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

Direct Trifluoromethylation of the CH Bond

(2013) Hui Liu et al.   ADVANCED SYNTHESIS & CATALYSIS

Rhodium(I)-Catalyzed Redox-Economic Cross-Coupling of Carboxylic Acids with Arenes Directed by N-Containing Groups

(2013) Fei Pan et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Optimization of Chloronitrobenzamides (CNBs) as Therapeutic Leads for Human African Trypanosomiasis (HAT)

(2013) Jong Yeon Hwang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of Dual PLD1/2 and PLD2 Selective Inhibitors from a Common 1,3,8-Triazaspiro[4.5]decane Core: Discovery of ML298 and ML299 That Decrease Invasive Migration in U87-MG Glioblastoma Cells

(2013) Matthew C. O’Reilly et al.   JOURNAL OF MEDICINAL CHEMISTRY

Torsion Angle Preferences in Druglike Chemical Space: A Comprehensive Guide

(2013) Christin Schärfer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Palladium-Catalyzed Picolinamide-Directed Alkylation of Unactivated C(sp3)–H Bonds with Alkyl Iodides

(2013) Shu-Yu Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Mild Palladium-Catalyzed C–H Alkylation Using Potassium Alkyltrifluoroborates in Combination with MnF3

(2013) Sharon R. Neufeldt et al.   ORGANIC LETTERS

Palladium-Catalyzed CH Oxidation of Isoquinoline N-Oxides: Selective Alkylation with Dialkyl Sulfoxides and Halogenation with Dihalo sulfoxides

(2012) Bo Yao et al.   ADVANCED SYNTHESIS & CATALYSIS

Copper-Catalyzed Difluoromethylation of β,γ-Unsaturated Carboxylic Acids: An Efficient Allylic Difluoromethylation

(2012) Zhengbiao He et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Copper-Mediated Difluoromethylation of (Hetero)aryl Iodides and β-Styryl Halides with Tributyl(difluoromethyl)stannane

(2012) G. K. Surya Prakash et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Scaffold-hopping with zwitterionic CCR3 antagonists: Identification and optimisation of a series with good potency and pharmacokinetics leading to the discovery of AZ12436092

(2012) Ash Bahl et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis and SAR of 2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-ones as 5-HT2C receptor agonists

(2012) John M. Fevig et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

S-Adenosyl-Methionine-Dependent Methyltransferases: Highly Versatile Enzymes in Biocatalysis, Biosynthesis and Other Biotechnological Applications

(2012) Anna-Winona Struck et al.   CHEMBIOCHEM

A Potent and Selective S1P1 Antagonist with Efficacy in Experimental Autoimmune Encephalomyelitis

(2012) Jean Quancard et al.   CHEMISTRY & BIOLOGY

Discovery of [(2R,5R)-5-{[(5-Fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1-yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanone (MK-6096): A Dual Orexin Receptor Antagonist with Potent Sleep-Promoting Properties

(2012) Paul J. Coleman et al.   ChemMedChem

Methyl Effects on Protein–Ligand Binding

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

A New Reagent for Direct Difluoromethylation

(2012) Yuta Fujiwara et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Copper-Mediated Difluoromethylation of Aryl and Vinyl Iodides

(2012) Patrick S. Fier et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Practical and innate carbon–hydrogen functionalization of heterocycles

(2012) Yuta Fujiwara et al.   NATURE

Finding the sweet spot: the role of nature and nurture in medicinal chemistry

(2012) Michael M. Hann et al.   NATURE REVIEWS DRUG DISCOVERY

Methane: a new frontier in organometallic chemistry

(2012) Vincent N. Cavaliere et al.   Chemical Science

Efficient Difluoromethylation of sp3Carbon Nucleophiles by Bromodifluoromethylation Reagents with Organic Bases

(2012) Guokai Liu et al.   ChemistryOpen

Innate and Guided C–H Functionalization Logic

(2011) Tobias Brückl et al.   ACCOUNTS OF CHEMICAL RESEARCH

Weak Coordination as a Powerful Means for Developing Broadly Useful C–H Functionalization Reactions

