Synthesis and In Vivo Hypolipidemic Effect of Some N-(Benzoylphenyl)-Carboxamide Derivatives in Triton WR-1339-Induced Hyperlipidemic Rats

A series of N-(benzoylphenyl)-carboxamide derivatives (2a, 2b, 3a, 3b, 4a, 4b, 5a, 5b, 6a and 6b) was prepared with good yields by reacting the corresponding carbonyl chlorides with aminobenzophenones at room temperature. This was followed by evaluating the hypotriglyceridemic and hypocholesterolemic effects of 3b, 5a and 5b. Triton WR-1339 (300 mg/kg) was intraperitoneally administered to overnight-fasted rats to induce hyperlipidemia. Rats were divided into six groups: control, hyperlipidemic, hyperlipidemic plus compounds 3b, 5a and 5b and hyperlipidemic plus bezafibrate. Results showed that after 18 h of treatment at a dose of 15 mg/kg body weight of each of the test compounds, the elevated plasma levels of triglycerides (TG) and total cholesterol (TC) were significantly lowered by compounds 5b and 3b (p < 0.001) and by 5a (p < 0.0001), compared to the hyperlipidemic control group. Compounds 3b and 5a significantly increased levels of high-density lipoprotein cholesterol (HDL-C) by 58 and 71%, respectively. In addition, compounds 3b and 5a caused significant reduction (p < 0.0001) of low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. These results suggest a promising potential for compounds 3b, 5a and 5b as lipid-lowering agents, which may contribute to reducing the risk of atherosclerosis and cardiovascular disease

Neonatal screening program for hemoglobinopathies in the city of São Carlos, state of São Paulo, Brazil: analysis of a series of cases / Triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil: análise de uma série de casos

OBJECTIVE: To analyze the neonatal screening program for hemoglobinopathies in São Carlos, Southeast Brazil, by investigating a series of cases in which the screening test was abnormal. More specifically, it was aimed to know the information regarding the neonatal screening received by mothers at the hospital and at primary health care, in addition to information related to genetic counseling. METHODS: A descriptive study that enrolled 119 mothers, accounting for 73% of all children born between 2010 and 2011 with abnormal results of neonatal screening for hemoglobinopathies. The mothers completed a questionnaire that assessed the information received at hospital and primary health care, and issues related to genetic counseling. Descriptive statistics was performed. RESULTS: Of the 119 participating mothers, 69 (58%) had children with sickle cell trait, 22 (18.5%) with hemoglobin C trait, 18 (15.1%) with alpha thalassemia trait and, in 10 cases (8.4%), the result was inconclusive. At the hospital, 118 mothers (99.2%) received information about where to go to collect the test and 115 (96.6%) were informed about the correct time to collect the test. Only 4 mothers (3.4%) were informed about which diseases are investigated and the risks of not performing the screening. Seventeen mothers (14.3%) recognized the difference between trait and disease, and 42 (35.3%) considered that a positive screening test could have implications for future pregnancies. In 70 cases (58.8%), the child's physician was not informed about the screening test results. CONCLUSIONS: The neonatal screening program needs further improvement. In both scenarios investigated, health professionals demonstrated a lack of training in providing information to mothers and families. .

OBJETIVO: Fazer uma análise do programa de triagem neonatal de hemoglobinopatias no município de São Carlos, São Paulo, Brasil, por meio da investigação de série de casos cujo resultado do teste de rastreio foi alterado. Objetivou-se conhecer as informações a respeito da triagem neonatal recebidas pelas mães na maternidade e na atenção primária à saúde, além das informações relacionadas à orientação genética. MÉTODOS: Estudo descritivo, no qual participaram 119 mães cujos filhos apresentaram teste de triagem de hemoglobinopatia alterado, o que correspondeu a 73% das crianças nascidas entre 2010 e 2011 com resultado de triagem neonatal para hemoglobinopatia anormal. As mães responderam um questionário que avaliou informações recebidas na maternidade e na atenção primária à saúde, além de aspectos relacionados à orientação genética. Foi feita estatística descritiva dos dados. RESULTADOS: Das 119 mães participantes, 69 (58%) tinham filhos com traço falciforme, 22 (18,5%) traço C, 18 (15,1%) traço alfatalassêmico e 10 (8,4%) resultado inconclusivo. Na maternidade, 118 mães (99,2%) receberam informação sobre onde ir e 115 (96,6%) foram orientadas sobre o momento correto para coleta do teste. Somente quatro mães (3,4%) foram informadas sobre quais doenças seriam investigadas e os riscos de não fazer o rastreio. Das 119 mães participantes, 17 (14,3%) reconheceram a diferença entre traço e doença e 42 (35,3%) consideraram que um teste alterado poderia ter implicações para futuras gestações. Em 70 casos (58,8%), o médico da criança não foi informado sobre o resultado da triagem. CONCLUSÕES: O programa de triagem neonatal necessita de aperfeiçoamento. Nos dois cenários investigados, os profissionais de saúde carecem de treinamento para orientar mães e famílias. .

