Synthesis and pharmacological activities of 1,8-naphthyridine derivatives

In the present study, a series of 2-substituted-4-methyl-7-amino/4,7-dimethyl-1,8-naphthyridines were synthesized and characterized by IR, 1H-NMR and elemental analysis. The compounds were investigated for anticonvulsant (125, 250 mg/kg), cardiac and antimicrobial activities. The compounds were screened for antibacterial activity against gram (+) bacteria (Staphylococcus epidermidis, Bacillus subtilis, Enterococcusfaecalis and Micrococcus luteus) and gram (-) bacteria (Proteus vulgaris, Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi). All the compounds except 2-(3'-phenylaminopropyloxy)-4-methyl-7-amino-1,8-naphthyridine exhibited significant anticonvulsant activity. The anticonvulsant activity of 2-(3-morpholino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine, 2-(3'-diphenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine and 2-(3'-diethanolamino-propyloxy)-4,7-dimethy-1,8-naphthyridine at the dose of 250 mg/kg were found to be equivalent to diazepam (5 mg/kg). Sympathetic blocking activity was observed with 2-(3'-phenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine, 2-(3'-diethanolamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine and 2-(3'-diphenylamino-2'-hydroxypropyloxy)-4-methyl-7-amino-1,8-naphthyridine only. All the compounds were devoid of antibacterial activity against the tested bacteria.     

Synthesis, cytotoxicity, hypolipidemic and anti-inflammatory activities of amine-boranes and esters of boron analogues of choline and thiocholine.

Boron analogues of carbamoylcholine and thiocholine and esters of these analogues were prepared. These compounds were fairly stable toward hydrolysis and demonstrated moderate anti-inflammatory and hypolipidemic activities in mice. The hypolipidemic activity of the compounds at a dose of 8 mg/kg/day was equivalent in reducing lipid levels in serum to those of clofibrate at 150 mg/kg/day and lovastatin at 8 mg/kg/day. The compounds demonstrated significant cytotoxic activity against the growth of murine and human tumor cells; all were active against the growth of human HeLa-S3 uterine suspended cells, and some were active against murine L1210 lymphoid leukemia, human Tmolt3 leukemia cells, colorectal adenocarcinoma, KB nasopharynx, osteosarcoma, and glioma. These studies demonstrated that antimetabolite analogues of acetylcholine exhibit the same types of pharmacological activity as other boron-substituted betaine and amino acids. Furthermore, a strong positive correlation exists between hypolipidemic activity and cytotoxicity for these new choline derivatives, as has previously been demonstrated for other boron-containing amino acids, amides, esters, and peptides.     

Synthesis and pharmacological activities of calcium modulatory hexahydroquinolinones.

Hexahydroquinolinones of type 6 are accessible from Hantzsch-like cyclization of 1,3-cyclohexanedione with aromatic aldehydes and different beta-aminocrotonates and acetoacetates/ammonia, respectively. Reaction with pyridiniumbromideperbromide leads to the octahydrofuro[3,4-b] guinoline-diones 6h and 6i. 6j was obtained by N-alkylation. Positive inotropic effects were observed on electrically stimulated left atria of guinea pigs whereas BaCl2-induced contractions of the ileum were inhibited in a dose dependent manner. On electrically stimulated guinea pig papillary muscle 6h exhibits contractility promoting effects which can be attributed to calcium agonism.     

3,4-二氢-4-芳基香豆素类化合物的合成及其生物活性研究

目的 设计合成一系列3,4-二氢4-芳基香豆素类化合物,并评价其抗氧化、抗肿瘤活性.方法 以取代苯甲醛为原料,经缩合及Ponndorf反应制得目标化合物.采用DPPH法测定目标化合物的抗氧化活性;采用MTT法以胃癌细胞BGC-823为测试细胞株对目标化合物进行体外抗肿瘤活性评价.结果 与结论合成了10个新的3,4-二氢...     

