Kamal M. Dawood

Microwave-assisted synthesis and in-vitro anti-tumor activity of 1,3,4-triaryl-5-N-arylpyrazole-carboxamides

Regioselective 1,3-dipolar cycloaddition of nitrilimines with 5-arylidene-2-arylimino-4-thiazolidinones and with 2-(4-arylidene)thiazolo[3,2-a]benzimidazol-3(2H)-ones afforded the corresponding 1,3,4-triaryl-5-N-arylpyrazole-carboxamides and pyrazolylbenzimidazoles. All reactions were carried out under conventional thermal heating and/or microwave irradiation. Both the pyrazole-5-carboxamides and pyrazolylbenzimidazoles were examined for their in-vitro anti-tumor activities against two tumor cell lines, Hep-2 and colon CaCo-2. Most of the obtained compounds exhibited significant activity against CaCo-2 and Hep-2 cell lines.

Convenient synthesis and antimicrobial evaluation of some novel 2-substituted-3-methylbenzofuran derivatives

The reaction of 3-methylbenzofuran-2-carbohydrazide (1) with l-phenyl-2-bromoethanone (2a) or 2-chloro-1-(4-chlorophenyl)ethanone (2b) afforded (Z)-1,2-di[(3-methylbenzofuran-2-carbohydrazido]-1-arylethenes 5a and 5b, respectively. Single crystal X-ray analyses of compound 5a proved that the reaction proceeds in 2:1 molar ratio and ruled out the other possible structures 1,3,4-oxadiazine derivative 6 or E-isomer 7. Furthermore, both of 3-(3-methylbenzofuran-2-yl)-3-oxopropanenitrile (9) and 3-methyl-2-benzofuranoyl chloride (15) were used as starting materials for the synthesis of several compounds, such as pyrazoles 10 and 14, oxime 11, hydrazones 12a, b and 3,1-bezoxazine 19. The newly synthesized compounds were tested for their antimicrobial activity against five fungal species and four bacterial species also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Some of these compounds exhibited a significant antimicrobial activity.

Benzofuran derivatives: a patent review

Introduction: Benzofuran moiety constitutes the core of several interesting pharmacologically active natural products. Benzofurans are among feasible potent active inhibitors against many diseases, viruses, microbes, fungus and enzymes. Several series of therapeutically important synthetic and naturally occurring benzofuran-containing compounds are reported in this chapter. Areas covered: The current chapter focuses on the recent applications of benzofuran scaffolds and their wide range of biological activities during 1999 – 2012. The pharmacological areas covered included anti-inflammatory, antitumor, cytotoxic, antimicrobial, antitubercular, antioxidant, antiplasmodial, trypanocidal and insecticidal activities as well as enzyme inhibitory, HCV and HIV inhibitory activities. Expert opinion: The results reported in the chapter indicate that some benzofuran derivatives may be useful as potent drugs. From the structure–activity relationship (SAR), the presence of certain functions like -OH, -OMe in the benzofuran derivatives contributed greatly in increasing the potency of their therapeutic activities when compared with standards. For example, presence of the -OH and -OMe have made some benzofuran compounds more potent HIV-RT inhibitory activity than the standard atevirdine, and more potent antitumor agent when compared with standards (fluorouracil, doxorubicin and cytarabine). In addition, the enzyme aromatase CYP19 inhibitory activity of benzofurans having -OH and -OMe were greater than that observed for the reference arimidex.

Synthesis and reactivity of 3-(benzothiazol-2-yl)-3-oxopropanenitrile

The versatile, hitherto unreported 3-(benzothiazol-2-yl)-3-oxopropanenitrile (3) was prepared by two convenient routes: either by the reaction of ethyl 2-benzothiazolecarboxylate (1) with acetonitrile in the presence of sodium hydride or by treatment of 2-bromoacetylbenzothiazole (2) with potassium cyanide. Reaction of 3 with heterocyclic diazonium salts furnished the corresponding hydrazones 6, 7 and 13, respectively. The latter products underwent intramolecular cyclization into the corresponding pyrazolo[5,1-c]-1,2,4-triazine, 1,2,4-triazolo[5,1-c]-1,2,4-triazine and 1,2,4-triazolo[4,3-a]benzimidazole derivatives 8, 9 and 14, respectively, upon boiling in pyridine. Compound 3 coupled also with diazotized aromatic amines and gave the corresponding arylhydrazones 16a-c which undergo cyclocondensation with hydrazine and phenylhydrazine to afford the pyrazole derivatives 17a-c and 18a-c, respectively. Cyclocondensation of compound 3 with hydrazine derivatives afforded the corresponding aminopyrazoles 19 and 20, respectively in good yields.

