@phdthesis{Wahler2013,
  author    = {Wahler, Johannes},
  title     = {Borole als Synthesebausteine f{\"u}r neue Organoborverbindungen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-84095},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Die vorliegende Arbeit befasst sich mit der Synthese neuer Borolderivate des Typs Ph4C4BR' (R' = Substituent am Borzentrum). Zudem wurde die Reaktivit{\"a}t ausgew{\"a}hlter Borole gegen{\"u}ber Lewis-Basen, ges{\"a}ttigten und unges{\"a}ttigten Substraten sowie unter Reduktionsbedingungen untersucht. Auf diese Weise konnten neue Strategien f{\"u}r die Synthese von Bor-haltigen konjugierten Systemen erschlossen werden. Alle wichtigen Strukturmotive wurden durch Multikern-NMR-Spektroskopie in L{\"o}sung sowie durch Einkristall-R{\"o}ntgenstrukturanalyse im Festk{\"o}rper charakterisiert.},
  subject      = {Chemische Synthese},
  language  = {de}
}
@article{TackeLangeBentlageetal.1983,
  author    = {Tacke, Reinhold and Lange, Hartwig and Bentlage, Anke and Sheldrick, William S. and Ernst, Ludger},
  title     = {2.2.5.5-Tetraorganyl-1.4-dioxa-2.5-disilacyclohexane/2,2,5,5-Tetraorganyl-1,4-dioxa-2,5-disilacyclohexanes},
  series = {Zeitschrift f{\"u}r Naturforschung B},
  volume    = {38},
  journal   = {Zeitschrift f{\"u}r Naturforschung B},
  number    = {2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128423},
  pages     = {190-193},
  year      = {1983},
  abstract  = {The 2,2,5,5-tetraorganyl-1,4-dioxa-2,5-disilacyclohexanes 2a-2c were prepared by condensation of the corresponding (hydroxymethyl)diorganylsilanes 1 a-1 c. The constitution of the heterocycles was confirmed by elemental analyses, cryoscopic measurements, mass spectrometry, and NMR-spectroscopic \((^1H, ^{13}C)\) investigations. The molecular structure of 2 b was determined by X-ray diffraction analysis.},
  language  = {de}
}
@unpublished{StennettBissingerGriesbecketal.2019,
  author    = {Stennett, Tom E. and Bissinger, Philipp and Griesbeck, Stefanie and Ullrich, Stefan and Krummenacher, Ivo and Auth, Michael and Sperlich, Andreas and Stolte, Matthias and Radacki, Krzysztof and Yao, Chang-Jiang and W{\"u}rthner, Frank and Steffen, Andreas and Marder, Todd B. and Braunschweig, Holger},
  title     = {Near-Infrared Quadrupolar Chromophores Combining Three-Coordinate Boron-Based Superdonor and Superacceptor Units},
  series = {Angewandte Chemie, International Edition},
  journal   = {Angewandte Chemie, International Edition},
  doi       = {10.1002/anie.201900889},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180391},
  year      = {2019},
  abstract  = {In this work, two new quadrupolar A-π-D-π-A chromophores have been prepared featuring a strongly electron- donating diborene core and strongly electron-accepting dimesitylboryl F(BMes2) and bis(2,4,6-tris(trifluoromethyl)phenyl)boryl (BMes2) end groups. Analysis of the compounds by NMR spectroscopy, X-ray crystallography, cyclic voltammetry and UV-vis-NIR absorption and emission spectroscopy indicated that the compounds possess extended conjugated π-systems spanning their B4C8 cores. The combination of exceptionally potent π-donor (diborene) and π- acceptor (diarylboryl) groups, both based on trigonal boron, leads to very small HOMO-LUMO gaps, resulting in strong absorption in the near-IR region with maxima in THF at 840 and 1092 nm, respectively, and very high extinction coefficients of ca. 120,000 M-1cm-1. Both molecules also display weak near-IR fluorescence with small Stokes shifts.},
  language  = {en}
}
@article{SeethalerHertleinWeckleinetal.2019,
  author    = {Seethaler, Marius and Hertlein, Tobias and Wecklein, Bj{\"o}rn and Ymeraj, Alba and Ohlsen, Knut and Lalk, Michael and Hilgeroth, Andreas},
  title     = {Novel small-molecule antibacterials against Gram-positive pathogens of Staphylococcus and Enterococcus species},
  series = {Antibiotics},
  volume    = {8},
  journal   = {Antibiotics},
  number    = {4},
  issn      = {2079-6382},
  doi       = {10.3390/antibiotics8040210},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193130},
