Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds

A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The behavior of the cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives towards nitrogen and carbon nucleophiles was investigated. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, 1H-NMR 13C-NMR and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines, namely hepatocellular carcinoma (liver) HePG-2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity

Synthesis of various fused pyrimidine rings with their pharmacological and antimicrobial evaluation

Various fused pyrimidine such as furo[2,3-d]pyrimidine, triazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine were synthesized from the reactions of thioxopyrimidine-6(1H)-ones with ethyl chloroacetate (under different reaction conditions), thiourea, and sodium nitrite. Pyrimidine thiones reacted with POCl3/PCl5 to give the chloro derivatives which reacted with sodium azide, and thiourea to give the tetrazolo[1,5-c]pyrimidine, pyrimido pyrimidine. Thioxopyrimidine-6(1H)-ones reacted with benzyl amine to give pyrrolo[2,3-d]pyrimidinethione. Theoretical calculation using MIDO/3, Fukui indices and the heat of formation of some compounds were carried out. The pharmacological and antimicrobial activities of some of the synthesized products were also evaluated

6-Iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one as building block in heterocyclic synthesis

<p>As a part of ongoing studies in the synthesis of a variety of heterocycles of biological importance, we report here an efficient and convenient method for the synthesis of novel compounds from 6-iodo-2-isopropyl-4<i>H</i>-3,1-benzoxazin-4-one <b>1</b> as building block. The reaction of benzoxazinone <b>1</b> with various reagents such as diethylmalonate, sodium azide, and phosphorus pentasulfide yielded the compounds <b>2–5</b>. The behavior of benzothiazin-4-thione <b>5</b> toward formamide and hydrazine hydrate was investigated, forming the compounds <b>6</b> and <b>7</b>. The reaction of quinazolinone derivative <b>8</b> with β-D-glucose pentaacetate, ethyl 2-methyl-5-((1S,2R,3R)-1,2,3,4-tetrahydroxybutyl)furan-3-carboxylate, epichlorohydrin and benzenesulphonyl chloride afforded quinazolinone derivatives <b>9, 10, 12,</b> and <b>13</b> respectively. The reaction of quinazolinone derivative <b>10</b> with acetic anhydride resulted in formation of the acylated compound <b>11</b>. The behavior of quinazolinylacetohydrazide derivative <b>14</b> toward carbon electrophiles^[<a href="#CIT0016" target="_blank">¹⁶</a>^] has been investigated by its reaction with ethyl benzoylacetate, potassium thiocyanate, and phenyl isothiocyanate, affording the quinazolinone derivatives <b>15, 16,</b> and <b>18</b>, respectively. Treatment of compound <b>16</b> with sodium hydroxide followed by hydrochloric acid yielded the mercapto-triazole derivative <b>17</b>. The structures of the newly synthesized compounds were confirmed by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and mass spectra. The antimicrobial activities of some of the synthesized compounds were preliminarily evaluated.</p

Regioselectivity and regiospecificity of benzoxazinone (2-isopropyl-4<i>H</i>-3,1-benzoxazinone) derivatives toward nitrogen nucleophiles and evaluation of antimicrobial activity

<p>A novel group of 6-iodoquinazolin-4(<i>3H</i>)-one derivatives was prepared. The reaction of the benzoxazinone <b>3</b> with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone <b>4</b> with hydrazonyl chloride have been shown to proceed with a high degree of regioselectivity at C(2). Spiro heterocycles have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties; thus reaction of acetohydrazides <b>10a–c</b> afforded the spiro compounds <b>11a–c</b>. The acetohydrazide derivative <b>7</b> reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds <b>12–16</b>, respectively. The structures of all the synthesized compounds were inferred by infrared, ¹H NMR, and mass spectra as well as elemental analyses. The antimicrobial activities of some of the synthesized products were preliminarily evaluated.</p