Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Johan Broddefalk is active.

Publication


Featured researches published by Johan Broddefalk.


Journal of Medicinal Chemistry | 2015

Discovery of AZD6642, an Inhibitor of 5-Lipoxygenase Activating Protein (FLAP) for the Treatment of Inflammatory Diseases

Malin Lemurell; Johan Ulander; Susanne Winiwarter; Anders Dahlén; Öjvind Davidsson; Hans Emtenäs; Johan Broddefalk; Marianne Swanson; Daniel Hovdal; Alleyn T. Plowright; Anna Pettersen; Marie Rydén-Landergren; Jonas G. Barlind; Antonio Llinas; Margareta Herslöf; Tomas Drmota; Kalle Sigfridsson; Sara Moses; Carl Whatling

A drug discovery program in search of novel 5-lipoxygenase activating protein (FLAP) inhibitors focused on driving a reduction in lipophilicity with maintained or increased ligand lipophilic efficiency (LLE) compared to previously reported compounds led to the discovery of AZD6642 (15b). Introduction of a hydrophilic tetrahydrofuran (THF) ring at the stereogenic central carbon atom led to a significant shift in physicochemical property space. The structure-activity relationship exploration and optimization of DMPK properties leading to this compound are described in addition to pharmacokinetic analysis and an investigation of the pharmacokinetic (PK)-pharmacodynamic (PD) relationship based on ex vivo leukotriene B4 (LTB4) levels in dog. AZD6642 shows high specific potency and low lipophilicity, resulting in a selective and metabolically stable profile. On the basis of initial PK/PD relation measured, a low dose to human was predicted.


Journal of Medicinal Chemistry | 2013

Discovery of Agonists of Cannabinoid Receptor 1 with Restricted Central Nervous System Penetration Aimed for Treatment of Gastroesophageal Reflux Disease

Alleyn T. Plowright; Karolina Nilsson; Madeleine Antonsson; Kosrat Amin; Johan Broddefalk; Jörgen Jensen; Anders Lehmann; Shujuan Jin; Stephane St-Onge; Miroslaw Tomaszewski; Maxime Tremblay; Christopher Walpole; Zhongyong Wei; Hua Yang; Johan Ulander

Agonists of the cannabinoid receptor 1 (CB1) have been suggested as possible treatments for a range of medical disorders including gastroesophageal reflux disease (GERD). While centrally acting cannabinoid agonists are known to produce psychotropic effects, it has been suggested that the CB1 receptors in the periphery could play a significant role in reducing reflux. A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries. Development of this series focused on improving potency and efficacy at the CB1 receptor, reducing lipophilicity and limiting the central nervous system (CNS) exposure while maintaining good oral absorption. Improvement of the series led to compounds having excellent potency at the CB1 receptor and high levels of agonism, good physical and pharmacokinetic properties, and low penetration into the CNS. A range of compounds demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.


Bioorganic & Medicinal Chemistry | 2011

Design of Small Molecule Inhibitors of Acetyl-Coa Carboxylase 1 and 2 Showing Reduction of Hepatic Malonyl-Coa Levels in Vivo in Obese Zucker Rats.

Christoffer Bengtsson; Stefan Blaho; David Blomberg Saitton; Kay Brickmann; Johan Broddefalk; Öjvind Davidsson; Tomas Drmota; Rutger H. A. Folmer; Kenth Hallberg; Stefan Hallén; Ragnar Hovland; Emre M. Isin; Petra Johannesson; Bengt Kull; Lars-Olof Larsson; Lars Löfgren; Kristina Nilsson; Tobias Noeske; Nick Oakes; Alleyn T. Plowright; Volker Schnecke; Pernilla Ståhlberg; Pernilla Sörme; Hong Wan; Eric Wellner; Linda Öster

Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.


