Archiv der Pharmazie via MedWorm.com

Design and Synthesis of Novel Pyrazino[2,1-a]isoquinolin Derivatives with Potent Antifungal Activity

Archiv der Pharmazie — Tue, 16 Mar 2010 00:00:00 +0100

A series of novel pyrazino[2,1-a]isoquinolin compounds were designed, synthesized, and their antifungal activities in vitro were evaluated. The results showed that all of the title compounds exhibited antifungal activities. Most of them exhibited stronger antifungal activities than the lead compounds; compound 7c is more potent than fluconazole against two of the three tested fungal strains. The studies presented here provide a new structural type for the development of novel antifungal agents. (Source: Archiv der Pharmazie)

Design, Synthesis, and Pharmacological Investigation of Iodined Salicylimines, New Prototypes of Antimicrobial Drug Candidates

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

A series of 3,5-diiodo-salicylalidene Schiff bases (compounds 1-35) has been synthesized and tested for antimicrobial activity. The compounds were assayed for antibacterial activities by the MTT method. Some of the compounds inhibit the growth of a broad range of bacteria including the species of Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae. Among them, compounds 2-[(4-chloro-phenylimino)methyl]-4,6-diiodo-phenol 11 and 2,4-diiodo-6-[(2-morpholin-4-yl-ethylimino)methyl]phenol 19 showed the most potent antibacterial activity with MIC of 3.1, 12.9, 3.3, 6.5, 12.9, 3.3 and 3.2, 12.8, 3.2, 12.8, 12.8, 3.2 [mu]M against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. Coli, and E. cloacae, respectively...

Synthesis and Antifungal Activity of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides and 3-Aroyl-4-aryl-1-phenethyl-4-piperidinols

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

Mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides, 1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, and semi-cyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols, 1b, 2b, 3b, 4b, 5b, 6b, 7b, 8b, 9b, were synthesized by a non-classical Mannich reaction. The aryl part was: C6H5 for 1a, 1b; 4-CH3C6H4 for 2a, 2b; 4-CH3OC6H4 for 3a, 3b; 4-ClC6H4 for 4a, 4b; 4-FC6H4 for 5a, 5b; 4-BrC6H4 for 6a, 6b; 2,4-(Cl)2C6H3 for 7a, 7b; 4-NO2C6H4 for 8a, 8b; and C4H3S(2-yl) i. e., 2-thienyl for 9a, 9b. Piperidinol compounds 2b, 3b, 4b, 5b, 7b, 8b, and 9b are reported here for the first time. The synthesized compounds were tested against seven types of plant pathogenic fungi and three types of human pathogenic fungi using the agar dilution assay. Itraconazole was tested against Candida...

Synthesis of New 2,3-Dihydroquinazolin-4(1H)-one Derivatives for Analgesic and Anti-inflammatory Evaluation

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

Starting from isatoic anhydrides, several new 2,3-dihydroquinazolin-4(1H)-one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti-inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic-acid-induced writhing-response method and carrageenan-induced edema method, respectively. The study showed that the chalcones bearing a 4-chlorophenyl group 4c or 4-nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N-phenyl pyrazole bearing 4-methoxy phenyl group 5b showed a higher anti-inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygen...

Synthesis and Antidepressant Evaluation of Five Novel Heterocyclic Tryptophan-Hybrid Derivatives

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

This study aimed at evaluating the reactivity of L-Tryptophan (TRP) 1 towards various chemical reagents to produce new bi- and tri-heterocyclic systems providing basic pharmacological activities. Indol-3-yl hydroxyoxazol-2-yl acetonitrile derivatives 5 and 6, indol-3-yl-hydroxyoxazol-2-yl-1,2,4-triazine derivatives 8 and 9, indol-3-yl-hydroxyoxazol-2-yl-aminopyrazole derivatives 11a, b, and indol-3-yl-hydroxyoxazol-2-yl-aminoisoxazole derivative 12 were synthesized via straightforward and efficient methods. The structures were characterized by spectral data (IR, 1H-NMR, 13C-NMR, and MS) and the purity was ascertained by microanalysis. Also, this work was extended to study the potential role of the novel synthesized TRP derivatives 5, 6, 9, 11a, and 12 as antidepressant and sedative agents ...

Thieno[2,3-d]pyrimidines in the Synthesis of Antitumor and Antioxidant Agents

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

Dimethyl acetylenedicarboxylate, ethyl propiolate, and E-dibenzoylethylene react with thienopyrimidines (cyclo-pentyl, -hexyl, and -heptyl) derivatives to form thiazolo[3,2-a]thieno-[2,3-d]pyrimidin-2-ylidene) acetates, thieno[2,3-d]pyrimidin-2-ylthioacrylates, and thieno[2[prime],3[prime]:4,5]pyrimido[2,1-b][1,3]thiazin-6-ones, respectively. Reactions proceed via cyclization and thio-addition processes. Some derivatives of thienopyrimidines showed high inhibition of Hep-G2 cell growth compared with the growth of untreated control cells. However, the fused heptyl of thienopyrimidothiazines indicates a promising specific antitumor agent against Hep-G2 cells with IC50 < 20 [mu]M. (Source: Archiv der Pharmazie)

Antioxidant Activity of Newly Synthesized 2,7-Diazaphenothiazines

Archiv der Pharmazie — Mon, 15 Mar 2010 00:00:00 +0100

A series of 19 derivatives of 2,7-diazaphenothiazine was synthesized and evaluated for their antioxidant activity bearing in mind the structural similarity with "classical" phenothiazines several of which are considered powerful antioxidants. Among the new derivatives that inhibited in vitro Fe2+/ascorbate-induced lipid peroxidation of rat liver microsomal membranes, several exhibited significant antioxidant activity with IC50 values in the range of 64-125 [mu]M. Although N-substitution led to a variable degree of antioxidant activity, the latter appears to correlate with the lipophilicity (expressed as clogP values) of the substituted derivatives. Reduced lipophilicity may also explain the relatively lower protection offered by these derivatives against lipid peroxidation when compared to...

Platinum and Palladium-triazole Complexes as Highly Potential Antitumor Agents

Archiv der Pharmazie — Wed, 10 Mar 2010 00:00:00 +0100

The palladium complexes [(dppe)Pd(L)2PdCl2], [(dppe)Pd(L)2PtCl2], [(dppp)Pd(L)2PdCl2], [(dppm) Pd(L)2NiCl2], and [(dppm)Pd(L)2SnCl4] 15-19 were prepared. The antiproliferative activity of the newly synthesized complexes as well as their previously prepared analogues 3-14 and 20-26 were screened against a large panel of human cancer cell lines derived from haematological CD4+ human T-cells containing an integrated HTLV-1 genome (MT-4). The complex 12a, b exhibited remarkable antiproliferative activity against MT-4, CD4+ human acute T-lymphoblastic leukemia (CCRF-CEM), human splenic B-lymphoblastoid cells (WIL-2NS), human acute B-lymphoblastic leukemia (CCRF-SB), skin melanoma (SK-MEL-28), and prostate carcinoma (DU145) cell lines (CC50 = 0.5 [mu]M, 0.4 ± 0.05 [mu]M, 0.6 ± 0.05 [mu]M, 0.4 ...

Novel Conjugates of Aspirin with Phenolic Acid as Anti-inflammatory Agents Having Significantly Reduced Gastrointestinal Toxicity

Archiv der Pharmazie — Wed, 10 Mar 2010 00:00:00 +0100

A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro. (Source: Archiv der Pharmazie)

Ring Expansions of Tetrahydroprotoberberines and Related Dibenzo[c,g]azecines Modulate the Dopamine Receptor Subtype Affinity and Selectivity

Archiv der Pharmazie — Wed, 10 Mar 2010 00:00:00 +0100

The affinities of tetrahydroprotoberberines for dopamine receptors dramatically decrease after cleaving the central C-N bond to the analogous ten-membered dibenzo[c,g]azecines [1]. In the present work, we also synthesized eleven-membered homologues of these heterocycles and measured the affinities of the resulting dibenzazaundecenes and their underlying homoberberines for human dopamine receptors as well as the cytotoxic effects of all target compounds on human glia cells. The tetracyclic iso-C-homoberberine-derivatives revealed to be D4-selective antagonists, while all other active compounds showed a significant D1/D5 selectivity. Distances in energy-minimized conformations were measured in order to explain our findings. (Source: Archiv der Pharmazie)

Synthesis and in-vitro Cytotoxic Evaluation of Novel Pyridazin-4-one Derivatives

Archiv der Pharmazie — Wed, 10 Mar 2010 00:00:00 +0100

A new series of N-aryl-4-oxo-1,4-dihydro-pyridazine-3-carboxylic acids has been synthesized by condensation of aryldiazonium with 4-hydroxy-6-methyl-2-pyrone. Some of these compounds exhibited in-vitro cytotoxic activity with moderate to excellent growth inhibition against the murine P815 mastocytoma cell line. Compound 5b showed an important cytotoxic activity against cell line P815 (IC50 = 0.40 [mu]g/mL). (Source: Archiv der Pharmazie)

Synthesis, in-vitro Antimicrobial and Cytotoxic Studies of Novel Azetidinone Derivatives

Archiv der Pharmazie — Fri, 05 Mar 2010 00:00:00 +0100

Developing novel antimicrobial drugs is increasingly important in the modern pharmaceutical industry. A series of novel 3-chloro-4-[4-(2-oxo-2H-chromen-4-ylmethoxy)phenyl]-1-phenylazetidin-2-ones 5a-o have been synthesized from 4-bromomethylcoumarins 1a-e and 4-aryliminomethyl-phenols 3a-c. These compounds were screened for their in-vitro antibacterial activity against two Gram-positive (Staphylococcus aureus and Vancomycin resistant enteroccoccus) and two Gram-negative (Escherichia coli and Shigella dysentery) bacterial strains and antifungal activity against Aspergillus fumigatus, Candida albicans, and Penicillium. Results revealed that compounds 5c, 5f, 5h, 5j, and 5m showed excellent activity against a panel of microorganisms. The brine-shrimp bioassay was also carried out to study the...

Synthesis and Antimycobacterial Activity of Azetidine-, Quinazoline-, and Triazolo-thiadiazole-containing Pyrazines

Archiv der Pharmazie — Thu, 04 Mar 2010 00:00:00 +0100

The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N-[2-(substituted aryl)-3-chloro-4-oxoazetidin-1-yl]-2-(pyrazin-2-yloxy)acetamide, 6-(substituted aryl)-3-[(pyrazin-2-yloxy)methyl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole, and N-[6-({2-[(pyrazin-2-yloxy)acetyl] hydrazino}sulfonyl)-2-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)yl]-substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed...

