Journal ArticleDOI
Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals
TLDR
This review reports on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals, and reports detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.Abstract:
Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.read more
Citations
More filters
Journal ArticleDOI
Advances in Electrochemical Decarboxylative Transformation Reactions.
TL;DR: This minireview summary of the recent advances and discoveries on the electrochemical decarboxylative transformations on C-C and C-heteroatoms bond formations shows good tolerance with various functional groups.
Journal ArticleDOI
The Development of a Weighted Index to Optimise Compound Libraries for High Throughput Screening.
TL;DR: Known Drug Indexes are advantageous tools in identifying the most well‐balanced screening compounds based on the properties of known drugs; the screening collection can be optimised to only include quality compounds, which in turn produce tractable hit and lead compounds from the screening campaign.
Journal ArticleDOI
Enantioselective N-Alkylation of Indoles via an Intermolecular Aza-Wacker-Type Reaction.
TL;DR: Isotopic-labeling experiments support a syn amino-palladation mechanism for this new class of aza-Wacker reactions, and Allylic and homoallylic alcohols with a variety of functional groups are compatible with the reaction in high enantioselectivity.
Journal ArticleDOI
Kinetic Resolution and Deracemization of Racemic Amines Using a Reductive Aminase
Godwin A. Aleku,Juan Mangas-Sanchez,Joan Citoler,Sarah L. Montgomery,Rachel S. Heath,Matthew P. Thompson,Nicholas J. Turner +6 more
TL;DR: By using the AspRedAm W210A variant it was possible to generate the opposite R enantiomers with efficiency comparable to, or even better than, the wildtype Asp redox system.
Journal ArticleDOI
Modular, stereocontrolled Cβ-H/Cα-C activation of alkyl carboxylic acids.
Ming Shang,Karla S. Feu,Julien C. Vantourout,Lisa M. Barton,Heather L. Osswald,Nobutaka Kato,Kerstin Gagaring,Case W. McNamara,Gang Chen,Liang Hu,Shengyang Ni,Paula Fernández-Canelas,Miao Chen,Rohan R. Merchant,Tian Qin,Stuart L. Schreiber,Stuart L. Schreiber,Bruno Melillo,Bruno Melillo,Jin-Quan Yu,Phil S. Baran +20 more
TL;DR: A C–H activation of ubiquitous carboxylic acids followed by their decarboxylative functionalization provides modular access to difunctionalized carbon frameworks with distinctly controlled stereochemistry in a way that is modular and thus, amenable to rapid diversity incorporation.
References
More filters
Journal ArticleDOI
Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group.
Irwin Goldstein,Tom F. Lue,Harin Padma-Nathan,Raymond C. Rosen,William D. Steers,Pierre A. Wicker +5 more
TL;DR: Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction and is associated with improved erectile function in the dose-response study.
Journal ArticleDOI
Marine indole alkaloids: potential new drug leads for the control of depression and anxiety
TL;DR: Information is provided on current and potential pharmaceuticals including small molecule natural indole alkaloids to their biological properties, structure-activity relationship studies, and especially their potential for the treatment of neurological disorders, including depression.
Journal ArticleDOI
Rings in Drugs
TL;DR: Analysis of rings, ring systems, and frameworks in drugs listed in the FDA Orange Book gives insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond.
Journal ArticleDOI
Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery.
TL;DR: The evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated and promoted to promote innovative insights into drug development.
Journal ArticleDOI
Metallodrugs in Medicinal Inorganic Chemistry
Katja Dralle Mjos,Chris Orvig +1 more