Pyrido[2,3-b][1,4]diazepinones with CNS activity

In the interests of developing our research on compounds with a pyrazinone nucleus, cyclohomologues, characterised by the presence of one diazepinone nucleus, were prepared. The 5-[(dialkylamino)alkyl]-3,5-dihydro-2-methyl/phenyl-4H-pyrido[2,3- b][1,4]diazepin-4-ones obtained by means of condensation of the 2-(dialkylamino)alkylamino-3-aminopyridines with ethyl acetyl- or benzoyl- acetate, were subjected to pharmacological experimentation in order to evaluate their effect upon mice with regard to exploratory activity, motor coordination, and spontaneous activity. In addition their analgesic activity was evaluated and also their anti-strychnine, anti-cardiazole, anti-amphetamine and anti-reserpine activities.     

Synthesis and antiproliferative activity in vitro of new pyrido[1,4-b]diazepine derivatives and imidazo[4,5-b]pyridine

A novel series of esters 8-10 and hydrazones 4-6 was synthesized from 4-aryl-2-phenacylidene-1,3,4,5-tetrahydropyrido[2,3-b][1,4]diazepine (1-3). Subsequent treatment of hydrazone 4 with p-chlorbenzaldehyde furnished azine 7. Long-standing heating of ester 8 with hydrazine hydrate afforded 3-[1-(p-chlorophenylene)-2-(5-phenyl-1H-pyrazol-3-yl)-ethyl]-1,3-dihydroimidazo[4,5-b]pyridin-2-one (11). The structures of 4-6 and 8-10 were identified by the results of elemental analysis and their IR, 1H-NMR and MS spectra. Additionally, the structure of 11 was confirmed by X-ray diffraction method. Compounds 8-10 and 11 were examined for their antiproliferative activity in vitro against the cells of 5 human cancer cell lines, using SRB or MTT technique. Among tested compounds, only 11 revealed cytotoxic activity in vitro against all cell lines applied with ID50 (inhibitory dose 50%) values lower than 4 microg/mL, which is an international activity criterion for synthetic compounds. All compounds inhibit the proliferation of HL-60 human promyelocytic leukemia cell line.     

Synthesis and properties of dipyrimido-[4,5-b][5,4-f]-1,4-thiazepine derivatives

Derivatives of dipyrimido[4,5-b][5,4-f]-1,4-thiazepine were synthesized and some of their properties were studied. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 2, pp. 10–13, February, 2008. This is communication No. 59 in the series “Studies of nitrogen-and sulfur-containing heterocyclic compounds”; for communication No. 58 see [1].     

Synthesis and pharmacological screening of 1,3,4-thiadiazino[2,3-b]quinazoline derivatives

Derivatives of 1,3,4-thiadiazino[2,3-b]quinazoline 7, 9, 9a, 12, 12a, and 13 were prepared from the 3-amino-6-bromo-2,3-dihydro-2-thioxo-4-(1H)-quinazolinone (2) and its analogue without bromine. A series of the title derivatives with or without bromine was tested and the results of pharmacological screening are discussed.     

Synthesis and cytotoxicity of novel 6H-indolo[2,3-b]quinoxaline derivatives

A series of new 6-[(N ₁-aryl-1H-1,2,3-triazol-4-yl)methyl]-6H-indolo[2,3-b]quinoxa-line derivatives 7a _i–ix and 7b _i–vi is synthesized by a simple multi-step protocol starting from isatin 1a or 5-fluoroisatin 1b. These compounds are screened against lung (A-549), cervical (HeLa), and prostate (DU-145) human cancer cell lines to evaluate their cytotoxic effect. Of all the compounds tested, five compounds showed moderate cytotoxicity against human reproductive organ cell lines, while others exhibited lower cytotoxicity against different human cancer cell lines. An elegant synthesis of these complex molecules and their cytotoxicity data are presented.     

Synthesis and biological activity of pyrido(2,3-e)-1,4-diazepine and of pyrido(2,3-b)(1,4)diazepine]

The Schmidt reaction on tetrahydro-1,8-naphthyridin-4-ones gave pyrido [2,3-e]-1,4-diazepines and pyrido[2,3-b][1,4]diazepines. The preliminary pharmacological screening of some of these compounds showed no appreciable activity.     

Synthesis of Some New Derivatives of Thiazolo[4,3-b]- and Thiazolo[2,3-b] quinazolone

The new 5H-thiazolo[4,3-b]quinazoline-3,5(1H)-diones 3, 4a–c, 5a–c and 5H-thiazolo[2,3-b]quinazoline-3,5(2H)-diones 9a–c, 11a–c were prepared by reaction of anthranilic acid with the 2-thiazolidinone-4-thione derivatives 1b, 6a–c, 7a–c and the 5-substituted 2-(alkylmercapto)-2-thiazolin-4-ones 8a-c, 10a-c , respectively.     

Synthesis and anticonvulsant activity of pyrano[4′,3′:4,5]pyrido[2,3-b]thieno[3,2-d] pyrimidine derivatives and pyrimido[5′,4′:2,3]-thieno[2,3-c]isoquinoline derivatives

Methods for the synthesis of condensed thieno[3,2-d]pyrimidines based on pyrano[4,3-d]thieno[2,3-b]pyridines and thieno[2,3-b]isoquinolines have been developed and a series of new derivatives have been synthesized. The anticonvulsant activity of the synthesized compounds has been studied. Several compounds possessing specific anticonvulsant activity with respect to corazole-induced convulsions are revealed. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 9, pp. 14–16, September, 2007.