  year      = {2019},
  abstract  = {Defeat of the antibiotic resistance of pathogenic bacteria is one great challenge today and for the future. In the last century many classes of effective antibacterials have been developed, so that upcoming resistances could be met with novel drugs of various compound classes. Meanwhile, there is a certain lack of research of the pharmaceutical companies, and thus there are missing developments of novel antibiotics. Gram-positive bacteria are the most important cause of clinical infections. The number of novel antibacterials in clinical trials is strongly restricted. There is an urgent need to find novel antibacterials. We used synthetic chemistry to build completely novel hybrid molecules of substituted indoles and benzothiophene. In a simple one-pot reaction, two novel types of thienocarbazoles were yielded. Both indole substituted compound classes have been evaluated as completely novel antibacterials against the Staphylococcus and Enterococcus species. The evaluated partly promising activities depend on the indole substituent type. First lead compounds have been evaluated within in vivo studies. They confirmed the in vitro results for the new classes of small-molecule antibacterials.},
  language  = {en}
}
@article{SeethalerHertleinHopkeetal.2022,
  author    = {Seethaler, Marius and Hertlein, Tobias and Hopke, Elisa and K{\"o}hling, Paul and Ohlsen, Knut and Lalk, Michael and Hilgeroth, Andreas},
  title     = {Novel effective fluorinated benzothiophene-indole hybrid antibacterials against S. aureus and MRSA strains},
  series = {Pharmaceuticals},
  volume    = {15},
  journal   = {Pharmaceuticals},
  number    = {9},
  issn      = {1424-8247},
  doi       = {10.3390/ph15091138},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288253},
  year      = {2022},
  abstract  = {Increasing antibacterial drug resistance threatens global health, unfortunately, however, efforts to find novel antibacterial agents have been scaled back by the pharmaceutical industry due to concerns about a poor return on investment. Nevertheless, there is an urgent need to find novel antibacterial compounds to combat antibacterial drug resistance. The synthesis of novel drugs from natural sources is mostly cost-intensive due to those drugs' complicated structures. Therefore, it is necessary to find novel antibacterials by simple synthesis to become more attractive for industrial production. We succeeded in the discovery of four antibacterial compound (sub)classes accessible in a simple one-pot reaction based on fluorinated benzothiophene-indole hybrids. They have been evaluated against various S. aureus and MRSA strains. Structure- and substituent-dependent activities have been found within the (sub)classes and promising lead compounds have been identified. In addition, bacterial pyruvate kinase was found to be the molecular target of the active compounds. In conclusion, simple one-pot synthesis of benzothiophene-indoles represents a promising strategy for the search of novel antimicrobial compounds.},
  language  = {en}
}
@phdthesis{Mohrschladt2003,
  author    = {Mohrschladt, Christian J.},
  title     = {Synthese und Untersuchung der photochemischen und photophysikalischen Eigenschaften Donor-Akzeptor-substituierter Anthracenderivate},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8486},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {In der vorliegenden Arbeit wurde gezeigt, dass Donor-Akzeptor-substituierte Anthracen- und Ethenoanthracenderivate bemerkenswerte photophysikalische und photochemische Eigenschaften aufweisen. So bieten derartige Anthracenderivate eine interessante Grundlage sowohl zur Entwicklung von Fluoreszenzsonden beispielsweise f{\"u}r Schwermetallionen wie auch zur Entwicklung von molekularen Schaltern f{\"u}r die Datenverarbeitung. Weiterhin stellen die untersuchten Anthracene und Ethenoanthracene hervorragende Systeme zur systematischen Untersuchung von Substituenteneinfl{\"u}ssen auf Photoreaktionen dar.},
  subject      = {Anthracenderivate},