Microwave mediated facile synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and triazolo[1,5-a]pyrimidine pendant to pyrrole

The synthetic potency of E-3-[dimethylamino]-1-[1H-pyrrol-2-yl]prop-2-en-1-one towards some nitrogen nucleophiles was investigated under microwave irradiations as a convenient route for the synthesis of some novel pyridine, pyrimidine, pyrazole, pyrazolo [1,5-a] pyrimidine and Triazolo[1,5-a] pyrimidine derivatives

3-cyanoacetylindole as a building block in the synthesis of nonfused and fused pyridine, pyrimidine, diazepine and pyranone derivatives

The reaction of 3-cyanoacctylindole I with trichloroacetonitrile afforded trichloroll1cthylpropen-1-one derivative 3 which upon the reaction with an excess of trichloroacetonitrilc yielded the ditrichlorome-thylpyrimidine derivative 5. It was converted to a variety of pyrazolo 7, dihydrazino 9. and isoxazolo pyrimidine II derivatives. The enaminonitrile 2 was used as a substrate to form the pyridine 13, 14, 16, diazepine 20 and pyranone 22 as well as 1, 2, 4-triazolo-25. 1, 2, 3, 4-tetrazolo-27, and benzimidazolo-pyrimidine 29 derivatives

reaction of cyanoacetyl hydrazide with cyclopentanone: synthesis of coumarin, pyridine and thiazole derivatives

This work concerns with studying the reaction of cyanoacetyl hydrazide with cyclopentanone to give the hydrazide-hydrazone derivative 3. The reactivity of compound 3 towards different chemical reagents was studied to give coumarin, pyridine and thiazole derivatives. The antimicrobial evaluation of the synthesized products was studied where most of them showed interesting activities

Synthesis and biological evaluation of certain 2H-pyran-2-ones and some derived 1H-pyridin-2-one analogs as antimicrobial agents

Pyran-2-one and pyridine-2-one analogs are known to be biological versatile compounds possessing variety of pharmacological activities. Some 4-[4-nitrophenyl]-5,6-diphenyl-pyran-2-ones and their 1H-pyridin-2-one analogs were synthesized and evaluated for their in vitro antimicrobial activities. The chemistry of the reactions employed for the synthesis of the intermediates and target compounds was discussed. The results revealed that some compounds exhibited promising antibacterial and antifungal activities. Compound 8; 1-hydroxy-4-[4-nitrophenyl]-5,6-diphenyl-1H-pyridin-2-one; showed the most potent broad spectrum antimicrobial activity. 1-Methyl-4-[4-nitrophenyl]-5,6-diphenyl-1H-pyridin-2-thione 12; was able to exert weak growth inhibitory effect against the Mycobacterium tuberculosis

Synthesis of some new pyrazolo [4, 3-b] pyridine-3-one and dihydropyrazolo [4, 3-c] [1, 2] oxazine derivatives

Mixtures of malononitrile, aromatic aIdeyde, and 4-nitrosoantipyrine [5] were interacted in ethanolic piperidine solutions, in one-pot reaction to give the corresponding 6-aryl-1-methyl-3-oxo-2-phenyl-2, 3-dihydro-1H-pyrazolo [4, 3-b] pyridine-5 carbonitriles [3] or their corresponding 6-alkyl-4-hydroxy- 1-methyl-3-oxo-2-phenyl- 1, 2, 3, 4-tetrahydro-SH-pyrazolo [4,-3-b] pyridine-5, 5-dicarbonitrile [4] depending on reaction temperature. However, carrying out the above reaction using 3-methyl-4-oximmno-1-phenyl-1H-pyrazolin-5-one [15b] instead of compound [5], the corresponding 6-aryl-7a-hydroxy-3-methyl-1-phenyl- 1, 7a-dihydro-pyrazolo [4, 3-c] [1, 2] oxazine-7-carbonitrile [17] were obtained. Chalcones [9] were reacted also with compounds [5] and [15b], to afford the corresponding 5-aroyl-6-aryl-1-methel-2phenyl-1, 2-dihydro-3H-pyrazolo [4, 3-b] pyridine-3 ones [12], and aryl [6-aryl-3-methyl-1-phenyl-1, 4-dihydropyrazolo [4, 3-c] [1, 2] oxazin-5-yl] methan-ones [20]. Aniline hydrochloride was condensed with compounds [3] in acetic acid to give the corresponding N-phenyl-2, 3-dihydro-1 H-pyrazolo [4, 3-b] pyridine-5-carboximidamides 6, which were converted into the corresponding 1-phenyl-1 H-imidazole-4, 5-diones [7] by their reaction with oxaly 1 chloride. However, on reaction of ethylenediamine with compounds [3] in the presence of p-toluenesulfonic acid, the corresponding 6-aryl-5-[4, 5-dihydro-1 H-imidazol-2-y1]-1-methyl-2-phenyl-1, 2-dihydropyrazolo [4, 3-b] pyridin-3-ones [8] were obtained

Development of pharmacophoric model of condensed pyridine and pyrimidine analogs as hydroxymethyl glutaryl coenzyme A reductase inhibitors.

