of dihydrobenzoxathiins with modifications at the C-3 position is presented. A series of 3-alkyl, 3-cycloalkyl, and 3-heteroaryl dihydrobenzoxathiin analogs 1 were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. In general, the compounds were found to exhibit a high degree of selectivity for ERα over ERβ, but were less potent than the original lead compound 1a in the inhibition of estradiol-driven uterine proliferation.

2-Substituted-3H-indol-3-one-1-oxides: Preparation and Radical Trapping Properties

A series of 2-alkyl and 2-aryl substituted-3H-indol-3-one-1-oxides was prepared and evaluated for its radical trapping properties. Spin trapping and electron paramagnetic resonance experiments demonstrate the ability of these indolone-1-oxides to trap hetero- and carbon-centered radicals. The most stable spin adducts (lifetime of several hours) are obtained with 2-alkyl substituted nitrones, the 2-ethyl-5,6-dioxolo-3H-indolone-1-oxide, 5e and the 2-secbutyl-3H-indolone-1-oxide, 5f. These two nitrones are also sensitive to redox reactions in solution. Therefore this indolone-1-oxide series lacking a β-hydrogen atom gives rise to highly stable adducts with free radicals.

Estrogen receptor ligands. Part 3: The SAR of dihydrobenzoxathiin SERMs

A series of 3-alkyl, 3-cycloalkyl, and 3-heteroaryl dihydrobenzoxathiin analogs 1 were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. In general, the compounds were found to exhibit a high degree of selectivity for ERα over ERβ, but were less potent than the original lead compound 1a in the inhibition of estradiol-driven uterine proliferation.

Quinoxalin‐2‐ones. Part 5. Synthesis and Antimicrobial Evaluation of 3‐Alkyl‐, 3‐Halomethyl‐ and 3‐Carboxyethylquinoxaline‐2‐ones Variously Substituted on the Benzo‐Moiety.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Quinoxalin-2-ones: Part 5. Synthesis and antimicrobial evaluation of 3-alkyl-, 3-halomethyl- and 3-carboxyethylquinoxaline-2-ones variously substituted on the benzo-moiety

A new series of 3-alkyl-, 3-trifluoromethyl-, 3-carboxyethyl- and 3-bromomethylquinoxaline-2-ones and 2,3-bis(bromomethyl)quinoxalines bearing Cl, CF 3, morpholine on the benzo-moiety, were synthesised and submitted to a preliminary in vitro evaluation for antibacterial and anticandida activities. Results of the screening showed that compounds 9b, 14b and 19b (MIC=62.5 μg/ml) and 10b (MIC=15.6 μg/ml) were the most active against Vibrio alginolyticus.

3-Alkyl- and 3-aryl-7H-furo[3,2-g]-1-benzopyran-7-ones: synthesis, photoreactivity, and fluorescence properties.

A series of 3-alkyl- and 3-aryl-7H-furo[3, 2-g]-1-benzopyran-7-ones, known as linear furocoumarins, was synthesized and evaluated for their dark- and photobinding (crosslink formation) with DNA as well as for their spectrophotometric and fluorescent properties, lipophilicity, and ability to photobleach N, N-dimethyl-p-nitrosoaniline (RNO) after irradiation with UVA light. 8-Methoxypsoralen (8-MOP, 9-methoxy-7H-furo[3, 2-g]-1-benzopyran-7-one) and 4, 5', 8-trimethylpsoralen (TMP, 2, 5, 9-trimethyl-7H-furo[3, 2-g]-1-benzopyran-7-one) were used as reference compounds in all tests. The investigations support the formation of a molecular complex between the furocoumarins and DNA. Crosslink formation with DNA after irradiation with UVA light was detectable for compounds with a methyl or phenyl substituent in position 3, but not for those bearing either a tert-butyl, a 4-methoxyphenyl, or a 2, 5-dimethoxyphenyl group. All furocoumarins exhibited sufficient absorption in the UVA wavelength range and are fluorescent. All compounds showed a higher lipophilicity than 8-MOP. Generally the 3-alkyl substituted furocoumarins had a capacity to photobleach RNOwhich was higher than that of the 3-aryl substituted ones. Some of the 3-aryl substituted furocoumarins displayed a photobleaching ability which was similar to or lower than that of 8-MOP.