Atropisomerism in Drug Discovery: A Medicinal Chemistry Perspective Inspired by Atropisomeric Class I PI3K Inhibitors

Fragment-Based Discovery of MRTX1719, a Synthetic Lethal Inhibitor of the PRMT5•MTA Complex for the Treatment of MTAP-Deleted Cancers

(2022) Christopher R. Smith et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent Advances in Catalytic Asymmetric Construction of Atropisomers

(2021) Jun Kee Cheng et al.   CHEMICAL REVIEWS

PI3K inhibitors are finally coming of age

(2021) Bart Vanhaesebroeck et al.   NATURE REVIEWS DRUG DISCOVERY

Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C

(2020) Jason G. Kettle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of an Atropisomeric PI3Kβ Selective Inhibitor through Optimization of the Hinge Binding Motif

(2020) Stephane Perreault et al.   ACS Medicinal Chemistry Letters

Driving Potency with Rotationally Stable Atropisomers: Discovery of Pyridopyrimidinedione-Carbazole Inhibitors of BTK

(2020) Anurag S. Srivastava et al.   ACS Medicinal Chemistry Letters

Disparate Catalytic Scaffolds for Atroposelective Cyclodehydration

(2019) Yongseok Kwon et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Metabolism by Aldehyde Oxidase: Drug Design and Complementary Approaches to Challenges in Drug Discovery

(2019) Nenad Manevski et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors

(2019) Brian A. Lanman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent encounters with atropisomerism in drug discovery

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

Atropisomerism in medicinal chemistry: challenges and opportunities

(2018) Sean T Toenjes et al.   Future Medicinal Chemistry

Atropisomerism by Design: Discovery of a Selective and Stable Phosphoinositide 3-Kinase (PI3K) β Inhibitor

(2018) Jayaraman Chandrasekhar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design

(2018) Nicholas A. Meanwell   JOURNAL OF MEDICINAL CHEMISTRY

Targeting the PI3K pathway in cancer: are we making headway?

(2018) Filip Janku et al.   Nature Reviews Clinical Oncology

Class 1 PI3K Clinical Candidates and Recent Inhibitor Design Strategies: A Medicinal Chemistry Perspective

(2018) Aimie E. Garces et al.   JOURNAL OF MEDICINAL CHEMISTRY

The role of chromatographic and chiroptical spectroscopic techniques and methodologies in support of drug discovery for atropisomeric drug inhibitors of Bruton’s tyrosine kinase

(2017) Jun Dai et al.   JOURNAL OF CHROMATOGRAPHY A

Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856

(2017) Stephane Perreault et al.   JOURNAL OF MEDICINAL CHEMISTRY

2,4,6-Triaminopyrimidine as a Novel Hinge Binder in a Series of PI3Kδ Selective Inhibitors

(2016) Leena Patel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability

(2016) Leena Patel et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

Atropisomerism in 3-arylthiazolidine-2-thiones. A combined dynamic NMR and dynamic HPLC study

(2016) A. Ciogli et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Exploiting Atropisomerism to Increase the Target Selectivity of Kinase Inhibitors

(2015) Davis E. Smith 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

Structural, Biochemical, and Biophysical Characterization of Idelalisib Binding to Phosphoinositide 3-Kinase δ

(2015) John R. Somoza et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Chromatographic resolution of atropisomers for toxicity and biotransformation studies in pharmaceutical research

(2015) Tony Qi Yan et al.   JOURNAL OF CHROMATOGRAPHY A

A twist of nature – the significance of atropisomers in biological systems

(2015) Jamie E. Smyth et al.   NATURAL PRODUCT REPORTS

Vibrational Circular Dichroism (VCD) Chiral Assignment of Atropisomers: Application to γ-Aminobutyric Acid (GABA) Modulators Designed as Potential Anxiolytic Drugs

(2013) Don E. Pivonka et al.   APPLIED SPECTROSCOPY

A rapid alternative to X-ray crystallography for chiral determination: Case studies of vibrational circular dichroism (VCD) to advance drug discovery projects

(2013) Steven S. Wesolowski et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

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

CAL-101, a p110  selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability

(2010) B. J. Lannutti et al.   BLOOD

Phosphatidylinositol 3-kinase-  inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals

(2010) S. E. M. Herman et al.   BLOOD

Atroposelective Total Synthesis of Axially Chiral Biaryl Natural Products

(2010) Gerhard Bringmann et al.   CHEMICAL REVIEWS

The p110δ structure: mechanisms for selectivity and potency of new PI(3)K inhibitors

(2010) Alex Berndt et al.   Nature Chemical Biology