(2011) Keary M. Engle et al.   ACCOUNTS OF CHEMICAL RESEARCH

Radical-Mediated Enzymatic Methylation: A Tale of Two SAMS

(2011) Qi Zhang et al.   ACCOUNTS OF CHEMICAL RESEARCH

Regio- and Chemoselective Metalation of Arenes and Heteroarenes Using Hindered Metal Amide Bases

(2011) Benjamin Haag et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

“Molecular Switches” on mGluR Allosteric Ligands That Modulate Modes of Pharmacology

(2011) Michael R. Wood et al.   BIOCHEMISTRY

Pd-Catalyzed ortho-Methylation of Acetanilides via Directed C-H Activation

(2011) Min-Jung Jang et al.   BULLETIN OF THE KOREAN CHEMICAL SOCIETY

The Methylation Effect in Medicinal Chemistry

(2011) Eliezer J. Barreiro et al.   CHEMICAL REVIEWS

Guiding principles for site selective and stereoselective intermolecular C–H functionalization by donor/acceptor rhodium carbenes

(2011) Huw M. L. Davies et al.   CHEMICAL SOCIETY REVIEWS

Enantiocontrolled Synthesis of β-Branched α-Amino Acids by Using CuI-Catalyzed 1,4-Addition of Glycine Imines to β-Substituted gem-Diactivated Olefins

(2011) Jorge Hernández-Toribio et al.   CHEMISTRY-A EUROPEAN JOURNAL

Discovery and SAR of Methylated Tetrahydropyranyl Derivatives as Inhibitors of Isoprenylcysteine Carboxyl Methyltransferase (ICMT)

(2011) Weston R. Judd et al.   JOURNAL OF MEDICINAL CHEMISTRY

1-[(1-Methyl-1H-imidazol-2-yl)methyl]-4-phenylpiperidines as mGluR2 Positive Allosteric Modulators for the Treatment of Psychosis

(2011) Lei Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biphenyl-Substituted Oxazolidinones as Cholesteryl Ester Transfer Protein Inhibitors: Modifications of the Oxazolidinone Ring Leading to the Discovery of Anacetrapib

(2011) Cameron J. Smith et al.   JOURNAL OF MEDICINAL CHEMISTRY

Palladium-Catalyzed Coupling of Arene C–H Bonds with Methyl- and Arylboron Reagents Assisted by the Removable 2-Pyridylsulfinyl Group

(2011) José A. Romero-Revilla et al.   JOURNAL OF ORGANIC CHEMISTRY

Divergent C–H Functionalizations Directed by Sulfonamide Pharmacophores: Late-Stage Diversification as a Tool for Drug Discovery

(2011) Hui-Xiong Dai et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Catalysis for fluorination and trifluoromethylation

(2011) Takeru Furuya et al.   NATURE

Trifluoromethylation of arenes and heteroarenes by means of photoredox catalysis

(2011) David A. Nagib et al.   NATURE

Cobalt-Catalyzed Coupling of Alkyl Grignard Reagent with Benzamide and 2-Phenylpyridine Derivatives through Directed C–H Bond Activation under Air

(2011) Quan Chen et al.   ORGANIC LETTERS

A New Method for Aromatic Difluoromethylation: Copper-Catalyzed Cross-Coupling and Decarboxylation Sequence from Aryl Iodides

(2011) Kenichi Fujikawa et al.   ORGANIC LETTERS

Direct Alkylation of Heteroaryls Using Potassium Alkyl- and Alkoxymethyltrifluoroborates

(2011) Gary A. Molander et al.   ORGANIC LETTERS

Palladium-Catalyzed Alkylation ofortho-C(sp2)–H Bonds of Benzylamide Substrates with Alkyl Halides

(2011) Yingsheng Zhao et al.   ORGANIC LETTERS

RNA methylation by Radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift

(2011) F. Yan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Radically Different Mechanism for S-Adenosylmethionine-Dependent Methyltransferases

