Radioiodination of N-[3-(4-morphilino)propyl]-N-methyl-2-hydroxy-5-iodo-3-methyl-benzylamine (ERC9) via isotopic exchange reaction

Summary A simple method for labeling ERC9 with radioactive iodine has been carried out via nucleophilic substitution radioiodination. The factors affecting the radiochemical yield of the labeling of ERC9, such as pH of the medium, substrate concentration and temperature were investigated. Chromatographic analysis technique was used to determine the radiochemical yield and purity. Kinetics and thermodynamic parameters indicated a second order reaction. Activation energy for the isotopic exchange reaction between ERC9 and ¹²⁵I^- was calculated to be 24.4 kJ/mol.     

Synthesis of piperidine analogs of 1-(3-chlorophenyl)piperazine,a well known serotonin ligand

Synthesis of arylpiperideines 3a-3d and arylpiperidines 4a-4d as analogs of a well known serotonin ligand 1-(3-chlorophenyl)piperazine is reported. Starting aryllithium derivatives were treated with 1-methyl-piperdin-4-one to provide the corresponding hydroxy derivatives 6a and 6b. N-Methylpiperideine derivatives 3a and 3c were obtained by their dehydration while the corresponding N-unsubstituted compounds 3b and 3d were prepared indirectly by a three-step procedure. Hydrogenation of piperideine 3a provided the corresponding piperidine derivative 4a which after demethylation yielded 4b. Similar 4-pyridyl derivatives 4c and 4d were prepared by a similar strategy via the corresponding methoxy derivatives.     

Synthesis and antimycobacterial screening of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline derivatives

A new series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline ( 6a-t ) have been synthesized by a click reaction of 4-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)quinoline ( 4a-d ) with a substituted benzyl azide ( 5a-e ). The starting alkyne derivatives 4a-d are obtained from Bestmann-Ohira reaction of 1-phenyl-3-(quinolin-4-yl)-1H-pyrazole-4-carbaldehyde and dimethyl(1-diazo-2-oxopropyl)phosphonate. The newly synthesized compounds are screened against M. tuberculosis H37Ra dormant and active, Escherichia coli, Pseudomonas fluorescence, Staphylococcus aureus and Bacillus subtilis strains at 30 μg/mL concentration. Most of the screened compounds showed good to moderate antibacterial activity against S. aureus, B. subtilis, and Mycobacterium tuberculosis H37Ra strains. The synthesized derivatives of quinolinyl-pyrazole-4-carbaldehyde and quinolinyl-pyrazole-4-ethyne reportd good to moderate activity against both strains of M. tuberculosis H37Ra. Ten derivatives of quinolinyl-pyrazole presented good activity against B. subtilis. These results suggested that further optimization and development of quinolinyl-pyrazolyl-1,2,3-triazole moeity could serve as lead compounds for antimycobacterial activity.     

Photochromism of 2-benzyl-3-benzoyl-4(1H)-quinolone derivatives

A series of 2-benzyl-3-benzoyl-4(1H)-quinolone derivatives was investigated. The UV–vis spectra of all photochromic derivatives and the corresponding colored photoenols are similar and almost solvent independent. In contrast, the stability of the photoenols depends strongly on the substituents at the quinolone moiety and solvent. We conclude that conversion of the photoinduced forms into the initial quinolones occurs through ionization rather than usual for photochromic compounds thermal relaxation or sigmatropic H-shift. The experimental observations are in good agreement with the results of quantum mechanical calculations.     

Synthesis and characterization of novel 2-(1-benzyl-3-[4-fluorophenyl]-1H-pyrazol-4-yl)-7-fluoro-4H-chromen-4-one derivatives

Novel 1-benzyl-3-(4-fluorophenyl)-1H-pyrazole-4-carbaldehydes 3a to 3e were synthesized via Vilsmeier-Haack reaction of the appropriate 1-benzyl-2-(1-(4-fluorophenyl)ethylidene)hydrazines, derived from 4-fluoroacetophenone 1 with substituted 2-benzylhydrazines 2a to 2e . The base catalyzed condensation of 1-benzyl-3-(4-fluorophenyl)-1H-pyrazole-4-carbaldehydes 3a to 3e with 1-(4-fluoro-2-hydroxyphenyl)ethanone 4 gave (E)-3-(1-benzyl-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-ones 5a to 5e . On cyclization with dimethyl sulfoxide (DMSO)/I₂, compounds 5a to 5e gave 2-(1-benzyl-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-7-fluoro-4H-chromen-4-ones 6a to 6e . Structures of all novel compounds were confirmed by infrared (IR), proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), and mass spectral data. All the synthesized compounds were screened for their antibacterial activities.     