Synthesis and Biological Evaluation of 7-Azaisoindigo Derivatives

Archiv der Pharmazie — Wed, 24 Feb 2010 00:00:00 +0100

A series of novel 7-azaisoindigo derivatives 3-14 were designed, synthesized, and structurally characterized by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analyses. Their antiproliferative activities were evaluated in a hormone-independent prostate cancer cell line DU145. Among them, compounds 8, 9, 14 showed the highest activities. Our study also showed that compounds 7, 11, 12 exhibited higher inhibitory activities on CDK2/cyclin A than that of the positive control meisoindigo. Western blot analysis on DU145 cells treated with compounds 7 and 9 demonstrated that 7-azaisoindigo derivatives could decrease the level of CDK2 activity (phosphorylation) and the expression of cyclin D1, and increase the expression of endogenous cyclin-dependent inhibitor p27. (Source: Archiv der Pharmazie...

Ibuprofen and Lipoic Acid Diamides as Potential Codrugs with Neuroprotective Activity

Archiv der Pharmazie — Tue, 23 Feb 2010 00:00:00 +0100

Current evidences support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, our attention was focused on ibuprofen (IBU) used in clinical trails to prevent Alzheimer's disease, and (R)-[alpha]-lipoic acid (LA) considered as a potential neuroprotective agent in AD therapy. In particular, we investigated a series of lipophilic molecular combinations obtained by joining (R)-[alpha]-lipoic acid and ibuprofen via an amide bond. These new entities might allow targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation seem related to Alzheimer's disease. Our study included the synthesis of conjugates 1-3 and the evaluation of thei...

Synthesis and In Vitro Antibacterial Activity of 7-(3-Alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)-fluoroquinolone Derivatives

Archiv der Pharmazie — Tue, 23 Feb 2010 00:00:00 +0100

A series of novel 7-(3-alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized, and characterized by 1H-NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 [mu]g/mL). In particular, compounds 14, 19, 28, and 29 are fourfold more potent than ciprofloxacin against MSSA 08-49. Compounds 23, 26, and 27 are twofold more potent than ciprofloxacin aga...

Stereoselective Synthesis and Antiviral Activity of (1E,2Z,3E)-1-(Piperidin-1-yl)-1-(arylhydrazono)-2-[(benzoyl/benzothiazol- 2-oyl)hydrazono]-4-(aryl1)but-3-enes

Archiv der Pharmazie — Tue, 23 Feb 2010 00:00:00 +0100

The reaction of benzoyl hydrazine 1a or benzothiazole-2-carbohydrazide 1b with 2-oxo-N-arylpropanehydrazonoyl chlorides 2a-d yielded (1Z,2E)-2-[(benzoyl/benzothiazol-2-oyl)hydrazono]-N-(aryl)propanehydrazonoyl chlorides 3a-e. The reaction of 3a-c with sodium benzenesulphinate furnished sulphones 5a-c while the reaction of 5d, e with hydroxyl amine afforded hydroxomoyl derivatives 6a, b. The one-pot sterioselective reaction of N-(aryl)propanehydrazonoyl chlorides 3 with certain aromatic aldehydes in the presence of piperidine resulted in the formation of (1E,2Z,3E)-1-(piperidin-1-yl)-1-(arylhydrazono)-2-[(benzoyl/benzothiazol-2-oyl)hydrazono]-4-(aryl1)-but-3-enes 7a-g. X-ray analysis of piperidinyl amidrazone 7g showed a conversion of its geometrical structure with respect to that of compou...

Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives

Archiv der Pharmazie — Thu, 28 Jan 2010 00:00:00 +0100

A series of new 3-hydroxy-6-hydroxymethyl/methyl-2-substituted 4H-pyran-4-ones were synthesized and prepared by the reaction of kojic acid or allomaltol with piperidine derivatives and formaline as potential anticonvulsant compounds. The structure of the synthesized compounds was confirmed using the elemental analysis results and the spectroscopic techniques such as IR, 1H-NMR, and ESI-MS. Anticonvulsant activities were examined by maximal electroshock (MES) and subcutaneous Metrazol (scMet)-induced seizure tests. Neurotoxicity was determined by the rotorod toxicity test. All these tests were performed in accordance with the procedures of the Antiepileptic Drug Development (ADD) program. According to the activity studies and at all doses, 3-hydroxy-2-[(4-hydroxy-4-phenylpiperidin-1-yl)meth...

Synthesis and Biological Activity of Some 1,3-Dihydro-2H-3-benzazepin-2-ones with a Piperazine Moiety as Bradycardic Agents

Archiv der Pharmazie — Wed, 27 Jan 2010 00:00:00 +0100

A series of 1,3-dihydro-2H-3-benzazepin-2-ones with a piperazine moiety were designed and synthesized by treating the common intermediate of 1,3-dihydro-7,8-dimethoxy-3-[3-(1-piperazinyl)propyl]-2H-3-benzazepin-2-ones with a variety of N-aryl-2-chloroacetamides and acyl chlorides. Their structures have been characterized by 1H-NMR, MS, and elemental analysis. The title compounds were evaluated for their bradycardic activity in vitro. Most of the synthesized compounds exhibited some vasorelaxant activity and heart-rate-reducing activity with bradycardic potency. (Source: Archiv der Pharmazie)

Synthesis and Evaluation of Novel Indolylthiadiazinoazetidinones and Indolylthiadiazinothiazolidinones as Antimicrobial Agents

Archiv der Pharmazie — Wed, 27 Jan 2010 00:00:00 +0100

Some new 5-methoxy/ethoxy-2,3-[2[prime]-(3[prime][prime]-chloro-2[prime][prime]-oxo-4[prime][prime]-substituted-aryl-1[prime][prime]-azetidinyl)-1[prime],3[prime],4[prime]-thiadiazino]indoles 13-20 and 5-methoxy/ethoxy-2,3-[2[prime]-(2[prime][prime]-substituted-aryl-4[prime][prime]-oxo-1[prime][prime],3[prime][prime]-thiazolidin-3[prime][prime]-yl)-1[prime],3[prime],4[prime]-thiadiazino]indoles 21-28 have been synthesized from 5-methoxy/ethoxy-2,3-[2[prime]-(substituted-benzylidinylimino)-1[prime],3[prime],4[prime]-thiadiazino]indoles 5-12. These newly synthesized compounds were characterized by elemental and spectral analysis. Further, compounds 5-28 of the present series have been screened for their antibacterial and antifungal activities. Both minimal inhibitory concentration (MIC) and ...

Novel Fused Pyrrole Heterocyclic Ring Systems as Structure Analogs of LE 300: Synthesis and Pharmacological Evaluation as Serotonin 5-HT2A, Dopamine and Histamine H1 Receptor Ligands

Archiv der Pharmazie — Wed, 27 Jan 2010 00:00:00 +0100

LE 300 represents a structurally novel type of antagonists acting preferentially at the dopamine D1/D5 receptors and the serotonin 5-HT2A receptor. This compound consists of a ten-membered central azecine ring fused to an indole ring on one side and a benzene moiety on the other side. To estimate the importance of the indole and / or phenyl moieties in this highly active benz-indolo-azecine, both rings were removed and replaced with a 1H-pyrrole counterpart. Accordingly, some new analogs of LE 300 namely, pyrrolo[2,3-g]indolizine, pyrrolo[3,2-a]quinolizine rings and their corresponding dimethylpyrrolo[2,3-d]azonine, and dimethylpyrrolo[2,3-d]azecine were synthesized to be evaluated for their activity at the 5-HT2A and dopamine D1, D2L, D4, D5 receptors in relation to LE 300. In addition, t...

Synthesis and Evaluation of Novel 2-Substituted-quinazolin-4(3H)-ones as Potent Analgesic and Anti-inflammatory Agents

Archiv der Pharmazie — Wed, 27 Jan 2010 00:00:00 +0100

A novel series of 2-substituted-quinazolin-4(3H)-ones were synthesized by reacting 3,5-disubstituted-anthranilic acid with acetic anhydride/benzoyl chloride, which were further reacted with different primary amines to obtain 2,6,8-substituted-quinazolin-4(3H)-ones 6a-f, 7, 8. All the synthesized compounds were characterized and screened for analgesic and anti-inflammatory activities. Compounds 6,8-dibromo-2-phenyl-3-(4[prime]-carboxyl phenyl)quinazolin-4(3H)-one 7 and 6,8-dibromo-2-phenyl-3-(2[prime]-phenylethanoic acid)quinazolin-4(3H)-one 8 displayed good analgesic and anti-inflammatory activity in comparison to the reference standards acetyl salicylic acid and indomethacin, respectively. (Source: Archiv der Pharmazie)

QSAR Modeling of a Set of Pyrazinoate Esters as Antituberculosis Prodrugs

Archiv der Pharmazie — Sat, 23 Jan 2010 00:00:00 +0100

In conclusion, the QSAR model generated can be used as a valuable tool to optimize the activity of future pyrazinoic acid esters in the designing of new antituberculosis agents. (Source: Archiv der Pharmazie)

Synthesis of [alpha]- and [beta]-Pyran Naphthoquinones as a New Class of Antitubercular Agents

Archiv der Pharmazie — Fri, 15 Jan 2010 00:00:00 +0100

A series of [alpha]- and [beta]-pyran naphthoquinones (lapachones) have been synthesized and evaluated for their in-vitro antibacterial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar-Blue susceptibility test; the activity was expressed as the minimum inhibitory concentration (MIC) in [mu]g/mL. The synthetic methodology consisted of the formation of methylene and aryl o-quinone methides (o-QMs) generated by Knoevenagel condensation of 2-hydroxy-1,4-naphthoquinone with formaldehyde and arylaldehydes. These o-QMs then undergo facile hetero Diels-Alder reactions with dienophiles in aqueous ethanol media. Some naphthoquinones exhibited inhibition with MIC values of 1.25 [mu]g/mL, similar to that of pharmaceutical concentrations currently used in tuberculo...

Synthesis of Imidazole Derivatives with Antimycobacterial Activity

Archiv der Pharmazie — Thu, 03 Dec 2009 00:00:00 +0100

4-Substituted 1-(p-methoxybenzyl)imidazoles were designed and synthesized in order to mimic parts of the structure of highly potent antimycobacterial 6-aryl-9-(p-methoxybenzyl)purines. 4-Haloimidazoles were subjected to Pd-catalyzed cross-coupling in order to introduce a (hetero)aryl group, or they were converted to Grignard reagents and reacted with (hetero)arylaldehydes. Further transformations of the adducts gave a variety of potential antimycobacterials with different "spacers" between the imidazole and (hetero)aryl group. The adduct from furfural was rearranged to a cyclopentenone derivative when treated with methanol under acidic conditions. Several target compounds exhibited antimycobacterial activity in vitro (IC90 13 [mu]g/mL for the best inhibitors), but they were not as active a...