(2011) T. L. Grove et al.   SCIENCE

Structural Basis for Methyl Transfer by a Radical SAM Enzyme

(2011) A. K. Boal et al.   SCIENCE

Silver-Catalyzed C-C Bond Formation Between Methane and Ethyl Diazoacetate in Supercritical CO2

(2011) A. Caballero et al.   SCIENCE

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

(2011) Matthew A. J. Duncton   MedChemComm

The identification of novel orally active mGluR5 antagonist GSK2210875

(2010) Maria Pilla et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore

(2010) Lianhai Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors

(2010) Josef R. Bencsik et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A Graphical Journey of Innovative Organic Architectures That Have Improved Our Lives

(2010) Nicholas A. McGrath et al.   JOURNAL OF CHEMICAL EDUCATION

Discovery of a Selective Small-Molecule Melanocortin-4 Receptor Agonist with Efficacy in a Pilot Study of Sexual Dysfunction in Humans

(2010) Mark I. Lansdell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Severe Acute Respiratory Syndrome Coronavirus Papain-like Novel Protease Inhibitors: Design, Synthesis, Protein−Ligand X-ray Structure and Biological Evaluation

(2010) Arun K. Ghosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Medicinal Chemist’s Guide to Molecular Interactions

(2010) Caterina Bissantz et al.   JOURNAL OF MEDICINAL CHEMISTRY

Asymmetric Deprotonation ofN-Boc Piperidine: React IR Monitoring and Mechanistic Aspects

(2010) Darren Stead et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

RlmN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA

(2010) Feng Yan et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Auxiliary-Assisted Palladium-Catalyzed Arylation and Alkylation of sp2and sp3Carbon−Hydrogen Bonds

(2010) Dmitry Shabashov et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Spirastrellolide studies. Synthesis of the C(1)–C(25) southern hemispheres of spirastrellolides A and B, exploiting anion relay chemistry

(2010) Amos B. Smith et al.   TETRAHEDRON

Discovery of a Potent and Orally Bioavailable CCR2 and CCR5 Dual Antagonist

(2010) Alexander Pasternak et al.   ACS Medicinal Chemistry Letters

Biocatalytic Friedel-Crafts Alkylation Using Non-natural Cofactors

(2009) Harald Stecher et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Conformational analysis of N,N-disubstituted-1,4-diazepane orexin receptor antagonists and implications for receptor binding

(2009) Christopher D. Cox et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Carbonic anhydrase inhibitors. Inhibition of the fungal β-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids

(2009) Alessio Innocenti et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors

(2009) Markus Boehringer et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Formal Highly Enantioselective Organocatalytic Addition of Alkyl Anions to α,β-Unsaturated Aldehydes: Application to the Synthesis of Isotope-Enantiomers

(2009) Andrea-Nekane Alba et al.   CHEMISTRY-A EUROPEAN JOURNAL

Increasing Selectivity of CC Chemokine Receptor 8 Antagonists by Engineering Nondesolvation Related Interactions with the Intended and Off-Target Binding Sites

(2009) Igor Shamovsky et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Two-Step, Formal [4 + 2] Approach toward Piperidin-4-ones via Au Catalysis

(2009) Li Cui et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Direct palladium-catalyzed alkenylation, benzylation and alkylation of ethyl oxazole-4-carboxylate with alkenyl-, benzyl- and alkyl halides

(2009) Cécile Verrier et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Biphenyl amide p38 kinase inhibitors 3: Improvement of cellular and in vivo activity

(2008) Richard Angell et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors

(2008) David J. Kopecky et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ8−Δ7Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity

(2008) Francesco Berardi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cyclization Reactions Involving Palladium-Catalyzed Carbene Insertion into Aryl Halides

(2008) Romas Kudirka et al.   JOURNAL OF ORGANIC CHEMISTRY

Pd(II)-Catalyzed Cross-Coupling of sp3C−H Bonds with sp2and sp3Boronic Acids Using Air as the Oxidant

(2008) Dong-Hui Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Palladium-Catalyzed Methylation of Aryl C−H Bond by Using Peroxides

(2008) Yuhua Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY