Type 2 diabetes mellitus is a vast growing progressive disease that almost affects one person among every twelve globally. Regardless the availability of wide variety of oral hypoglycemics, only one-third of patients achieves proper glycemic control. With the advantage of the low risk of hypoglycemia, DPP-IV attracted the attention of medicinal chemists as a new target for oral hypoglycemics. In this report, a lead compound 1, with antipyrine scaffold, was obtained, and its binding mode was calculated. Several derivatives with bridged nitrogenous heterocycles have been synthesized via multicomponent reaction under controlled microwave heating conditions. The antidiabetic activity versus DPP-IV protein was evaluated and compared with sitagliptin. Compounds with smaller- or medium-sized nitrogenous bridges were comparable with sitagliptin in terms of DPP-IV inhibitory activity, potentially via targeting Glu203 and Glu204. The oral hypoglycemic activities of compounds with submicromolar IC50 values were further evaluated using diabetic mouse model.

A number of interesting heterocycles were prepared through interaction of the intermediate 3-amino-8-hydroxy-4-imino-6-methyl-5-phenyl-4,5-dihydro-3H-chromeno-[2,3-d]pyrimidine (1) and reagents such as hydrazonyl halides 2 to furnish triazine derivatives 4a–l. Reaction of 1 with phenacyl bromide afforded compound 5. Moreover, the title compound 1 was subjected to condensation with active methylene compounds (ethyl acetoacetate and ethyl benzoylacetate) to give triazipinones 8a,b. The condensation with aromatic aldehydes afforded either the triazole derivatives 10a–d or Schiff base 11. In addition, the behaviour of compound 1 towards activated unsaturated compounds namely dimethyl acetylene dicarboxylate and ethoxymethylenemalonitrile was studied and it was found to furnish the triazine 13 and triazepine derivative 15, respectively. Combination of title compound 1 with chlorinated active methylene compounds delivered the triazine derivatives 18a–c. Reaction of 1 with chloroacetonitrile furnished compound 20. The structures of the products were elucidated based on their microanalyses and spectroscopic data. Finally, the antitumor activity of the new compounds 4a and 8a against human breast cell MCF-7 line and liver carcinoma cell line HepG2 were recorded.

Design and synthesis of novel anti-HIV-1 NNRTIs based on a pyrazolo[4,3-d]isoxazole backbone scaffold.

In this paper, the synthesis of bis-thiazoles and bis-1,3,4-thiadiazoles linked to a thienothiophene nucleus is described. The synthesis was achieved through interaction between 2,5-diacetylthieno[2,3-b]thiophene bis-thiosemicarbazones with a variety of hydrazonyl halides in a basic medium. All the synthesised compounds were characterised by IR, 1 H NMR, 13 C NMR and mass spectroscopic analyses. The newly synthesised compounds represent a variety of novel polyheteroatomic moieties containing nitrogen and sulfur. Most of the synthesised compounds were evaluated for their antitumour activity against the breast cancer MCF-7 cell line. The results revealed that four compounds are equipotent to tamoxifen (

in Wiley Online Library (wileyonlinelibrary.com).The current study in this article concerned with construction of five-membered heterocycles with multiple heteroatoms as nitrogen and sulfur from readily available starting materials and reagents. Treatment of 1-(2oxo-2H-chromene-3-carbonyl)-3-phenyl-1H-pyrazol-5(4H)-one with each of phenylisothiocyanate in alcoholic potassium hydroxide and carbon disulfide in basic medium gave rise to a thioanilide and methylthio derivatives, respectively. Treatment of the latter compounds with a variety of hydrazonoyl halides resulted in construction of thiadiazole moiety linked to pyrazole ring. Furthermore, triazole derivatives were synthesized from the thioanilide derivative through its reaction with methyl iodide followed by reaction with hydrazonoyl halides. 5α-Reductase inhibition activity for the prepared compounds was investigated against the reference drug anastrozole, and the results showed that the inhibition activity of compounds 5g and 11g is more potent than anastrozole. Also compounds bearing triazole moiety is more potent than compounds bearing thiadiazole one. Moreover, the anti-prostate cancer screening anti-androgenic bioassay in human prostate cancer cells for the tested compounds was evaluated, and the results showed great inhibition growth and potential antiandrogens.

The reaction of 2-[1-(naphthalen-2-yl)ethylidene]hydrazinecarbothioamide with hydrazonoyl halides afforded new thiazole derivatives, whilst reaction with compounds containing an activated double bond such as ethoxymethylenemalononitrile and benzylidenemalononitrile yielded the respective pyrimidine derivatives. A 4-thiazolidin-4-one was obtained by reaction of the hydrazinecarbothioamide with ethyl bromoacetate. Subsequent condensation of the thiazolidinone with aromatic aldehydes afforded the corresponding arylidene derivatives. Treatment of the hydrazinecarbothioamide with dimethyl acetylenedicarboxylate resulted in the formation of a (methoxycarbonylmethylidene) thiazolinone. Reaction of the hydrazinecarbothioamide with 2-chloro-1,3-dicarbonyl compounds gave the respective thiazole derivatives. The structures of the newly synthesised compounds were confirmed by their elemental analysis and spectral data.

Reaction of 1‐[4‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐2‐phenylsulfonyl‐1‐ethanone (1) with phenyl isothiocyanate afforded the 4‐(3‐mercapto‐3‐(phenylamino)‐2‐(phenylsulfonyl)acryloyl)‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one (2). Treatment of compound 2 with hydrazonoyl chlorides 3a–h afforded the corresponding1,3,4‐thiadiazole derivatives 5a–h. Cyclocondensation reaction of compound 2 with the appropriate α‐halo‐compounds 6, 8, 10, 12a,b or 14 (ethyl 2‐chloroacetate, chloroacetonitrile, 1‐chloropropan‐2‐one, 2‐bromo‐1‐phenylethanone, 2‐bromo‐1‐p‐tolylethanone, and 2‐bromoacetyl‐3H‐benzo [f]chromen‐3‐one) afforded the 1,3‐thiazole derivatives 7, 9, 11, 13a,b, and 15, respectively. Coupling of the ketosulphone 1 with the appropriate diazotized 4H‐1,2,4‐triazol‐3‐amine 16 and 2‐aminobenzimidazole 19 afforded triazolo[5,1‐c][1, 2, 4]triazine 18 and benzo[4,5]imidazo[2,1‐c][1, 2, 4]triazine 21, respectively. The structures of the synthesized compounds were confirmed on the basis of their elemental analysis and spectral data and evaluated as potential anti‐breast cancer agents. Moreover, the computational studies using MOE 2014.09 software are confirming the results in biological activity.

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