Health safety of parabens evaluated by selected in vitro methods.

Seven selected parabens (4 allowed, 3 banned in cosmetics) were tested in order to confirm and expand historical data on their toxicological properties and safety. The aim was to apply novel in vitro methods, which have been sufficiently technically and scientifically validated for the purposes of toxicological testing of chemicals. The study included several toxicological endpoints such as skin/eye irritation, skin sensitization, endocrine disruption and genotoxicity.

Imidazo[1,2-c]pyrimidin-5(6H)-one inhibitors of CDK2: Synthesis, kinase inhibition and co-crystal structure.

Pharmacological inhibition of cyclin-dependent kinases has emerged as a possible treatment option for various cancer types. We recently identified substituted imidazo[1,2-c]pyrimidin-5(6H)-ones as inhibitors of cyclin-dependent kinase 2 (CDK2). Here, we report the synthesis of derivatives modified at positions 2, 3, 6 or 8 prepared using Suzuki-Miyaura cross-coupling, halogenation, Dimroth-type rearrangement and alkylation as the main synthetic methods.

New Mono- and Diesters with Imidazoquinolinone Ring- Synthesis, Structure Characterization, and Molecular Modeling.

The objective of the studies was to synthesize and characterize new mono- and diesters with an imidazoquinolin-2-one ring with the use of 2,3-dihydro-2-thioxo-1H-imidazo[4 ,5-c]-quinolin-4(5)-ones and ethyl bromoacetate. The products were isolated at high yield and characterized by instrumental methods (IR, H-, C-, and N- NMR, MS-ESI, HR-MS, EA). In order to clarify the places of substitution and the structure of the derivatives obtained, molecular modeling of substrates and products was performed.

Imidazo[1,2-c]pyrimidin-5(6H)-one as a novel core of cyclin-dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring.

We report on the synthesis, activity testing, docking, and quantum mechanical scoring of novel imidazo[1,2-c]pyrimidin-5(6H)-one scaffold for cyclin-dependent kinase 2 (CDK2) inhibition. A series of 26 compounds substituted with aromatic moieties at position 8 has been tested in in vitro enzyme assays and shown to inhibit CDK2. 2D structure-activity relationships have ascertained that small substituents at position 8 (up to the size of naphtyl or methoxyphenyl) generally lead to single-digit micromolar IC values, whereas bigger substituents (substituted biphenyls) decreased the compounds' activities.

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents.

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I/HIO gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions.

Homolytic, Heterolytic, Mesolytic - As You Like It: Steering the Cleavage of a HC(sp )-C(sp )H Bond in Bis(1H-2,1-benzazaborole) Derivatives.

A set of (3,3')-bis(1-Ph-2-R-1H-2,1-benzazaborole) compounds, in which R=tBu (Bab-tBu) , R=Dipp (Bab-Dipp) or R=tBu and Dipp (Bab-Dipp)(Bab-tBu), was synthesized and fully characterized using H, B, C, and N NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The central HC(sp )-C(sp )H bond with restricted rotation at the junction of both 1H-2,1-benzazaborole rings displayed an intriguing reactivity. It was demonstrated that this bond is easily mesolytically cleaved using alkali metals to form the respective aromatic 1Ph-2R-1H-2,1-benzazaborolyl anions M (THF) (Bab-tBu) (M=Li, Na, K) and K (THF) (Bab-Dipp) .

Germylenes and stannylenes stabilized within N2PE rings (E = Ge or Sn): combined experimental and theoretical study.

