A Simple, Mild, Catalytic, Enantioselective Addition of Terminal Acetylenes to AldehydesNeel K. Anand, Erick M. Carreira|Journal of the American Chemical Society|2001 ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA Simple, Mild, Catalytic, Enantioselective Addition of Terminal Acetylenes to AldehydesNeel K. Anand and Erick M. CarreiraView Author Information Laboratorium für Organische Chemie ETH-Zürich, Universitätstrasse 16 CH-8092 Zürich, Switzerland Cite this: J. Am. Chem. Soc. 2001, 123, 39, 9687–9688Publication Date (Web):September 7, 2001Publication History Received10 June 2001Published online7 September 2001Published inissue 1 October 2001https://pubs.acs.org/doi/10.1021/ja016378uhttps://doi.org/10.1021/ja016378urapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views8662Altmetric-Citations429LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Addition reactions,Alcohols,Aldehydes,Hydrocarbons,Ligands Get e-Alerts
Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)Kenneth D. Rice, Naing Aay, Neel K. Anand et al.|ACS Medicinal Chemistry Letters|2012 The ERK/MAP kinase cascade is a key mechanism subject to dysregulation in cancer and is constitutively activated or highly upregulated in many tumor types. Mutations associated with upstream pathway components RAS and Raf occur frequently and contribute to the oncogenic phenotype through activation of MEK and then ERK. Inhibitors of MEK have been shown to effectively block upregulated ERK/MAPK signaling in a range of cancer cell lines and have further demonstrated early evidence of efficacy in the clinic for the treatment of cancer. Guided by structural insight, a strategy aimed at the identification of an optimal diphenylamine-based MEK inhibitor with an improved metabolism and safety profile versus PD-0325901 led to the discovery of development candidate 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-[(2S)-piperidin-2-yl]azetidin-3-ol (XL518, GDC-0973) (1). XL518 exhibits robust in vitro and in vivo potency and efficacy in preclinical models with sustained duration of action and is currently in early stage clinical trials.
Asymmetric Synthesis of γ-Hydroxy α,β-Unsaturated Aldehydes via Enantioselective Direct Addition of Propargyl Acetate to AldehydesWe report the first example of enantioselective and diastereoselective aldehyde additions of propargyl acetate to aldehydes using the methodology recently reported from our laboratories. Subsequent O-silyl protection, Pd-catalyzed isomerization, AcOH addition, and hydrolysis result in optically active gamma-hydroxy alpha,beta-unsaturated aldehydes as powerful building blocks. Reaction: see text.