  language  = {de}
}
@phdthesis{Merdanovic2005,
  author    = {Merdanovic, Melisa},
  title     = {Charakterisierung von NadR : das essentielle Enzym der NAD-Synthese bei Haemophilus influenzae},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-14907},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {I Zusammenfassung Haemophilus influenzae, ein Gram-negatives, Bakterium der Familie Pasteurellaceae, kann beim Menschen eine Vielzahl an Erkrankungen ausl{\"o}sen: Die bekapselte St{\"a}mme, v. a. mit Typ b Kapsel k{\"o}nnen Cellulitis, septische Arthritis, Epiglottitis und Meningitis verursachen. Die nicht-bekapselte St{\"a}mme k{\"o}nnen Otitis media, Sinusitis, Pneumonie und in selteneren F{\"a}llen Bakter{\"a}mie verursachen. Ein besonderes Merkmal des Metabolismus von H. influenzae ist dessen Unf{\"a}higkeit Nikotinamid-Adenin-Dinukleotid (NAD+) de novo zu synthetisieren. Daher sind die Enzyme bzw. Transporter, die an NAD+ Aufnahme und Resynthese beteiligt sind, als putative antimikrobielle Ziele von Interesse. In unserer Arbeitsgruppe konnte gezeigt werden, dass NAD+ zu Nikotinamidribosyl degradiert werden muss, bevor es in die Zelle aufgenommen werden kann. Auch Proteine, die an der Degradation des exogenen NAD+ zu Nikotinamidribosyl und dessen anschließender Aufnahme in die Zelle verantwortlich sind, konnten identifiziert und charakterisiert werden. Wie Nikotinamidribosyl im Cytoplasma wiederum zu NAD+ synthetisiert wird, ist auch erst k{\"u}rzlich gekl{\"a}rt worden: f{\"u}r NadR konnte sowohl eine Ribosyl-Nukleotid-Kinase (RNK) Aktivit{\"a}t als auch eine Nikotinamid-Mononukleotid-Adenylyltransferase (NMNAT) Aktivit{\"a}t in vitro gezeigt werden. Die Kristallstruktur von hiNadR im Komplex mit NAD+ wurde auch aufgekl{\"a}rt. In dieser Arbeit sollte NadR, insbesondere dessen RNK Dom{\"a}ne, in vivo und in vitro n{\"a}her charakterisiert werden. Um zu untersuchen, ob beide Dom{\"a}nen in vivo essentiell sind, wurden Deletionsmutanten erzeugt, bei welchen die komplette bzw. der C-terminale Teil der RNK Dom{\"a}ne fehlten. Diese Deletionen konnten im nadV+ Hintergrund erzeugt werden. Die Deletionen konnten in H. influenzae nur zusammen mit dem nadV-Gen transferiert werden oder alternativ nur in die Zellen, die mit pNadRKan Plasmid transformiert wurden. Dies verdeutlicht, dass nicht nur die NMNAT Dom{\"a}ne sondern auch die RNK Dom{\"a}ne bzw. sogar nur wenige C-terminal fehlende Aminos{\"a}uren des NadR Proteins essentiell f{\"u}r die Lebensf{\"a}higkeit von H. influenzae sind. Gleichzeitig zeigen diese Experimente, dass die RNK-Dom{\"a}ne in Anwesenheit von NadV redundant ist. Ein weiterer Ph{\"a}notyp der RNK-Deletionsmutante zeigte sich beim Nikotinamidribosyl-Transport. Im Gegensatz zum Wt, welcher ca. 60-80\% des 14C-Nikotinamidribosyls aufnahm, konnte f{\"u}r die RNK-Deletionsmutante nur 2-5\% Aufnahme gemessen werden. Dies konnte durch das pNadRKan Plasmid komplementiert werden. Weiterhin wurde festgestellt, dass spontan Aminopyridin-resistente H. influenzae Zellen Mutationen im nadR Gen haben, insbesondere im Walker A-Motif (P-Loop) der RNK Dom{\"a}ne. Zus{\"a}tzlich konnte in dieser Arbeit gezeigt werden, dass NadR aus Aminopyridin und ATP Aminopyridin-Adenin-Dinukleotid synthetisieren kann. Somit konnte gezeigt werden, dass die wachstumshemmende Wirkung eigentlich durch das aus Aminopyridin synthetisierte Aminopyridin-Adenin-Dinukleotid entsteht, welches NAD+ in Redox-Reaktionen verdr{\"a}ngt, wodurch es letztendlich zum Stillstand des Metabolimus kommt. Durch Einf{\"u}hren von gezielten AS-Substitutionen im Walker A und B Motif und in der LID-Dom{\"a}ne von NadR, konnten einige Aminos{\"a}uren identifiziert werden, welche essentiell f{\"u}r die Aktivit{\"a}t der RNK Dom{\"a}ne sind. Alle Aminos{\"a}uren-Substitutionen f{\"u}hrten zum Verlust der RNK Aktivit{\"a}t, die NMNAT Aktivit{\"a}t jedoch war nicht beeintr{\"a}chtigt. Desweiteren wurden diese NadR Punktmutanten in vivo untersucht. F{\"u}r alle konnte eine signifikante Defizienz in der Nikotinamidribosyl-Aufnahme beobachtet werden, die