Synthesis and anti‐HIV activity of new chiral 1,2,4‐triazoles and 1,3,4‐thiadiazoles

5‐substituted 4‐(4‐chlorophenyl)‐4H‐1,2,4‐triazol‐3‐thiones 3 and 2‐substituted 5‐(4‐chlorophenylamino)‐1,3,4‐thiadiazoles 4 were prepared from the intermediate thiosemicarbazides 2 under basic and acidic conditions, respectively. The thiosemicarbazides, in turn, were prepared by the reaction of hydrazides 1 with 4‐chlorophenylisothiocyanate in MeOH. Some of the new synthesized compounds were assayed against HIV‐1 and HIV‐2 in MT‐4 cells. All the compounds were inactive except 3f , which showed an EC₅₀ value of 23.9 μg/mL and 9.9 μg/mL against HIV‐1 and HIV‐2 with a therapeutic index of 3 and 7, respectively. It means that compound 3f was cytotoxic to MT‐4 cells at CC₅₀ of 72.7 μg/mL in both strains. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:316–322, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20282     

Synthesis and antiviral evaluation of 1,3-dimethyl-6-(1H-1,2,3-triazol-1-YL)pyrimidine-2,4(1H,3H)-dione derivatives

Some 6-(1H-1,2,3-triazol-1-yl)pyrimidine-2,4(1H,3H)-dione derivatives were synthesized via the reaction of 6-azido-1,3-dimethyluracil with ethyl acetoacetate in the presence of sodium ethoxide. The antiviral activities of these compounds against Hepatitis A virus (HAV, MBB-cell culture adapted strain) and Herpes simples virus type-1 (HSV-1) were tested.     

Amino Acid Derivatives,IV [1]: Synthesis and Antiviral Evaluation of New α-Amino Acid Esters Bearing Methyl β-<Emphasis Type="SmallCaps">d</Emphasis>-Ribofuranoside Side Chain

Summary. Methyl 2,3-O-isopropylidene-β-d-ribofuranoside was synthesized and oxidized with HIO₄ to afford the corresponding carboxylic acid. The latter was coupled with the appropriate acylated amino acids in the presence of HOBt and DDC as coupling reagents to give the corresponding amides. The methyl acetate derivative was hydrolyzed with 2 N KOH/MeOH to the corresponding carboxylic acid, which was coupled with l-glycine methyl ester to furnish the amide. Deprotection was carried out with 70% AcOH at reflux temperature. The prepared glycopeptides were tested for antiviral activity against Herpes Simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV). The plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds.     

Amino Acid Derivatives, IV [1]: Synthesis and Antiviral Evaluation of New α-Amino Acid Esters Bearing Methyl β-d -Ribofuranoside Side Chain

Methyl 2,3-O-isopropylidene-β-d-ribofuranoside was synthesized and oxidized with HIO₄ to afford the corresponding carboxylic acid. The latter was coupled with the appropriate acylated amino acids in the presence of HOBt and DDC as coupling reagents to give the corresponding amides. The methyl acetate derivative was hydrolyzed with 2 N KOH/MeOH to the corresponding carboxylic acid, which was coupled with l-glycine methyl ester to furnish the amide. Deprotection was carried out with 70% AcOH at reflux temperature. The prepared glycopeptides were tested for antiviral activity against Herpes Simplex virus type-1 (HSV-1) and hepatitis-A virus (HAV). The plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds.     

Synthesis,Spectral Characterization,and In Vitro Biological Evaluation of Some Novel Isoquinolinone‐based Heterocycles as Potential Antitumor Agents

A series of new N‐substituted isoquinolin‐1,3‐dione derivatives were prepared, starting from reaction of (Z)‐4‐((E)‐3‐phenylallylidene)isochromane‐1,3‐dione 4 with different nitrogen nucleophiles. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, ¹H NMR, ¹³C NMR, and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of three human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, colon cancer HCT‐116, and mammary gland breast MCF‐7. Also, they were tested as antioxidants. Some of the tested compounds showed very strong cytotoxic activity with respect to the standard.     

Synthesis and Antiviral Evaluation of Some 5‐N‐Arylaminomethyl‐2‐glycosylsulphanyl‐1,3,4‐oxadiazoles and Their Analogs against Hepatitis A and Herpes Simplex Viruses

N‐Arylaminomethyl‐3H‐1,3,4‐oxadiazole‐2‐thiones 2a,b were prepared from the corresponding N‐arylglycinoylhydrazides. A number of their thioglycoside derivatives 4–7a–c and S‐functionalized analogs 8–11a,b were synthesized by the reaction with different acetobromosugars and acyclic hydroxyalkylating agents. The antiviral activity of a number of the synthesized compounds against herpes simplex virus type 1 (HSV‐1) and hepatitis A virus (HAV) was evaluated. Compounds 5a and 5b showed promising results against HAV.     