Synthesis and Antistaphylococcal Activity of N-Substituted-1H-benzimidazole-sulphonamides

Archiv der Pharmazie — Fri, 20 Nov 2009 00:00:00 +0100

A series of N-substituted-1H-benzimidazole-5(6)-sulfonamides and 3-(5,6-dichloro-1H-benzimidazol-2-yl)-N-substituted benzensulfonamides were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Certain compounds inhibit bacterial growth with low MIC ([mu]g/mL) values. The most active compounds 30, 31, and 32 have the lowest MIC values with 0.39 to 0.19 [mu]g/mL. Among the compounds having sulfonamido moities, 16, 23, and 24 exhibited the strongest antibacterial activity with 1.56 [mu]g/mL MIC values. (Source: Archiv der Pharmazie)

Synthesis and Antiproliferative Activitiy of Novel Diaryl Ureas Possessing a 4H-Pyrido[1,2-a]pyrimidin-4-one Group

Archiv der Pharmazie — Thu, 19 Nov 2009 00:00:00 +0100

We herein disclose a series of novel diaryl urea derivatives possessing a 4H-pyrido[1,2-a]pyrimidin-4-one group as novel potent anticancer compounds. The structures were confirmed by IR, 1H-NMR, and MS. All the compounds were screened for their antiprofilerative activity agaist the human breast cancer cell line (MDA-MB-231). The pharmacological results indicated that most of the compounds showed moderate activity. The best of this series is compound 4c (IC50 = 0.7 [mu]mol/L), with a potency 3.6-fold higher than Sorafenib (IC50 = 2.5 [mu]mol/L), which was approved in 2005. (Source: Archiv der Pharmazie)

Fungicide Activity of 5-(4-Chlorobenzylidene)-(Z)-2-dimethylamino-1,3-thiazol-4-one against Cryptococcus Neoformans

Archiv der Pharmazie — Thu, 19 Nov 2009 00:00:00 +0100

The present work describes the synthesis and antifungal evaluation of new 5-arylidene-(Z)-2-dimethylamino-1,3-thiazol-4-ones 4a-f, obtained by the reaction of aromatic aldehydes 1 and rhodanine 2 followed by treatment with DMF. All compounds were tested against a panel of yeasts, hialohyphomycetes, and dermatophytes using the microbroth dilution method. Compounds 4a and 4c showed antifungal activity, with compound 4a being the most active one. Compound 4a demonstrated to be fungicidal rather than fungistatic and selective activity against Cryptococcus neoformans and dermatophytes. MIC100, MIC80, and MIC50 of 4a were determined against a panel of clinical isolates of C. neoformans showing ranges of MICs between 2 and 16 [mu]g/mL. (Source: Archiv der Pharmazie)

2-Aryl-3-(1H-Azol-1-yl)-1H-Indole Derivatives: A New Class of Antimycobacterial Compounds - Conventional Heating in Comparison with MW-Assisted Synthesis

Archiv der Pharmazie — Tue, 17 Nov 2009 00:00:00 +0100

2-Aryl-3-(1H-imidazol-1-yl and 1H-1,2,4-triazol-1-yl)-1H-indole derivatives were synthesized and tested for their in-vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H37Rv. (Source: Archiv der Pharmazie)

Synthesis and Biological Evaluation of Novel 5,8-Disubstituted-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b] indoles as 5-HT6 and H1 Receptors Antagonists

Archiv der Pharmazie — Tue, 17 Nov 2009 00:00:00 +0100

Synthesis, biological evaluation, and structure-activity relationships (SAR) for a series of novel [gamma]-carboline analogues of Dimebon are described. Among the studied compounds, tetrahydro-[gamma]-carboline 5b (2,8-dimethyl-5-[cis-2-pyridin-3-ylvinyl]-2,3,4,5-tetrahydro-carboline) has been identified as the most potent small molecule antagonist, in particular against histamine H1 and serotonin 5-HT6 receptors (IC50 < 0.45 [mu]M and IC50 = 0.73 [mu]M, respectively). A thorough comparative SAR study performed for the tested compounds has revealed significant correlations between the nature of side substituents and the related antagonistic activity. (Source: Archiv der Pharmazie)

Arylazoamidoximes and Related Compounds as NO-modulators

Archiv der Pharmazie — Tue, 17 Nov 2009 00:00:00 +0100

Three amidinoarylhydrazines 1, three arylazoamidines 2, and nine arylazoamidoximes 3 have been synthesized and investigated for their potential to function as nitric oxide (NO) modulators. In-vitro studies demonstrated that 2 and 3 inhibited platelet aggregation (2c, IC50 = 3 [mu]M) which could also be shown in vivo by inhibition of thrombus formation in arterioles (3a, 22%). Moreover, for all compounds antihypertensive effects were examined in vivo with SHR rats, with 2a being the most potent candidate by lowering blood pressure by 19%. However, no common underlying mechanism of action could be shown. Some of these compounds released HNO non-enzymatically. Incubations with NO synthase isoforms (NOSs) revealed, that compounds 1 to 3 were weak substrates for NOSs but arylazoamidoximes 3 rem...

Facile Synthesis and In-Vitro Antitumor Activity of Some Pyrazolo[3,4-b]pyridines and Pyrazolo[1,5-a]pyrimidines Linked to a Thiazolo[3,2-a]benzimidazole Moiety

Archiv der Pharmazie — Tue, 17 Nov 2009 00:00:00 +0100

The key precursor E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5-amino-3-aryl-1-phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4-b]pyridines 7a, b. Similarly, pyrazolo[1,5-a]pyrimidines 10a, b and 14a-f were prepared by reaction of enaminone 4 with 5-amino-1H-pyrazoles 8a, b and 12a-f, respectively. The structure of pyrazolo[1,5-a]pyrimidine 10b was determined by X-ray diffraction. The synthesized compounds were tested for their in-vitro antitumor activity against the colon cancer cell line CaCo-2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds ex...

N-Malonyl-1,2-dihydroisoquinoline as a Novel Carrier for Specific Delivery of Drugs to the Brain

Archiv der Pharmazie — Sat, 07 Nov 2009 00:00:00 +0100

N-Malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as a novel carrier system for site-specific and sustained delivery of drugs to the brain. Such carriers are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. Reduction of the prepared isoquinolinium quaternary derivatives with sodium dithionite afforded a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (CDS). The synthesized N-malonyl-1,2-dihydroisoquinoline chemical delivery systems were subjected to various chemical and biological investigations to evaluate their ability to cross the blood-brain barrier (BBB), and to be oxidized biologically into their corresponding quaternary derivatives. The in-vitro...

Synthesis and Antimycobacterial Activity of a Novel Series of Isonicotinylhydrazide Derivatives

Archiv der Pharmazie — Fri, 06 Nov 2009 00:00:00 +0100

A novel series of 14 new isonicotinyl hydrazide derivatives 2a-g, 3a-g containing a 4-thiazolidinone / 2-azetidinone nucleus were synthesized by reacting N[prime]-substituted arylidene / heteroarylidene isonicotinyl hydrazide 1a-g with thioglycollic acid in the presence of dry benzene and with chloroacetyl chloride in the presence of triethylamine, respectively. Structures of all newly synthesized compounds were characterized on the basis of elemental analyses and spectral data (IR and 1H-NMR). All the title compounds were tested for their in-vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using Alamar-Blue susceptibility test, and the activity is expressed as the minimum inhibitory concentration (MIC) in [mu]g/mL. Among the series, compounds 2b, 2g, 3b, and 3g di...

Protein Kinase C Activators as Synaptogenic and Memory Therapeutics

Archiv der Pharmazie — Fri, 06 Nov 2009 00:00:00 +0100

The last decade has witnessed a rapid progress in understanding of the molecular cascades that may underlie memory and memory disorders. Among the critical players, activity of protein kinase C (PKC) isoforms is essential for many types of learning and memory and their dysfunction, and is critical in memory disorders. PKC inhibition and functional deficits lead to an impairment of various types of learning and memory, consistent with the observations that neurotoxic amyloid inhibits PKC activity and that transgenic animal models with PKC[beta] deficit exhibit impaired capacity in cognition. In addition, PKC isozymes play a regulatory role in amyloid production and accumulation. Restoration of the impaired PKC signal pathway pharmacologically results in an enhanced memory capacity and synap...

Synthesis of Monomeric and Dimeric Acridine Compounds as Potential Therapeutics in Alzheimer and Prion Diseases

Archiv der Pharmazie — Fri, 06 Nov 2009 00:00:00 +0100

Starting from substituted 9-chloroacridines, a series of quinacrine and spacered dimeric acridine compounds was prepared. Their ability to interrupt the protein association of prion- and Alzheimer-specific proteins and Ab peptides was explored using a fast screening system based on FACS analysis. The bis-acridines displayed a higher activity than the corresponding monomers. Among these derivatives, best results were obtained with the 2,4-dimethoxy-6-nitro compound 7h for A[beta]-peptides and the 2-methoxy-6-nitro compound 7f for PrP. (Source: Archiv der Pharmazie)

Synthesis and Anti-HIV-1 Integrase Activitiy of Cyano Pyrimidinones

Archiv der Pharmazie — Fri, 06 Nov 2009 00:00:00 +0100

A series of 2-phenethyl/benzylthio-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile were synthesized and tested against recombinant HIV-1 integrase in an enzyme assay. 2-(Phenethylthio)-4-(4-chlorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 4m and 2-(phenethylthio)-4-(3-chlorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 4o showed significant inhibition against integrase in the assay (strand transfer: IC50 values of 16 and 17 [mu]M, respectively). (Source: Archiv der Pharmazie)

Design, Synthesis, and Antifungal Activity of Novel Conformationally Restricted Triazole Derivatives

Archiv der Pharmazie — Fri, 06 Nov 2009 00:00:00 +0100

A series of new triazole derivatives were designed and synthesized on the basis of the active site of lanosterol 14[alpha]-demethylase from Candida albicans (CACYP51). 2-(2,4-Difluorophenyl)-3-(methyl-(3-phenoxyalkyl)amino)-1-(1H-1,2,4-triazol-1-yl)propan-2-ols show excellent in-vitro activity against most of the tested pathogenic fungi. The MIC80 value of compound 8a against Candida albicans is 0.01 [mu]M, which provides a good starting template for further structural optimization. The binding modes of the designed compounds were investigated by flexible molecular docking. The compounds interacted with CACYP51 through hydrophobic, van-der-Waals, and hydrogen-bonding interactions. (Source: Archiv der Pharmazie)

Contents: Archiv der Pharmazie 11/2009

Archiv der Pharmazie — Sat, 31 Oct 2009 14:01:41 +0100

No Abstract. (Source: Archiv der Pharmazie)

Synthesis, Cytotoxicity by Bioluminescence Inhibition, Antibacterial and Antifungal Activity of ([1,2,4]Triazolo[1,5-c]quinazolin-2-ylthio)carboxylic Acid Amides

Archiv der Pharmazie — Fri, 30 Oct 2009 00:00:00 +0100

We report in this work the synthesis, cytotoxicity, and antimicrobial activity of ([1,2,4]triazolo[1,5-c]quinazolin-2-ylthio)carboxylic acid amides 4-7 in connection with our previous research in the preparation of triazoloquinazoline derivatives. Due to simplicity, general availability of starting materials, and high yields, the most reliable method of synthesis appeared to be the one with N,N-carbonyldiimidazole activation stage. The chemical structures of all obtained substances were deduced from FT-IR, 1H-NMR, EI-MS, and LC-MS spectral data. The results of cytotoxicity evaluated by bioluminescence inhibition of bacterium Photobacterium leiognathi, strain Sh1 showed that compounds 4.1, 4.6, and 6.1 were the most cytotoxic. Investigation of the antimicrobial and antifungal activity of am...

