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Your search keyword '"Lustenberger, Philipp"' showing total 3 results
Start Over Author "Lustenberger, Philipp" Publisher elsevier science ltd
3 results on '"Lustenberger, Philipp"'

1. Design, synthesis and evaluation of MCH receptor 1 antagonists--Part I: Optimization of HTS hits towards an in vivo efficacious tool compound BI 414.

Author

Müller SG, Heckel A, Kley JT, Lehmann T, Lustenberger P, Oost T, Roth GJ, Rudolf K, Arndt K, Lenter M, Lotz RR, Maier GM, Markert M, Schindler M, and Stenkamp D

Subjects
ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Animals, Body Weight drug effects, Cytochrome P-450 CYP2D6 metabolism, Cytochrome P-450 Enzyme Inhibitors chemical synthesis, Cytochrome P-450 Enzyme Inhibitors pharmacology, Drug Design, Eating drug effects, High-Throughput Screening Assays, Obesity drug therapy, Rats, Receptors, G-Protein-Coupled drug effects, Receptors, G-Protein-Coupled metabolism, Structure-Activity Relationship, Alkynes chemical synthesis, Alkynes pharmacology, Anti-Obesity Agents chemical synthesis, Anti-Obesity Agents pharmacology, Pyridines chemical synthesis, Pyridines pharmacology, Receptors, Somatostatin antagonists & inhibitors
Abstract

Despite recent approvals of anti-obesity drugs there is still a high therapeutic need for alternative options with higher efficacy in humans. As part of our MCH-R1 antagonist program for the treatment of obesity, a series of biphenylacetamide HTS hits was evaluated. Several issues of the initial lead structures had to be resolved, such as potency, selectivity over related GPCRs and P-gp efflux limiting brain exposure in this series. We could demonstrate that all parameters can be significantly improved by structural modifications resulting in BI 414 as a potent and orally available MCH-R1 antagonist tool compound with acceptable in vivo efficacy in an animal model of obesity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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2. Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.

Author

Bouyssou T, Hoenke C, Rudolf K, Lustenberger P, Pestel S, Sieger P, Lotz R, Heine C, Büttner FH, Schnapp A, and Konetzki I

Subjects
Administration, Inhalation, Animals, Benzoxazines chemical synthesis, Bronchodilator Agents administration & dosage, Bronchodilator Agents pharmacology, CHO Cells, Cricetinae, Cricetulus, Dogs, Guinea Pigs, Humans, Male, Molecular Structure, Recombinant Proteins genetics, Stereoisomerism, Treatment Outcome, Adrenergic beta-2 Receptor Agonists, Benzoxazines chemistry, Benzoxazines pharmacology, Bronchodilator Agents chemistry
Abstract

Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human beta2-adrenoceptor with a high beta1/beta2-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5h was demonstrated for 4p in a guinea pig in vivo model without any signs of cardiovascular effects up to 10-fold above the first dose reaching 100% bronchoprotection. The enantiomerically pure (R)-form of 4p exerted a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects. Formoterol which was tested as comparator in the same in vivo models of acetylcholine-induced bronchoconstriction did not retain efficacy after 24 h. In summary, the preclinical profile of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety profile., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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3. Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action.

Author

Bouyssou T, Rudolf K, Hoenke C, Lustenberger P, Schnapp A, and Konetzki I

Subjects
Adrenergic beta-1 Receptor Agonists, Animals, Asthma drug therapy, Bronchodilator Agents chemical synthesis, Bronchodilator Agents pharmacology, Ethanolamines chemical synthesis, Ethanolamines pharmacology, Guinea Pigs, Heart Rate, Humans, Receptors, Adrenergic, beta-1 metabolism, Receptors, Adrenergic, beta-2 metabolism, Adrenergic beta-2 Receptor Agonists, Bronchodilator Agents chemistry, Ethanolamines chemistry
Abstract

Beta2-adrenoceptor agonists with basic and acidic groups attached via an alkyl linker to the phenyl ethanolamine core were prepared and investigated in vitro and in vivo. The compounds exhibited a high potency in a functional cellular assay and a bronchoprotective effect in a guinea pig model which lasted over the complete study period of 5h.

Published
2009
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