Reactions with 3,6‐diaminothieno[2,3‐b]‐pyridines: Synthesis and characterization of several new fused pyridine heterocycles

6‐Aminopyridine‐2(1H)thiones 1 reacting with α‐halo‐compounds 2a–c afforded the alkylthiopyridine derivatives 3a–c which in turn cyclized to the corresponding thieno[2,3‐b]pyridine derivatives 4a–c . Several thieno[2,3‐b]pyridine derivatives 7, 16, 19 , pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine derivatives 6a,b, 11a–c, 21 and pyrido[3′,2′:4,5]thieno[3,2‐c]pyridazine derivatives 13, 17 were prepared starting from compounds 4a–c . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:405–413, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20313     

Synthesis and antitumor activity evaluation of some schiff bases derived from 2‐aminothiazole derivatives

A novel series of thiazolyl Schiff bases have been designed and synthesized. These new compounds were obtained by the reactions of 4‐phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl) thiazol‐2‐amine and substituted aromatic aldehydes and were characterized on the basis of ¹H NMR and elemental analysis. The newly synthesized compounds were screened for their antitumor activity against human cancer cell lines, namely HL‐60 (leukemia), BGC‐823 (stomach), and HEP‐2 (larynx cancer). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:55–59, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20256     

Substituted pyridopyrimidinones, 1: Convenient PTC alkylation and halogenation of 2‐hydroxy‐4H‐pyrido[1,2‐a]pyrimidin‐4‐one

Alkylation of 2‐hydroxy‐4H‐pyrido[1,2‐a]pyrimidin‐4‐one ( 1 ) was investigated under solid–liquid phase transfer catalysis conditions (PTC), using tetrabutylammonium bromide and potassium carbonate. The reaction with alkyl halides led to the formation of various 2‐alkoxy products, in fair yields. Reaction of compound 1 with epichlorohydrin and chloroacetonitrile, under the same PTC conditions, afforded novel O1,O3‐disubstituted glycerol and oxazolopyridopyrimidone betaine derivatives, respectively. Some 3‐halo‐, 3,3‐dihalo, and/or 2,3‐dihalopyrido[1,2‐a]pyrimidines were also prepared using different halogenating agents at different reaction conditions. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:19–27, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20245     

Microwave‐assisted synthesis and anti‐HIV activity of new benzenesulfonamides bearing 2,5‐disubstituted‐1,3,4‐oxadiazole moiety

New benzenesulfonamides, most of which are chiral, incorporating 1,3,4‐oxadiazole, and selected amino acid entities have been synthesized, using the microwave irradiation method. Most of the synthesized compounds were tested against HIV activity. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:425–431, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20316     

Synthesis,structures, and biological activities of new 1H‐1,2,4‐triazole derivatives containing pyridine unit

Fourteen new 1H‐1,2,4‐triazole derivatives containing pyridine moiety were synthesized by condensation of 1‐(pyridine‐3‐yl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethanone with aryl aldehydes, and their reaction conditions were studied. The title compounds were screened for their antibacterial and plant growth regulatory activities. The screening data revealed that most of the compounds showed some antifungal and plant growth regulatory activities. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:376–380, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20308     

Palladium‐mediated synthesis of novel nimesulide derivatives

Synthesis of a series of compounds structurally related to the anti‐inflammatory agent nimesulide has been accomplished via Pd‐catalyzed C? C bond forming reactions. Thus 4‐iodo derivative, prepared from nimesulide, participated in Sonogashira (copper‐free), Heck and Suzuki coupling reactions to afford the corresponding alkynyl, alkenyl and aryl substituted products. Some of the compounds synthesized were tested for anti‐inflammatory activities in vivo. Copyright © 2010 John Wiley & Sons, Ltd.     

Design,synthesis, and antimicrobial activity of some new pyrazolo[3,4‐d]pyrimidines

2‐Benzyl‐ and 2‐aryloxymethyl‐3‐amino‐1‐phenyl‐pyrazolo[3,4‐d]pyrimidine‐4‐ones 5a–f have been synthesized by reacting the corresponding arylacetylamino derivatives 3a–f with hydrazine hydrate. Thionation of compounds 5d–f by action of P₂S₅ in pyridine yielded 2‐aryloxy‐methyl‐3‐amino‐1‐pheny‐lpyrazolo[3,4‐d]pyrimidin‐4‐thions 6a–c . 2,5‐Diphenyl‐2,3‐dihydro‐1H‐pyrazolo[5′,1′:4:5]pyrazolo[3,4‐d]pyrimidine‐8‐one ( 8 ) was also obtained via reaction of ethyl‐2‐cinnamoylamino‐1‐phenyl‐pyrazole‐4‐car‐boxylate ( 7 ) with hydrazine hydrate. The prepared compounds were screened in vitro for their antimicrobial activity. Some of the tested compounds were found to be active at 100 μg/ml compared with reference compounds (Ampicillin and Trivid) as antibacterial agents and claforan as antifungal agent. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:530–534, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10187     

Synthesis and biological activities of novel bis‐heterocyclic pyrrodiazole derivatives

Novel structures of bis‐heterocyclic pyrrodiazole derivatives containing pyrazole were designed and synthesized. The title compounds were characterized by ¹H NMR, IR, MS, and elemental analysis. Biological activities of three intermediate compounds and 25 pyrrodiazole derivatives were tested in vivo and in vitro. Some of the title compounds exhibited certain herbicidal activities against barnyardgrass and rape. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:21–27, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20369     

Synthesis and antiviral activity of new substituted pyrimidine glycosides

A number of N‐substituted pyrimidine glycosides were synthesized by coupling reaction of the pyrimidine base with acetobromosugars followed by deprotection. The synthesized compounds were tested for their antiviral activity against Hepatitis B Virus (HBV). Plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with tested compounds which showed moderate to high anti viral activities. J. Heterocyclic Chem., (2011).     

Synthesis and in vitro antibacterial evaluation of 1‐substituted‐4‐ethoxycarbonylmethylthiosemicarbazides and products of their dehydrocyclization

A series of s‐triazoles and thiohydantoines were synthesized by dehydrocyclization of 1‐substituted‐4‐ethoxycarbonylmethylthiosemicarbazides. The molecular structure proposed for s‐triazoles was confirmed by the X‐ray crystal structure analysis of one compound that was prone to crystallization. All compounds were tested in vitro for their antibacterial activity. Some of them showed low levels of activity against Gram‐positive species, MIC range 100–400 μg/mL or higher. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:131–138, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20597     

Synthesis of some novel imidazolidine derivatives and their metal complexes with biological and antitumor activity

Halogenated imidazo(pyrazine,[1,4]diazocine and quinoxaline), 9,10‐anthraquinone‐ [6,7‐e], phenanthroline[5,6‐e] {imidazo[4,5‐b]pyrazine}, and naphtho[1,8‐ef]imidazo[4,5‐b][1,4] diazipen were obtained through interaction of imidazolidineiminothiones with the corresponding diamino compounds. Imidazo[4,5‐e] triazine and pyrrolo[2,3‐d]imidazole were prepared when the iminothiones were reacted with thiocarbohydrazide and with ethylphenyl acetate, separately. Some of the synthesized compounds exhibited better biological and antitumor activities. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:634–647, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20244     

New bis(diphenylphosphino)aniline derivatives: Synthesis and spectroscopic characterization

Six new multidentate bis(diphenyl‐phosphino)amine [R–N(PPh₂)₂] ligands have been prepared from the reaction of aniline derivatives, R–NH₂, with Ph₂PCl in the presence of triethylamine. All of the compounds were obtained in good yields and were characterized by NMR, IR, and microanalysis. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:613–616, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20362     

Synthesis,structure and characterization of some Schiff bases bearing phenylferrocene

Some novel Schiff bases bearing phenylferrocene were synthesized by condensation reaction of 4‐ferrocenylaniline with different aromatic aldehydes. The compounds prepared were characterized by spectroscopic methods (IR, UV–visible, ¹H and ¹³C NMR) and elemental analysis. The single crystal analysis of compound F1 [monoclinic, space group, P2₁/c (no. 14), a = 19.858(2), b = 7.416(2), c = 12.095(5) Å, β = 106.257(14) ] indicates a trans imine bond with a bond length of 1.270(2) Å, typical of a carbon‐nitrogen double bond. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of acyclic nucleoside phosphonates as antiviral compounds

Reaction of 6‐chloropyrimidines with diethyl [(2‐aminoethoxy)methyl]phosphonate allows for a ready access to acyclic nucleoside phosphonates. A series of 5‐substituted pyrimidines bearing a phosphonate side chain at position 6 were synthesized and tested against herpes simplex viruses (HSV‐1 and HSV‐2) and human immunodeficiency virus (HIV‐1). Some compounds showed weak antiviral activity against HSV‐1.