Relationship Between Anticancer Activity and Stereochemistry of Saldach Ligands and their Iron(III) Complexes

Archiv der Pharmazie — Fri, 30 Oct 2009 00:00:00 +0100

(R,R)-, (S,S)- and (R,S)-N,N[prime]-bis(salicylidene)-1,2-diaminocyclohexane (saldach) and their iron(III) complexes were screened for anticancer activity against MCF-7 and MDA-MB 231 breast cancer as well as HT-29 colon carcinoma cells. Antiproliferative effects depended on the presence of the central atom iron but were independent on the configuration at the saldach ligand. While the free ligands were inactive, the iron(III) derivatives displayed anticancer activity within a concentration range of 1 to 5 [mu]M irrespective of the used cell line. At 5 [mu]M they were even more active than cis-platin. A mode of action comparable to cis-platin can be excluded because it is very likely that the DNA is not the primary target of [FeIII (saldach)] complexes. (Source: Archiv der Pharmazie)

Synthesis of Novel Uracil Non-Nucleoside Derivatives as Potential Reverse Transcriptase Inhibitors of HIV-1

Archiv der Pharmazie — Fri, 23 Oct 2009 23:00:00 +0100

Novel emivirine and TNK-651 analogues 5a-d were synthesized by reaction of chloromethyl ethyl ether and / or benzyl chloromethyl ether, respectively, with uracils having 5-ethyl and 6-(4-methylbenzyl) or 6-(3,4-dimethoxybenzyl) substituents. A series of new uracil non-nucleosides substituted at N-1 with cyclopropylmethyloxymethyl 9a-d, 2-phenylethyloxymethyl 9e-h, and 3-phenylprop-1-yloxymethyl 9i-l were prepared on treatment of the corresponding uracils with the appropriate acetals 8a-c. Some of the tested compounds showed good activity against HIV-1 wild type. Among them, 1-cyclopropylmethyloxymethyl-5-ethyl-6-(3,5-dimethylbenzyl)uracil 9c and 5-ethyl-6-(3,5-dimethylbenzyl)-1-(2-phenylethyloxymethyl)uracil 9g showed inhibitory potency equally to emivirine against HIV-1 wild type. Further...

Synthesis of 2-Fluoro N10-Substituted Acridones and Their Cytotoxicity Studies in Sensitive and Resistant Cancer Cell Lines and Their DNA Intercalation Studies

Archiv der Pharmazie — Thu, 22 Oct 2009 23:00:00 +0100

A series of 2-fluoro N10-substituted acridone derivatives with varying alkyl side chain length with propyl, butyl substitution, and a tertiary amine group at the terminal end of the alkyl side chain were synthesized and screened against cancer cell lines SW 1573, SW 1573 2R 160 (P-gp substrate) which are non-small lung cancer cell lines, MCF-7, MCF-7/MR (BCRP substrate) are breast cancer cell lines, 2008 WT, 2008MRP1, 2008MRP2, 2008MRP3 are ovarian cancer cell lines, and human embryo kidney cell lines like HEK293, HEK293 MRP4, and HEK293 MRP5i. The propyl-series compounds showed lipophilicity in the range of 1.93 to 4.40 and the butyl series in the range of 2.37 to 4.78. The compounds 4, 7, and 8 showed good cytotoxicity against the 60 human cancer cell line panel of the National Cancer In...

Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo[1,5-a]quinazolines

Archiv der Pharmazie — Thu, 22 Oct 2009 23:00:00 +0100

Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and then with sodium azide. The structures of these compounds have been confirmed by IR, MS, 1H-NMR, and elementary analysis. Anticonvulsant activities were evaluated using the maximal electroshock (MES) test. Most of the synthesized compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg. Antidepressant activities were investigated by forced swimming test. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose level. (Source: Archiv der Pharmazie...

Proline Analogue of Nitrosourea as a New Cytotoxic Prodrug

Archiv der Pharmazie — Thu, 22 Oct 2009 23:00:00 +0100

In conclusion, carmustine and AC cause changes in the antioxidative system of normal and MOLT4 cells and are a reason of oxidative stress formation. (Source: Archiv der Pharmazie)

Contents: Archiv der Pharmazie 10/2009

Archiv der Pharmazie — Sat, 26 Sep 2009 16:28:06 +0100

No Abstract. (Source: Archiv der Pharmazie)

Synthesis and Biological Evaluation of 2-Mercapto-1,3-benzothiazole Derivatives with Potential Antimicrobial Activity

Archiv der Pharmazie — Mon, 14 Sep 2009 23:00:00 +0100

The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 [mu]g/mL against Staphylococcus aureus and 25 [mu]g/mL against Escherichia coli, respectively. The replacement of the S-H by th...

Synthesis and Cytotoxic Evaluation of 6-(3-Pyrazolylpropyl) Derivatives of 1,4-Naphthohydroquinone-1,4-diacetate

Archiv der Pharmazie — Sun, 13 Sep 2009 23:00:00 +0100

Several new 6-(3-pyrazolylpropyl) derivatives of 1,4-naphthohydroquinone-1,4-diacetate (NHQ-DA) have been prepared by chemical modifications of the Diels-Alder adduct of [alpha]-myrcene and 1,4-benzoquinone. All these new compounds and precursors have been evaluated in vitro for their cytotoxicity against cultured human cancer cells of MB-231 breast-adeno carcinoma, A-549 lung carcinoma, and HT-29 colon carcinoma. GI50 values ranged in and below the micromolar concentration level. (Source: Archiv der Pharmazie)

Synthesis and In-vitro Activity of 4[prime]-Modified Analogues of ddA as Potent Anti-HIV Agents

Archiv der Pharmazie — Sun, 13 Sep 2009 23:00:00 +0100

This paper reports the synthesis of novel 4[prime]-hydrophobic pocket deoxythreosyl C-nucleosides. The key threose-like intermediates 9 and 14 were constructed from acyclic ketone derivatives, respectively. The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The 9-deaza-adenine derivatives 10 and 20 showed good anti-HIV activity without exhibiting significant cytotoxicity. (Source: Archiv der Pharmazie)

Contents: Archiv der Pharmazie 9/2009

Archiv der Pharmazie — Mon, 31 Aug 2009 23:00:00 +0100

No Abstract. (Source: Archiv der Pharmazie)

Synthesis and Pharmacological Evaluation of Thiazole and Isothiazole Derived Apomorphines

Archiv der Pharmazie — Thu, 27 Aug 2009 23:00:00 +0100

We have presented the synthesis of novel thiazolo- and isothiazolo-apomorphines 12-17 resulting-in part-from an unexpected isomerization step occurred during the acid-catalyzed rearrangement of precursor thiazolo-morphinandienes 3-5. These 2,3-disubstituted apomorphines represent a new group of A-ring substituted aporphines. The receptor binding studies revealed that with the exception of two derivatives all the tested compounds have limited affinity for dopamine-receptor subtypes. Functional calcium assay for the most active isothiazolo-apomorphine showed higher affinities for D1 and D2L subtypes. The docking of these ligands has been modelled to human D2 and D3 receptors. On the basis of the predicted models, we identified an important cation-p interaction for the binding of isothiazolo-...

Synthesis and Cytotoxicity Studies of New Cryptophycin Analogues

Archiv der Pharmazie — Wed, 26 Aug 2009 23:00:00 +0100

Two analogues of cryptophycin were synthesized and biologically evaluated for their in-vitro cytotoxicities against several solid tumors and leukemia cell lines. The results revealed that both analogues exhibited a broad range of cytotoxic activity with observed IC50 values in the [mu]M-range, and compound 4 was more effective than compound 3 in most assays studied. (Source: Archiv der Pharmazie)

Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents

Archiv der Pharmazie — Wed, 26 Aug 2009 23:00:00 +0100

A series of 3,5-bis(arylidene)-4-piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3-c]pyridines, pyrido[4,3-d]pyrimidines, and pyrido[3,2-c]pyridines, carrying an arylidene moiety, and some pyrano[3,2-c]pyridines, like flavone and coumarin isosteres, were synthesized and screened for their in-vitro antitumor activity at the National Cancer Institute (NCI, USA). The tested compounds 7, 9, 10, 12, 13, 15, 17, and 19 exhibited a broad spectrum of antitumor activity. Compounds belonging to the pyrazolo[4,3-c]pyridine series proved to be more active than those of the pyrido[3,2-c]pyridine and pyrano[3,2-c]pyridine analogues, in which the monomethoxylated derivatives showed better antitumor activity when compared with their corresponding dimethoxylated...

Antitumoractive Endoperoxides from Triterpenes

Archiv der Pharmazie — Mon, 24 Aug 2009 23:00:00 +0100

A series of triterpene endoperoxides was synthesized and screened for antitumor activity in a panel of 15 human cancer cell lines by a sulforhodamine-B (SRB) assay. The compounds induce apoptosis and show excellent antitumor activity. (Source: Archiv der Pharmazie)

Synthesis and Anti-HIV-1 Activity of 1-Substiuted 6-(3-Cyanobenzoyl) and [(3-Cyanophenyl)fluoromethyl]-5-ethyl-uracils

Archiv der Pharmazie — Sun, 26 Jul 2009 23:00:00 +0100

1-Substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyl-uracils were synthesized and evaluated in cell-based assays against HIV-1 wild-type and its clinically relevant non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants. Some of the synthesized compounds showed activity against HIV-1 wild-type in the same range as Emivirine (MKC-442). 3-{[3-(Allyloxymethyl)-5-ethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]fluoromethyl}-benzonitrile 11b showed moderate activity against the Y181C HIV-1 mutant strain. (Source: Archiv der Pharmazie)

Synthesis and In-Vitro Anti-Hepatitis-B Virus Activity of 6H-[1]Benzothiopyrano[4,3-b] quinolin-10-ols

Archiv der Pharmazie — Sun, 26 Jul 2009 23:00:00 +0100

A series of 9-methoxy-6H-[1]benzothiopyrano[4,3-b]quinolin-10-ols with a Mannich side chain were synthesized and evaluated for their anti-Hepatitis B virus (HBV) activity in HepG2.2.15 cells. Some compounds showed significant anti-HBV activity with IC50 values less than 41 [mu]M. Among them, compound 9b was the most effective anti-HBV agent (IC50 = 1.7 [mu]M, SI = 60.3). (Source: Archiv der Pharmazie)

Novel l[beta]-Methylcarbapenems Having Cyclic Sulfonamide Moieties: Synthesis and Evaluation of in-vitro Biological Activity - Part II

Archiv der Pharmazie — Mon, 13 Jul 2009 23:00:00 +0100

The synthesis of a new series of 1[beta]-methylcarbapenems having cyclic sulfonamide moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of a substituent on the pyrrolidine ring was investigated. One particular compound IIIe having a [1,2,5]thiadiazolidin 1,1-dioxide moiety showed the most potent antibacterial activity. (Source: Archiv der Pharmazie)

3-Imidazolyl-Substituted Flavans as Potential Antifungal Agents: Synthesis, Stereochemical Properties, and Antifungal Activity

Archiv der Pharmazie — Mon, 13 Jul 2009 23:00:00 +0100

A new series of 3-imidazolyl-substituted flavan derivatives being equipped with a N-(phenethyl)-azole scaffold as the common pharmacophore of azole antifungals, were synthesized. The stereochemical and conformational properties of compounds were also characterized by 1H-NMR data. The results of the antifungal evaluation of trans-3-imidazolyl-substituted flavan-4-ones and (Z)-trans-3-imidazolyl-substituted flavan-4-one oximes in comparison with the reference drug fluconazole indicated that most target compounds possessed significant in-vitro antifungal activities against the tested fungi, comparable or superior to fluconazole. (Source: Archiv der Pharmazie)

Synthesis of (1R,2R)- and (1S,2R)-1,2-Epoxy-3-hydroxypropylphosphonates as Analogues of Fosfomycin

Archiv der Pharmazie — Mon, 13 Jul 2009 23:00:00 +0100

Cyclohexylammonium (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonate was conveniently synthesized from dibenzyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3-trihydroxypropylphosphonate by a reaction sequence including mesylation, hydrolysis of acetal, intramolecular Williamson reaction, and hydrogenation in the presence of cyclohexylamine. For dibenzyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3-trihydroxypropylphosphonates the same approach was not successful, since prior the epoxide-ring closure tritylation of HO-C3 in dibenzyl (1R,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonate was necessary and the hydrogenolysis of dibenzyl (1S,2R)-1,2-epoxy-3-trityloxypropylphosphonate yielded a complex reaction mixture. (Source: Archiv der Pharmazie)

6-Substituted Indolo[1,2-c]quinazolines as New Antimicrobial Agents

Archiv der Pharmazie — Mon, 13 Jul 2009 23:00:00 +0100

A series of 2-o-arylidineaminophenylindoles and their cyclic derivatives (indolo[1,2-c]quinazolines) were synthesized. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. Molecular structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, MS spectra, and elemental analyses. Furthermore, all the final products were screened for in-vitro antibacterial activity against three Gram-positive and three Gram-negative bacteria and also tested for their inhibitory action against three strains of fungi. Compound IIc showed potent activity against all the bacterial (except S. typhimurium) and fungal strains. Especially, compounds IIi and IIj which have isoquinolyl and pyridyl substituents displayed potent antibacterial as well a...

Synthesis and Characterization of New Liver Targeting 5-Fluorouracil-Cholic Acid Conjugates

Archiv der Pharmazie — Mon, 13 Jul 2009 23:00:00 +0100

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70°C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results wer...

Benzothiazole Incorporated Barbituric Acid Derivatives: Synthesis and Anticonvulsant Screening

Archiv der Pharmazie — Mon, 29 Jun 2009 23:00:00 +0100

A series of 1-(6-substituted-1,3-benzothiazol-2-yl)-3-(substituted phenyl)hexahydro-2,4,6-pyrimidinetriones 4a-t were synthesized starting from substituted anilines. These compounds contained two active anticonvulsant pharmacophores, benzothiazole and barbituric acid. Structures of the compounds were confirmed on the basis of different spectroscopic techniques. All the compounds were evaluated for their anticonvulsant activity. Three compounds 4c, 4d, and 4s showed promising anticonvulsant activities in Maximal Electroshock Seizure test (MES) and subcutaneous pentylenetetrazole test (scPTZ). They also displayed a wide safety profile when tested for the minimal motor impairment test. (Source: Archiv der Pharmazie)

Synthesis of Dimeric Quinazolin-2-one, 1,4-Benzodiazepin-2-one, and Isoalloxazine Compounds as Inhibitors of Amyloid Peptides Association

Archiv der Pharmazie — Sun, 28 Jun 2009 23:00:00 +0100

The synthesis of dimeric compounds derived from quinazolin-2-one and 1,4-benzodiazepin-2-one possessing a piperazine or homopiperazine spacer was investigated. In addition, a piperazine spacered bis-isoalloxazine and a bis-riboflavin compound were prepared and their ability to interrupt the association of prion proteins and Alzheimer-specific A[beta] peptides was investigated using a fast screening system based on flow cytometry. The bis-isoalloxazine 14 was identified as a new lead structure. (Source: Archiv der Pharmazie)

Synthesis of Novel 2,5-Disubstituted 1,3,4-Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies

Archiv der Pharmazie — Sun, 28 Jun 2009 23:00:00 +0100

A series of novel N1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N4-(4-substituted benzaldehyde)-semicarbazone 1-12, N1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N4-[1-(4-substituted phenyl)ethanone]-semicarbazone 13-16, and N1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N4-[1-(4-substituted phenyl) (phenyl) methanone]-semicarbazone 17-20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, 1H-NMR, 13C-NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant...

Multi-Component Synthesis of Dihydropyrimidines by Iodine Catalyst at Ambient Temperature and in-vitro Antimycobacterial Activity

Archiv der Pharmazie — Sun, 28 Jun 2009 23:00:00 +0100

An efficient and simple three-component domino synthesis of some new dihydropyrimidines (DHPMs) from aromatic aldehydes, 1,3-dicarbonyl compounds and N-(3-chloro-4-fluorophenyl)urea using molecular iodine as catalyst is described. The 1-substituted dihydropyrimidines were isolated in good to excellent yields (78-90%) within a short reaction time (4-6 h) at ambient temperature. The biological evaluation revealed that the newly synthesized compounds (4a-i and 5a-i) exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis H37 RV. (Source: Archiv der Pharmazie)

Synthesis and Cytotoxic Activity of Novel Amidine Analogues of Bis(2-chloroethyl)amine

Archiv der Pharmazie — Sun, 28 Jun 2009 23:00:00 +0100

Novel nitrogen mustard agents 7-12 involving 4-(N,N-bis(2-chloroethyl)aminophenyl)propylamine linked to a 5-(4-N-alkylamidinophenyl)-2-furancarboxylic acid moiety by the formation of an amide bond have been synthesized, characterized, and evaluated for their in-vitro cytotoxic activity against MDA-MB-231 and MCF-7 human breast cancer cells. Evaluation of the cytotoxicity of 7-12 employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA demonstrated that these compounds exhibit remarkable cytotoxic effects in comparison with 4-[bis(2-chloroethyl)amino]benzenebutanoic acid. Compounds 7 and 9, which possess a cationic amidine and 4,5-dihydro-1H-imidazol function moiety are approximately ten times more potent than 4-[bis(2-chloroethyl)amino]benzenebutanoic acid. The new comp...

Synthesis and Anti-Inflammatory Activity of Novel (4-Hydroxyphenyl)(2,4-dimethoxyphenyl) Methanone Derivatives

Archiv der Pharmazie — Fri, 12 Jun 2009 04:00:00 +0100

In the scope of the research program aiming to perform the synthesis and pharmacological evaluation of novel possible anti-inflammatory compounds, in this manuscript, we report the synthesis of novel carboxamide 9a-d and thioamide 10a-d derivatives from the benzophenone and piperidine nucleus. Variation in the functional group at the N-terminal of piperidine led to two sets of compounds, bearing the carboxamide and thioamide, respectively. The characterization of this new class of compounds was performed with 1H-NMR, LC-MS, IR, and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory activity by carrageenan-induced foot pad oedema assay and were compared with a standard drug. All the compounds exhibited anti-inflammatory activity at the dose of 30 m...

Synthesis, in-vitro Microbial and Cytotoxic Studies of New Benzimidazole Derivatives

Archiv der Pharmazie — Wed, 10 Jun 2009 04:00:00 +0100

Several new classes of benzimidazole derivatives were synthesized and evaluated for in-vitro antimicrobial and cytotoxic activities. The results showed that all synthesized compounds exhibited moderate antimicrobial activity, and compounds 2, 4, and 13 displayed cytotoxic activity (as LD50) at the concentration 1×10-3 M against Artemia salina. (Source: Archiv der Pharmazie)

Synthesis, Antiviral and Cytostatic Evaluation of Unsaturated Exomethylene and Keto D-Lyxopyranonucleoside Analogues

Archiv der Pharmazie — Sat, 30 May 2009 04:00:00 +0100

This report describes the synthesis of unsaturated exomethylene lyxopyranonucleoside analogues as potential biologically active agents. Commercially available 1,2,3,4-tetra-O-acetyl-[alpha]-D-lyxopyranose 1 was condensed with silylated thymine and uracil, respectively, deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-[alpha]-D-lyxopyranosyl)thymine 4a and 1-(2,3-O-isopropylidene-[alpha]-D-lyxopyranosyl)uracil 4b. The new derivatives 1-(2,3,4-trideoxy-4-methylene-[alpha]-pent-2-enopyranosyl)thymine 8a and 1-(2,3,4-trideoxy-4-methylene-[alpha]-pent-2-enopyranosyl)uracil 8b were prepared via two different key intermediates, 7a, b and 13a, b in order to elucidate the influence of 2[prime],3[prime]-unsaturation and to clarify the difference between the keto and exomethylene group o...

Pyrazolo[3,4-d]pyrimidine Derivatives as COX-2 Selective Inhibitors: Synthesis and Molecular Modelling Studies

Archiv der Pharmazie — Thu, 28 May 2009 04:00:00 +0100

The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin-4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5-benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5-aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a-d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological results. (Source: Archiv der Pharmazie)

Synthesis and Antibacterial Activity of a New Series of 3-[3-(Substituted Phenyl)-1-Isonicotinoyl-1H-Pyrazol-5-yl]-2H-Chromen-2-one Derivatives

Archiv der Pharmazie — Wed, 27 May 2009 04:00:00 +0100

A novel series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives 4a-k have been synthesized by the reaction of 3-[2,3-dibromo-3-(substituted phenyl) propanoyl]-2H-chromen-2-one 3a-k and isonicotinic acid hydrazide in the presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in-vitro antibacterial activity against Gram-positive and Gram-negative bacteria. Among the series, compounds 4e, 4i, and 4k displayed an encouraging antibacterial activity profile as compared to the reference drug ampicillin against tested bacterial strains. (Source: Archiv der Pharmazie)

Generation and Evaluation of a Homology Model of PfGSK-3

Archiv der Pharmazie — Wed, 27 May 2009 04:00:00 +0100

Plasmodial GSK-3 is a potential new target for malaria therapy. For a structure-based design project, the three-dimensional information of the designated target is needed. Unfortunately, experimental structure data for plasmodial GSK-3 is not yet available. Homology building can be used to generate such three-dimensional structure data using structure information of a homologous protein. GSK-3 possesses a very flexible ATP-binding site, a fact reflected in the variety of X-ray structures of the human GSK-3[beta] which are deposited in the protein data base and are crystallized with different ligands. We used ten different HsGSK-3[beta] templates for the model building of plasmodial GSK-3 and generated 200 models for each template with different modeling protocols. The quality of the models...