The deprotonation of aminophosphanes PhP(NHR)2 (R = t-Bu or Dip; Dip = 2,6-i-Pr2C6H3) and t-BuP(NHDip)2 using n-BuLi gave, depending on the stoichiometry, both the dilithium compounds {[PhP(Nt-Bu)2]Li2}2 (), [PhP(Nt-Bu)(NDip)]Li2·(Et2O) (), [t-BuP(NDip)2]Li2·(Et2O)2 () and [t-BuP(NDip)2]Li2·(tmeda)2 (), and the monolithium compounds [PhP(NHt-Bu)(NR)]Li·(tmeda) (R = t-Bu , Dip ) and [t-BuP(NHDip)(NDip)]Li·(tmeda) (). Treatment of , and with GeCl2·dioxane or SnCl2 in a 1 : 1 stoichiometric ratio gave the corresponding tetrylenes [PhP(Nt-Bu)2]E (E = Ge , Sn ), [PhP(Nt-Bu)(NDip)]Ge () and [t-BuP(NDip)2]E (E = Ge , Sn ). The heteroleptic germylene [Ph(H)P(Nt-Bu)2]GeCl () was obtained by the reaction of the monolithium compound [PhP(NHt-Bu)(Nt-Bu)]Li·(tmeda) () with GeCl2·dioxane in a 1 : 1 stoichiometric ratio, as a result of a spontaneous NH → PH tautomeric shift in the ligand backbone.

Analytical Characterization of Erythritol Tetranitrate, an Improvised Explosive.

Erythritol tetranitrate (ETN), an ester of nitric acid and erythritol, is a solid crystalline explosive with high explosive performance. Although it has never been used in any industrial or military application, it has become one of the most prepared and misused improvise explosives. In this study, several analytical techniques were explored to facilitate analysis in forensic laboratories.

From Stiba- and Bismaheteroboroxines to N,C,N-Chelated Diorganoantimony(III) and Bismuth(III) Cations-An Unexpected Case of Aryl Group Migration.

An unprecedented transfer of an aryl group from boron to Sb and Bi is observed in the reaction of heteroboroxines of general formula ArM[(OBR)2O] [where M = Sb, Bi; Ar = C6H3-2,6-(CH2NMe2)2; R = Ph, 4-CF3C6H4, 4-BrC6H4] with corresponding boronic acid RB(OH)2. Using this procedure, ion pairs [ArMR](+)[R4B5O6](-) were obtained [where M = Sb and R = Ph (4), 4-CF3C6H4 (5), 4-BrC6H4 (6); where M = Bi and R = Ph (7), 4-CF3C6H4 (8), 4-BrC6H4 (9)]. All compounds were characterized using elemental analysis, electrospray ionization mass spectrometry, and multinuclear NMR spectroscopy, and molecular structures of 4 and 7 were determined by single-crystal X-ray diffraction analysis.

An anomalous course of the reduction of 2-(3-oxo-3,4-dihydroquinoxalin-2-yl)benzene diazonium salt: a reinvestigation.

The 1H,13C and 15N NMR spectra of the reduction product of 2-(3-oxo-3,4-dihydroquinoxalin-2-yl)benzene diazonium salt with sodium sulfite were measured and analysed. It is shown that the reaction product corresponds to 1-(indazol-3-yl)-1,2-dihydro-benzimidazol-2-on and not 6H-quinoxalino[1,2-c] [1,2,3]benzotriazin-12(13H)-one as published previously. The correctness of the structure was confirmed by an independent synthesis.

15N NMR spectra of some ionic liquids based on 1,3-disubstituted imidazolium cations.

15N NMR spectra of twelve neat ionic liquids derived from 1,3-disubstituted imidazolium salts were measured, and effects of nitrogen atoms substitution, type of anions and influence of solvents used for dilution of neat ionic liquids were studied. Changes in charge distribution are discussed.

Cytogenetic effects of acrylamide in the bone marrow of mice.

A single i.p. injection of 100 mg/kg acrylamide monomer elevated the frequency of chromosome aberrations and micronucleated polychromatic erythrocytes in the bone marrow of male ICR mice.

Benzidine and 3,3'-dichlorobenzidine (DCB) induce micronuclei in the bone marrow and the fetal liver of mice after gavage.

Single oral dose of benzidine (300 mg/kg) and DCB (1000 mg/kg) to male ICR mice elicited positive response in the bone marrow micronucleus test. In the transplacental micronucleus test, the compounds were administered to pregnant females in the same manner. A significant increase in the frequency of micronuclei occurred in the fetal liver, but not in the bone marrow of mothers.