Atropisomerism in medicinal chemistry: challenges and opportunities

Recent encounters with atropisomerism in drug discovery

(2018) Peter W. Glunz   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and Assessment of Atropisomers of (±)-Lesinurad

(2017) Jianfei Wang et al.   ACS Medicinal Chemistry Letters

Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2

(2016) Scott A. Foster et al.   CANCER CELL

Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton’s Tyrosine Kinase (BTK) Conformationally Constrained by Two Locked Atropisomers

(2016) Scott H. Watterson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Exploiting Atropisomerism to Increase the Target Selectivity of Kinase Inhibitors

(2015) Davis E. Smith et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV Integrase Inhibitor

(2015) Keith R. Fandrick et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for Atropselective Chemical Transformations

(2015) Elango Kumarasamy et al.   CHEMICAL REVIEWS

Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?

(2015) Dean G. Brown et al.   JOURNAL OF MEDICINAL CHEMISTRY

Atroposelective Synthesis of Axially Chiral Biaryldiols via Organocatalytic Arylation of 2-Naphthols

(2015) Ye-Hui Chen et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-Catalyzed Atroposelective Bromination

(2015) Matthew E. Diener et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

FDA-approved small-molecule kinase inhibitors

(2015) Peng Wu et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Catalytic Enantioselective Synthesis of Atropisomeric Biaryls: A Cation-Directed Nucleophilic Aromatic Substitution Reaction

(2014) Roly J. Armstrong et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

New Frontiers in Kinases: Second Generation Inhibitors

(2014) Stefan Laufer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Distinct Binding Mode of Multikinase Inhibitor Lenvatinib Revealed by Biochemical Characterization

(2014) Kiyoshi Okamoto et al.   ACS Medicinal Chemistry Letters

Kinase Drug Discovery – What’s Next in the Field?

(2013) Philip Cohen et al.   ACS Chemical Biology

Profound Methyl Effects in Drug Discovery and a Call for New CH Methylation Reactions

(2013) Heike Schönherr et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Developing Irreversible Inhibitors of the Protein Kinase Cysteinome

(2013) Qingsong Liu et al.   CHEMISTRY & BIOLOGY

Biological Stereoselectivity of Atropisomeric Natural Products and Drugs

(2013) Arie Zask et al.   CHIRALITY

Discovery of Selective Small Molecule Type III Phosphatidylinositol 4-Kinase Alpha (PI4KIIIα) Inhibitors as Anti Hepatitis C (HCV) Agents

(2013) Anna L. Leivers et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis, Resolution, and Biological Evaluation of Atropisomeric (aR)- and (aS)-16-Methyllamellarins N: Unique Effects of the Axial Chirality on the Selectivity of Protein Kinases Inhibition

(2013) Kenyu Yoshida et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enantiomeric Atropisomers Inhibit HCV Polymerase and/or HIV Matrix: Characterizing Hindered Bond Rotations and Target Selectivity

(2013) Steven R. LaPlante et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enantioselective Synthesis of Atropisomeric Benzamides through Peptide-Catalyzed Bromination

(2013) Kimberly T. Barrett et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Asymmetric Synthesis of QUINAP via Dynamic Kinetic Resolution

(2013) Vikram Bhat et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

DrugBank 4.0: shedding new light on drug metabolism

(2013) Vivian Law et al.   NUCLEIC ACIDS RESEARCH

Methyl Effects on Protein–Ligand Binding

(2012) Cheryl S. Leung et al.   JOURNAL OF MEDICINAL CHEMISTRY

Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks

(2012) Tjeerd Barf et al.   JOURNAL OF MEDICINAL CHEMISTRY

Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives

(2012) Kate M. Clapham et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Structural and Spectroscopic Analysis of the Kinase Inhibitor Bosutinib and an Isomer of Bosutinib Binding to the Abl Tyrosine Kinase Domain

(2012) Nicholas M. Levinson et al.   PLoS One

Discovery of atrop fixed alkoxy-aminobenzhydrol derivatives: Novel, highly potent and orally efficacious squalene synthase inhibitors

(2011) Masanori Ichikawa et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Revealing Atropisomer Axial Chirality in Drug Discovery

(2011) Steven R. LaPlante et al.   ChemMedChem

Assessing Atropisomer Axial Chirality in Drug Discovery and Development

(2011) Steven R. LaPlante et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates

(2011) Stephen D. Roughley et al.   JOURNAL OF MEDICINAL CHEMISTRY

Comprehensive analysis of kinase inhibitor selectivity

(2011) Mindy I Davis et al.   NATURE BIOTECHNOLOGY

Atropisomerism Observed in Indometacin Derivatives

(2011) Hideyo Takahashi et al.   ORGANIC LETTERS

Biocatalytic Desymmetrization of an Atropisomer with both an Enantioselective Oxidase and Ketoreductases

(2010) Bo Yuan et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Synthesis, SAR, and atropisomerism of imidazolopyrimidine DPP4 inhibitors

(2010) Stephen P. O’Connor et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products

(2010) Gerhard Bringmann et al.   CHEMICAL REVIEWS

Targeted covalent drugs of the kinase family

(2010) Juswinder Singh et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Insights into the Origins of Configurational Stability of Axially Chiral Biaryl Amines with an Intramolecular N−H−N Hydrogen Bond

(2010) Kazuhiro Hayashi et al.   JOURNAL OF ORGANIC CHEMISTRY

Dynamic Kinetic Resolution of Biaryl Atropisomers via Peptide-Catalyzed Asymmetric Bromination

(2010) J. L. Gustafson et al.   SCIENCE

Cardiotoxicity Associated with Targeting Kinase Pathways in Cancer

(2010) Howard R. Mellor et al.   TOXICOLOGICAL SCIENCES

The Challenge of Atropisomerism in Drug Discovery

(2009) Jonathan Clayden et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Atropisomeric small molecule Bcl-2 ligands: Determination of bioactive conformation

(2009) John Porter et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy

(2009) M. H. Kang et al.   CLINICAL CANCER RESEARCH

Enantioselective Synthesis of an Atropisomeric Diaryl Ether

(2008) Jonathan Clayden et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (−)-ephedrine or a proline-derived diamine

(2008) Ann Bracegirdle et al.   Beilstein Journal of Organic Chemistry

Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors

(2008) John Porter et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Total and Percent Atropisomers of Gossypol and Gossypol-6-methyl Ether in Seeds from Pima Cottons and Accessions of Gossypium barbadense L

(2008) Robert D. Stipanovic et al.   JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY

Structural Requirements for Eszopiclone and Zolpidem Binding to the γ-Aminobutyric Acid Type-A (GABAA) Receptor Are Different

(2008) Susan M. Hanson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Axially Chiral Binaphthyl Surrogates with an Inner N−H−N Hydrogen Bond

(2008) Takeo Kawabata et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The exploration of macrocycles for drug discovery — an underexploited structural class

(2008) Edward M. Driggers et al.   NATURE REVIEWS DRUG DISCOVERY

Pharmacological PKA Inhibition: All May Not Be What It Seems

(2008) A. J. Murray   Science Signaling