Synthesis and reactions of novel thienotetrahydroisoquinoline compounds

Chloroacetylation of 1-Aminocarboxamide 1 afforded the chloroacetylamino 2 which underwent ring closure upon reflux with acetic anhydride to afford the chloromethylpyrimido 3. The latter compounds under went nucleophilic substitution reactions with various primary and secondary amines which underwent Mannich reaction to give theimidazopyrimidothienoisoquinolines 5a-c. Compound 1 react with phthalic an hydride in acetic acid and DMF to afford phthalimido and isoindolopyrimido thienotetrahydroisoquinoline 6, 7 respectively. Reaction with diethylmalonate afforded the pyrimidocarboxylate 8 which react with hydrazine hydrate to give the carbohydrazide 9 which react with triethyl orthoformate for synthesis of triazepinopyrimido 10. Reaction of 1 with carbon disulfide in pyridine afforded the pyrimidinethione 13 which underwent double Mannich reaction to give the novel thiadiazinopyrimido compound 14. Reaction of tetrahydroisoquinolinethione 15 with 2-chloromethylbenzimidazole followed by Thorpe-Zeigler cyclization to afford the aminobenzoimidazolyl 18 which proved its versatility as starting material for synthesis of novel heterocycliccompounds 19-22. Imidazole; triazepine; thiadiazine; pyrimidine; synthesis; reactions

SYNTHESIS AND REACTIONS OF SOME NEW MORPHOLINYLPYRROLYL TETRAHYDROTHIENO[2,3-c] ISOQUINOLINE

 Hydrazinolysis of ethyl-5-morpholin-4-yl-1-(1H-pyrrol-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]iso- quinoline-2-carboxylate  afforded the corresponding carbo- hydrazide which upon condensation with aromatic aldehydes, acetyl acetone and/ or carbon disulfide gave N- arylidinecarbohydrazide, dimethylpyrazolyl methanone, [1,3,4]oxadiazole-2-thiol and its ethyl ester derivatives respectively. Diazotization of the carbohydrazide with nitrous acid afforded the corresponding carboazide which was used for synthesis of carbamates and substituted carboxamides. Boiling of the carboazide in dry xylene afforded the pyrazinone compound which was used for synthesis of other heterocycles containing pyrrolopyrazinothinoisoquinoline moeity

A FACILE SYNTHESIS AND REACTIONS OF AMINO SELENOLO[2,3-b]PYRIDINE CARBOXYLATE

 Incorporating selenium metal bonded to the pyridine nucleus was achieved by the reaction of selenium metal with 2-chloropyridine carbonitrile 1 in the presence of sodium borohydride as reducing agent. The resulting non isolated selanyl sodium salt was subjected to react with various α-halogenated carbonyl compounds to afford the selenyl pyridine derivatives 3a-f  which compounds 3a-d underwent Thorpe-Ziegler cyclization to give 1-amino-2-substitutedselenolo[2,3-b]pyridine compounds 4a-d, while the other compounds 3e,f failed to be cyclized. Basic hydrolysis of amino selenolo[2,3-b]pyridine carboxylate 4a followed by decarboxylation furnished the corresponding amino selenolopyridine compound 6 which was used as a versatile precursor for synthesis of other heterocyclic compound 7-16. All the newly synthesized compounds were established by elemental and spectral analysis (IR, 1H NMR) in addition to mass spectra for some of them hoping these compounds afforded high biological activity

Burden of diarrhea in the Eastern Mediterranean Region, 1990-2015: Findings from the Global Burden of Disease 2015 study

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The biological activity of new thieno[2,3-c]pyrazole compounds as anti-oxidants against toxicity of 4-nonylphenol in Clarias gariepinus

Synthesis of bi functionally substituted thieno[2,3-c]pyrazole compounds was carried out by a new method. The substituted group at position five is namely (carbonitrile, carboxamide, N-(substitutedphenyl) carboxamide and benzoyl group). Chloroacetylation of the amino thieno[2,3-c]pyrazolecarboxamide compound afforded the chloroacetyl amino derivative. The chemical structure of the newly synthesized compounds was established by elemental and spectral analysis including IR, 1H NMR spectra in addition to 13C NMR and mass spectra for most of them. In the present work, we assessed the role of the new synthesized thieno[2,3-c]pyrazole compounds as antioxidants against the toxicity of the 4-nonylphenol on the red blood cells of the most economically important Nile fishes namely African catfish (Clarias gariepinus). The erythrocytes alterations were used as biological indicators to detect those effects. After exposure to 4-nonylphenol, the erythrocytes malformations (swelled cells, sickle cells, tear drop like cells, acanthocytes, and vacuolated cells) were recorded in highest number in comparison with other groups control and those injected with thieno[2,3-c]pyrazole compounds. So, the new thieno[2,3-c]pyrazole compounds can be used as antioxidants against toxicity of 4-nonylphenol on fishes

Efficient synthesis of some novel furo[3,2-<i>e</i>]pyrazolo[3,4-<i>b</i>]pyrazines and related heterocycles

<p>A series of novel 6-functionalized-5-amino-3-methyl-1-phenyl-1<i>H</i>-furo[3,2-<i>e</i>]pyrazolo[3,4-<i>b</i>]pyrazines <b>(4a–c)</b> was synthesized by the reaction of 3-methyl-6-oxo-1-phenyl-6,7-dihydro-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyrazine-5-carbonitrile <b>(2)</b> with α-halocarbonyl compounds such as: diethyl 2-bromomalonate, phenacyl bromide and chloroacetone. Cyclocondensation of the amino benzoyl <b>4b</b> with diethyl malonate yielded the oxopyridine carboxylate derivative <b>5</b>. Also, the starting intermediate amino ester compound <b>4a</b> was allowed to react with ethanol amine to afford the hydroxyethyl caboxamide derivative <b>6</b>. Furthermore, hydrazinolysis of the amino ester <b>4a</b> afforded the corresponding amino carbohydrazide <b>7</b> which was used as a versatile precursor for synthesis of other heterocyclic compounds attached or fused to the furopyrazolopyrazine moiety. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry hoping these molecules should allow us to investigate their pharmacological activities in the future study.</p

Synthesis, reactions, and antioxidant activity of 3-(pyrrol-1-yl)-4,6-dimethyl selenolo[2,3-<i>b</i>]pyridine derivatives

<p>Ethyl 4,6-dimethyl-3-(pyrrol-1-yl) selenolo[2,3-<i>b</i>]pyridine-2-carboxylate <b>(2)</b> was synthesized by the reaction of previously prepared ethyl 3-amino-4,6-dimethyl selenolo[2,3-<i>b</i>]pyridine-2-carboxylate <b>(1)</b> with 2,5-dimethoxytetrahydrofuran in acetic acid. The pyrrolyl ester <b>(2)</b> was converted into the corresponding carbohydrazide <b>3</b> which reacted with acetyl acetone, aromatic aldehydes, carbon disulfide in pyridine, and sodium nitrite to afford the corresponding dimethyl pyrazolyl <b>4</b>, arylidene carbohydrazides <b>5a–d</b>, oxadiazolyl thiole <b>6,</b> and caboazide compound <b>8,</b> respectively. The carboazide <b>8</b> reacted with different alcohols and amines to give the corresponding carbamates <b>9a–c</b> and the aryl urea derivatives <b>10a–d</b>. Heating of carboazide <b>8</b> in dry xylene afforded the pyridoselenolo-pyrrolopyrazinone <b>11</b>. The latter compound was used as a versatile starting precursor for synthesis of other pyridoselenolo-pyrrolopyrazine compounds. The newly synthesized compounds and their derivatives were characterized by elemental analysis and spectroscopy (IR, ¹H-NMR, and mass spectra). Some of the newly synthesized pyrrolyl selenolopyridine compounds showed remarkable antioxidant activity compared to ascorbic acid.</p

Burden of diarrhea in the eastern mediterranean region, 1990-2013: Findings from the global burden of disease study 2013

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low-and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.</p