Maher A. El-Hashash

A Novel Synthesis of Some New Pyrimidine and Thiazolopyrimidine Derivatives for Anticancer Evaluation

Diaryl-oxiran-2-yl methanones ( 2 ) were prepared and reacted with thiourea to give 2-thioxo-tetrahydro-pyrimidine-5(2H)-ones ( 3 ).The latter compounds reacted with bromoacetic acid to afford the title compounds ( 4 ). Also some new derivatives were prepared from the reaction of compounds ( 3 ) and ( 4 ) with different reagents. Compounds ( 3 ) were glycosidated with 2,3,4,6-tetra-O-acetyl-α -D-glucopyranosylbromide (α -ABG) to afford the corresponding nucleosides.

Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents.

In trying to develop new anticancer agents, a series of 1H-pyrazolo[3,4-b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivatives was investigated as a potential mechanism for the anticancer activity using DNA/methyl green assay and association constants assay. Compounds 19, 20, 21, 24 and 25 exhibited good activity against the four cancer cells comparable to that of doxorubicin. Interestingly, DNA binding assay results were in agreement with that of the cytotoxicity assays where the most potent anticancer compounds showed good DNA binding affinity comparable to that of doxorubicin and daunorubicin. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, DNA (PDB-code: 152d).

Synthesis, Antimicrobial and Anti-inflammatory Activity of Some New Benzoxazinone and Quinazolinone Candidates

Benzoxazinones and quinazolinones have a wide spectrum of biological activity. In this paper we focused on studying the antimicrobial and anti-inflammatory activities of some newly synthesized benzoxazinone and quinazolinone derivatives. Thus we prepared 2-[α-benzoylaminostyryl]-6,8-dibromo-3,1-benzoxazin-4(H)-one 2 which underwent a reaction with primary and secondary amines, and hydrazine hydrate to give compounds 3, 4 and 5, respectively. Treatment of 2 with hydroxylamine hydrochloride, formamide and/or NaN3/AcOH afforded compounds 7, 8, 11 and 12, respectively. Also, compound 2 reacted with maleic anhydride, aromatic hydrocarbons and/or active methylene compounds to produce compounds 13, 15a-c and 16, respectively. Most of the newly synthesized compounds showed significant antimicrobial and anti-inflammatory activities comparable to ampicillin, mycostatine and indomethacin positive controls.

Synthesis and Antibacterial Activity of Some New 4(3H)Quinazolin-4-one Derivatives

2-Phenylamino-6,8-dibromo-4H-3,1-benzoxazinone has been reacted with nitrogen nucleophiles, such as hydrazine hydrate, amines, and formamide, yielding 4(3H)quinazolinone derivatives; and with sulfur nucleophiles producing the corresponding thioesters. The behavior of aminoquinazolinone and 4(3H)quinazolinone towards some carbon electrophiles under different conditions has been studied.

Synthesis and Antifungal Activity of Novel Quinazolin-4(3H)-one Derivatives

Abstract A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared starting from 6-iodo-2-ethoxy-4H-3,1-benzoxazin-4-one (3) via action of various nitrogen nucleophiles such as primary and secondary amines, hydrazine hydrate, and its derivatives. The 3-amino-2-hydrazinyl-6-iodoquinazolin-4(3H)-one (15) was used as a key starting material to prepare new heterocyclic compounds. The structures of all synthesized compounds were inferred from the infrared, mass spectral, and 1H NMR spectral data as well as elemental analysis. The fungicidal activities of the target compounds were preliminarily evaluated. GRAPHICAL ABSTRACT

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

ABSTRACT A novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared. The reaction of the benzoxazinone 3 with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone 4 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 10a–c afforded the spiro compounds 11a–c. The acetohydrazide derivative 7 reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds 12–16, 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. GRAPHICAL ABSTRACT

The Uses of 2-Ethoxy-(4H)-3,1-benzoxazin-4-one in the Synthesis of Some Quinazolinone Derivatives of Antimicrobial Activity.

