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Search for "NSAID" in Full Text gives 7 result(s) in Beilstein Journal of Organic Chemistry.
HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines
- Luan A. Martinho and
- Carlos Kleber Z. Andrade
Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55
- 1 [13] and include alpidem (anxiety disorders), minodronic acid (osteoporosis), miroprofen (non-steroidal anti-inflammatory drug, NSAID), necopidem (insomnia), olprinone (acute heart failure), saripidem (type A GABA receptor agonist), zolimidine (gastroesophageal reflux disease), and zolpidem
Graphical Abstract
Figure 1: Selected examples of commercial drugs containing the imidazo[1,2-a]pyridine core [13].
Figure 2: Examples of application of HPW as catalyst in the synthesis of heterocyclic compounds through multi...
Scheme 1: a) Reported phosphomolybdic acid-catalyzed synthesis of imidazo[1,2-a]pyridines via GBB-3CR. b) Att...
Scheme 2: Substrate scope of the HPW-catalyzed GBB reactions using a range of aromatic/heteroaromatic aldehyd...
Scheme 3: Substrate scope of the HPW-catalyzed GBB reaction using aliphatic aldehydes. Reaction conditions: 2...
Scheme 4: Unsuccessful substrates for the HPW-catalyzed GBB-3CR for the synthesis of imidazo[1,2-a]pyridines.
Scheme 5: 10-Fold scale-up of the HPW-catalyzed GBB reaction (5.0 mmol) between 2-aminopyridine (1a), 4-nitro...
Scheme 6: Plausible reaction mechanism for the HPW-catalyzed GBB reaction.
Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams
- Edorta Martínez de Marigorta,
- Jesús M. de Los Santos,
- Ana M. Ochoa de Retana,
- Javier Vicario and
- Francisco Palacios
Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104
- , nintedanib is employed against pulmonary fibrosis [32], tenidap [33] is a nonsteroidal anti-inflammatory drug (NSAID), while indolidan [34] and adibendan [35] are potent long-acting cardiotonic agents and SM-130686 is a GHSR agonist [36] (Figure 5). Other kinase inhibitors such as sunitinib [37] and
Graphical Abstract
Figure 1: γ-Lactam-derived structures considered in this review.
Figure 2: Alkaloids containing an isoindolinone moiety.
Figure 3: Alkaloids containing the 2-oxindole ring system.
Figure 4: Drugs and biological active compounds containing an isoindolinone moiety.
Figure 5: Drugs and biologically active compounds bearing a 2-oxindole skeleton.
Scheme 1: Three-component reaction of benzoic acid 1, amides 2 and DMSO (3).
Scheme 2: Copper-catalysed three-component reaction of 2-iodobenzoic acids 10, alkynylcarboxylic acids 11 and...
Scheme 3: Proposed mechanism for the formation of methylene isoindolinones 13.
Scheme 4: Copper-catalysed three-component reaction of 2-iodobenzamide 17, terminal alkyne 18 and pyrrole or ...
Scheme 5: Palladium-catalysed three-component reaction of ethynylbenzamides 21, secondary amines 22 and CO (23...
Scheme 6: Proposed mechanism for the formation of methyleneisoindolinones 24.
Scheme 7: Copper-catalysed three-component reaction of formyl benzoate 29, amines 2 and alkynes 18.
Scheme 8: Copper-catalysed three-component reaction of formylbenzoate 29, amines 2 and ketones 31.
Scheme 9: Non-catalysed (A) and phase-transfer catalysed (B) three-component reactions of formylbenzoic acids ...
Scheme 10: Proposed mechanism for the formation of isoindolinones 36.
Scheme 11: Three-component reaction of formylbenzoic acid 33, amines 2 and fluorinated silyl ethers 39.
Scheme 12: Three-component Ugi reaction of 2-formylbenzoic acid (33), diamines 41 and isocyanides 42.
Scheme 13: Non-catalysed (A, B) and chiral phosphoric acid promoted (C) three-component Ugi reactions of formy...
Scheme 14: Proposed mechanism for the enantioselective formation of isoindolinones 46.
Scheme 15: Three-component reaction of benzoic acids 33 or 54, amines 2 and TMSCN (52).