gemessene Aufnahme lag im Bereich der RNK-Deletionsmutante. Dadurch konnte eine direkte Korrelation zwischen der RNK Aktivit{\"a}t und der Nikotinamidribosyl-Aufnahme gezeigt werden. In weiteren in vitro Experimenten konnte f{\"u}r NadR eine Feedback-Inhibition durch das NAD+ gezeigt werden, wobei NAD+ in erster Linie die RNK Dom{\"a}ne von NadR inhibiert. Eine graduelle Erh{\"o}hung der NAD+ Konzentration f{\"u}hrte in den in vitro Assays zu einer graduellen Abnahme der RNK. Bei der NMNAT Aktivit{\"a}t jedoch zeigte sich keine signifikante Inhibition in Anwesenheit von NAD+. Begleitende in vivo Experimente, zeigten eine 2/3 Reduktion der Nikotinamidribosyl-Aufnahme bei den Zellen, die mit NAD+ inkubiert wurden, d. h. h{\"o}here intrazellul{\"a}re NAD+ Konzentration hatten. F{\"u}r die genauere Analyse der Feedback-Inhibition durch NAD+ wurden weitere Punktmutanen hergestellt. Bei zwei der Punktmutanten wurde eine Beeintr{\"a}chtigung der NadR-Aktivit{\"a}t beobachtet, daher wurden diese Punktmutanten von weiteren Analysen im Bezug auf NAD+-Feedback Inhibition ausgeschlossen. Eine Mutante (NadRW256F) jedoch, zeigte {\"a}hnliche Aktivit{\"a}t wie das Wt-NadR. In Anwesenheit von NAD+ wurde die RNK Aktivit{\"a}t dieser Punktmutante, im Gegensatz zum Wt-Protein, kaum gehemmt. Dadurch konnte W256 als eine der Aminos{\"a}uren identifiziert werden, die an der Vermittlung der NAD+-bedingten Inhibition der RNK-Dom{\"a}ne beteiligt ist.},
  subject      = {Haemophilus influenzae},
  language  = {de}
}
@article{MateraKaukCirilloetal.2023,
  author    = {Matera, Carlo and Kauk, Michael and Cirillo, Davide and Maspero, Marco and Papotto, Claudio and Volpato, Daniela and Holzgrabe, Ulrike and De Amici, Marco and Hoffmann, Carsten and Dallanoce, Clelia},
  title     = {Novel Xanomeline-containing bitopic ligands of muscarinic acetylcholine receptors: design, synthesis and FRET investigation},
  series = {Molecules},
  volume    = {28},
  journal   = {Molecules},
  number    = {5},
  issn      = {1420-3049},
  doi       = {10.3390/molecules28052407},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311249},
  year      = {2023},
  abstract  = {In the last few years, fluorescence resonance energy transfer (FRET) receptor sensors have contributed to the understanding of GPCR ligand binding and functional activation. FRET sensors based on muscarinic acetylcholine receptors (mAChRs) have been employed to study dual-steric ligands, allowing for the detection of different kinetics and distinguishing between partial, full, and super agonism. Herein, we report the synthesis of the two series of bitopic ligands, 12-Cn and 13-Cn, and their pharmacological investigation at the M\(_1\), M\(_2\), M\(_4\), and M\(_5\) FRET-based receptor sensors. The hybrids were prepared by merging the pharmacophoric moieties of the M\(_1\)/M\(_4\)-preferring orthosteric agonist Xanomeline 10 and the M\(_1\)-selective positive allosteric modulator 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) 11. The two pharmacophores were connected through alkylene chains of different lengths (C3, C5, C7, and C9). Analyzing the FRET responses, the tertiary amine compounds 12-C5, 12-C7, and 12-C9 evidenced a selective activation of M\(_1\) mAChRs, while the methyl tetrahydropyridinium salts 13-C5, 13-C7, and 13-C9 showed a degree of selectivity for M\(_1\) and M\(_4\) mAChRs. Moreover, whereas hybrids 12-Cn showed an almost linear response at the M\(_1\) subtype, hybrids 13-Cn evidenced a bell-shaped activation response. This different activation pattern suggests that the positive charge anchoring the compound 13-Cn to the orthosteric site ensues a degree of receptor activation depending on the linker length, which induces a graded conformational interference with the binding pocket closure. These bitopic derivatives represent novel pharmacological tools for a better understanding of ligand-receptor interactions at a molecular level.},
  language  = {en}
}
@phdthesis{Markl2011,
  author    = {Markl, Christian},
