87,250 research outputs found
Synthesis of a group of novel Xanomeline/77-LH-28-1 hybrid ligands and their FRET investigation at muscarinic acetylcholine receptor subtypes
No full textIn connection with our interest in investigating novel rationally designed bitopic (i.e., orthosteric/allosteric) derivatives targeting muscarinic acetylcholine receptor (mAChR) subtypes (1,2,3), in this study we designed and synthesized a new set of ligands that integrate in the same molecular skeleton the pharmacophoric moieties of Xanomeline and of 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone). Xanomeline is a well-known M1/M4-preferring orthosteric agonist, which ameliorated cognitive impairments in Alzheimer’s disease patients and showed activity in various models of schizophrenia, thus being potentially beneficial for treatment of positive, negative and cognitive symptoms (4). On the other hand, 77-LH-28-1 was characterized as an M1-selective, positive allosteric modulator, thus representing an interesting pharmacological tool with cognition enhancing properties (5). As illustrated below, we planned the novel bipharmacophoric derivatives as merged structures, with the tetrahydropyridine nucleus of Xanomeline as the central core.
In the last years, different receptor sensors, based on the fluorescence resonance energy transfer (FRET), were generated for various G protein-coupled receptors, and represented a valuable tool to investigate real time receptor activation as well as ligand-receptor interactions. Recently, this analysis was performed also on a set of bitopic ligands designed for a selective interaction with M1 mAChRs (6). Our preliminary results on the group of Xanomeline/77-LH-28-1 hybrid compounds indicate, for the M1 sensor, a reproducible activation response, which depends on the linker length. Conversely, no FRET-related effect could be detected at the M2 sensor. Thus, a critical spacer length of the hybrid compounds induces conformational changes with a degree of selectively for the M1 muscarinic receptor. The synthesis and the results of pharmacological investigation will be presented and discussed.
References: 1. J. Antony, K. Kellershohn, M. Mohr-Andrä, A. Kebig, S. Prilla, M. Muth, E. Heller, T. Disingrini, C. Dallanoce et al., FASEB J 2009, 23, 442-450. 2. A. Bock, B. Chirinda, F. Krebs, R. Messerer, J. Bätz, M. Muth, C. Dallanoce et al., Nat. Chem. Biol. 2014, 10, 18-20. 3. A. Bock, M. Bermudez, F. Krebs, C. Matera, B. Chirinda, D. Sydow, C. Dallanoce et al., J. Biol. Chem. 2016, 291, 16375-16389. 4. S. Barak, I. Weiner, Int. J. Neuropsychoph. 2011, 14, 1233-1246. 5. C. J. Langmead, N. E. Austin, C. L. Branch, J. T. Brown, K. A. Buchanan, C. H. Davies, I. T. Forbes et al., Br. J. Pharmacol. 2008, 154, 1104-1115. 6. R. Messerer, M. Kauk, D. Volpato, M. C. Alonso Canizal, J. Klöckner, U. Zabel, S. Nuber, C. Hoffmann, U. Holzgrabe, ACS Chem. Biol. 2017, 12, 833-843
H. C. Branner, M. Hoffmann, Der Mensch als Spielball zivischen Gewalt und Recht
No full textH. C. Branner, M. Hoffmann, Der Mensch als Spielball zivischen Gewalt und Recht. In: Revue internationale de droit comparé. Vol. 12 N°2, Avril-juin 1960. pp. 432-433
H. C. Branner, M. Hoffmann, Der Mensch als Spielball zivischen Gewalt und Recht
No full textH. C. Branner, M. Hoffmann, Der Mensch als Spielball zivischen Gewalt und Recht. In: Revue internationale de droit comparé. Vol. 12 N°2, Avril-juin 1960. pp. 432-433
The Feldstein-Horioka puzzle and a new measure of international capital mobility
No full textIn intertemporal optimization models of current account dynamics, the budget constraint will induce high degrees of positive comovement in the levels of savings and investment and the two variables are likely to be cointegrated. Error correction will then also influence the correlations of the cyclical components which will therefore be uninformative about capital mobility.As an alternative we suggest a new measure of long-run capital mobility based on Johansen's (1988) procedure. We apply our method to historical British and US data and find surprisingly high levels of long-run capital mobility throughout the century
Le vilayet d'Erzeroum. D'après les documents fournis par M. Vital Cuinet, M. C., Secrétaire de l'Administration de la dette publique ottomane, à Constantinople. Seconde et dernière partie
No full textHoffmann Louis-Frédéric. Le vilayet d'Erzeroum. D'après les documents fournis par M. Vital Cuinet, M. C., Secrétaire de l'Administration de la dette publique ottomane, à Constantinople. Seconde et dernière partie. In: Le Globe. Revue genevoise de géographie, tome 30, 1891. pp. 222-233
Ad Alterum Jubilaum Genethiliacum, Natalem Secularem Secundum Theandri Ac Prophetae Germaniae, D. Martini Lutheri, A. MCCCC LXXXIII. d. X. Novemb. Islebiae in vicinia nati, A. MDCLXXXIII. d. X. Novemb. Schola Schwarburgico-Francohusana Actu Ludo Oratorio ob merita in Ecclesiam collata grato ex animo celebrantum, Omnes Scholae Nostrae Patronos, Inspctores Et Fautores ... invitat M. Joh. Hoffmann/ P. L. C. Scholae Rect.
