Synthesis and anti-inflammatory activity of some [4,6-(4-substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives

A series of [4,6-(substituted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid (4a-r) has been synthesized by the base catalyzed condensation of beta-aroylpropionic acid, thiourea with aldehyde in ethanol. Structures of the new compound were established on the basis of (1)H NMR and IR spectral data. Anti-inflammatory activity in vivo were evaluated and compared with standard drug diclofenac sodium. Some compounds have shown moderate activity.     

Synthesis and immunobiological activity of base substituted 2-amino-3-(purin-9-yl)propanoic acid derivatives

2-Amino-3-(purin-9-yl)propanoic acids substituted at position 6 of the purine base moiety by dimethylamino, cyclopropylamino, pyrrolidin-1-yl, hydroxy, and sulfanyl group as well as their 2-aminopurine analogues were prepared from corresponding 9-(2,2-diethoxyethyl)purines and 2-aminopurines, respectively, by the Strecker synthesis. 2-Aminopropanoic acid derivatives were tested for their immunostimulatory and immunomodulatory potency. Some of these compounds significantly enhanced secretion of chemokines RANTES and MIP-1alpha, the most potent was 2-amino-6-sulfanylpurine derivative. Most of these compounds also augmented NO biosynthesis triggered primarily by IFN-gamma.     

Synthesis, hypolipidemic and hypoglycemic activity of some novel 2-(4-(2-substituted aminothiazole-4-yl) phenoxy)-2-methyl propanoic acid derivatives

An improved synthetic protocol for a novel series of 2-(4-(2-substituted aminothiazole-4-yl) phenoxy)-2-methyl propanoic acid derivatives has been developed using different methods of synthesis. The synthesized compounds are evaluated for their hypolipidemic and hypoglycemic activity by high fat diet induced hyperlipidemia and hyperglycemia in Sprague-Dawley rats.     

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.     

Synthesis,structure and antibacterial activity of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives

A series of new 2-(1-(2-(substituted-phenyl)-5-methyloxazol-4-yl)-3-(2-substitued-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7-substitued-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized. The results showed that compounds 9q and 10q can strongly inhibit Staphylococcus aureus DNA gyrase and Bacillus subtilis DNA gyrase (with IC_50s of 0.125 and 0.25 μg/mL against S. aureus DNA gyrase, 0.25 and 0.125 μg/mL against B. subtilis DNA gyrase). On the basis of the biological results, structure–activity relationships were also discussed.     

Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines

Abstract-Reaction of 6a–f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a–f in excellent yield. The newly synthesized heterocycles were characterized by IR, ¹H NMR, and mass spectral data. Compounds 7a–f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.     

Synthesis of novel 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives and their cytotoxic activity

The propargyl alcohol on reaction with aldoxime and NaOCl in DCM gave exclusively (3-arylisoxazol-5-yl) methanol 1. The compound 1 was oxidized to an aldehyde 2 followed by reaction with aniline resulted in Schiff’s base 3. The compounds 3 were further reacted with various aldehydes having α-hydrogen using molecular iodine as catalyst and which yielded 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives 4. All the final compounds 4 were screened against four human cancer cell lines (A549, COLO 205, MDA-MB 231 and PC-3) and among these compounds 4n showed potent cytotoxicity against all the cell lines at IC₅₀ values of <12 μM.     

Synthesis and anti-inflammatory activity of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid and its ester derivatives

Different esters of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (1), an anti-inflammatory principle of Acronychia baueri Schott (Rutaceae), were synthesized. Their topical anti-inflammatory activity was evaluated using the Croton oil ear test in mice as a model of acute inflammation. The activity of the paracetamol, guaiacol and hydroquinone esters of (1) was higher than that of the parent compound, being similar to that exerted by indomethacin, used as reference drug.     

Synthesis and anti-angiogenic activity of 6-(1,2,4-thiadiazol-5-yl)-3-amino pyridazine derivatives

General screening for inhibitors of microvessel growth in vitro in the rat aortic ring assay led to the discovery of a novel series of thiadiazole pyridazine compounds with potential anti-angiogenic activity. Chemical optimization produced orally active compounds with potent in vitro and in vivo anti-angiogenesis and anti-tumor activities.     