  title     = {Neue mono- und dimere Melatonin-Analoga als subtypselektive Liganden der Melatoninrezeptoren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54618},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Die vorliegende Arbeit befasst sich mit der Synthese von Liganden der Melatonin-Rezeptoren (MR). Die zwei humanen MR-Subtypen, MT1 und MT2, geh{\"o}ren zur Familie der G-Protein-gekoppelten Rezeptoren. Als „Schlafhormon" wirkt es schlafinduzierend und vermittelt den circadianen Rhythmus. Zum genauen Verst{\"a}ndnis der physiologischen Funktionen der MT1- und MT2-Rezeptoren ist die Verf{\"u}gbarkeit von subtypselektiven MR-Liganden unentbehrlich. Zum Design von MT2-selektiven MR-Liganden modifizierte man die Melatonin-Grundstruktur durch formale Substitution in 2-Stellung, z.B. mit dem 2-Methylen-N-methyl-anilin- oder 2-Methylen-1´-indol-Rest. Weiterhin wurden trizyklische Derivate mit 1,2,3,4-Tetrahydro-pyrazino[1,2-a]indol- oder 2,3,4,5-Tetrahydro-1H-[1,4]diazepino[1,2-a]indol-Grundger{\"u}st hergestellt. Das Synthesekonzept f{\"u}r dieses Teilprojekt basierte auf dem Synthesebaustein 3-Cyanomethyl-5-methoxy-1H-indol-2-carbons{\"a}ure. Da bislang nur wenige MT1-selektive MR-Liganden bekannt sind, wurde zur Untersuchung der Voraussetzung f{\"u}r MT1-Selektivit{\"a}t, die 5-Methoxygruppe von Melatonin formal durch Phenylalkyloxy-Reste verschiedener Kettenl{\"a}ngen substituiert. Die Synthese der Derivate erfolgte ausgehend von N-Acetylserotonin. Als Referenzverbindung wurde der bis heute MT1-selektivste MR-Antagonist (Descamps-Francois et al. 2003) hergestellt. Zu dessen Synthese ben{\"o}tigte man Agomelatin als Ausgangsverbindung. Eine neuartige vierstufige Route zu Agomelatin wurde daher entwickelt. Die Testung der Referenzverbindung ergab eine drastische Abweichung vom Literaturwert, da diese als nahezu unselektiv getestet wurde. Unter den O-Phenylalkyl-N-Acetylserotonin-Derivaten wurden zwei Verbindungen mit einer 11-fachen MT1-Selektivit{\"a}t getestet. Zur Absicherung der Reinheit wurden die Verbindungen mit RP-HPLC untersucht. Schließlich wurden noch melatoninerge Dimere mit einem 1-1´, 1-2´ und 5-5´ Verkn{\"u}pfungsmuster hergestellt.},
  subject      = {G-Protein gekoppelte Rezeptoren},
  language  = {de}
}
@phdthesis{Kelm2002,
  author    = {Kelm, Bernd},
  title     = {A New Synthesis of enantiopure C-3-substituted Glutamates by Utilization of Ortho Ester protected (S)-Pyroglutamic acid},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-1296},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Priority tasks of the present thesis were to generate various enantiopure C-3-substituted pyroglutamates as well as C-3-substituted glutamates, and furthermore to ameliorate the serious drawback of the bad atom-economy in the reaction sequence of previously published silylether-mediated procedures. To meet these requirements, the ortho ester functionality (OBO ester) developed by Corey was introduced. According to the plan of synthesis, the starting material, non-racemic (S)-pyroglutamic acid, was converted to the corresponding oxetane ester via a DCC-mediated esterification. The latter was N-protected to provide N-acceptor substituted pyroglutamic acid oxetane esters (Acceptor=Boc,Cbz,CO2Me). After rearrangement with boron trifluoride, the ortho ester derivatives (Acceptor=Cbz,CO2Me) were at hand and exclusively the N-Cbz derivative was converted to the corresponding alpha,beta-unsaturated lactam via a syn-elimination reaction. The formation of the C-3-substituted ortho ester compounds (R=methyl,ethyl,butyl,allyl,phenyl,4-chlorophenyl,biphenyl,naphthyl) was performed via a copper-mediated conjugate addition to the alpha,beta-enone system of the N-Cbz-alpha,beta-unsaturated lactam. The OBO functionality hence was envisaged to support perfect trans selectivity in this cuprate addition to the Michael system of the N-Cbz-alpha,beta-unsaturated lactam. Spectroscopic NMR-data, on the basis of 1H-, 13C- and DEPT spectra, proved the assumption that the C-3-substituted ortho ester derivatives exclusively are trans-configurated, i.e. the alkyl derivatives (R=methyl,ethyl,butyl,allyl) are (2S,3S)-configurated and the aryl derivatives (R=phenyl,4-chlorophenyl,biphenyl,naphthyl) are (2S,3R)-configurated). The C-3-substituted ortho ester derivatives were completely deprotected to yield the C-3-substituted pyroglutamates (R=ethyl,phenyl,4-chlorophenyl,naphthyl). Finally, ring opening reaction via route A-2 lead to the desired enantiopure C-3-substituted glutamates. Alternatively, latter preferably were reacted via route A-1 to yield the C-3-substituted glutamates (R=methyl,ethyl,butyl,phenyl,4-chlorophenyl,naphthyl). Their (2S,3R)-configuration (R=aryl) and (2S,3S)-configuration (R=alky), respectively, unambiguously was proved on the basis of available spectroscopic NMR-data. To ensure this assumption, diastereomeric (2S,3R)-3-methyl glutamic acid (i.e. cis-configurated) examplarily was synthesized via route A-3 and spectroscopic NMR-data was compared to that of (2S,3S)-3-methyl glutamic acid (i.e. trans-configurated). Conclusively, there can be recorded the fact that the serious drawback of the bad atom-economy in the reaction sequence previously used can be circumvented by the introduction of the OBO functionality, so the concept of an improved atom-economy is achieved. Additionally, in comparison to the silyl-ether-mediated synthesis, the OBO functionality provided crystalline ortho ester derivatives, which facilitated their purification as well as characterization.},
  subject      = {Glutamate},
  language  = {en}
}
@article{GehrmannHertleinHopkeetal.2021,
  author    = {Gehrmann, Robin and Hertlein, Tobias and Hopke, Elisa and Ohlsen, Knut and Lalk, Michael and Hilgeroth, Andreas},
  title     = {Novel small-molecule hybrid-antibacterial agents against S. aureus and MRSA strains},
  series = {Molecules},
  volume    = {27},
  journal   = {Molecules},
  number    = {1},
  issn      = {1420-3049},
  doi       = {10.3390/molecules27010061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252371},
  year      = {2021},
  abstract  = {Ongoing resistance developments against antibiotics that also affect last-resort antibiotics require novel antibacterial compounds. Strategies to discover such novel structures have been dimerization or hybridization of known antibacterial agents. We found novel antibacterial agents by dimerization of indols and hybridization with carbazoles. They were obtained in a simple one-pot reaction as bisindole tetrahydrocarbazoles. Further oxidation led to bisindole carbazoles with varied substitutions of both the indole and the carbazole scaffold. Both the tetrahydrocarbazoles and the carbazoles have been evaluated in various S. aureus strains, including MRSA strains. Those 5-cyano substituted derivatives showed best activities as determined by MIC values. The tetrahydrocarbazoles partly exceed the activity of the carbazole compounds and thus the activity of the used standard antibiotics. Thus, promising lead compounds could be identified for further studies.},
  language  = {en}
}
@article{DarwishAttia2012,
  author    = {Darwish, Hany W. and Attia, Mohamed I.},
  title     = {New spectrofluorimetric methods for determination of melatonin in the presence of N-{2-[1-({3-[2-(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl} acetamide: a contaminant in commercial melatonin preparations},
  series = {Chemistry Central Journal},
  volume    = {6},
  journal   = {Chemistry Central Journal},
  number    = {36},
  doi       = {10.1186/1752-153X-6-36},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134606},
  year      = {2012},
