Regressionsanalyse von Struktur‐Wirkungs‐Beziehungen (Hansch‐Analyse)

Druckrey, E.

doi:10.1002/pauz.19750040503

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…Plots of log( K d ) = f ( ν )(left) and log( K d ) = f (π) (right) using the mean values of the K d values (nM) of compounds ( S )-1f – ( S )-1l (Table ) and the following values for ν(Å): , 0.00 (H), 0.27 (F), 0.52 (CH 3 ), 0.55 (Cl), 0.65 (Br), 0.78 (I), 0.91 (CF 3 ); and π: 0.00 (H), 0.14 (F), 0.55 (CH 3 ), 0.71 (Cl), 0.86 (Br), 0.88 (CF 3 ), 1.12 (I). Regression analysis was performed by linear regression; n denotes the amount of data points, s denotes the standard deviation of the regression equation, and R 2 denotes the coefficient of determination. , For linear regressions in black, all data points were considered, while for linear regression in red, the data for CF 3 were excluded.…”

Section: Resultsmentioning

confidence: 99%

“…Regression analysis was performed by linear regression; n denotes the amount of data points, s denotes the standard deviation of the regression equation, and R 2 denotes the coefficient of determination. 60,61 For linear regressions in black, all data points were considered, while for linear regression in red, the data for CF 3 were excluded. IPB-Glu N-terminally on their somatostatin analogues to simplify the solid-phase synthesis of the peptides.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Plots of log(AUC 0−48 h [Organ]) = f(log(K d [HSA])) using the mean values of AUC (Figure 9A and TableS2) and K d (nM, Table3) of compounds [64 Cu]Cu-NODAGA-cLAB(1−4)-TATEs. Regression analysis was performed by linear regression; n denotes the amount of data points, s denotes the standard deviation of the regression equation, and R 2 denotes the coefficient of determination 60,61.…”

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confidence: 99%

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“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

et al. 2021

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The intentional binding of radioligands to albumin gains increasing attention in the context of radiopharmaceutical cancer therapy as it can lead to an enhanced radioactivity uptake into the tumor lesions and, thus, to a potentially improved therapeutic outcome. However, the influence of the radioligand’s albumin-binding affinity on the time profile of tumor uptake has been only partly addressed so far. Based on the previously identified N ε-4-(4-iodophenyl)butanoyl-lysine scaffold, we designed “clickable” lysine-derived albumin binders (cLABs) and determined their dissociation constants toward albumin by novel assay methods. Structure–activity relationships were derived, and selected cLABs were applied for the modification of the somatostatin receptor subtype 2 ligand (Tyr3)octreotate. These novel conjugates were radiolabeled with copper-64 and subjected to a detailed in vitro and in vivo radiopharmacological characterization. Overall, the results of this study provide an incentive for further investigations of albumin binders for applications in endoradionuclide therapies.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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confidence: 99%

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“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

et al. 2021

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“…Plots of log( k inact / K I ) = f (ν) (left) and log( k inact / K I ) = f ( E S ) (right) using the mean values of the inactivation constants (M –1 s –1 ) of compounds 6a and 7a – e (Table ) and the following values for ν(Å): ,, 0.00 (H), 0.27 (F), 0.52 (CH 3 ), 0.55 (Cl), 0.65 (Br), and 0.78 (I); and E S : , 0.00 (H), −0.46 (F), −1.24 (CH 3 ), −0.97 (Cl), −1.16 (Br), and −1.40 (I). Regression analysis was performed by linear regression; n denotes to the amount of data points, s to the standard deviation of the regression equation, and R 2 to the coefficient of determination. , …”

Section: Resultsmentioning

confidence: 99%

N^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling

et al. 2018

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Transglutaminase 2 (TGase 2)-catalyzed transamidation represents an important post-translational mechanism for protein modification with implications in physiological and pathophysiological conditions, including fibrotic and neoplastic processes. Consequently, this enzyme is considered a promising target for the diagnosis of and therapy for these diseases. In this study, we report on the synthesis and kinetic characterization of N-acryloyllysine piperazides as irreversible inhibitors of TGase 2. Systematic structural modifications on 54 new compounds were performed with a major focus on fluorine-bearing substituents due to the potential of such compounds to serve as radiotracer candidates for positron emission tomography. The determined inhibitory activities ranged from 100 to 10 000 M s, which resulted in comprehensive structure-activity relationships. Structure-activity correlations using various substituent parameters accompanied by covalent docking studies provide an advanced understanding of the molecular recognition for this inhibitor class within the active site of TGase 2. Selectivity profiling of selected compounds for other transglutaminases demonstrated an excellent selectivity toward transglutaminase 2. Furthermore, an initial pharmacokinetic profiling of selected inhibitors was performed, including the assessment of potential membrane permeability and liver microsomal stability.

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Akute Toxizität von Endomid® und seinen Metaboliten. Korrelation zwischen biologischer Aktivität und lipophilen Eigenschaften

Koch

Bodmann

1976

Archiv der Pharmazie

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Die LDm von Endomid (1) und von funf seiner Metaboliten 2-6 wurde an der Maus bestimmt. Die Toxizitit nimmt in der Reihenfolge von 1 bis 6 kontinuierlich ab, eine potentielle Gefahr als Folge der Metabolisierung kann daher ausgeschlossen werden Die Loslichkeit, der n-Octanoy Wasser-Verteilungskoefffizient, der RM-Wert und die Permeationsgeschwindigkeit in einem Invitro-Resorptionsmodell von 1-6 wurden bestimmt und zur biologischen Aktivitat in Beziehung gesetzt.Acute Toxicity of Endomide and Its Metabolites. Correlation between Biological Activity and Lipophilic PropertiesThe medium letal doses of endomide (1) and of five of its metabolites 2-6 have been estimated in the mouse. Toxicity decreases from 1 to 6. A risk as a consequence of metabolization can thus be excluded. The solubilities, the n-octanoywater partition coefficients, the RM values and the permeation rates in an in vitro absorption model have been estimated for 1-6 and put into relation with the biological activities.

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Regressionsanalyse von Struktur‐Wirkungs‐Beziehungen (Hansch‐Analyse)

Cited by 4 publications

References 3 publications

“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

N^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling

Akute Toxizität von Endomid® und seinen Metaboliten. Korrelation zwischen biologischer Aktivität und lipophilen Eigenschaften

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Regressionsanalyse von Struktur‐Wirkungs‐Beziehungen (Hansch‐Analyse)

Cited by 4 publications

References 3 publications

“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

“Clickable” Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals

Nε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling

Akute Toxizität von Endomid® und seinen Metaboliten. Korrelation zwischen biologischer Aktivität und lipophilen Eigenschaften

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N^ε-Acryloyllysine Piperazides as Irreversible Inhibitors of Transglutaminase 2: Synthesis, Structure–Activity Relationships, and Pharmacokinetic Profiling