No full textAD ALTERUM JUBILAUM GENETHILIACUM, NATALEM SECULAREM SECUNDUM THEANDRI AC PROPHETAE GERMANIAE, D. MARTINI LUTHERI, A. MCCCC LXXXIII. D. X. NOVEMB. ISLEBIAE IN VICINIA NATI, A. MDCLXXXIII. D. X. NOVEMB. SCHOLA SCHWARBURGICO-FRANCOHUSANA ACTU LUDO ORATORIO OB MERITA IN ECCLESIAM COLLATA GRATO EX ANIMO CELEBRANTUM, OMNES SCHOLAE NOSTRAE PATRONOS, INSPCTORES ET FAUTORES ... INVITAT M. JOH. HOFFMANN/ P. L. C. SCHOLAE RECT.
Ad Alterum Jubilaum Genethiliacum, Natalem Secularem Secundum Theandri Ac Prophetae Germaniae, D. Martini Lutheri, A. MCCCC LXXXIII. d. X. Novemb. Islebiae in vicinia nati, A. MDCLXXXIII. d. X. Novemb. Schola Schwarburgico-Francohusana Actu Ludo Oratorio ob merita in Ecclesiam collata grato ex animo celebrantum, Omnes Scholae Nostrae Patronos, Inspctores Et Fautores ... invitat M. Joh. Hoffmann/ P. L. C. Scholae Rect. ([1])
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Eine nach dem Actu Oratorio abgesungene Danck- und Wunsch-Ode ([6]
Ad Auspicatissima Genethliaca d. XV. Octob. recurrentia Illustrissimi Comitis ac Domini, Dn. Ludovici Friderici, S.R.I. Quatuor-Viri, Comitis Schwarzburgi & Hohnsteni ... nec non Ad Examen Autumnale, Superiorum mandato d. XVIII. Octob. instituendum itemque Ad Leges Scholasticas Renovatas ... Ad Collegae Tertii Et Quinti solennem introductionem Patronos Et Inspectores Scholae ... invitat M. Johannes Hoffmann/ P. L. C. Scholae Francohusanae Rector.
No full textAD AUSPICATISSIMA GENETHLIACA D. XV. OCTOB. RECURRENTIA ILLUSTRISSIMI COMITIS AC DOMINI, DN. LUDOVICI FRIDERICI, S.R.I. QUATUOR-VIRI, COMITIS SCHWARZBURGI & HOHNSTENI ... NEC NON AD EXAMEN AUTUMNALE, SUPERIORUM MANDATO D. XVIII. OCTOB. INSTITUENDUM ITEMQUE AD LEGES SCHOLASTICAS RENOVATAS ... AD COLLEGAE TERTII ET QUINTI SOLENNEM INTRODUCTIONEM PATRONOS ET INSPECTORES SCHOLAE ... INVITAT M. JOHANNES HOFFMANN/ P. L. C. SCHOLAE FRANCOHUSANAE RECTOR.
Ad Auspicatissima Genethliaca d. XV. Octob. recurrentia Illustrissimi Comitis ac Domini, Dn. Ludovici Friderici, S.R.I. Quatuor-Viri, Comitis Schwarzburgi & Hohnsteni ... nec non Ad Examen Autumnale, Superiorum mandato d. XVIII. Octob. instituendum itemque Ad Leges Scholasticas Renovatas ... Ad Collegae Tertii Et Quinti solennem introductionem Patronos Et Inspectores Scholae ... invitat M. Johannes Hoffmann/ P. L. C. Scholae Francohusanae Rector. ([1])
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41. Salat (P.), Desbordes (F.), Le Boulluec (Α.), Daraki (M.), Saïd (S.), Zaslawsky (D.), Demont (P.), Biet (C), Études de littérature ancienne, tome 2 :i
No full textHoffmann Philippe. 41. Salat (P.), Desbordes (F.), Le Boulluec (Α.), Daraki (M.), Saïd (S.), Zaslawsky (D.), Demont (P.), Biet (C), Études de littérature ancienne, tome 2 :i. In: Revue des Études Grecques, tome 97, fascicule 460-461, Janvier-juin 1984. pp. 293-295
Hoffmann, Jacob (Death, 1904-01-05)
No full textAddress: 2527 Colerain Ave.Age at death: 47 yrs.Pg 3/1904/110/M W M/City/Dr. C. C. Agin/Jos. Schreiber/Spring GroveOriginal record filed in drawer labeled 'HOFFMANN-HOLMES'
Le Bassin Pétrolifère de Péchelbronn (Alsace). Etude géologique (Planches I-III)
No full textGignoux M., Hoffmann C. Le Bassin Pétrolifère de Péchelbronn (Alsace). Etude géologique (Planches I-III). In: Bulletin du Service de la carte géologique d'Alsace et de Lorraine, tome 1, n°1, 1920. pp. 1-46
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