  abstract  = {Background: Melatonin (MLT) has many health implications, therefore it is of valuable importance to develop specific analytical methods for determination of MLT in the presence of its main contaminant, N-{2-[1-({3-[2(acetylamino)ethyl]-5-methoxy-1H-indol-2-yl}methyl)-5-methoxy-1H-indol-3-yl]ethyl}acetamide (10). For development of these analytical methods, compound 10 had to be prepared in an adequate amount. Results: Compound 10 was synthesized in six steps starting from 5-methoxyindole-2-carboxylic acid (1). Analytical performance of the proposed spectrofluorimetric methods was statistically validated with respect to linearity, accuracy, precision and specificity. The proposed methods were successfully applied for the assay of MLT in laboratory prepared mixtures containing up to 60 \% of compound 10 and in commercial MLT tablets with recoveries not less than 99.00 \%. No interference was observed from common pharmaceutical additives and the results were favorably compared with those obtained by a reference method. Conclusions: This work describes simple, sensitive, and reliable second derivative spectrofluorimetric method in addition to two multivariate calibration methods, principal component regression (PCR) and partial least square (PLS), for the determination of MLT in the presence of compound 10.},
  language  = {en}
}
@article{AttiaHerdeisBraeunerOsborne2013,
  author    = {Attia, Mohamed I. and Herdeis, Claus and Br{\"a}uner-Osborne, Hans},
  title     = {GABA(B)-Agonistic Activity of Certain Baclofen Homologues},
  series = {Molecules},
  volume    = {18},
  journal   = {Molecules},
  number    = {9},
  doi       = {10.3390/molecules180910266},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129690},
  pages     = {10266-10284},
  year      = {2013},
  abstract  = {Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABAB receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABAB receptors, we report here the synthesis of certain baclofen homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1a-h as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as GABABR agonists. Compound 1a is an agonist to GABAB receptors with an EC50 value of 46 μM on tsA201 cells transfected with GABAB1b/GABAB2/Gqz5, being the most active congener among all the synthesized compounds.},
  language  = {en}
}
@phdthesis{Attia2003,
  author    = {Attia, Mohamad Ibrahim},
  title     = {Design, synthesis and pharmacological evaluation of certain GABAB agonists},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-7551},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Ziel dieser Arbeit war die Synthese von (RS)-5-Amino-3-aryl(methyl)-pentans{\"a}ure Hydrochloride, 3-Aminomethyl-5-chlor-benzols{\"a}ure Hydrochlorid und(RS)-4-Amino-3-(4´-ethynyl(jod)-phenyl)-butans{\"a}ure Hydrochloride und die Testung der pharmakologischen Aktivit{\"a}t dieser Verbindungen. Die synthetisierten Verbindungen wurden als GABAB-Rezeptor Agonisten, in einem auf Ca2+-Messungen basierenden Funktional-Assay (in vitro tsA Zellen mit GABAB1b/GABAB2/G\&\#945;q-z5 transfektiert), getestet und daraus ein Struktur-Aktivit{\"a}ts Modell abgeleitet. Im allgemein Teil dieser Arbeit wird ein {\"U}berblick, {\"u}ber die Neurotransmitter- Rezeptoren (Liganden gesteuerte Ionen-Kanal-Rezeptoren und G Protein-gekoppelte Rezeptoren) des zentralen Nervensystems und deren Agonisten und Antagonisten, gegeben. Eine ausf{\"u}hrliche Diskussion zur Synthesestrategie der Verbindungen der Zwischenstufen und der Ausgangsmaterialien wird in den Schemata 2-6 beschrieben. Die synthetisierten Verbindungen wurden als GABAB Agonisten gepr{\"u}ft. Zus{\"a}tzlich wurden diese im 3D Homologie Modell mit FlexiDock Programm gedockt. Daraus wurde ein Modell zur Voraussage der Aktivit{\"a}t von Analogen und Homologen des Baclofens abgeleitet. Letztendlich wurde ein Pharmakophor-Modell f{\"u}r GABAB Agonisten mit DISCO (DIStance COmparisons) Programm erstellt.},
  subject      = {Baclofen},
  language  = {en}
}
@article{AshrafYasrebiHertleinetal.2017,
  author    = {Ashraf, Kerolos and Yasrebi, Kaveh and Hertlein, Tobias and Ohlsen, Knut and Lalk, Michael and Hilgeroth, Andreas},
  title     = {Novel effective small-molecule antibacterials against \(Enterococcus\) strains},
  series = {Molecules},
  volume    = {22},
  journal   = {Molecules},
  number    = {12},
  doi       = {10.3390/molecules22122193},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172628},
  year      = {2017},
  abstract  = {\(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.},
  language  = {en}
}