Synthesis and pp60c-Src Tyrosine Kinase Inhibitory Activities of Novel Indole-3-Imine and Amine Derivatives Substituted at N1 and C5

Archiv der Pharmazie — Wed, 27 May 2009 04:00:00 +0100

A series of novel 1,3,5-trisubstituted indole derivatives, namely, N-benzyl 5-phenyl indole-3-imine, N-benzyl-5-(p-fluorophenyl)indole-3-imine and their corresponding amine congeners, were designed and synthesized as pp60c-Src tyrosine kinase inhibitors, and their inhibitory activities toward pp60c-Src tyrosine kinase were evaluated by in-vitro kinase assay. Pre-screening at two doses of compounds against kinase target revealed that, except for the N-benzyl-5-phenyl indole imine derivatives 7a-7d, all indole derivatives show the target inhibition at varying levels. Consequently, the compounds, 8c, 8f, 8g, and 8h, were selected for prescreening tests. The dose-response curves for up to six concentrations (250 to 7.8 [mu]M) of the active compounds were obtained by tyrosine kinase assay and t...

Synthesis and Biological Evaluation of Some Novel Polysubstituted Pyrimidine Derivatives as Potential Antimicrobial and Anticancer Agents

Archiv der Pharmazie — Thu, 07 May 2009 04:00:00 +0100

Synthesis and evaluation of the antimicrobial and cytotoxic activity of two series of polysubstituted pyrimidines comprising the thioether functionality and other pharmacophores, reported to contribute to various chemotherapeutic activities are described. All newly synthesized compounds were subjected to in-vitro antibacterial and antifungal screening. Out of the compounds tested, 18 derivatives displayed an obvious inhibitory effect on the growth of the tested Gram-positive and Gram-negative bacterial strains, with special effectiveness against the Gram-positive strains. Compounds 1, 2, 6, 7, 9, 10, 11, 21, and 24 revealed remarkable broad antibacterial spectrum profiles. Among those, compounds 1, 2, 6, 7, 9, and 24 exhibited an appreciable antifungal activity against C. albicans. Compoun...

Synthesis and Studies of New 2-(Coumarin-4-yloxy)-4,6-(substituted)-s-Triazine Derivatives as Potential Anti-HIV Agents

Archiv der Pharmazie — Mon, 04 May 2009 04:00:00 +0100

Novel 2-(coumarin-4-yloxy)-4,6-(substituted)-s-triazine derivatives i. e., diaryltriazine (DATA) are reported as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus HIV-1 (III-B), HIV-2 (ROD), and the double RT mutant HIV-1 (K103N and Y181C) were assessed. Modifications at positions 4 and 6 of the coumarinyl-triazine scaffold generated interesting derivatives displaying good to moderate anti-HIV activity against selected HIV strains as compared to nevirapine and efavirenz. The synthesized compounds were characterized by FTIR, 1H-NMR, and mass spectral data together with elemental analysis. (Source: Archiv der Pharmazie)

N-(Indazolyl)benzamido Derivatives as CDK1 Inhibitors: Design, Synthesis, Biological Activity, and Molecular Docking Studies

Archiv der Pharmazie — Mon, 04 May 2009 04:00:00 +0100

A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1 / cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by the above-mentioned compounds. (Source: Archiv der Pharmazie)

Novel 3,6-Disubstituted 7H-1,2,4-Triazolo[3,4-b][1,3,4]thiadiazines: Synthesis, Characterization, and Evaluation of Analgesic / Anti-inflammatory, Antioxidant Activities

Archiv der Pharmazie — Mon, 04 May 2009 04:00:00 +0100

In this study, the synthesis of a new series of 3,6-disubstituted-7H-1,2,4-triazolo[3,4-b][1,3,4]thiadiazine 1a-4c compounds derived from 4-amino-3-substituted-1,2,4-triazole-5-thiones 1-4 is described. All of the synthesized compounds were screened for their possible analgesic / anti-inflammatory, antioxidant activities and gastric toxicity. The compound 2c was found to have both significant analgesic and consistent anti-inflammatory activity without inducing any gastric lesions along with minimal lipid peroxidation. A deep insight into the structures of the active compounds revealed that the compounds carrying an electron withdrawing group (a chloride or fluoride) on the phenyl ring at 6-position of the condensed heterocyclic derivatives exhibited noticeable higher activity. (Source: Arc...

Synthesis and Biological Activities of 2,4-Diaminopteridine Derivatives

Archiv der Pharmazie — Mon, 04 May 2009 04:00:00 +0100

Substituted 2,4-diaminopteridine derivatives 10a-10l were prepared in moderate to good yield. Their structures were confirmed by 1H-NMR and MS spectroscopy, as well as by elemental analysis. Their inhibitory properties against inducible nitric oxide synthase (iNOS) were evaluated in vitro. Biological tests indicated that compound 10a, 10d, 10e, 10h, 10i, and 10l showed potent inhibitory activities similar to that of methotrexate (MTX), while the activities of compound 10b, 10c, 10f, 10g, 10j, and 10k are stronger than MTX. Two compounds, i. e., 10b (IC50 = 18.85 [mu]M) and 10i (IC50 = 24.08 [mu]M) were further studied for their effect on septic shock in rats and immunologically liver injured mice (in vivo). The results demonstrated that 10b and 10i had the capacity to increase the blood pr...

Synthesis and Biological Evaluation of Novel Pyrazoles and Pyrazolo[3,4-d]pyrimidines Incorporating a Benzenesulfonamide Moiety

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines are reported. Fourteen compounds were selected by the NCI and tested for their preliminary in-vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in-vitro antimicrobial activity. Compound 12a was proven to possess the highest anticancer activity with a broad spectrum profile. It showed particular effectiveness towards leukemia HL-60 (TB), K-562, non-small cell lung cancer NCI-H23, and colon cancer HT 29, KM 12 cell lines (GI50 = 6.59, 4.44, 1.37, 3.33, and 9.63 [mu]M, respectively). Out of the synthesized compounds, thirteen derivatives were found to display pronounced antimicrobial activity especially against P. aeruginosa. Compounds 2c, 5b, 10, 11b, 17b, 18b, and 19...

Immunomodulatory and Anticancer Activities of Some Novel 2-Substituted-6-bromo-3-methylthiazolo[3,2-a]benzimidazole Derivatives

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

Ethyl 6-bromo-3-methyl-1,3-thiazolo[3,2-a]benzimidazole-2-carboxylate 2 was prepared by the ambient temperature bromination of ethyl 3-methyl-1,3-thiazolo[3,2-a]benzimidazole-2-carboxylate 1. The acid hydrazide 4 was obtained by the reaction of ester 2 with hydrazine hydrate. Treatment of compound 4 with benzaldehyde or 2-thiophenaldehyde yielded the corresponding hydrazones 6a and 6b, respectively, while the reaction of acid hydrazide 4 with ethoxymethylene malononitrile (7a) or with ethyl ethoxymethylene cyanoacetate (7b) in refluxing ethanol afforded pyrazole derivatives 9a and 9b, respectively. Taken together, from the biological investigations compounds 9a and 9b were the most significant inhibitors of LPS-stimulated NO generation from Raw murine macrophage 264.7, and, as another resu...

Design and Synthesis of a Gossypol Derivative with Improved Antitumor Activities

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

A novel chemical process has been devised for the synthesis of a new derivative of gossypol, 6,7,6[prime],7[prime]-tetrahydroxy-5,5[prime]-diisopropyl-3,3[prime]-dimethyl-[2,2']binaphthalenyl-1,4,1[prime],4[prime]-tetraone (Apogossypolone). This new process has only four steps, with a shorter synthesis span, a simple purification process, and improved yield and quality. The structure of apogossypolone was characterized by 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, mass spectroscopy, infrared spectroscopy, and elemental analysis. Cell-cytotoxicity assay demonstrates that apogossypolone is three- to six-fold more potent than the parent compound, (-)-gossypol, in inhibiting the human prostate tumor cell lines PC-3 and DU-145 as well as the human breast cancer cell line MDA...

Studies on Synthesis and Pharmacological Activities of 1,2,4-Triazolo[3,4-b]1,3,4-thiadiazoles and their Dihydro Analogues

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

4-Amino-5-substituted aryl-3-mercapto-1,2,4-triazoles are versatile synthons for constructing various biologically active heterocycles. Starting from 4-amino-5-substituted aryl-3-mercapto-1,2,4-triazole 3a-c, a series of new 3,5-disubstituted-1,2,4-triazolo-[3,4-b]1,3,4-thiadiazoles and their 5,6-dihydrotriazolothiadiazoles were prepared. The structures of all the newly synthesized compounds have been confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR, and mass spectra. The antimicrobial effects of the synthesized compounds were investigated using the paper disc method. Anti-inflammatory and analgesic activities of the synthesized compounds were assessed by carrageenan-induced rat paw oedema method and by Eddy's hot plate method, respectively. Some of the compounds exhibited promising an...