The behavior of 2-ethoxy-(4H)-3,1-benzoxazin-4-one (1) towards nitrogen nucleophiles, e.g. ethanolamine, aromatic amines (namely: p-toluidine, p-anisidine, p-hydroxyaniline, o-hydroxyaniline, o-bromoaniline, o-phenylenediamine, p-phenylenediamine, o-tolidinediamine) p-aminobenzoic acid, glucosamine hydrochloride, 2-aminonicotinic acid, 1-naphthalenesulfonic acid hydrazide, n-decanoic acid hydrazide, benzoic acid hydrazide, semicarbazide, aminoacids (e.g. D,L-alanine, L-asparagine, L-arginine) and derivatives of 2-aminothiodiazole has been investigated. The behavior of the benzoxazinone towards a selected sulfur nucleophile, L-cysteine, has also been discussed. Formation of an amidine salt as a reaction intermediate has been assumed. The effect of solvent in some reactions has been elucidated. The structures of all the novel quinazoline and quinazolinone derivatives, obtained by heterocyclic ring opening and ring closure were inferred by the IR, MS as well as 1H-NMR spectral analysis. Moreover, the antimicrobial potential of some of the new synthesized derivatives has been evaluated.

Synthesis of Novel Series of Phthalazine Derivatives with Antibacterial and Antifungal Evaluation

The oxirane derivative (2) was allowed to react with hydrazine hydrate, 4-aminobenzoic acid and o-phenylene diamine to give β-hydrazine alcohol derivative (3) and β-amino derivatives (4) and (5). The hydrazide (8) reacted with glucose, phthalic anhydride and aromatic aldehydes to give the phthalazine derivatives (9), (15) and (16a-c). A new heterocyclic molecules were synthesized using ethyl acetoacetate, acetyl acetone and benzoyl chloride with the hydrazide (8) to give the pyrazole derivatives (12), (14) and the oxadiazole derivative (18). The new compounds were synthesized with the objective of studying their antifungal and antimicrobial activity. Some of them gave positive results. The newly synthesized compounds were characterized on the basis of their spectral (1H-NMR, Mass spectrum, IR and Elementary analysis).

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

ABSTRACT 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-4H-3,1-benzoxazin-4-one 1 as building block. The reaction of benzoxazinone 1 with various reagents such as diethylmalonate, sodium azide, and phosphorus pentasulfide yielded the compounds 2–5. The behavior of benzothiazin-4-thione 5 toward formamide and hydrazine hydrate was investigated, forming the compounds 6 and 7. The reaction of quinazolinone derivative 8 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 9, 10, 12, and 13 respectively. The reaction of quinazolinone derivative 10 with acetic anhydride resulted in formation of the acylated compound 11. The behavior of quinazolinylacetohydrazide derivative 14 toward carbon electrophiles[16] has been investigated by its reaction with ethyl benzoylacetate, potassium thiocyanate, and phenyl isothiocyanate, affording the quinazolinone derivatives 15, 16, and 18, respectively. Treatment of compound 16 with sodium hydroxide followed by hydrochloric acid yielded the mercapto-triazole derivative 17. 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. GRAPHICAL ABSTRACT

Reactivity of 2-ethoxyquinazolin- 4-yl hydrazine and its use in synthesis of novel quinazoline derivatives of antimicrobial activity.

The reactions of 2-ethoxy-4-hydrazinoquinazoline 2 with diethyl oxalate and ethyl chloroacetate gave 6-ethoxy-2H-[1,2,4] triazino [4,3-c] quinazoline-3,4-dione 3 and 6-ethoxy-2,3-dihydro-4H-[1,2,4] triazino [4, 3-c] quinazolin-4-one 4 respectively. A series of 5-ethoxy-2-X-[1, 2, 4] triazolo [1, 5-c] quinazolines 5a-d was also produced by reacting 2 with the acid chlorides namely: benzoyl, crotonyl, cinnamyl and 2-furoyl chlorides via Dimroth rearrangement. Also, 2 reacted with ethyl chloroformate giving 6. Condensation of 2 with acetone gave Schiff base 7, and with monosaccharides gave the sugar hydrazones 8a-e which was thereafter acetylated giving the corresponding 9a-e. Cyclization of 8a-e by iron(III) chloride gave triazoloquinazolines 10a-e acyclic C-nucleosides which, by acetylation, afforded 11a-e. All products were confirmed by elemental, IR, MS, and 1H-NMR analysis. Products 8-11 were chosen for biological screening test against gram (+ ive) and gram (- ive) bacteria.