Locomotive with MTRR on fender, 3 men on ground, 4 on wood pile, 2 on flat car

from left: 1 - Wm. Tate, conductor, on pilot [others unidentified]

MHD program review : hearings before the Subcommittee on Fossil and Nuclear Energy Research, Development and Demonstration of the Committee on Science and Technology, U.S. House of Representatives, Ninety-fifth Congress, second session, May 2, 4, August 3, 1978.

"No. 76."

Uber 1.3-Diketo-2.4-tetrachlorhydronaphtalin und dessen Umwandlungsprodukte.

Thesis (doctoral)--Universitat Marburg.

Synthese des 2,4'-dioxyflavonols 3-oxyflavonols.

Thesis (doctoral)--

Organic reactions in ionic liquids: ionic liquid-accelerated facile synthesis of 3-alkyl-2,4-thiazolidinediones

The room temperature ionic liquid [bmim]PF6 is a new green solvent for the N-alkylation of 2,4-thiazolidinones. Significant rate enhancement and improved yields have been observed.

Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions

A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.

Synthesis and evaluation of N-(3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-1H-indole-carboxamides as cholecystokinin antagonists

The structure-activity relationship optimization of the pyrazoline template 3a resulted in novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides 4a-4e. These non-peptidal CCK ligands have been shown to act as potent CCK 1 ligands in a [125]I-CCK-8 receptor binding assay. The best amides (4c and 4d) of this series displayed an IC50 of 20/25 CCK 1 for the CCK 1 receptor. In a subsequent in-vivo evaluation using various behaviour pharmacological assays, an anxiolytic effect of these novel 3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-indole carboxamides was found at high doses in the elevated plus-maze. In the despair swimming test, a model for testing antidepressants, an ED50 of 0.33/0.41 mg kg -1 was determined for amide 4c/4d and the antidepressant effect had a magnitude comparable to desimipramine. © 2006 The Authors.

Novel 5-HT7 ligands as antidepressants:automated synthesis of N-substituted-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]-arylsulfon amides

The 5-HT7 receptor is linked with various CNS disorders. Using an automated solution phase synthesis a combinatorial library of 384 N-substituted N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]-arylsulfonamides was prepared with 24 chemically diverse amines 1-24 and 16 sulfonyl chlorides A-P. The chemical library of alkylated sulfonamides was evaluated in a receptor binding assay with [3]H-5-CT as ligand. The key synthetic step was the alkylation of a sulfonamide with iodide E, which was prepared from butanediol in 4 synthetic steps. The target compounds 1A, 1B .....24A ... 24P were purified by solvent extraction on a Teacan liquid handling system. Sulfonamide J20, B23, D23, G23, G23, J23 , I24 and O24 displayed a binding affinity IC50 between 100 nM and 10 nM. The crystalline J20 (IC50=39 nM) and O24 (IC50=83 nM) were evaluated further in the despair swimming test and the tail suspension assay. A significant antidepressant activity was found in mice of a greater magnitude than imipramine and fluoxetine at low doses. © 2006 Bentham Science Publishers Ltd.

Crystal structures of a family of layered coordination polymers containing divalent metal ions (Mn2+, Co2+, Ni2+ and Zn2+) and the 3-amino 4-methyl benzoate ion

Peer reviewed

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

Crystal structures of a family of layered coordination polymers containing divalent metal ions (Mn2+, Co2+, Ni2+ and Zn2+) and the 3-amino 4-methyl benzoate ion

Peer reviewed

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole is a ligand and shows species-specific partial agonism of the Aryl Hydrocarbon Receptor

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) and related compounds are a series of anti-cancer candidate pharmaceuticals (Table 1.), that have been shown to activate the AhR. We show that these compounds are high affinity ligands for the rat AhR, but a quantitative assay for their ability to induce CYP1A1 RNA in H4IIEC3 cells, a measure of activation of the AhR, showed a poor relationship between affinity for the AhR and ability to induce CYP1A1 RNA. 5F 203, an agonist with low potency, was able to antagonise the induction of CYP1A1 RNA by TCDD, while IH 445, a potent agonist, did not antagonise the induction of CYP1A1 RNA by TCDD, and Schild analysis confirmed 5F 203 to be a potent antagonist of the induction of CYP1A1 RNA by TCDD in H4IIEC3 cells. In contrast, several benzothiazoles show potent induction of CYP1A1 RNA in human MCF-7 cells, and 5F 203 is unable to detectably antagonise the induction of CYP1A1 RNA in MCF-7 cells, showing a species difference in antagonism. Evaluation of the antiproliferative activity of benzothiazoles showed that the ability to agonise the AhR correlated with growth inhibition both in H4IIEC3 cells for a variety of benzothiazoles, and between H4IIEC3 and MCF-7 cells for 5F 203, suggesting an important role of agonism of the AhR in the anti-proliferative activity of benzothiazoles.