New inhibitors of 5-lipoxygenase catalytic activity based on 2-(3-methylphenyl)propanoic acid and 4-substituted morpholine derivatives

New potential inhibitors of 5-lipoxygenase (5-LOX) based on the structure of 2-(3-benzoylphenyl)propanoic acid (an active component of the nonsteroidal antiinflammatory drug Ketoprofen) were designed using the SARD-21 program. The docking of these compounds in the active site of 5-LOX suggested that seven compounds can interact with this enzyme. Two of them can also be dual inhibitors of 5-LOX and two isoforms of cyclooxygenase.     

Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of new 2-(4-isobutylphenyl)propanoic acid derivatives

Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl)propanoic acid derivatives containing 1,3,4-thiadiazole and thiadiazolo[3,2-a][1,3,5]triazine-5-thione nucleus is reported here. The structures of new compounds are supported by IR, (1)H & (13)C NMR data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA). Compound 4i and 5f showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid-induced writhings and 0.7 and 0.65 of severity index, respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen.     

Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives

A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents.     

Synthesis and dopaminergic activity of some E-3-(piperidin-1-yl)-1-(4-substituted phenyl)prop-2-en-1-one derivatives

A convenient route for the synthesis of some 2-propen-1-one derivatives with E isomeric configuration is described. The activity of the synthesized compounds was evaluated through behavioral studies of apomorphine-induced licking in animal models. It was demonstrated that most of the synthesized compounds showed moderate activity in inhibition of lickings, among which 6a, was the most active compound at 30 mg/kg.     

Synthesis and anti-HIV-1 activity of 4-[4-(4,6-bisphenylamino-triazin-2-ylamino)-5-methoxy-2-methylphenylazo]-5-hydroxynaphthalene-2,7-disulfonic acid and its derivatives

A structure-based design approach has been used to optimize a lead HIV-1 entry inhibitor targeted to the envelope glycoprotein gp41. The docking study on this lead compound revealed important structural requirements that need to be preserved as well as structural non-requirements that could be eliminated to substantially reduce the molecular size of the lead compound. Based on the results from docking study, a limited number of analogues were designed and synthesized. This approach yielded a new analogue (compound 4) that retained the anti-HIV-1 activity with reduced molecular size approaching towards more drug-like character.     

Synthesis and antimicrobial activity of some new N-glycosides of 2-thioxo-4-thiazolidinone derivatives

5-Arylidene-2-thioxo-4-thiazolidinones 3a-f react with each of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl and α-d-galactopyranosyl bromides 4a,b in acetone in the presence of aqueous potassium hydroxide at room temperature to afford N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl) or N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl) 2-thioxo-4-thiazolidinone derivatives 5a-f. Similarly, the reaction of 5-cycloalkylidene-2-thioxo-4-thiazolidinones 7a,b with 4a gave the corresponding N-glucosides 8a,b. Also, 5-pyrazolidene rhodanines 10a-e react with 4a to afford the new N-glucosides 11a-e. Treatment of compounds 15 and 16 with 4a in the presence of few drops of triethylamine or in KOH solution accomplished the mono- and bis-nucleosides 17 and 18, respectively. Some selected products were tested for their antimicrobial activities.     

Synthesis and antibacterial activity of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[(2-5-bromothiophen-2-yl)-2-oximinoethyl] derivatives of piperazinyl quinolones

A series of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[2-(5-bromothiophen-2-yl)-2-oximinoethyl]derivatives of piperazinyl quinolones were synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit comparable or better activity against Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis, than ciprofloxacin, norfloxacin and enoxacine as reference drugs.     

Synthesis and biological activity of 2-decarboxy-2-(tetrazol-5-yl)prostaglandins

The synthesis of 2-decarboxy-2-(tetrazol-5-yl)prostaglandins of the E₁, E₂, F₁α and F₂α series is described together with their biological effects on gerbil colon smooth muscle and rat blood pressure.     

Synthesis and biological activity of 2-decarboxy-2-(tetrazol-5-yl)prostaglandins

The synthesis of 2-decarboxy-2-(tetrazol-5-yl)prostaglandins of the E₁, E₂, F₁α and F₂α series is described together with their biological effects on gerbil colon smooth muscle and rat blood pressure.