Synthesis and pharmacological activities of cyclic analogues of fentanyl (author's transl)]

Synthesis and Pharmacological Activities of Cyclic Analogues of Fentanyl . Cyclic analogues of fentanyl were synthesized and pharmacologically tested. Cyclisation of the acyl group with C-2 of the aromatic ring yielded a change in stereochemical structure. Therefore the analgesic activity of fentanyl was lost and strong antihistaminic activities appeared.     

Synthesis and pharmacological activities of hydrazones, Schiff and Mannich bases of isatin derivatives

Schiff bases and phenyl hydrazone of isatins were prepared by reacting isatin and the appropriate aromatic primary amine/hydrazines. A new series of the corresponding N-mannich bases were synthesized by reacting them with formaldehyde and diphenylamine. The chemical structures were confirmed by means of their 1H-NMR, IR spectral data and elemental analysis. The compounds were screened for analgesic, antiinflammatory and antipyretic activity. 1-Diphenylaminomethyl-3-(1-naphthylimino)-1,3-dihydroindol-3-one (4), 3-(1-naphthylimino)-5-bromo-1,3-dihydroindol-2-one (2) and 1-diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) were found to exhibit the highest analgesic, anti-inflammatory and antipyretic activity respectively. 1-Diphenylaminomethyl-3-(4-methylphenylimino)-1,3-dihydroindol-3-one (7) was found to be the most active compound of the series.     

Pyrrolidone and piperidone derivatives with antihistaminic and antianaphylactic activities. Synthesis and pharmacological study

The preparation of several derivatives to oxatomide (A), with the benzimidazolinone moiety replaced by another heterocyclic residue is described. In some cases changes to the basic chain of (A) were also considered. All the new compounds were evaluated as antihistaminics (H1) and antianaphylactics. The derivatives where the heterocyclic moiety was an unsubstituted or phenylsubstituted 2-pyrrolidone or 2-piperidone residue showed antihistaminic and antianaphylactic activities similar to those of oxatomide while modification of the basic side chain with elimination of the benzhydryl group, gave a complete loss of activity. The pharmacological screening was completed by the evaluation of the barbiturate induced sleep prolongation and of acute toxicity.     

Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride.

Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro- 4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.     

Synthesis and pharmacological activities of 2-(3'-substituted-2'-hydroxypropylamino)pyridines

In the present study, a series of 2-(3'-substituted-2'-hydroxypropylamino)pyridines were synthesized and characterized by IR, 1H-NMR and elemental analysis. The compounds were investigated for anticonvulsant (150, 300 mg/kg) and cardiac activity. 2-(3'-Diethylamino-2'-hydroxypropylamino)pyridine 3 was found to exhibit the highest anticonvulsant activity. 2-(3'-Dimethylamino-2'-hydroxypropylamino)pyridine 2 and 2-[3'-(4'-nitrophenylamino)-2'-hydroxypropylamino]pyridine 6 were found to exhibit negative ionotropic activity. 2-(3'-Dimethylamino-2'-hydroxypropylamino)pyridine 2, 2-[3'-(4'-nitrophenylamino)-2'-hydroxypropylamino]pyridine 6 and 2-(3'-piperidino-2'-hydroxypropylamino)pyridine 8 were found to antagonize exhibit beta-adrenergic activity.     

Synthesis and pharmacological characterization of a series of leukotriene analogues with antagonist and agonist activities

The synthesis and biological characterization of a series of novel leukotriene antagonists and agonists are reported. All of these compounds are derivatives of (5S,6R,7Z)-5-hydroxy-6-mercapto-9-phenyl-7-nonenoic acid. One of the more potent compounds is (5S,6R,7Z)-6-[[(4-carboxy-2-methoxyphenyl)methyl]thio]-5-hydroxy-9 -(4- heptylphenyl)-7-nonenoic acid (3f). In vitro evaluation of this compound on guinea pig trachea revealed that it is a competitive antagonist of LTD4 and LTE4 with pKB values of 6.4 and 5.8, respectively. On guinea pig ileum, the pKB values obtained for it with LTD4 and E4 were both 7.2. The selectivity of 3f was shown by its lack of effect on carbachol, histamine, and barium chloride concentration-response curves in guinea pig trachea.     

Synthesis of metabolites of mosapramine. II. Synthesis of phenolic metabolites of mosapramine and their pharmacological activities]

Four phenolic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a-octahydroimidazo[1,2- a]pyridine-3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H-dibenz [b,f]azepine (mosapramine), a new antipsychotic drug, were synthesized in order to determine their chemical structures. Pharmacological activities of the three main metabolites were compared with those of mosapramine. The activities of the metabolites were far less potent than those of mosapramine.     

Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding beta-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin.     

Synthesis and pharmacological activities of some new 3-substituted-4-amino-5-mercapto-1,2,4-triazoles

In this study, various 3-β-[(N-benzenesulphonyl/tosyl)-4-(un) substituted anilino]ethyl-4-amino-5-mercapto-4(H)-1,2,4-triazoles (5a-f), with biologically active 'sulphonamide' moiety as the side chain have been prepared. The structures of the newly synthesised compounds have been established on the basis of their spectral data and elemental analysis. All the compounds were evaluated for antimicrobial activities against Escherichia coli, Bacillus cirroflagellosus, Aspergillus niger and Colletotrichum capsici. Most of the compounds investigated exhibited significant antifungal activity against Colletotrichum capsici, even greater than fluconazole, the standard used. Only two compounds 3f (59%) and 5e (67%), have shown moderate antituberculosis activity. All the triazoles exhibited moderate degree of antiinflammatory activity and least ulcerogenecity. Most of the compounds have shown significant analgesic activity (81.02-120.72%) in comparison with aspirin (49.39%). In the MES method, only compound 3e exhibited a protection of 66.66%, whereas others exhibited minimum protection of (33.33%).     

Synthesis of and pharmacological studies on the antidepressant and anticonvulsant activities of some 1,3,5-trisubstituted pyrazolines

Eighteen 1-phenyl-, 1-thiocarbamoyl- and 1-N-substitutedthiocarbamoyl-3-phenyl-5-heteroaryl-2-pyrazoline derivatives were synthesized and tested for their antidepressant and anticonvulsant activities. Their chemical structures were proved by spectral and microanalysis. The antidepressant activities of the compounds were investigated by the "forced swimming test". Results showed that compounds II-a, b, c, III-1b, 1c, 4a showed activities equivalent to or higher than pargyline hydrochloride (CAS 306-07-0) and tranylcypromine sulfate (CAS 13492-01-8) that were used as reference antidepressant drugs. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES), subcutaneous metrazol (ScMet.) and rotarod toxicity tests in mice according to the phase I tests of the Antiepileptic Drug Development programme. Compounds I-a, II-a, b, c, III-1b, 2a, 2c were found protective against MES and III-1b, 1c, 2a, 2c were found protective against ScMet.     

Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory,immunomodulatory and antioxidant activities

Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole—non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1–10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC₅₀ value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski’s parameters suggested the compounds to be bear drug like properties.     

重楼皂苷的药理活性及药代动力学研究进展

目的综述重楼皂苷的药理活性及药代动力学研究进展,为重楼皂苷的进一步研究提供参考。方法查阅相关文献,整理重楼皂苷药理活性及药代动力学研究的相关资料,对其进行总结归纳。结果重楼皂苷是一种甾体皂苷,具有抗肿瘤、免疫调节、抗菌消炎、止血、调节血管和抗氧化等作用;重楼皂苷的药物浓度多采用高效液相色谱及色谱-质谱联用技术进行测定,以评价其体内药代动力学过程。结论整理和总结重楼皂苷的药理作用及体内药代动力学的研究进展,以期为重楼皂苷的深入研究和开发利用提供参考。