Quantitative structure-activity relationship (QSAR) has been established on a series of thirty-eight compounds of four different sets of condensed pyridine and pyrimidine analogs, for their hydroxymethyl glutaryl coenzyme (HMG-CoA) reductase inhibitor activity, in order to understand the essential structural requirement for binding with receptor, in terms of common biophoric and secondary sites employing APEX-3D software. Among several 3D pharmacophoric models with different sizes and arrangements, one model was selected based on r2 = 0.8, chance<0.001, match equivalent to 0.38 and all the 38 compounds were considered. The results suggest that hydrophobicity, hydrogen acceptor and optimum steric refractivity play a dominant role in the inhibition of HMG-CoA reductase. The information obtained from the present study can be used to design and predict more potent molecules as HMG-CoA reductase inhibitors, prior to their synthesis.

Activated nitriles in heterocyclic synthesis: synthesis of substituted pyrazolopyridine, pyridine, 4H-pyran and naphthodiapyran derivatives

Several new pyrazolopyridines VIa-c were synthesized by reacting 4-nitrosoantipyrine [IIa] with arylidenemalononitriles Ia-c or ethyl arylidenecyanoacetates If-h. Reaction of Ia-c with 4-[azidomethylcarbonyl] antipyrine [IIb] afforded the pyridine derivatives XVI. The 4H-pyrans and naphthodipyran derivatives XVIII- XXI were prepared by reacting I with polyhydric phenols

Reaction of 1,3-dicarbonyl compounds with nitriles: synthesis of pyrazolo [1,5-c] -1,2,4-triazines, pyridines 4H-indeno [1,2-b] pyran derivatives

Several new pyrazolopyridotriazines, pyridines, 4H-pyran and H-indeno [1,2-b] pyran derivatives were prepared from beta-dicarbonyl compounds I, II and the ylidenes III and IV as starting materials

Enaminonitrile in heterocyclic synthesis: synthesis of thiazolo [4,5-b] pyridine and thiazolo [4,5-d] pyrimidine derivatives

Ammoniumn- phenyldithiocarbamate reacted with bromomalononitrile and alpha chloroacetylacetone to afford thiazole derivatives 3a, b. Compound 3a reacted with benzylidenemalononitrile, malononitrile, phenylisothiocyanate, benzoylisothiocyanate, trichloroacetonitrile, formamide, carbon disulphide and triethylorthoformate to afford thiazolo [4,5-b] pyridine derivatives 6,9 and thiazolo [4,5-d] pyrimidine derivatives 13, 16, 18, 19, 20 and 21. Most of the synthesized products show high fungicidal and bactericidal activities

Synthesis of polyfunctionally substituted pyrimidines and pyridines condensed with other heterocyclic systems

Treatment of benzoylacetonitrile with anisaldehyde afforded alpha- cyanochalcone [I], which on reaction with malononitrile yielded 2-amino-3,5-dicyano-4-[p-methoxyphenyl]-6-phenyl-4H-pyran [III]. Compound III underwent Michael reaction with aniline derivatives to give 3,5-dicyano-4-[p-methoxyphenyl]-6-phenyl-2-[p-substituted arylamino] pyridine derivatives Va-d. Reaction of III with hydroxylamine hydrochloride, acetic anhydride, malononitrile and benzoylisothiocyanate gave, respectively, compounds IX, X, XI and XIV

New benzopyrans and pyridine derivatives from [2-hydroxyaryl] - propenones

The [2-hydroxyaryl]-propenones [1] react with malononitrile in the presence of piperidine or catalytic amount of potassium hydroxide to give the corresponding benzopyrans. Warming [3] with excess ammonium acetate in absolute ethanol affords the hitherto unknown dihydropyridines [4], whereas, on boiling the propenones [1] with malononitrile in presence of ammonium acetate. Benzopyranopyridines [7] are produced along with the dihydropyridines [4]. [7] could be also obtained by reacting 3- cyano-8-methoxy coumarinimide with the corresponding ketone. Hydrolysis of both benzopyranopyridines [7] and dihydropyridines [4] affords oxo-analogues [8]. Reaction mechanisms have been discussed