4-(3-氯苯乙基)呱啶的简便合成

以廉价易得的N-Boc呱啶-4-甲醇（1）和间氯苄氯（3）为原料,经Swern 氧化、Wittig反应、钯碳催化加氢和脱保护基反应合成目标化合物4-(3-氯苯乙基)呱啶盐酸盐(7)。路线总收率达到56%,化学纯度96.6%。加氢不脱氯反应的最佳反应条件为：以含量为10%干钯碳催化加氢,二氧六环为溶剂,反应时间3h。化合物7的结构及纯度经¹H NMR,¹³C NMR和MS（EI）确证。该合成方法具有反应条件温和、操作简单、收率高等优点。      

新型1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物的合成

以二乙醇胺为原料,经溴化、环合、N-烷基化和还原4步反应制得关键中间体——4-[4-(4-甲氧基苯基)哌嗪-1-基]苯胺(4);4与酰氯经酰基化反应合成了11个新型的1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物,其结构经1H NMR,FT-IR,ESI-MS和元素分析表征。     

3, 6-endoxocyclohexanes and -cyclohexenes. XXV. Some reactions of dimethyl 4,5-(1-benzyl-1, 2, 3-triazoline)-3, 6-endoxohexahydrophthalate

The anhydride and dimethyl ester of 4, 5-(1-benzyl-1, 2, 3-triazoline)-3, 6-endohexahydrophthalic acid, having a triazoline ring with an exo-cis configuration, are synthesized by reaction of benzyl azide with the furan-maleic anhydride adduct. Opening of the triazoline ring under the action of hydrochloric and acetic acids takes place with the separation of nitrogen and formation of the chloro and acetoxy derivatives, respectively, unaccompanied by a Wagner-Meerwein type of rearrangement.Part XXIV, see [1].     

Steric controls in the preparation of 1-benzyl-1,4-dihydro-3-(2H)isoquinolones and 1-benzyl-1,2,4,5-tetrahydro(3H)-2-benzazepin-3-ones via Beckmann rearrangement

The effect of substituents in the 1-position of 2-indanones and 2-tetralones on the course of Beckmann rearrangement reactions was studied. Nmr spectral anaylses of the intermediate oximes and final products demonstrated that steric controls were operative both before and during rearrangement. Use of the appropriate substituents and reaction conditions makes this reaction scheme attractive for preparation of the title compounds.     

Synthetic access of new 6-purineselenyl and 8-(1,3,4-thiadiazolyl)-7-benzyl-1, 3-dimethyl-1H-purine-2,6-(3H,7H)-dione derivatives

Abstract

New 6-purineselenyl, 1, 3, 4-thiadiazols bearing 7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones and (8-[2-(3-phenyl-5-substituted-1,3,4-thiadiazol-2(3H)-ylidene) hydrazinyl)-7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones derivatives were synthesized. The structures of the newly synthesized compounds were elucidated by spectroscopic methods (1H-NMR, 13C-NMR, and MS spectrometry) and elemental analysis.     

4-Hydroxy-3-(polynitromethyl-ONN-azoxy)furazans and some of their derivatives

Methods for the synthesis of 4-hydroxy-3-(polynitromethyl-ONN-azoxy)furazans, 4-alkoxy-3-(polynitromethyl-ONN-azoxy)furazans and their derivatives were developed, which included the substitution of the nitro group in 3-(dinitromethyl-ONN-azoxy)-4-nitrofurazan upon treatment with aqueous alkalis, mono- and diatomic alcohols (in the presence of inorganic bases) with subsequent nitration or fluorination of the nitroalkyl fragment in the substitution products formed.     

Asymmetric syntheses of (1r,3R,4S)- and (1s,3R,4S)-(3,4-difluorocyclopentyl)-alanine derivatives

By employing a sequence of epoxide opening, asymmetric alkylation, and fluorination, polyfluorinated cyclopentylamino acids with defined stereochemistries were prepared.     

Design,synthesis and biological estimation of 1-（benzoxazole-2-yl）piperazine and 4-（benzoxazole-2-yl）piperidine derivatives as potential α1-AR antagonists

Two series of 1-（benzoxazole-2-yl）piperazine （Sa-i） and 4-（benzoxazole-2-yl）piperidine compounds （10a-i） were designed, synthesized and evaluated for their α1-AR antagonistic activities. Biological assay in vitro indicated that 10h showed slightly stronger α1-AR antagonistic activity to that of our lead compound 1.     

Synthesis of 4-(4-iodophenyl)piperazine and the 1-carboxamidino derivative

The previously unreported 4-(4-iodophenyl)piperazine ( 2 ) was synthesized in a 70% yield and characterized. The reaction of 2 with S-methylthiouronium sulfate gave the corresponding carboxamidino derivative 4 in a 61% yield. The tlc properties of 4 were identical with those of the radioiodinated material that had been prepared and evaluated as a potential myocardial imaging radiopharmaceutical.     

Synthesis of radioiodinated 4-[*I]iodoantipyrine via isotopic exchange

Radioiodinated 4-[*I]iodoantipyrine labeled with radioiodine (i.e., ¹²³I or ¹²⁵I or ¹³¹I) has been used for modeling radiation damage on cell nuclei of tumor cells where the characteristic high linear energy transfer (high-LET) of the Auger electron could be demonstrated. Also, the compound is currently used for the measurement of regional cerebral blood flow (rCBF) in autoradiography. 4-[¹³¹I]iodoantipyrine was synthesized by two methods via a nucleophilic isotopic exchange reaction between ¹³¹I as iodide ion [¹³¹I^–] and inactive 4-[¹²⁷I]iodoantipyrine: either in absolute ethyl alcohol catalyzed by ammonium acetate or in dry state molten ammonium acetate (m.p. 114 °C) as an isotopic exchange medium without carrier addition. The first one is called wet method: where a solution of 4-iodoantipyrine and ammonium acetate in absolute ethyl alcohol and lyophilized Na¹³¹I was heated briefly up to boiling (80 to 90 °C) for 30 minutes under reflux. The second one is called dry state-molten method: where the alcoholic solution containing 4-iodoantipyrine and ammonium acetate and the lyophilized Na¹³¹I were heated briefly in a nitrogen stream to dryness at 120 to 125 °C for 5 minutes or melted by gradual heating at 150 to 160 °C for 5 minutes. A radiochemical yield ranged between 90%–95% in each method has been obtained for 4-[¹³¹I]iodoantipyrine. In both methods, the reaction proceeds properly without carrier addition by an addition – elimination mechanism. The physico-chemical parameters affecting the radiochemical yield of the isotopic exchange reaction [i.e., reaction time, temperature, exchange medium, concentration of the reactants, carrier (KI) addition and pH] were investigated. Chromatographic analysis i.e., TLC and HPLC were used to determine the radiochemical yield as well as the purity of the final product, which was as pure as 99.9%.     

Radioiodination of (<Emphasis Type=Italic>N</Emphasis>-diethylaminoethyl)-4-iodobenzamide (IBZA) as a new potent melanoma imaging and therapeutic agent via isotopic exchange reaction

Guidelines for the assessment of internal doses from monitoring suggest default measurement of uncertainties (i.e. lognormal scattering factor, SF) to be used for different types of monitoring data. In this paper, SF values have been evaluated for internal contamination due to ⁶⁰Co in two cases using whole body counting data. SF values of 1.04 and 1.03 were obtained for case I and II, respectively while SF value of 1.03 was obtained using bioassay data for case I. SF evaluated is in good agreement with the default values given by IDEAS guidelines. The present study also presents the follow up study of a case I of ⁶⁰Co internal contamination using whole body counting and bioassay analysis. The effect of medical intervention applied on the subject is studied. Medical intervention of d-Penicillamine (250 mg × 4 daily) was orally administered from 13th day of initial exposure for about a fortnight, which showed reduction of activity present by 33.4% through urine.