Facile construction of substituted pyrimido[4,5-d] pyrimidones by transformation of enaminouracil

The reaction of 6-amino-1,3-dimethylpyrimidine-2,4[1H,3H]-dione [1] as a binucleophile with primary aromatic or heterocyclic amines and formaldehyde or aromatic [heterocyclic] aldehydes in a molar ratio [1:1:2] gave the pyrimido[4,5-d]pyrimidin-2,4-dione ring systems 2-5. Treatment of 1 with diamines and formalin in molar ratio [2:1:4] gave the bis-pyrimido[4,5-d]pyrimidin- 2,4-diones 6-8. Furthermore, substituted pyrimido[4,5-d]pyrimidin-2,4-diones with uracil derivative 11 or spiro indole 16 were synthesized. Synthesis of pyrimido[4,5-d]pyrimidin-2,4-diones with different substitution at C-5 and C-7 was achieved to give 13 and 18, respectively

Facile preparation of 3-functional chromen-2-ones

The reaction of 3-carbethoxy-chromen-2-one [1] with thiosemicarbazide in pyridine afforded 3-[5-sulphonyl-2H-[1, 2, 4] triazol-3-yl]-chromen-2-one [2]. The alkylation of compound 2 with methyl iodide, ethyl chloroformate and ethyl bromoacetate in dry acetone gave the corresponding alky lated product 3a-c, respectively. The thiol group was readily substituted by various nitrogen nucleophiles such as hyurazine hydrate. urea and thiourea and primary amines gave the hydrazino-derivative 4, urea and thiourea derivatives 6a and 6b and amino-derivatives 7a-c. The hydrazino-derivative 4 was converted to triazolo [4, 3-b] triazolo-6-yl chromen-2-one derivatives 5a and 5b when refluxed with formic and acetic acid. The addition of thiol group in compound 2 to maleic and phthalic anhydrides was carried to give succinic and benzoic acid derivatives 8 and 10, respectively, which condensed with hydrazine hydrate to give the corresponding pyridazine derivative 9 and phthalazine derivative 11, respectively. The reaction between compound 2 and aroylacrylic acid derivatives afforded the corresponding 12a and 12b derivatives. Refluxing 12b in acetic anhydride yielded the furan derivative 13. Compounds 12b and 13 were converted to pyridazine derivative 14

Effect of combination of dizocilpine with general antiepileptic drugs on amygdala kindling models in rats / 药学学报

<p><b>AIM</b>To investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs.</p><p><b>METHODS</b>To establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose. The influence of dizocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observed.</p><p><b>RESULTS</b>Dizocilpine (0.1-0.25 mg.kg-1, i.p.) was shown to dose-dependently inhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P < 0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P < 0.01). Dizocilpine (0.1-0.25 mg.kg-1, i.p.) significantly prolonged the latency and reduced the rate of convulsions and death in mice.</p><p><b>CONCLUSION</b>Dizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital, valproate and nicardipine, indicating that these combination may provide a new approach for treating epilepsy.</p>

Synthesis of some new 1, 2, 3-selena and thiadiazole derivatives

Several compounds of 1,2,3-selena and/or thioadizoles with evident biological activity were previously reported by the authors, certainly as antibacterial and antifungal agents [1-6] e.g. 1,2,3-thiadiozolo and/or selenadiazolo-4-yl-pheynyl-hydrazophyrazolones [10] were tested in vitro against a variety of Gram positive strains of bacteria. Certain compounds show strong activity against Bacillus sub., staphylococcus areus and Mycobacterium phlei. Thus, pyridine [7], furan [8] and thiophene [9] containing 1,2,3-selena and thiadiazoles motivated their synthesis and testing as biologically active compounds. In this work, compounds [1-3] were easily condensed with semicarbazide to give the corresponding semicarbazones [4-6] respectively. On the other hand, the purified semicarbazones [4-6] were then oxidized either with selenium dioxide [11] in glacial acetic acid to give 1,2,-3-selenadiazole Derivatives[9,11] or with thionyl chloride[12] to afford, 1,2,3-thiadiazole derivatives[10,12]

Efeito ansiolítico da semicarbazida dinamizada em ratos submetidos ao teste do labirinto em cruz elevado / Ansiolytic effects of semicarbazide dinamized in mice submitted to the \"labirinto em cruz elevado\"experiment

O presente trabalho mostra a açäo preventiva da semicarbazida dinamizada (6CH) sobre a ansiedade produzida experimentalmente em animais

Effect of histamine on wound healing.

Using incision, excision and dead space wound models in rats, a study was conducted on the effect of histamine on wound healing. Exogenous histamine given either ip or locally was without any effect. Semicarbazide as (histamine synthesis inhibitor) suppressed healing process (breaking strength of skin incision wound), decreased breaking strength and hydroxyproline content of granulation tissue and delay in period of epithelization. On the other hand compound 48/80 (a promoter of histamine forming capacity) was found to promote wound healing. Exogenous histamine (topical) reversed the anti-healing effect of semicarbazide on incision and excision wounds.

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.

Tiossemicarbazonas heterocíclicas potencialmente antimaláricas: I. Aspectos estruturais / Potentially antimalarial heterocyclic thiosemicarbazones: I. Structural aspects

Com o objetivo de elucidar a estrutura de tiossemicarbazonas de aldeídos heterocíclicos, potencialmente antimaláricos, foram preparados quatro compostos desta classe, sendo analisados mediante espectrometria de infravermelho e de ressonância magnética protônica. A análise estrutural sugere grande conjugaçäo por deslocalizaçäo eletrônica, estabilizando a cadeia lateral em determinada configuraçäo, onde um dos prótons tioureídicos interage com o grupo carbonila e o outro com o átomo de nitrogênio da dupla ligaçäo