Synthesis of 3,3′-bi-1,2,4-Triazolo[4,5-a]- benzimidazole, 5,5′-bi-1,3,4-Thiadiazole, and Thiazolo[3,2-a]benzimidazole Derivatives

Abstract A series of novel 3,3′-bi-1,2,4-triazolo[4,5-a]benzimidazole and thiazolo[3,2-a]-benzimidazole derivatives were synthesized via the reaction of bis-hydrazonoyl chlorides with 2-methylthiobenzimidazole and with benzimidazol-2-thiol, respectively. A direct synthesis of 5,5′-bi-1,3,4-thiadiazole and 4,5-bis-phenylhydrazono-2,3,4,5-tetrahydrothiazole derivatives is also described.

Reactions with Hydrazonoyl Halides XXX: Synthesis of Some 2,3-Dihydro-1,3,4-Thiadiazoles and Unsymmetrical Azines Containing Benzothiazole Moiety

Abstract C-Benzothiazoloyl-N-arylhydrazonoyl bromides 1a,b have been caused to react with each of methyl 2-thiazolylcyanomethinecarbodithioate (2), alkyl carbodithioates 8–10, and methyl thiocarbamates 14a-c in the presence of triethylamine to give 2,3-dihydro-1,3,4-thiadiazoles in good yields. In contrast, hydrazonoyl bromides react with each of phenylthiourea (19a), phenylthiosemicarbazide (19b), and benzoylthiosemicarbazide (19c) afforded 5-arylazothiazole 22–24(a-c) derivatives, respectively. Structures of the new compounds were elucidated on the basis of elemental analyses, spectral data, and alternative methods of synthesis whenever possible.

Facile Syntheses of Bi-1,2,4-triazoles via hydrazonyl halides

Reaction of oxalodihydrazonyl dihalides 1 with sodium azide afforded the corresponding di-azides 2. Reduction of the latter with LiAlH4 yielded the diamidrazones 4 which react with acyl halides to give the bi-1,2,4-triazoles 5. The latter products were alternatively prepared by reaction of 2 with triphenylphosphine to give the phosphinimines 6 followed by treatment of the latter with acyl halides.

Facile synthesis of novel polysubstituted thiopene and 1,3,4-thiadiazole derivatives

Abstract 3-(Benzothiazol-2-yl)-3-oxopropanenitrile ( 1 ) reacts with phenylisothiocyanate in the presence of potassium hydroxide followed by addition of the hydrazonoyl bromides 2a-c to afford the novel 1,3,4- thiadiazole derivatives 6a-c via the intermediate 4 . Reaction of 4 with 2-bromoacetylbenzothiazole ( 3 ) furnished the new polysubstituted thiophene 13 . Treatment of the latter product with aromatic diazonium salts resulted in the formation of 2-arlazothiophene derivatives 16a-c . A suggested mechanisms of the investigated reactions were presented.

One-step synthesis of novel 2,2′-bi(4,5-dihydro-1,3,4-thiadiazole) and 2,3-disubstituted 1,4-benzothiazine derivatives

N,N′-Diaryloxalodihydrazonoyl dihalides 2 react with potassium thiocyanate or thiourea and yield the hitherto unkown bi-4,5-dihydrothiadiazol-5-imine derivatives 5. Reaction of 5 with acetic anhydride, benzoyl chloride and nitrous acid yield N-acetyl, N-benzoyl and N-nitroso derivatives 7, 8 and 9, respectively. Thermolysis of 9 afforded the bi-4,5-dihydrothiadiazol-5-ones 10. The dihalides 2 react also with 2-aminothiophenol to afford the 1,4-benzothiazine derivatives 11 which upon oxidation gave 12.

Synthesis of 2-Phenylazonaphtho[1,8-ef][1,4]diazepines and 9-(3-Arylhydrazono)pyrrolo[1,2-a]perimidines as Antitumor Agents

Two series of naphtho[1,8-ef][1,4]diazepines and pyrrolo[1,2-a]perimidines were prepared starting from 1,8-diaminonaphthalene and hydrazonoyl chlorides. The structures of the products were determined on the basis of their spectral data and elemental analyses. The mechanism of formation of such products was also discussed. The prepared compounds were screened for their antitumor activity against three cell lines, namely, MCF-7, TK-10 and UACC-62, and some derivatives showed promising activity.