Synthesis and Characterization of Hydroxylated Mesocarb Metabolites for Doping Control

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

The synthesis and method of analysis of hydroxylated mesocarb metabolites are described. Six potential hydroxylated mesocarb metabolites were prepared, characterized, and compared with the mesocarb metabolites synthesized enzymatically in vitro using human liver proteins and also compared with metabolites extracted from human urine after oral administration of mesocarb. p-Hydroxymesocarb was the most prevalent metabolite (conjugated and non-conjugated) observed. With respect to doping analysis, synthesis of p-hydroxymesocarb, the main urinary metabolite of mesocarb, and its availability as a reference material is important. (Source: Archiv der Pharmazie)

Contents: Archiv der Pharmazie 4/2009

Archiv der Pharmazie — Wed, 01 Apr 2009 04:00:00 +0100

No Abstract. (Source: Archiv der Pharmazie)

Breast Cancer, Estrogen Receptor and Ligands

Archiv der Pharmazie — Mon, 09 Mar 2009 04:00:00 +0100

This review emphasizes the relationship of breast cancer, estrogen receptor and ligands, especially the centrality of the estrogen receptor, which mediates on one hand the hormone-induced gene transcription and on the other hand the anti-estrogen action against breast cancer. The characterization of the estrogen receptor ligand-binding domain co-crystallized with agonists or antagonists provided a molecular basis to gain an insight into the regulation of estrogen receptor and, thereby, to describe the mechanism of the hormone therapy in treating breast cancer. (Source: Archiv der Pharmazie)

Contents: Archiv der Pharmazie 3/2009

Archiv der Pharmazie — Sun, 01 Mar 2009 05:00:00 +0100

No Abstract. (Source: Archiv der Pharmazie)

Cerulenin Analogues as Inhibitors of Efflux Pumps in Drug-resistant Candida albicans

Archiv der Pharmazie — Sat, 28 Feb 2009 05:00:00 +0100

Overexpression of the ABC transporters Cdr1 and Cdr2 or the major facilitator Mdr1 causes multidrug resistance in the human fungal pathogen Candida albicans. The fatty acid synthesis inhibitor cerulenin and the structurally unrelated Golgi transport inhibitor brefeldin A are substrates for both types of efflux pumps in Candida albicans. In an effort to overcome efflux pump-mediated drug resistance in Candida albicans, cerulenin analogues were generated using a variety of synthesis pathways. The so obtained cerulenin derivatives were tested on multidrug-resistant Candida albicans isolates which constitutively overexpress either Mdr1 or Cdr1 and Cdr2. Some of these compounds were found to decrease Mdr1-mediated resistance to brefeldin A up to eightfold compared to the control. (Source: Archi...

Synthesis and In-Vitro Antitumor Activities of Some Mannich Bases of 9-Alkyl-1,2,3,4-tetrahydrocarbazole-1-ones

Archiv der Pharmazie — Fri, 13 Feb 2009 05:00:00 +0100

A novel series of 2-substituted aminomethyl-9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 5a-q was synthesized via aminomethylation of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 4a-e with hydrochlorides of the respective amines 6a-m. The structures of these newly synthesized compounds were characterized by 1H-NMR, MS, and elemental analysis. All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines including human non-small lung cancer cells (A549), human gastric adenocarcinoma (SGC), human colon cancer cell (HCT116), human myeoloid leukemia cells (K562), and one multi-drug resistant subline (KB-VCR). Most compounds showed moderate to potent cytotoxic activity against the tested cell lines. Preliminary mechanism research indicated that the most pr...

Synthesis and Cytotoxicity Screening of Piperazine-1-carbodithioate Derivatives of 2-Substituted Quinazolin-4(3H)-ones

Archiv der Pharmazie — Wed, 11 Feb 2009 05:00:00 +0100

A new series of piperazine-1-carbodithioate derivatives of 2-substituted quinazolin-4(3H)-ones were synthesized via a five-steps procedure starting from 2-amino-5-methylbenzoic acid. The cytotoxicity of the resulting compounds against A-549 (human lung cancer), HCT-8 (human colon cancer), HepG2 (human liver cancer), and K562 (human myelogenous leukaemia) cell lines was determined by the MTT assay. Preliminary screening results of these compounds are reported. (Source: Archiv der Pharmazie)

Design, Synthesis, and In-Vivo Pharmacological Screening of N,3-(Substituted Diphenyl)-5-phenyl-1H-pyrazoline-1-carbothioamide Derivatives

Archiv der Pharmazie — Thu, 05 Feb 2009 05:00:00 +0100

Various 3,5-(substituted diphenyl)-4,5-dihydro-pyrazole-1-carbothioic acid phenylamides were synthesized starting from substituted acetophenones. Structures of the compounds were confirmed on the basis of spectral data. The compounds were evaluated for their anticonvulsant and antidepressant activity. Interestingly, out of 26 compounds, four (3f, 3g, 3t, and 3u) were found to protect 100% of the animals in the MES screen at a dose of 25 mg/kg. They were also found to have appreciable anticonvulsant activity in scPTZ screen. Two compounds, 3j and 3o, significantly reduced the duration of the immobility time at 25 mg/kg dose, when compared to control. (Source: Archiv der Pharmazie)

Nitric Oxide Synthase Inhibition by Pentacycloundecane Conjugates of Aminoguanidine and Tryptamine

Archiv der Pharmazie — Thu, 29 Jan 2009 05:00:00 +0100

This paper describes the synthesis and in-vitro activity of pentacycloundecane-conjugated aminoguanidine and tryptamine analogues on nitric oxide synthase (NOS) using rat brain homogenate. Both aminoguanidine and tryptamine-derived NOS inhibitors show selectivity towards the inducible and neuronal isoforms of the NOS enzyme, but are weak inhibitors and complete inhibition of the enzyme occurs only at high millimolar concentrations. In view of the increased NOS inactivation observed with alkyl substitution of these structures, the present study aimed to evaluate the effect of the pentacycloundecane cage moiety as an alkyl substituent on the in vitro NOS inhibition of aminoguanidine and tryptamine compounds. Comparison of the IC50 values of aminoguanidine (IC50 = 2.306×10-3 M) and 8-imino-N...

Synthesis and Biological Evaluation of Distamycin Analogues - New Potential Anticancer Agents

Archiv der Pharmazie — Wed, 28 Jan 2009 05:00:00 +0100

Eight of analogues of distamycin, potential minor-groove binders, were synthesized and tested for in-vitro cytotoxicity towards human breast cancer cells MCF-7 and MDA-MB-231. The method of synthesis is simple and convenient. All of the compounds 1-8 showed antiproliferative and cytotoxic effects against both cell lines in the range 3.47 to 12.53 [mu]M for MDA-MB-231 and 4.35 to 12.66 [mu]M for MCF-7. All compounds demonstrated activity against DNA topoisomerases I and II at a concentration of 50 [mu]M. The ethidium bromide assay showed that these compounds bind to plasmid pBR322, yet weaker than distamycin. Further investigations concerning the mechanism of cytotoxicity are now in progress, but the IC50 values suggest that synthetic distamycin analogues with a free amino group, 3-4 and 7-...

Synthesis and In-Vitro Cytotoxicity Evaluation of Novel Naphtindolizinedione Derivatives, Part II: Improved Activity for Aza-Analogues

Archiv der Pharmazie — Wed, 28 Jan 2009 05:00:00 +0100

Our previous investigation on potential antitumor agents now got enriched by the evaluation of in-vitro activity against a full panel of NCI cancer cell lines for five new compounds. The concurrent presence in the molecular structure of a nitrogen atom in the aromatic system and a N,N-dimethylaminoethyl amide chain play a decisive role to enhance cytotoxicity. The N,N-anti compound 14 shows a higher activity than its N,N-syn isomer, exhibiting the best selective inhibition against the melanoma MALME-3M cell line, with a GI50-value (= 30 nM) corresponding to a 330-fold increase in activity compared to the corresponding deaza-analogue. Compound 14 is efficiently synthesized by aminolysis of the ester obtained as a single regio-isomer by an one-pot three-component procedure involving metal-as...

Fluorinated 1,2,4-Triazolo[1,5-a]pyrimidine-6-carboxylic Acid Derivatives as Antimycobacterial Agents

Archiv der Pharmazie — Wed, 28 Jan 2009 05:00:00 +0100

A series of fluorinated 1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives was designed and synthesized as fluoroquinolone analogues. The synthesized compounds were screened against Mycobacterium tuberculosis H37Rv strain at 6.25 [mu]g/mL concentration. Compound 4, the 7-oxo-2-(trifluoromethyl)-4,7-dihydro-1,2,4-triazolo[5,1-a]pyrimidine-6-carboxylic acid was found to be a very potent inhibitor, being able to inhibit 92% growth of M. tuberculosis H37Rv at 6.25 [mu]g/mL concentration. At the same time, it proofed to be nontoxic to mammalian cells (IC50 > 62.5 [mu]g/mL in VERO cells). (Source: Archiv der Pharmazie)

N-Benzylsalicylthioamides: Highly Active Potential Antituberculotics

Archiv der Pharmazie — Sat, 10 Jan 2009 05:00:00 +0100

A gseries of 29 new derivatives of N-benzylsalicylthioamides was synthesized and the compounds were tested for in-vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. The activity was analyzed by quantitative structure-activity relationship (QSAR). Activity increased with increasing lipophilicity and electron donating effect of the substituents in the acyl moiety and decreased with the electrophilic superdelocalizability of the molecules. The most active compounds are more active than isoniazid (INH) and are active against INH-resistant potential pathogenic strains of mycobacterium. (Source: Archiv der Pharmazie)

Synthesis and in-vitro Antimycobacterial Evaluation of 1-(Cyclopropyl/2,4-difluorophenyl/tert-butyl)-1,4-dihydro- 8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids

Archiv der Pharmazie — Fri, 09 Jan 2009 05:00:00 +0100

Fifty one newer 1-(cyclopropyl/2,4-difluorophenyl/tert-butyl)-1,4-dihydro-8-methyl-6-nitro-4-oxo-7-(substituted secondary amino)quinoline-3-carboxylic acids were synthesized from 1,3-dichloro-2-methylbenzene and evaluated for in-vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2). Among the synthesized compounds, 1-cyclopropyl-1,4-dihydro-7-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid 9p was found to be the most active compound in vitro with a MIC value of 0.39 [mu]M against MTB. Against MDR-TB, compound 7-(2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-1-cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-...

Synthesis and Anticonvulsant Activity of N-(2-Hydroxy-ethyl)amide Derivatives

Archiv der Pharmazie — Sat, 13 Dec 2008 05:00:00 +0100

A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better pro...

New 1H-Pyrazole-4-Carboxamides with Antiplatelet Activity

Archiv der Pharmazie — Wed, 03 Dec 2008 05:00:00 +0100

Nine title compounds were synthesized and investigated in the Born test for their antiplatelet activities against collagen, ADP, adrenaline, and platelet activating factor (PAF) as inducers of the aggregation. Using collagen three compounds with IC50 values below 100 [mu]M were found (3b, 3e, 3i). Activities in nanomolar concentrations were observed against ADP (3b, IC50 = 9.4 nM), adrenaline (3i, IC50 = 5.8 nM), and platelet activating factor (3e, IC50 = 0.45 nM). (Source: Archiv der Pharmazie)

Synthesis and Pharmacological Evaluation of N-(Dimethylamino)ethyl Derivatives of Benzo- and Pyridopyridazinones

Archiv der Pharmazie — Tue, 02 Dec 2008 05:00:00 +0100

New N-(dimethylamino)ethyl derivatives of phthalazinones and pyridopyridazinones 7, 9 were synthesized and assayed as potential analgesic agents in the hot-plate, tail-flick, and writhing tests. Pharmacological assay demonstrated that eight (in ten) of the newly synthesized compounds showed antinociceptive activity. Especially, 2-[2-(dimethylamino)ethyl]-4-phenyl-2H-phthalazin-1-one 7a showed remarkably higher antinociceptive activity in all tests. This is connected with influence on supraspinal, spinal, and peripheral structures. The decreased sensitivity to the pain stimulus in the hot-plate was higher than that of metamizole. (Source: Archiv der Pharmazie)

Synthesis and Antimicrobial Activity of Some Novel 2-[4-(Substituted Piperazin-/Piperidin-1-ylcarbonyl)phenyl]-1H-benzimidazole Derivatives

Archiv der Pharmazie — Tue, 02 Dec 2008 05:00:00 +0100

In this study, we report the synthesis and antimicrobial evaluation of several new 4-(1H-benzimidazol-2-yl)benzamides (11-30) and 5-chloro-1-(p-fluorobenzyl)-2-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-1H-benzimidazole (33). Compound 20 exhibited the best antibacterial activity with MIC value of 6.25 [mu]g/mL against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Significant antifungal activities were obtained with the compounds 13, 14, 18, 19, and 33 with MIC values of 3.12 [mu]g/mL which are close to fluconazole. (Source: Archiv der Pharmazie)

Antifungal and Antibacterial Activity of the Newly Synthesized 2-Xanthone Derivatives

Archiv der Pharmazie — Tue, 02 Dec 2008 05:00:00 +0100

A series of 2-substituted xanthone derivatives 8-20 containing selected allyl, cinnamyl, morpholine, and imidazole moieties were synthesized and tested for their antifungal and antibacterial in-vitro properties. Of the newly synthesized derivatives, ten revealed antifungal activity especially against Trichophyton mentagrophytes (the biggest inhibition zones ranged 35 mm for 11 and 13). 2-(3-(Allylamino)propoxy)-9H-xanthen-9-one hydrochloride 9 inhibited growth of all of the examined fungal species. Significant efficacy against evaluated yeasts and dermatophytes was also observed for 6-chloro-2-methyl-9H-xanthen-9-one derivatives 11-13 containing encyclic amine moieties. Additionally, compounds 9, 11, and 12 hindered development of bacteria species but in a lesser degree. They were efficaci...

Synthesis and Anticonvulsant Activity of New N-(Alkyl/Sub-stituted aryl)-N[prime]-[4-(5-cyclohexylamino)-1,3,4-thiadiazole-2-yl)phenyl]thioureas

Archiv der Pharmazie — Thu, 27 Nov 2008 05:00:00 +0100

A series of novel thiourea derivatives carrying the 5-cylohexylamino-1,3,4-thiadiazole moiety was synthesized and their anticonvulsant activity was evaluated. Structures of the synthesized compounds have been confirmed by IR, 1H-NMR, and elemental analysis. All of the compounds were administered at a dose of 50 mg/kg. Some of the active compounds have different effects in pentylenetetrazole (PTZ) and maximal electroshock (MES) tests, indicating the therapeutical potential in petit mal seizures, but not in grand mal seizures. Compounds 10, 11, 13, and 14 carrying 2-methylphenyl, 4-chlorophenyl, allyl, and 4-methylphenyl on the thiourea pharmacophore, increased the survival rate in the PTZ model. The ED50 values of the active compounds 10, 11, 13, and 14 were found 68.42, 43.75, 18.75 and 25...

Synthesis, Antiplatelet and Vasorelaxing Activities of Xanthone Derivatives

Archiv der Pharmazie — Wed, 26 Nov 2008 05:00:00 +0100

A series of [omega]-aminoalkoxylxanthones was synthesized and tested in vitro for their ability to inhibit platelet aggregation and cause vasorelaxing action. Compounds 4, 5, 12, 17, and 18 showed significant antiplatelet effects on thrombin-, arachidonic acid (AA)-, collagen-, and platelet activating factor (PAF)-induced washed rabbit platelet aggregation and exhibited inhibition of primary and secondary aggregation induced by adenosine-5'-diphosphate (ADP) in human platelet-rich-plasma (PRP). Compounds 4, 17, and 18 revealed vasorelaxing activities in rat thoracic aorta. We concluded that these compounds may be developed as new antithrombotic agents. (Source: Archiv der Pharmazie)

Leishmanicidal Evaluation of Novel Synthetic Chromenes

Archiv der Pharmazie — Sat, 15 Nov 2008 05:00:00 +0100

In the present paper, twelve chromenes were synthesized by coupling of 2,2,8,8-tetramethyl-8H-pyrano[2,3-f]chroman-4-one 1 with various aryl and benzylmagnesium chlorides. The synthetic compounds were examined for in-vitro activity against Leishmania major, and some of them displayed efficient anti-leishmanial activity. Among the compounds tested, compounds 9 (4-(2-chloro-benzylidene)-2,2,8,8-tetramethyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromene 9a and 4-(2-chloro-benzyl)-2,2,8,8-tetramethyl-2H,8H-pyrano[2,3-f]chromene 9b) were the most active with an inhibitory activity of 73.4%. (Source: Archiv der Pharmazie)

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

Archiv der Pharmazie — Thu, 13 Nov 2008 05:00:00 +0100

G-protein-coupled receptors (GPCRs) respond to various physiological ligands such as photons, ions, and small molecules that include amines, fatty acids, and amino acids to peptides, proteins and steroids. Therefore, this family of proteins represents an attractive target for biopharmaceutical research [1]. The physiological role of fatty acids and other lipid molecules as important signal mediators is well studied in various metabolic pathways [2]. Acute administration of free fatty acids (FFAs) stimulates insulin release. Conversely, chronic exposure to high levels of free fatty acids leads to impairment of [beta] cell function and lipotoxicity. However, the receptors through which these fatty acids and lipids act were unknown, until the identification of fatty acid binding receptors: GP...

Synthesis and In-Vitro Activity of New 1[beta]-Methylcarbapenem Derivatives as Antibacterial Agents

Archiv der Pharmazie — Thu, 13 Nov 2008 05:00:00 +0100

The synthesis of a new series of 1[beta]-methylcarbapenems having pyrrolidine and piperidine moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. A particular compound III b having an oxime-pyrrolidine moiety showed the most potent antibacterial activity. (Source: Archiv der Pharmazie)

New 1-Benzyl-4-hydroxypiperidine Derivatives as Non-imidazole Histamine H3 Receptor Antagonists

Archiv der Pharmazie — Thu, 13 Nov 2008 05:00:00 +0100

A series of 1-benzyl-4-(3-aminopropyloxy)piperidine and 1-benzyl-4-(5-aminopentyloxy)piperidine derivatives has been prepared. The 1-benzyl-4-hydroxypiperidine derivatives obtained were evaluated for their affinities at recombinant human histamine H3 receptor, stably expressed in HEK 293T cells. All compounds investigated show moderate to pronounced in-vitro affinities. The most potent antagonists in this series 9b2 (hH3R, pKi = 7.09), 9b1 (hH3R, pKi = 6.78), 9b5 (hH3R, pKi = 6.99), and 9b6 (hH3R, pKi = 6.97) were also tested in vitro as H3 receptor antagonists - the electrically evoked contraction of the guinea-pig jejunum. The histaminergic H1 antagonism of selected compounds 9b1, 9b2, and 9b4-9b6 was established on the isolated guinea-pig ileum by conventional methods; the pA2 values we...

Synthesis and Positive Inotropic Evaluation of 2-(4-(4-Substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)-acetamides

Archiv der Pharmazie — Thu, 13 Nov 2008 05:00:00 +0100

In an attempt to search for more potent positive inotropic agents, a series of 2-(4-(4-substituted benzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamides was synthesized and their positive inotropic activities were evaluated by measuring left atrium stroke volume on isolated rabbit-heart preparations. Several compounds showed favorable activity compared with the standard drug Milrinone among which 2-(4-(4-(2-chlorobenzyloxy)-3-methoxybenzyl)-1,4-diazepan-1-yl)-N-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl)acetamide 6e was found to have the most desirable potency with the 6.79 ± 0.18% increased stroke volume (Milrinone: 1.67 ± 0.64%) at a concentration of 1×10-5 M in our in-vitro study. The chronotropic effects o...

Highly Active Potential Antituberculotics: 3-(4-Alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones and 3-(4-Alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dihiones Substituted in Ring-B by Halogen

Archiv der Pharmazie — Wed, 12 Nov 2008 05:00:00 +0100

A series of 6-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 7-chloro-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-bromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6,8-dibromo-3-(4-alkylphenyl)-4-thioxo-2H-1,3-benzoxazine-2(3H)-ones, 6-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 7-chloro-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones, 6-bromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones and 6,8-dibromo-3-(4-alkylphenyl)-2H-1,3-benzoxazine-2,4(3H)-dithiones was synthesized. The compounds exhibited in-vitro activity against Mycobacterium tuberculosis, M. kansasii (two strains), and M. avium. 6-bromo-3-(4-propylphenyl)-4-thioxo-2H-1,3-benzoxazin-2(3H)-one and 6-bromo-3-(4-propylphenyl)-2H-1,3-benzoxazin-2,4(3...

Synthesis and Anticonvulsant Activity of 5-Phenyl-[1,2,4]-triazolo[4,3-a]quinolines

Archiv der Pharmazie — Wed, 12 Nov 2008 05:00:00 +0100

A series of novel 5-phenyl-[1,2,4]-triazolo[4,3-a]quinoline derivatives was synthesized by the cyclization of 2-chloro-4-phenyl-1,2-dihydronaphthalene with formohydrazide. The starting material 2-chloro-4-phenyl-1,2-dihydronaphthalene was synthesized from ethyl-3-oxo-3-phenylpropanoate and substituted aniline. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The maximal electroshock test showed that 7-hexyloxy-5-phenyl-[1,2,4]-triazolo[4,3-a]quinoline 4f was found to be the most potent compound with an ED50 value of 6.5 mg/kg and a protective index (PI = ED50 / TD50) value of 35.1, which was much higher than the PI of the reference drug phenytoin. (Source: Archiv der Pharmazi...

Convenient Synthesis and Antimicrobial Activity of New 3-Substituted 5-(Benzofuran-2-yl)-pyrazole Derivatives

Archiv der Pharmazie — Thu, 25 Sep 2008 04:00:00 +0100

The reaction of ethyl 4-(benzofuran-2-yl)-2,4-dioxobutanoate 2 with two moles of hydrazine hydrate afforded 5-(benzofuran-2-yl)-1H-pyrazole-3-carbohydrazide 4a, while its reaction with equimolar amount of phenylhydrazine gave ester 3b which then converted to 5-(benzofuran-2-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide 4b. Various new compounds such as imides 5 and 6, acyl hydrazones 7 and 8, bi-pyrazoles 9-12, and 1,3-thiazole derivatives 14 and 15 were prepared from carbohydrazide derivatives 4a, b. The new compounds are tested for their antimicrobial activity. Compounds 2, 5, 7, and 8 showed antifungal activities against C. albicans. Also, compounds 2, 6, 8, and 15 showed antibacterial activities. (Source: Archiv der Pharmazie)

Synthesis and SAR Study of T-Type Calcium Channel Blockers. Part II