Publications

Wear behaviour of conventional and rapid tooling mould materials

No abstract is provided for this article.

Synthesis and antiherpes virus activity of 1,5-anhydrohexitol nucleosides

The synthesis of 1,5-anhydrohexitol nucleosides is described. These nucleoside analogues were obtained by alkylation of the heterocyclic bases with the tosylate 10 or by alkylation of the bases with the alcohol 12 under Mitsunobu conditions. The compounds were evaluated for antiviral and cytostatic activity. Highly selective activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) was noted for 1,5-anhydro-2,3-dideoxy-2-(5-iodouracil-1-yl)-D-arabino-hexitol 4b at a concentration of 0.07 microgram/mL. This activity must be dependent on a specific phosphorylation by the virus-encoded thymidine kinase (TK), since compound 4b was inactive against TK-deficient mutants of HSV-1. The corresponding cytosine 4c and guanine 4e analogues showed activity against HSV-1, HSV-2, and other herpes viruses (i.e. cytomegalovirus, varicella-zoster virus) at concentrations well below the cytotoxicity threshold (2 and 20 micrograms/mL, respectively). At these concentrations, compounds 4c and 4e proved also inhibitory to the growth of human T-cells (i.e. MT-4, CEM, MOLT-4).

Resistance development of human immunodeficiency virus type 1 towards mannose-specific plant lectins in cell culture

Synthesis of Purinyl<i>homo</i>-Carbonucleoside Derivatives of 2-Benzylcyclopenta[<i>c</i>]pyrazol

The first members of a new class of carbocyclic nucleoside analogs were synthesized via key intermediate (±)-(cis)-2-bencylcyclopenta[c]pyrazole-4,6-dimethanol, which was obtained from the easily prepared starting compound (±)-(exo,exo)-5,6-isopropylidenedioxy-4,5,6,7-tetrahydro-4,7-methano-2H-indazole by a reaction sequence in which the key step was a one-pot oxidative cleavage of glycol 9 and reduction of the resulting dialdehyde with NaBH4. Purine moieties were coupled by nucleophilic displacement following mesylation of the latter. The new compounds 15 and 17 are active against cytomagalovirus and varicella-zoster virus at subcytotoxical concentrations.

Synthesis of penicillamine- and cysteine-containing nucleoamino acids as potential antivirals and aminopeptidase B inhibitors

Nucleoamino acids, wherein D- and L-penicillamine and D-and L-cysteine are attached to uridine or thymidine through a carboxylic ester linkage, have been synthesized and evaluated as antivirals and aminopeptidase B (AP-B) inhibitors. The coupling of the α-amino-β-mercapto acids, N,S-protected as N-formylthiazolidines, to 2′,3′-O-isopropylideneuridine, 3′-O-acetylthymidine, 5′-O-tritylthymidine, and thymidine was achieved via the mixed anhydride formed from N,N-bis-(2-oxooxazolidin-3-yl)phosphorodiamidic chloride and the corresponding protected amino acid in the presence of 4-(dimethylamino)pyridine. Treatment of the protected compounds with 1 mol dm–3-HCl in refluxing MeOH, under argon, afforded the corresponding deprotected nucleoamino acids free of racemization. Neither the compounds herein described nor D-penicillamine showed anti-HIV-1 activity in MT-4 cells or antiviral activity against some other viruses at concentrations below the cytotoxicity threshold. Penicillamine and cysteine monoesters were equipotent with the corresponding free amino acid in inhibiting AP-B with an IC50 in the 10–4 mol dm–3 range, while the bis-(α-amino-β-mercaptoacyl)thymidine derivatives were approximately twice as potent as the monoesters.

Comparison of Aspect Ratio, Accuracy and Repeatability of a Laser Line Scanning Probe and a Tactile Probe

No abstract is provided for this article.

Synthesis and Antiviral Activity of Novel Fluorinated 2′,3′‐Dideoxynucleosides.

Abstract For Abstract see ChemInform Abstract in Full Text.

Discovery of diarylpyrimidine derivatives bearing piperazine sulfonyl as potent HIV-1 nonnucleoside reverse transcriptase inhibitors

HIV-1 reverse transcriptase is one of the most attractive targets for the treatment of AIDS. However, the rapid emergence of drug-resistant strains and unsatisfactory drug-like properties seriously limit the clinical application of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Here we show that a series of piperazine sulfonyl-bearing diarylpyrimidine-based NNRTIs were designed to improve the potency against wild-type and NNRTI-resistant strains by enhancing backbone-binding interactions. Among them, compound 18b1 demonstrates single-digit nanomolar potency against the wild-type and five mutant HIV-1 strains, which is significantly better than the approved drug etravirine. The co-crystal structure analysis and molecular dynamics simulation studies were conducted to explain the broad-spectrum inhibitory activity of 18b1 against reverse transcriptase variants. Besides, compound 18b1 demonstrates improved water solubility, cytochrome P450 liability, and other pharmacokinetic properties compared to the currently approved diarylpyrimidine (DAPY) NNRTIs. Therefore, we consider compound 18b1 a potential lead compound worthy of further study.