ACS Medicinal Chemistry Letters | 2018

Discovery of a Series of Indole-2 Carboxamides as Selective Secreted Phospholipase A2 Type X (sPLA2-X) Inhibitors

Laurent Knerr; Fabrizio Giordanetto; Peter Nordberg; Daniel Pettersen; Nidhal Selmi; Hans-Georg Beisel; Hannah de la Motte; Thomas Olsson; Tim D. J. Perkins; Margareta Herslöf; Åsa Månsson; Mikael Dahlström; Ingemar Starke; Johan Broddefalk; Gabrielle Saarinen; Fredrik Klingegård; Eva Hurt-Camejo; Birgitta Rosengren; Johan Brengdahl; Frank Jansen; Mattias Rohman; Jenny Sandmark; Kenth Hallberg; Tomas Åkerud; Robert Roth; Marie Ahlqvist

In order to assess the potential of sPLA2-X as a therapeutic target for atherosclerosis, novel sPLA2 inhibitors with improved type X selectivity are required. To achieve the objective of identifying such compounds, we embarked on a lead generation effort that resulted in the identification of a novel series of indole-2-carboxamides as selective sPLA2-X inhibitors with excellent potential for further optimization.


Archive | 2005

Therapeutic Compounds: Pyridine as Scaffold

Kosrat Amin; Johan Broddefalk; Helene Desfosses; Emma Evertsson; Ziping AstraZeneca R D Montréal Liu; Claire Milburn; Karolina Nilsson; Maxime Tremblay; Christopher Walpole; Zhongyong AstraZeneca R D Montreal Wei; Hua AstraZeneca R D Montreal Yang


Archive | 2006

Novel 3-Bicyclocarbonylaminopyridine-2-Carboxamides or 3-Bicyclocarbonylaminopyrazine-2-Carboxamides

Kosrat Amin; Johan Broddefalk; Yantao Chen; Helene Desfosses; Ziping Liu; Claire Milburn; Karolina Nilsson; Maxime Tremblay; Christopher Walpole; Zhongyong Wei; Hua Yang


Organic Process Research & Development | 2018

A Practical Telescoped Three-Step Sequence for the Preparation of (1R,2R)-2-(4-Bromobenzoyl)cyclohexanecarboxylic Acid: A Key Building Block Used in One of Our Drug Development Projects

Staffan Karlsson; Rolf Bergman; Johan Broddefalk; Christian Löfberg; Peter R. Moore; Andrew Stark; Hans Emtenäs


ACS Medicinal Chemistry Letters | 2018

Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1H-indol-1-yl]pyridine-2-yl}propanoic Acid.

Fabrizio Giordanetto; Laurent Knerr; Peter Nordberg; Daniel Pettersen; Nidhal Selmi; Hans-Georg Beisel; H. de la Motte; A. Mansson; Mikael Dahlström; Johan Broddefalk; G. Saarinen; F. Klingegard; Eva Hurt-Camejo; Birgitta Rosengren; J. Wikstrom; M. Wagberg; Johan Brengdahl; Mattias Rohman; Jenny Sandmark; Tomas Åkerud; Robert Roth; F. Jansen; Marie Ahlqvist


Archive | 2017

DERIVADOS DE PIRAZOL ÚTILES COMO INHIBIDORES DE PROTEÍNA ACTIVADORA DE 5-LIPOXIGENASA (FLAP)

Johan Broddefalk; Hans Emtenäs; Kenneth Granberg; Malin Lemurell; Daniel Pettersen; Alleyn T. Plowright; Lars Johan Andreas Ulander


Archive | 2017

COMPUESTOS DE PIRAZOL INHIBIDORES DE PROTEÍNA ACTIVADORA DE 5-LIPOXIGENASA (FLAP)

Alleyn T. Plowright; Lars Johan Andreas Ulander; Daniel Pettersen; Malin Lemurell; Kenneth Granberg; Hans Fredrik Emtens; Johan Broddefalk

Collaboration


Dive into the Johan Broddefalk's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge