FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2336885655> ?p ?o ?g. }

• W2336885655 endingPage "494" @default.
• W2336885655 startingPage "491" @default.
• W2336885655 abstract "Future Medicinal ChemistryVol. 8, No. 5 EditorialFree AccessDeuterium medicinal chemistry comes of ageRoger D TungRoger D Tung*Author for correspondence: E-mail Address: rtung@concertpharma.com Concert Pharmaceuticals, Inc., 99 Hayden Ave., Ste. 500, Lexington, MA 02421, USASearch for more papers by this authorPublished Online:15 Apr 2016https://doi.org/10.4155/fmc-2016-0032AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: drug designdrug developmentpharmacodynamicspharmacokineticsFirst draft submitted: 20 January 2016; Accepted for publication: 5 February 2016; Published online: 15 April 2016Deuterium is gaining increased appreciation and utilization as a component of active pharmaceutical ingredients. Deuterium-modified or -deuterated compounds retain the potency and selectivity of their hydrogen analogs. However, in certain cases, the deuterium isotope effect can significantly modify drug metabolism, offering the potential to positively impact safety, tolerability or efficacy properties [1–3]. Nevertheless, it has taken decades since deuterated drugs were first explored for them to reach late-stage clinical evaluation. Some earlier reviewers concluded that deuterium substitution would likely not significantly improve drugs and their commercialization was questionable or unlikely [4,5]. This editorial focuses on some recent advances in deuterium-modified drugs and discusses their unique development potential.The use of deuterium to create a new chemical entity can in principle be approached in two ways. First, deuterium can be a tool in the traditional medicinal chemistry approach of iterative optimization in the de novo design of new compounds. Second, starting with an existing drug, hydrogen can be replaced by deuterium at specific sites without otherwise modifying the drug scaffold. These approaches are distinct with respect to drug development and regulatory approval. The US FDA has allowed sponsors of deuterated drugs to reference data of the hydrogen analogs in a 505(b)(2) application but not, to our knowledge, for any other modifications to the active moiety [6]. This regulatory advantage is currently unique to the modification of an existing drug with deuterium.The first apparent substantial attempt to develop a deuterium-containing drug took the approach of utilizing deuterium to enable satisfactory properties in a novel molecular scaffold [7]. Since pharmaceutical companies have generally focused on developing novel chemotypes, this approach may likely continue as the more prevalent one in those institutions. The alternative approach, selectively incorporating deuterium as a targeted hydrogen replacement substituent in otherwise unchanged drug molecules, has been adopted by several companies such as Concert Pharmaceuticals and Auspex Pharmaceuticals (now a subsidiary of Teva Pharmaceuticals), and has seen considerable progress in recent years.The recent success of deuterated drug candidates is the result of multiple converging factors that have helped to demonstrate their utility and likely economic viability: The FDA and EMA accepted, with supporting evidence, on a case-by-case basis, that deuterated compounds are highly similar to their hydrogen analogs with respect to interactions with biological receptors, leading to generally indistinguishable biochemical potency and selectivity. As a result, in several cases, sponsors developing deuterated analogs of approved drugs have been able to reference data on the previously developed nondeuterated drug, reducing the cost and time necessary to support a submission package [6,8].Even with substantial similarities to existing drugs, metabolic differences imparted by deuterium substitution have proven sufficient to enable clinically important differences relative to their hydrogen analogs. In the past year, deuterated analogs of approved drugs have been granted Fast Track, Orphan and Breakthrough Therapy Designation by the FDA [6,9,10,6].Patent offices in numerous territories, including the USA, Europe, Japan and China, are granting patents on deuterated drugs, including composition of matter and method of use claims. A frequent basis of patentability is the unpredictability of the deuterium isotope effect, where the patent office determines that the differentiated compounds are nonobvious. The patentability of a deuterated compound was recently brought before a judicial body, which denied a request to invalidate a patent claiming deuterated venlafaxine [10].Detailed understanding of the individual contributions of a parent molecule and its metabolites to the therapeutic efficacy, safety, and tolerability of a given drug, which is currently possible only based on population pharmacokinetic and pharmacodynamic analyses, provides a rational basis for targeted metabolic modifications to improve clinical characteristics that can only be accomplished through deuterium incorporation.The cost of highly enriched D2O as a manufacturing feedstock is low enough to generally support a commercially acceptable cost of goods for manufacturing deuterated drugs.Advances in our understanding of human biology, as well as empirical clinical evidence from observational or investigator-initiated studies, provide continuing opportunities to deploy molecules possessing generally understood safety and efficacy parameters to new diseases. The potential for improved clinical properties and long-lived patent protection provide the justification to make the large investments necessary to develop deuterated drugs for new indications.In the past year, two companies which were largely or entirely focused on developing deuterium-containing drugs – Avanir Pharmaceuticals and Auspex – were each acquired for multibillion dollar sums. This tangible demonstration of the value of deuterated compounds is supportive of investments in both existing deuterated pipeline compounds and the identification of additional opportunities where deuteration of biologically active agents can create differentiated and valuable new drugs [11,12].A number of deuterated compounds are currently undergoing clinical development, including the following:AVP–786, a fixed-dose combination of d6-dextromethorphan with an ultra-low dose of quinidine, is currently enrolling Phase III clinical trials for the treatment of agitation associated with Alzheimer's Disease dementia, an indication that currently has no FDA-approved treatments and for which there is a great unmet need [13]. Avanir had previously obtained approval for a combination product consisting of 20 mg of dextromethorphan (nondeuterated) and 10 mg of quinidine for a different indication [14]. The product Nuedexta® was approved in the USA and is marketed by Avanir for pseudobulbar affect, which is characterized by uncontrollable crying, laughing or other emotional displays occurring secondary to neurologic disease or brain injury. Quinidine is a metabolic inhibitor that enables the active ingredient dextromethorphan to reach therapeutic concentrations.Avanir found that with AVP-786, due to its deuterium stabilization, a much lower amount of quinidine was needed to reach an equivalent plasma exposure of the active species – in this case, deuterated dextromethorphan. Due to the unmet need in Alzheimer's Disease-associated agitation, the FDA provided AVP-786 with Fast Track designation [15]. Phase II clinical studies in treatment refractory major depression and residual schizophrenia are currently ongoing [13].AVP-786 benefits from numerous worldwide patents, including composition of matter [16–18]. These patents on deuterated dextromethorphan and its combination with quinidine provide a period of exclusivity extending well beyond earlier patents protecting the nondeuterated drug combination.SD-809, d6-tetrabenazine, has completed two Phase III studies in the treatment of chorea due to Huntington's disease (sudden involuntary movements). Similar to deuterated dextromethorphan, deuterium incorporation markedly altered the pharmacokinetic behavior of tetrabenazine, increasing plasma half-life from 4.8 to 8.6 h and approximately doubling AUC exposure [19]. SD-809 ER, the clinical formulation of SD-809 used in its efficacy studies, adds extended release technology to further smooth out SD-809's pharmacokinetic curve. As a result of these stacked technologies, SD-809 is dosed less frequently than tetrabenazine, twice- versus three-times daily, and has a substantially smaller peak/trough ratio than does tetrabenazine [20].SD-809 has been developed following the 505(b)(2) regulatory pathway for the same indication for which tetrabenazine is approved [6]. Top-line results released by Auspex from a placebo-controlled Phase III study suggest that the SD-809 ER possesses a much more benign side effect profile than does commercial tetrabenazine, presumably due to reduced peak-related adverse effects [20,21]. SD-809 was granted Orphan Drug Designation for SD-809. Its degree of clinical differentiation from commercial tetrabenazine was sufficient to support a Breakthrough Therapy Designation by the FDA, which accepted a New Drug Application for SD-809 in August, 2015 [8,9].CTP-656, d9-ivacaftor, is currently being developed for the treatment of cystic fibrosis. Deuteration of ivacaftor provided unexpected results in that two isotopologs, respectively d9 and d18, while appearing similarly stabilized to hepatic metabolism in vitro, demonstrated differentiated pharmacokinetics from each other in vivo with differing rank order depending on the species studied. In rats, d18-ivacaftor provided greater exposure than did the d9-isotopolog, while in dogs the reverse was true. Both isotopologs were taken into a healthy volunteer crossover study, where d9-ivacaftor demonstrated greater human exposure than d18-ivacaftor.In a subsequent single ascending dose Phase I study of CTP-656 that included a crossover comparison with ivacaftor at 150 mg, CTP-656 provided about 3.5-fold greater AUC exposure than did ivacaftor, about a third longer plasma half-life and much greater exposure to the parent drug (the most active species) relative to metabolites than was observed with ivacaftor [22]. Concert Pharmaceuticals is planning to initiate efficacy studies in cystic fibrosis patients in 2016.In addition, a growing number of other deuterated compounds have started clinical development or been evaluated as potential new drugs. These include, among others, CTP-730 (deuterated apremilast), JZP-386 (deuterated sodium oxybate), CTP-499 (deuterated pentoxifylline metabolite), ALK-001 (deuterated vitamin A) and SD-560 (deuterated pirfenidone).With the advanced stage of development of the first wave of drug candidates and numerous additional deuterated agents progressing in the clinic, deuterium is now a validated component of the medicinal chemistry repertoire.Financial & competing interests disclosureThe author is employed by Concert Pharmaceuticals and owns stock and stock options in the company. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.Papers of special note have been highlighted as: • of interestReferences1 Baillie TA. The use of stable isotopes in pharmacological research. Pharmacol. Rev. 33(2), 81–132 (1981).Medline, CAS, Google Scholar2 Harbeson SL, Tung RD. Deuterium in drug discovery and development. In: Annual Reports in Medicinal Chemistry. Macor JE (Ed.). Elsevier, Oxford, UK, 403–418 (2011).Crossref, Google Scholar3 Gant TG. Using deuterium in drug discovery: leaving the label in the drug. J. Med. Chem. 57(9), 3595–3611 (2014).Crossref, Medline, CAS, Google Scholar4 Fisher MB, Henne KR, Boer J. The complexities inherent in attempts to decrease drug clearance by blocking sites of CYP-mediated metabolism. Curr. Opin. Drug Discov. Devel. 9(1), 101–109 (2006).Medline, CAS, Google Scholar5 Foster AB. Deuterium isotope effects in the metabolism of drugs and xenobiotics: implications for drug design. In: Advances In Drug Research. Testa B (Ed.). Academic Press, London, UK, 14, 1–39 (1985).Google Scholar6 Teva announces acceptance of SD–809 New Drug Application to the FDA. www.tevapharm.com/news/teva_announces_fda_acceptance_of_nda_for_sd_809_for_treatment_in_huntington_disease_08_15.aspx.Google Scholar7 Darland GK, Hajdu R, Kropp H et al. Oxidative and defluorinative metabolism of fludalanine, 2-2H-3-fluoro-D-alanine. Drug metabolism and disposition. 