Binding Optimization through Coordination Chemistry: CXCR4 Chemokine Receptor Antagonists from Ultrarigid Metal Complexes

A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties to the receptor protein in comparison to the drug AMD3100 (Plerixafor, Mozobil). The interaction of the metallodrug has been optimized by using ultrarigid chelator units that offer an equatorial site for coordination to the amino acid side chains of the protein. Binding competition assays with anti-CXCR4 antibodies show that the new compound stays bound longer and it has improved anti-HIV potency in vitro (EC(50) = 4.3 nM). X-ray structural studies using acetate as a model for carboxylate amino acid side chains indicate the nature of the coordination interaction.

Charpy impact testing of metallic selective laser melting parts

Selective laser melting (SLM) is a layer-additive manufacturing technology which makes it possible to create fully functional parts directly from standard metals without any intermediate binders or any additional post-processing steps. During SLM, a high-intensity laser beam selectively scans a powder bed according to the CAD data of the part to be produced and powder particles are completely melted. SLM is capable of producing near full density parts with an almost infinite geometric freedom. However, the mechanical properties obtained with SLM may differ from the ones of bulk material. In this study, Charpy impact tests are applied on the samples produced by SLM from different materials; Ti-6A1-4V, AISI 316L (X2CrNiMo18-14-3) and maraging steel 300 (X3CoMoTi18-9-5). The influence of the building axis as well as of various heat treatments applied on the samples after SLM is investigated. The evolution of the microstructures of the sample parts is also studied.

Synthesis and Biological Evaluation of a Series of Substituted 2-Pyridine C-Nucleosides

Abstract Condensation of 2-lithio-pyridine and the four isomers of 2-lithio-picoline with 2,4:3,5-di-O-benzylidene-aldehydo-D-ribose, gives the D-allo- and D-altro-isomers of 2-(2,4:3,5-di-O-benzylidenepentitol-l-yl)-pyridine and the corresponding isomers of the four picoline-addition products in a good yields. On treatment with dilute hydrochloric acid or formic acid the corresponding pentitols were obtained. None of these pentitols showed an inhibitory effect on virus replication or tumor cell growth.

Synthesis and Evaluation of Novel 4‐Substituted Styryl Quinazolines as Potential Antimicrobial Agents

In an attempt to afford possible antibacterial and anti-human immunodeficiency virus (HIV) agents, a series of 22 novel styryl quinazoline-based heterocyclic entities were designed and synthesized. Various substituted aryl urea and thiourea cores were incorporated at position 4 of quinazoline, followed by styrylation of position 2, aiming at an augmented biological potential. The synthesized compounds were well characterized through IR, (1) H NMR, (13) C NMR and elemental analyses. All compounds were screened for their in vitro anti-HIV activity against the HIV-1 (IIIB) and HIV-2 (ROD) strains. The antibacterial activity was also evaluated against various pathogenic Gram-positive and Gram-negative bacterial strains.

Predicting process induced temperature effects on CO2 laser cutting

No abstract is provided for this article.

Sensitive, reproducible and convenient fluorometric assay for the in vitro evaluation of anticytomegalovirus agents

ChemInform Abstract: Synthesis and Antitumor Activities of Novel Pyrimidine Derivatives of 2,3‐O,O‐Dibenzyl‐6‐deoxy‐L‐ascorbic Acid and 4,5‐Didehydro‐5,6‐dideoxy‐L‐ascorbic Acid.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

92 Ara-A-5′-phenyl methoxy alaninyl phosphate as a prodrug of the adenine arabinoside -monophosphate: synthesis and anti viral evaluation

Optimization and Dynamic Adaptation of the Cutter Inclination during Five-Axis Milling of Sculptured Surfaces

Five axis milling allows to machine free form surfaces with cylindrical or toric cutters instead of ball nose cutter. This drastically reduces the machining time. Commercial CAM modules however require the NC-programmer to specify the appropriate inclination of the tool with respect to the work piece surface normal. This is difficult especially for complex parts with vaving surface curvature. This paper presents five axis CAM software which vanes the tool inclination during the tool path generation, in order to achieve the best combination of scallop height, workpiece accuracy, surface roughness and machining cost. Machining time to produce some free form workpieces, given a maximum scallop height, could be reduced by 50%.

New Approaches Toward anti‐HIV Chemotherapy

Abstract For Abstract see ChemInform Abstract in Full Text.