Ueber Condensationsproducte des [delta] 1,4 Dihydroterephtalsauredimethylesters.

Thesis (doctoral)--Kaiser-Wilhelms-Universitat Strassburg.

Reports of cases determined in the United States District court of the district of Hawaii ... v. 1-4; [August, 1900-January 15, 1917]

"Rules of the United States District court for the territory of Hawaii, adopted as compiled January 31, 1918, based on Compiled rules of May 5, 1902, as amended": v. 4, p. 793-875

America annuals of education. v. 1-4, Jan. 18260-Dec. 1829; new ser., v. 1, no. 1-5, Jan.-July 1830; 3d ser., v.1-9, Aug. 1830-Dec. 1839.

From Jan. 1826-July 1830 title reads: American journal of education. In August 1830 the title was changed to American Annuals of Education and instruction. The numbers for August-Dec. 1830, however, were issued both under this later title (as 3d ser., b.1, no 1-4) and under the title American journal and annals of education and instruction, new ser., v.1 of the 3d ser. They are preceded by 24 pages ("Editor's address" and "Sketches of Hofwyl") reprinted from the numbers for Aug.-Dec. 1830) In 1838 the title was shortened to American annuals of education. Editors: 1826-29, Williams Russell.--1830-37, W.C. Woodbridge.--1837--38 W.A. Alcott.

Fragm. lat. III 34 - Liber Sextus Decretalium (1.4.1 - 4; 1.6.43 - 46; 1.22.2 - 3.3; 3.4.23 - 24), ohne Glosse

Trägerband: Inc. qu. 738; Inc. qu. 913; 'Vocabularius Ex quo'; Vorbesitzer: Dominikanerkloster Frankfurt am Main

Fragm. lat. I 62 - Bibelkommentar (Apc 5,13; 6,2; 12,1 - 4)

Trägerband: Ms. lat. oct. 26; Ms. lat. oct. 30; Vorbesitzer: Johann Hartmann Beyer

Fragm. lat. I 80 - Psalterium (Ps 67,31 - 36; 68,1 - 4; 73,10 - 23; 88,8 - 25)

Trägerband: Inc. fol. 237; Vorbesitzer: Bartholomaeusstift Frankfurt am Main

LIBERTAÇÃO NAS TRILHAS DA JUSTIÇA: Estudo histórico e hermenêutico de Isaías 42,1-4

O presente trabalho tem como objetivo propor um estudo do cântico do escravo de Javé em Isaías 42,1- 4. Javé apresenta uma nova liderança, com um novo jeito de pensar e de agir para reconstruir um mundo novo baseado no direito e na solidariedade. É uma tarefa desafiadora para mim e ao mesmo tempo uma alegria em poder compartilhar com os meus amigos o conteúdo de um texto do Antigo Testamento. Afinal, o cântico do escravo de Javé é uma fonte inesgotável de sabedoria. Saciou o povo judaíta exilado a de dois mil e quinhentos anos atrás e continua jorrando água viva até em nossos dias matando a sede de todos aqueles e aquelas que lutam pela justiça. Os versos escolhidos são frutos de uma experiência de vida concreta dos exilados desacreditados por todos no cativeiro da Babilônia. No fundo é uma crítica aos falsos deuses criados pelos poderosos para justificar um sistema de opressão. A criatividade do profeta está em retomar os eventos históricos que marcaram a vida do povo exilado e atualizá-los dentro de um novo contexto histórico. Isto demonstra sua agilidade no conhecimento. Cada palavra é pensada dentro de um contexto maior envolvendo a vida e a história. O profeta é um sábio poeta, que fala de Deus como ninguém falou antes. Utiliza símbolos, imagens e metáforas que apontam para um mundo novo que ainda não existe, onde reinará o direito, a justiça e a paz. Essa mudança acontecerá a partir da missão que a liderança eleita desempenhará junto do povo oprimido e injustiçado. O líder será como o fermento na massa para a nova sociedade, baseada na igualdade e na partilha. O espírito de Javé estará agindo sobre ele para que ele não desanime da missão e que ela possa alcançar o seu objetivo. Essa nova liderança eleita por Javé agirá discretamente em silêncio entre os pobres e enfraquecidos. A missão beneficiará primeiramente às nações. Aqueles e aquelas que vivem em terras estrangeiras como migrantes. Depois contemplará de modo especial os pobres que estão correndo risco de vida, cana rachada e pavio vacilante e por fim a missão atingirá todos os povos da terra. Essa perspectiva traduz a vontade de Deus que é a salvação de toda a humanidade.(AU)

Combinatorial solid phase synthesis of multiply substituted 1,4-benzodiazepines and affinity studies on the CCK2 receptor (Part 1)

One hundred sixty-eight multiply substituted 1,4-benzodiazepines have been prepared by a five-step solid-phase combinatorial approach using syn-phase crowns as a solid support and a hydroxymethyl-phenoxy-acetamido linkage (Wang linker). The substituents of the 1,4-benzodiazepine scaffold have been varied in the -3, -5, -7, and 8-positions and the combinatorial library was evaluated in a cholecystokinin (CCK) radioligand binding assay. 3-Alkylated 1,4-benzodiazepines with selectivity towards the CCK-B (CCK2) receptor have been optimized on the lipophilic side chain, the ketone moiety, and the stereochemistry at the 3-position. Various novel 3-alkylated compounds were synthesized and [S]3-propyl-5-phenyl-1,4-benzodiazepin-2-one, [S]NV-A, has shown a CCK-B selective binding at about 180 nM. Fifty-eight compounds of this combinatorial library were purified by preparative TLC and 25 compounds were isolated and fully characterized by TLC, IR, APCI-MS, and 1H/13C-NMR spectroscopy.

Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands

A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepines was developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-prophyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel ligand had ED50 values of 4.7 and 5.2 mg kg-1 in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was 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.

Combinatorial approach to multi-substituted 1,4-Benzodiazepines as novel non-peptide CCK-antagonists

For the drug discovery process, a library of 168 multisubstituted 1,4-benzodiazepines were prepared by a 5-step solid phase combinatorial approach. Substituents were varied in the 3,5, 7 and 8-position on the benzodiazepine scaffold. The combinatorial library was evaluated in a CCK radiolabelled binding assay and CCKA (alimentary) and CCKB (brain) selective lead structures were discovered. The template of CCKA selective 1,4-benzodiazepin-2-ones bearing the tryptophan moiety was chemically modified by selective alkylation and acylation reactions. These studies provided a series of Asperlicin naturally analogues. The fully optimised Asperlicin related compound possessed a similar CCKA activity as the natural occuring compound. 3-Alkylated 1,4-benzodiazepines with selectivity towards the CCKB receptor subtype were optimised on A) the lipophilic side chain and B) the 2-aminophenyl-ketone moiety, together with some stereochemical changes. A C3 unit in the 3-position of 1,4-benzodiazepines possessed a CCKB activity within the nanomolar range. Further SAR optimisation on the N1-position by selective alkylation resulted in an improved CCKB binding with potentially decreased activity on the GABAA/benzodiazepine receptor complex. The in vivo studies revealed two N1-alkylated compounds containing unsaturated alkyl groups with anxiolytic properties. Alternative chemical approaches have been developed, including a route that is suitable for scale up of the desired target molecule in order to provide sufficient quantities for further in vivo evaluation.