14(6), 668–673 (1986). • See also: Reinhold, DF. Processes for asymmetric conversion of 3-fluoro-L-alanine and 2-deutero-3-fluoro-L-alanine to their D-isomers. USPTO 3,950,411 (1976).Google Scholar8 Avanir announces that AVP-923 data can be referenced in AVP-786 clinical development and submission. www.prnewswire.com/news-releases/avanir-pharmaceuticals-announces-fda-acceptance-of-ind-for-avp–786–for-the-adjunctive-treatment-of-major-depressive-disorder–267930411.html.Google Scholar9 Auspex announces Breakthrough Therapy Designation for SD-809. www.tevapharm.com/news/teva_announces_breakthrough_therapy_designation_for_sd_809_granted_by_fda_for_the_treatment_of_tardive_dyskinesia_11_15.aspx.Google Scholar10 Neptune Generics, Llc V. Auspex Pharmaceuticals, Inc., U.S. Pat. 7456317, IPR2015-01313. http://fishpostgrant.com/wp-content/uploads/IPR2015–01313.pdf.Google Scholar11 Otsuka Pharmaceutical Completes Acquisition of Avanir Pharmaceuticals. www.otsuka.com/en/hd_release/release/pdf.php?news=1079.Google Scholar12 Teva Completes Acquisition of Auspex Pharmaceuticals. www.tevapharm.com/news/teva_completes_acquisition_of_auspex_pharmaceuticals_05_15.aspx.Google Scholar13 Clinical Trials Search: AVP-786. https://clinicaltrials.gov/ct2/results?term=avp–786&Search=Search.Google Scholar14 Nuedexta® product label, FDA New Drug Application no. 021879 dated 01/20/2015. www.accessdata.fda.gov/drugsatfda_docs/label/2015/021879s005lbl.pdf.Google Scholar15 Avanir announces Fast Track Designation for AVP-786. www.prnewswire.com/news-releases/avanir-pharmaceuticals-announces-initiation-of-phase-iii-trial-of-avp–786–for-agitation-in-patients-with-alzheimers-disease–300178893.html.Google Scholar16 Tung RD. US 7973049 B2 (2011). • All patents for Morphinan compounds.Google Scholar17 Tung RD. US 8541436 B2 (2013).Google Scholar18 Tung RD. US 7748450 B2 (2014).Google Scholar19 Stamler D, Bradbury M, Brown F. The pharmacokinetics and safety of deuterated-tetrabenazine. Neurology 80(1), P07.210 (2013).Google Scholar20 Auspex investor presentation at Jefferies 2014 Global Healthcare Conference. www.jefferies.com/CMSFiles/Jefferies.com/files/Conferences/060214/Presentations/Auspex.pdf.Google Scholar21 Xenazine® product label, FDA New Drug Application no. 021894 dated 06/02/2015. www.accessdata.fda.gov/drugsatfda_docs/label/2015/021894s010lbl.pdf.Google Scholar22 Harbeson SL, Nguyen S, Bridson G et al. Pharmacokinetic studies of deuterated isotopologs if ivacaftor in preclinical models and healthy volunteers. Presented at: 29th Annual North American Cystic Fibrosis Conference, Nashville, TN, USA, 8 October 2015. www.concertpharma.com/wp-content/uploads.Google ScholarFiguresReferencesRelatedDetailsCited ByThree Component syn ‐1,2‐Arylmethylation of Internal Alkynes**8 February 2023 | Angewandte Chemie International Edition, Vol. 20Organoboron Reagent‐Controlled Selective (Deutero)Hydrodefluorination12 January 2023 | Angewandte Chemie International Edition, Vol. 62, No. 7Organoboron Reagent‐Controlled Selective (Deutero)Hydrodefluorination12 January 2023 | Angewandte Chemie, Vol. 135, No. 7[ 13 C+D] Double Labeling with Calcium Carbide: Incorporation of Two Labels in One Step30 December 2022 | Chemistry – An Asian Journal, Vol. 18, No. 3Three Component syn‐1,2‐Arylmethylation of Internal Alkynes26 January 2023 | Angewandte ChemieTracking the Isotopologues: Process Improvement for the Synthesis of a Deuterated Pyrazole6 January 2023 | Organic Process Research & Development, Vol. 27, No. 1Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds22 July 2022 | Nature Communications, Vol. 13, No. 1Distal kinetic deuterium isotope effect: Phenyl ring deuteration attenuates N-demethylation of Lu AF35700Bioorganic & Medicinal Chemistry Letters, Vol. 72Novel deuterated Mnk1/2 protein degrader VNLG-152R analogs: Synthesis, In vitro Anti-TNBC activities and pharmacokinetics in miceEuropean Journal of Medicinal Chemistry, Vol. 238Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer's diseaseEuropean Journal of Medicinal Chemistry, Vol. 236Tunable Unsymmetrical Ferrocene Ligands Bearing a Bulky Di-1-adamantylphosphino Motif for Many Kinds of C sp 2 –C sp 3 Couplings15 April 2022 | ACS Catalysis, Vol. 6Selective Access of Deuterated Dibenzo‐Fused ϵ‐Lactones and ϵ‐Lactams via Palladium Carbene Migratory Insertion Enabled 1,4‐Pd Shift16 March 2022 | Asian Journal of Organic Chemistry, Vol. 11, No. 4Rh(III)‐Catalyzed Reaction of 2‐Aryl‐3‐acyl‐1 H ‐indoles with α‐Diazo Carbonyl Compounds: Synthesis of 5‐Carbonyl Substituted Benzo[ a ]carbazoles via [5+1] Annulation24 February 2022 | Asian Journal of Organic Chemistry, Vol. 11, No. 3Phase I clinical trial of HC‐1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single‐dose proportionality and effects of food22 November 2021 | The Prostate, Vol. 82, No. 2Overview: Background and Applications22 August 2022Deuterium Oxide and Deuteration Effects on Pharmacology22 August 2022Asymmetric Transfer Hydrogenation of α -Aryl Amidates Using Methanol as Hydrogen SourceChinese Journal of Organic Chemistry, Vol. 42, No. 11Nickel-Catalyzed Reductive Deoxygenation of Diverse C–O Bond-Bearing Functional Groups19 October 2021 | ACS Catalysis, Vol. 11, No. 21Transition Metal‐Catalyzed Cross‐Couplings of Benzylic Sulfone Derivatives15 September 2021 | The Chemical Record, Vol. 6Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool25 August 2021 | Metabolites, Vol. 11, No. 9A general, versatile and divergent synthesis of selectively deuterated amines1 January 2021 | Chemical Science, Vol. 12, No. 33The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD 3 Reagents7 July 2021 | Chemistry – A European Journal, Vol. 27, No. 46Green synthesis of α-deuterated boronates using DMTT reagentGreen Synthesis and Catalysis, Vol. 2, No. 3A New Highly Deuterated [ 18 F]AV-45, [ 18 F]D15FSP, for Imaging β-Amyloid Plaques in the Brain21 June 2021 | ACS Medicinal Chemistry Letters, Vol. 12, No. 7Harnessing Drug Repurposing for Exploration of New Diseases: An Insight to Strategies and Case StudiesCurrent Molecular Medicine, Vol. 21, No. 2Pd-Catalyzed ipso , meta -Dimethylation of ortho -Substituted Iodoarenes via a Base-Controlled C–H Activation Cascade with Dimethyl Carbonate as the Methyl Source22 March 2021 | Journal of the American Chemical Society, Vol. 143, No. 12Organocatalytic Deuteration Induced by the Dynamic Covalent Interaction of Imidazolium Cations with Ketones7 January 2021 | Advanced Synthesis & Catalysis, Vol. 363, No. 5Recent advances in visible-light photocatalytic deuteration reactions1 January 2021 | Organic Chemistry Frontiers, Vol. 8, No. 3Evaluation of Poorly Soluble Drugs’ Dissolution Rate by Laser Scattering in Different Water Isotopologues24 January 2021 | Molecules, Vol. 26, No. 3Reductive Transformations of Organo (pseudo) halides Catalyzed by Cobalt and/or Nickel CatalystJournal of Synthetic Organic Chemistry, Japan, Vol. 79, No. 2Breaking the Symmetry of a Meso Compound by Isotopic Substitution: Synthesis and Stereochemical Assignment of Monodeuterated cis -Perhydroazulene11 December 2020 | Organic Letters, Vol. 23, No. 1The Effect of Deuteration on the H2 Receptor Histamine Binding Profile: A Computational Insight into Modified Hydrogen Bonding Interactions18 December 2020 | Molecules, Vol. 25, No. 24Ru(II)-Catalyzed Tunable Cascade Reaction via C–H/C–C Bond Cleavage17 September 2020 | The Journal of Organic Chemistry, Vol. 85, No. 20Dependence of Biocatalysis on D/H Ratio: Possible Fundamental Differences for High-Level Biological Taxons11 September 2020 | Molecules, Vol. 25, No. 18Superelectrophilic Csp 3 –H bond fluorination of aliphatic amines in superacid: the striking role of ammonium–carbenium dications1 January 2020 | Chemical Communications, Vol. 56, No. 44Iodobenzene-catalyzed oxidative C H d-alkoxylation of quinoxalinones with deuterated alcoholsCatalysis Communications, Vol. 141The Influence of Deuterium on the Properties of Pharmaceutical Substances (Review)30 May 2020 | Drug development & registration, Vol. 9, No. 2Exhaustive Reduction of Esters Enabled by Nickel Catalysis22 April 2020 | Journal of the American Chemical Society, Vol. 142, No. 18NHC‐Stabilized Iridium Nanoparticles as Catalysts in Hydrogen Isotope Exchange Reactions of Anilines20 January 2020 | Angewandte Chemie, Vol. 132, No. 9NHC‐Stabilized Iridium Nanoparticles as Catalysts in Hydrogen Isotope Exchange Reactions of Anilines29 January 2020 | Angewandte Chemie International Edition, Vol. 59, No. 9Practical Method for Reductive Deuteration of Ketones with Magnesium and D 2 O22 January 2020 | Organic Letters, Vol. 22, No. 3Relevance of Hydrogen Bonds for the Histamine H2 Receptor-Ligand Interactions: A Lesson from Deuteration29 January 2020 | Biomolecules, Vol. 10, No. 2Mitochondrial activity of cancer and normal mesenchymal stem cells in vitro cultured in medium with different deuterium content6 July 2020 | BIO Web of Conferences, Vol. 22Hydrogen Isotope Separation within the Metal–Organic Framework Cu(I)-MFU-4 l26 November 2019 | The Journal of Physical Chemistry C, Vol. 123, No. 50Modular Dual-Tasked C–H Methylation via the Catellani Strategy12 September 2019 | Journal of the American Chemical Society, Vol. 141, No. 40A highly efficient cobalt-catalyzed deuterogenolysis of diboron: Synthesis of deuterated pinacolborane and vinylboronatesTetrahedron, Vol. 75, No. 31Diversity‐Oriented Desulfonylative Functionalization of Alkyl Allyl Sulfones5 June 2019 | Angewandte Chemie, Vol. 131, No. 29Diversity‐Oriented Desulfonylative Functionalization of Alkyl Allyl SulfonesAngewandte Chemie International Edition, Vol. 58, No. 29Applications of Deuterium in Medicinal Chemistry14 January 2019 | Journal of Medicinal Chemistry, Vol. 62, No. 11Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Phenylacetic Acid Esters and Amides23 April 2019 | Chemistry – A European Journal, Vol. 25, No. 26Palladium Catalyzed Hydrodefluorination of Fluoro-(hetero)arenes26 March 2019 | Organic Letters, Vol. 21, No. 7Scale-up synthesis of a deuterium-labeled cis-cyclobutane-1,3-Dicarboxylic acid derivative using continuous photo flow chemistryTetrahedron, Vol. 75, No. 5Catalytic α-Selective Deuteration of Styrene Derivatives9 January 2019 | Journal of the American Chemical Society, Vol. 141, No. 4Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae19 November 2018 | Journal of Medicinal Chemistry, Vol. 61, No. 23How intrinsic nuclear nonadiabaticity affects molecular structure, electronic density, and conformational stability: Insights from the multicomponent DFT calculations of Mu/H isotopologues20 July 2018 | International Journal of Quantum Chemistry, Vol. 118, No. 22Nickel and Nucleophilic Cobalt-Catalyzed Trideuteriomethylation of Aryl Halides Using Trideuteriomethyl p -Toluenesulfonate5 July 2018 | Organic Letters, Vol. 20, No. 14Highly Selective Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Aliphatic AmidesAngewandte Chemie, Vol. 130, No. 27Highly Selective Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Aliphatic AmidesAngewandte Chemie International Edition, Vol. 57, No. 27Deuterium- und tritiummarkierte Verbindungen: Anwendungen in den modernen Biowissenschaften4 January 2018 | Angewandte Chemie, Vol. 130, No. 7Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences4 January 2018 | Angewandte Chemie International Edition, Vol. 57, No. 7Temperature-Programmed Desorption for Isotope Separation in Nanoporous Materials18 January 2018 | The Journal of Physical Chemistry C, Vol. 122, No. 4Selective Deuteration of Organic Compounds Catalyzed by Ruthenium Pincer ComplexesEnantioselective semireduction of allenes4 October 2017 | Nature Communications, Vol. 8, No. 1Deutetrabenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?12 October 2017 | International Journal of Clinical Practice, Vol. 71, No. 11Total Synthesis and Metabolic Stability of Hispidulin and Its d-Labelled Derivative4 November 2017 | Molecules, Vol. 22, No. 11Efficient Brønsted-Acid-Catalyzed Deuteration of Arenes and Their Transformation to Functionalized Deuterated Products29 June 2017 | Asian Journal of Organic Chemistry, Vol. 6, No. 8Stereoretentive Deuteration of α-Chiral Amines with D 2 O6 October 2016 | Journal of the American Chemical Society, Vol. 138, No. 41 Vol. 8, No. 5 Follow us on social media for the latest updates Metrics History Published online 15 April 2016 Published in print April 2016 Information© Future Science LtdKeywordsdrug designdrug developmentpharmacodynamicspharmacokineticsFinancial & competing interests disclosureThe author is employed by Concert Pharmaceuticals and owns stock and stock options in the company. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download" @default.
• W2336885655 created "2016-06-24" @default.
• W2336885655 creator A5046617419 @default.
• W2336885655 date "2016-04-01" @default.
• W2336885655 modified "2023-10-08" @default.
• W2336885655 title "Deuterium medicinal chemistry comes of age" @default.
• W2336885655 cites W1551685198 @default.
• W2336885655 cites W2313227787 @default.
• W2336885655 doi "https://doi.org/10.4155/fmc-2016-0032" @default.
• W2336885655 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27079428" @default.
• W2336885655 hasPublicationYear "2016" @default.
• W2336885655 type Work @default.
• W2336885655 sameAs 2336885655 @default.
• W2336885655 citedByCount "75" @default.
• W2336885655 countsByYear W23368856552016 @default.
• W2336885655 countsByYear W23368856552017 @default.
• W2336885655 countsByYear W23368856552018 @default.
• W2336885655 countsByYear W23368856552019 @default.
• W2336885655 countsByYear W23368856552020 @default.
• W2336885655 countsByYear W23368856552021 @default.
• W2336885655 countsByYear W23368856552022 @default.
• W2336885655 countsByYear W23368856552023 @default.
• W2336885655 crossrefType "journal-article" @default.
• W2336885655 hasAuthorship W2336885655A5046617419 @default.
• W2336885655 hasBestOaLocation W23368856551 @default.
• W2336885655 hasConcept C121332964 @default.
• W2336885655 hasConcept C185544564 @default.
• W2336885655 hasConcept C185592680 @default.
• W2336885655 hasConcept C55493867 @default.
• W2336885655 hasConcept C58364064 @default.
• W2336885655 hasConcept C74187038 @default.
• W2336885655 hasConceptScore W2336885655C121332964 @default.
• W2336885655 hasConceptScore W2336885655C185544564 @default.
• W2336885655 hasConceptScore W2336885655C185592680 @default.
• W2336885655 hasConceptScore W2336885655C55493867 @default.
• W2336885655 hasConceptScore W2336885655C58364064 @default.
• W2336885655 hasConceptScore W2336885655C74187038 @default.
• W2336885655 hasIssue "5" @default.
• W2336885655 hasLocation W23368856551 @default.
• W2336885655 hasLocation W23368856552 @default.
• W2336885655 hasOpenAccess W2336885655 @default.
• W2336885655 hasPrimaryLocation W23368856551 @default.
• W2336885655 hasRelatedWork W1531601525 @default.
• W2336885655 hasRelatedWork W2319480705 @default.
• W2336885655 hasRelatedWork W2384464875 @default.
• W2336885655 hasRelatedWork W2398689458 @default.
• W2336885655 hasRelatedWork W2606230654 @default.
• W2336885655 hasRelatedWork W2607424097 @default.
• W2336885655 hasRelatedWork W2748952813 @default.
• W2336885655 hasRelatedWork W2899084033 @default.
• W2336885655 hasRelatedWork W2948807893 @default.
• W2336885655 hasRelatedWork W2778153218 @default.
• W2336885655 hasVolume "8" @default.
• W2336885655 isParatext "false" @default.
• W2336885655 isRetracted "false" @default.
• W2336885655 magId "2336885655" @default.
• W2336885655 workType "article" @default.