Compound 1 [(E)-4-fluoro-N-(6-((4-(2-hydroxypropan-2-yl)piperidin1-yl)methyl)-1-((1S,4S)-4-(isopropylcarbamoyl)cyclohexyl)-1Hbenzo[d]imidazol-2(3H)-ylidene)benzamide], a new, potent, selective anaplastic lymphoma kinase (ALK) inhibitor with potential application for the treatment of cancer, was selected as candidate to advance into efficacy studies in mice. However, the compound underwent mouse...

In the title mol-ecular salt, C12H24N(+)·NO3 (-), the cyclohexyl rings adopt chair conformations with the exocyclic C-N bonds in equatorial orientations. In the crystal, a bifurcated N-H⋯(O,O) hydrogen bond links the cation to the anion; the ion pairs are linked via C-H⋯O hydrogen bonds, forming layers in the ac plane.

N-[2-(Cyclohexylamino)-2-oxoethyl]-N-(4-octyloxy)phenyl-prop-2-enamide was prepared in good yield by coupling of 4(octyloxy)aniline, Cyclohexyl isocyanide, paraformaldehyde and acrylic acid by multicomponent Ugi reaction, at room temperature. The structure of the newly synthesized tripeptoid derivative was well characterized using elemental analysis, FTIR, NMR and mass spectral data.

The methyl–amide complex [TaCp*(NBu)Me(NMe2)] (1a) was isolated by reaction of the chloro–methyl [TaCp*(NBu)MeCl] complex with LiNMe2. Reaction of the mono-amide compounds [TaCp*(N Bu)XY] (X=NMe2, Y=Me (1a); X=NHBu, Y=Me (1b), Cl (1c)) with CO2 gives the h-carbamate derivatives [TaCp*(NBu)(h-O2CX)Y] (X=NMe2, Y=Me (2a); X=NHBu, Y=Me (2b), Cl (2c)). A similar reaction with the di-amide complex [T...

The cycloaddition of the von Leusen's reagent (p-tolylsulfonyl)methyl isocyanide (TosMIC) to alpha-aroylketene dithioacetals (AKDTAs) in the presence of sodium hydride in THF at rt resulted in a facile synthesis of the 4-aroyl-3-methylsulfanyl-2-tosylpyrroles 3 in good yield along with a minor amount of 4-[(4-methylphenyl)sulfonyl]-1-[(methylsulfanyl)methyl]-1H-imidazole 4. This study lead to t...

An ex vivo protocol was developed to assay the antidotal capacity of rePON1 variants to protect endogenous acetylcholinesterase and butyrylcholinesterase in human whole blood against OP nerve agents. This protocol permitted us to address the relationship between blood rePON1 concentrations, their kinetic parameters, and the level of protection conferred by rePON1 on the cholinesterases in human...

A preferred strategy for preventing nerve agents intoxication is catalytic scavenging by enzymes that hydrolyze them before they reach their targets. Using directed evolution, we simultaneously enhanced the activity of a previously described serum paraoxonase 1 (PON1) variant for hydrolysis of the toxic S(P) isomers of the most threatening G-type nerve agents. The evolved variants show ≤340-fol...

We have used thermospray LC-MS to confirm three highly polar metabolites (A, B. and G) of the herbicide hexazinone [3-cyclohexyl-6-(dimethylamino)-l-methy~-1,3.S-triazine-2,4( lH,3H)-dione]. and chemical ionization GC-MS to confirm two other metabolites (D and E) in extracts of soil and vegetation from a forest in the Central Alabama Piedmont. Selected-ion monitoring (SIM) of the protonated mol...

Abbreviations: AG, anaplastic glioma; BCNU, 1,3-bis( CCNU, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea; G ratio; O-meG, O-methylguanine; MGMT, O-methylgu MSP,methylation-specific PCR; PFS, progression-free surv temozolomide ⁎ Corresponding author at: Department of Neurol Washington, Box 356470, 1959 NE Pacific Street, Se Fax: +1 206 543 8315. E-mail address: [email protected] (J.R. Sil...

A polarographic method was developed to determine the antineoplastic agent carmustine and other nitrosoureas, such as N-methyl-N-nitrosourea and N-cyclohexyl-N-nitrosourea, in biological fluids at levels well below 1 microgram/ml or g. The stability of carmustine in different media was investigated to prevent losses during administration or assay. Examples of nitrosourea determination in biolog...