Scheme 16: Several variations of the three-component reaction of formylbenzoic acids 33, amines 2 and isatoic ...
Scheme 17: Proposed mechanism for the synthesis of isoindoloquinazolinones 57.
Scheme 18: Three-component reaction of isobenzofuranone 61, amines 2 and isatoic anhydrides 56.
Scheme 19: Palladium-catalysed three-component reaction of 2-aminobenzamides 59, 2-bromobenzaldehydes 62 and C...
Scheme 20: Proposed mechanism for the palladium-catalysed synthesis of isoindoloquinazolinones 57.
Scheme 21: Four-component reaction of 2-vinylbenzoic acids 67, aryldioazonium tetrafluoroborates 68, DABCO·(SO2...
Scheme 22: Plausible mechanism for the formation of isoindolinones 71.
Scheme 23: Three-component reaction of trimethylsilylaryltriflates 77, isocyanides 42 and CO2 (78).
Scheme 24: Plausible mechanism for the three-component synthesis of phthalimides 79.
Scheme 25: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, arenes 86 and diaryliodonium...
Scheme 26: Copper-catalysed three-component reaction of 2-formylbenzonitriles 85, diaryliodonium salts 87 and ...
Scheme 27: Proposed mechanism for the formation of 2,3-diarylisoindolinones 88, 89 and 92.
Scheme 28: Palladium-catalysed three-component reaction of chloroquinolinecarbaldehydes 97 with isocyanides 42...
Scheme 29: Palladium-catalysed three-component reaction of imines 99 with CO (23) and ortho-iodoarylimines 100....
Scheme 30: Palladium-catalysed three-component reaction of amines 2 with CO (23) and aryl iodide 105.
Scheme 31: Three-component reaction of 2-ethynylanilines 109, perfluoroalkyl iodides 110 and carbon monoxide (...
Scheme 32: Ultraviolet-induced three-component reaction of N-(2-iodoaryl)acrylamides 113, DABCO·(SO2)2 (69) an...
Scheme 33: Proposed mechanism for the preparation of oxindoles 115.
Scheme 34: Three-component reaction of acrylamide 113, CO (23) and 1,4-benzodiazepine 121.
Scheme 35: Multicomponent reaction of sulfonylacrylamides 123, aryldiazonium tetrafluoroborates 68 and DABCO·(...
Scheme 36: Proposed mechanism for the preparation of oxindoles 124.
Scheme 37: Three-component reaction of N-arylpropiolamides 128, aryl iodides 129 and boronic acids 130.
Scheme 38: Proposed mechanism for the formation of diarylmethylene- and diarylallylideneoxindoles 131 and 132.
Scheme 39: Three-component reaction of cyclohexa-1,3-dione (136), amines 2 and alkyl acetylenedicarboxylates 1...
Scheme 40: Proposed mechanism for the formation of 2-oxindoles 138.
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
- Michael K. Bogdos,
- Emmanuel Pinard and
- John A. Murphy
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- 33c). Examples such as the synthesis of a modified structure of naproxen, starting from the methyl ester of the well-known NSAID, demonstrate the full power of the protocol for its use as a LSF tool. The mild conditions, selectivity on certain substrates and the great opportunity for diversification
Graphical Abstract
Figure 1: Depiction of the energy levels of a typical organic molecule and the photophysical processes it can...
Figure 2: General catalytic cycle of a photocatalyst in a photoredox organocatalysed reaction. [cat] – photoc...
Figure 3: Structures and names of the most common photocatalysts encountered in the reviewed literature.
Figure 4: General example of a reductive quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocata...
Figure 5: General example of an oxidative quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocat...
Scheme 1: Oxidative coupling of aldehydes and amines to amides using acridinium salt photocatalysis.
Figure 6: Biologically active molecules containing a benzamide linkage.
Scheme 2: The photocatalytic reduction of amino acids to produce the corresponding free or protected amines.
Scheme 3: The organocatalysed photoredox base-mediated oxidation of thiols to disulfides.
Scheme 4: C-Terminal modification of peptides and proteins using organophotoredox catalysis.
Scheme 5: The reduction and aryl coupling of aryl halides using a doubly excited photocatalyst (PDI).
Figure 7: Mechanism for the coupling of aryl halides using PDI, which is excited sequentially by two photons.
Scheme 6: The arylation of five-membered heteroarenes using arenediazonium salts under organophotoredox condi...
Scheme 7: The C–H (hetero)arylation of five-membered heterocycles under Eosin Y photocatalysis.
Scheme 8: The C–H sulfurisation of imidazoheterocycles using Eosin B-catalyzed photochemical methods.
Scheme 9: The introduction of the thiocyanate group using Eosin Y photocatalysis.
Scheme 10: Sulfonamidation of pyrroles using oxygen as the terminal oxidant.
Scheme 11: DDQ-catalysed C–H amination of arenes and heteroarenes.
Scheme 12: Photoredox-promoted radical Michael addition reactions of allylic or benzylic carbons.
Figure 8: Proposed mechanistic rationale for the observed chemoselectivities.
Scheme 13: The photocatalytic manipulation of C–H bonds adjacent to amine groups.
Scheme 14: The perylene-catalysed organophotoredox tandem difluoromethylation–acetamidation of styrene-type al...
Figure 9: Examples of biologically active molecules containing highly functionalised five membered heterocycl...
Scheme 15: The [3 + 2]-cycloaddition leading to the formation of pyrroles, through the reaction of 2H-azirines...
Figure 10: Proposed intermediate that determines the regioselectivity of the reaction.
Figure 11: Comparison of possible pathways of reaction and various intermediates involved.
Scheme 16: The acridinium salt-catalysed formation of oxazoles from aldehydes and 2H-azirines.
Scheme 17: The synthesis of oxazolines and thiazolines from amides and thioamides using organocatalysed photor...
Figure 12: Biologically active molecules on the market containing 1,3,4-oxadiazole moieties.
Scheme 18: The synthesis of 1,3,4-oxadiazoles from aldehyde semicarbazones using Eosin Y organophotocatalysis.
Scheme 19: The dimerization of primary thioamides to 1,2,4-thiadiazoles catalysed by the presence of Eosin Y a...
Scheme 20: The radical cycloaddition of o-methylthioarenediazonium salts and substituted alkynes towards the f...
Scheme 21: The dehydrogenative cascade reaction for the synthesis of 5,6-benzofused heterocyclic systems.
Figure 13: Trifluoromethylated version of compounds which have known biological activities.
Scheme 22: Eosin Y-catalysed photoredox formation of 3-substituted benzimidazoles.
Scheme 23: Oxidation of dihydropyrimidines by atmospheric oxygen using photoredox catalysis.
Scheme 24: Photoredox-organocatalysed transformation of 2-substituted phenolic imines to benzoxazoles.
Scheme 25: Visible light-driven oxidative annulation of arylamidines.
Scheme 26: Methylene blue-photocatalysed direct C–H trifluoromethylation of heterocycles.
Scheme 27: Photoredox hydrotrifluoromethylation of terminal alkenes and alkynes.
Scheme 28: Trifluoromethylation and perfluoroalkylation of aromatics and heteroaromatics.
Scheme 29: The cooperative asymmetric and photoredox catalysis towards the functionalisation of α-amino sp3 C–...
Scheme 30: Organophotoredox-catalysed direct C–H amidation of aromatics.
Scheme 31: Direct C–H alkylation of heterocycles using BF3K salts. CFL – compact fluorescent lamp.
Figure 14: The modification of camptothecin, demonstrating the use of the Molander protocol in LSF.
Scheme 32: Direct C–H amination of aromatics using acridinium salts.
Scheme 33: Photoredox-catalysed nucleophilic aromatic substitution of nucleophiles onto methoxybenzene derivat...
Scheme 34: The direct C–H cyanation of aromatics with a focus on its use for LSF.
Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review
- Vânia André,
- Sílvia Quaresma,
- João Luís Ferreira da Silva and
- M. Teresa Duarte
Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239
- ) simplified packing of a gabapentin–Mn network. H atoms were omitted for clarity. Reprinted with permission from [49], copyright 2017 Elsevier. a) Mechanochemical reactivity between the excipient MgO and carboxylic acid NSAID molecules; b) NSAID molecules explored in mechanochemical reactions with MgO; c
Graphical Abstract
Figure 1: a) Detailed supramolecular packing of a gabapentin–Er network; b) view along the b-axis of the supr...
Figure 2: a) Mechanochemical reactivity between the excipient MgO and carboxylic acid NSAID molecules; b) NSA...
Figure 3: Mechanochemical reaction to form Cu3(BTC)2 and the structure of Cu3(BTC)2·(HKUST-1) as reported by ...
Figure 4: Mechanochemical syntheses of coordination polymers from ZnO and fumaric acid. Reprinted with permis...
Figure 5: Mechanochemical synthesis of pillared MOFs from ZnO, fumaric acid and two auxiliary ligands (bipy a...
Figure 6: a) Synthesis of ZIF-8; b) fragment of the crystal structure of ZIF-8. Reprinted with permission fro...
Figure 7: a) Mechanochemical reaction of salicylic acid with Bi2O3 yielding bismuth mono-, di- and trisalicyl...
Synthesis and characterization of pH responsive D-glucosamine based molecular gelators
- Navneet Goyal,
- Hari P. R. Mangunuru,
- Bargav Parikh,
- Sonu Shrestha and
- Guijun Wang
Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328
- anticipated that these types of gels may be useful for the controlled release of drugs or other agents under acidic conditions. We picked the nonsteroidal anti-inflammatory drug (NSAID) naproxen as an example and studied the release profile of the drug trapped in the gel matrix. To test the effectiveness of
Graphical Abstract
Figure 1: General structures of several D-glucose and D-glucosamine derivatives.
Scheme 1: Synthesis of amide and urea derivatives of the headgroup 3.
Figure 2: a) A translucent/opaque gel formed by compound 19 in EtOH/H2O (1:2) at 1.3 mg/mL; b) a gel formed b...
Figure 3: The rheological measurements of the gels formed by amide 11 (EtOH/H2O, 1:2) at 5.4 mg/mL, urea 16 (...
Figure 4: The optical micrographs of the wet gels formed by several amides. a) A gel formed by compound 8 in ...
Figure 5: The optical micrographs of the wet gel samples formed by several ureas. a) Compound 19 in DMSO/H2O ...
Figure 6: Stability test results under acidic conditions. a) A gel formed by compound 23 in DMSO/H2O (1:2) at...
Figure 7: Release of naproxen sodium from the gel formed by compound 16 to the aqueous phase.
Figure 8: Naproxen release study from the gel formed by compound 16 in the presence of acid.
An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles
- Marcus Baumann and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265
- work-up (Scheme 16, C). Etoricoxib (1.90) is a member of a new class of NSAID (non-steroidal anti-inflammatory drug) developed by Merck possessing a simple pyridine core [51]. It is reported to show a 160-fold selectivity for COX-2 over COX-1 (cyclooxygenase 1 and 2) and so it is hoped that it will not
Graphical Abstract
Scheme 1: Scaled industrial processes for the synthesis of simple pyridines.
Scheme 2: Synthesis of nicotinic acid from 2-methyl-5-ethylpyridine (1.11).
Scheme 3: Synthesis of 3-picoline and nicotinic acid.
Scheme 4: Synthesis of 3-picoline from 2-methylglutarodinitrile 1.19.
Scheme 5: Picoline-based synthesis of clarinex (no yields reported).
Scheme 6: Mode of action of proton-pump inhibitors and structures of the API’s.
Scheme 7: Hantzsch-like route towards the pyridine rings in common proton pump inhibitors.
Figure 1: Structures of rosiglitazone (1.40) and pioglitazone (1.41).
Scheme 8: Synthesis of rosiglitazone.
Scheme 9: Syntheses of 2-pyridones.
Scheme 10: Synthesis and mechanism of 2-pyrone from malic acid.
Scheme 11: Polymer-assisted synthesis of rosiglitazone.
Scheme 12: Synthesis of pioglitazone.
Scheme 13: Meerwein arylation reaction towards pioglitazone.
Scheme 14: Route towards pioglitazone utilising tyrosine.
Scheme 15: Route towards pioglitazone via Darzens ester formation.
Scheme 16: Syntheses of the thiazolidinedione moiety.
Scheme 17: Synthesis of etoricoxib utilising Negishi and Stille cross-coupling reactions.
Scheme 18: Synthesis of etoricoxib via vinamidinium condensation.
Figure 2: Structures of nalidixic acid, levofloxacin and moxifloxacin.
Scheme 19: Synthesis of moxifloxacin.
Scheme 20: Synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane 1.105.
Scheme 21: Synthesis of levofloxacin.
Scheme 22: Alternative approach to the levofloxacin core 1.125.
Figure 3: Structures of nifedipine, amlodipine and clevidipine.
Scheme 23: Mg3N2-mediated synthesis of nifedipine.
Scheme 24: Synthesis of rac-amlodipine as besylate salt.
Scheme 25: Aza Diels–Alder approach towards amlodipine.
Scheme 26: Routes towards clevidipine.
Figure 4: Examples of piperidine containing drugs.
Figure 5: Discovery of tiagabine based on early leads.
Scheme 27: Synthetic sequences to tiagabine.
Figure 6: Structures of solifenacin (2.57) and muscarine (2.58).
Scheme 28: Enantioselective synthesis of solifenacin.
Figure 7: Structures of DPP-4 inhibitors of the gliptin-type.
Scheme 29: Formation of inactive diketopiperazines from cis-rotameric precursors.
Figure 8: Co-crystal structure of carmegliptin bound in the human DPP-4 active site (PDB 3kwf).
Scheme 30: Improved route to carmegliptin.
Figure 9: Structures of lamivudine and zidovudine.
Scheme 31: Typical routes accessing uracil, thymine and cytosine.
Scheme 32: Coupling between pyrimidones and riboses via the Vorbrüggen nucleosidation.
Scheme 33: Synthesis of lamivudine.
Scheme 34: Synthesis of raltegravir.
Scheme 35: Mechanistic studies on the formation of 3.22.
Figure 10: Structures of selected pyrimidine containing drugs.
Scheme 36: General preparation of pyrimidines and dihydropyrimidones.
Scheme 37: Synthesis of imatinib.
Scheme 38: Flow synthesis of imatinib.
Scheme 39: Syntheses of erlotinib.
Scheme 40: Synthesis of erlotinib proceeding via Dimroth rearrangement.
Scheme 41: Synthesis of lapatinib.
Scheme 42: Synthesis of rosuvastatin.
Scheme 43: Alternative preparation of the key aldehyde towards rosuvastatin.
Figure 11: Structure comparison between nicotinic acetylcholine receptor agonists.
Scheme 44: Syntheses of varenicline and its key building block 4.5.
Scheme 45: Synthetic access to eszopiclone and brimonidine via quinoxaline intermediates.
Figure 12: Bortezomib bound in an active site of the yeast 20S proteasome ([114], pdb 2F16).
Scheme 46: Asymmetric synthesis of bortezomib.
Figure 13: Structures of some prominent piperazine containing drugs.
Figure 14: Structural comparison between the core of aplaviroc (4.35) and a type-1 β-turn (4.36).
Scheme 47: Examplary synthesis of an aplaviroc analogue via the Ugi-MCR.
Scheme 48: Syntheses of azelastine (5.1).
Figure 15: Structures of captopril, enalapril and cilazapril.
Scheme 49: Synthesis of cilazapril.
Figure 16: Structures of lamotrigine, ceftriaxone and azapropazone.
Scheme 50: Synthesis of lamotrigine.
Scheme 51: Alternative synthesis of lamotrigine (no yields reported).
Figure 17: Structural comparison between imiquimod and the related adenosine nucleoside.
Scheme 52: Conventional synthesis of imiquimod (no yields reported).
Scheme 53: Synthesis of imiquimod.
Scheme 54: Synthesis of imiquimod via tetrazole formation (not all yields reported).
Figure 18: Structures of various anti HIV-medications.
Scheme 55: Synthesis of abacavir.
Figure 19: Structures of diazepam compared to modern replacements.
Scheme 56: Synthesis of ocinaplon.
Scheme 57: Access to zaleplon and indiplon.
Scheme 58: Different routes towards the required N-methylpyrazole 6.65 of sildenafil.
Scheme 59: Polymer-supported reagents in the synthesis of key aminopyrazole 6.72.
Scheme 60: Early synthetic route to sildenafil.
Scheme 61: Convergent preparations of sildenafil.
Figure 20: Comparison of the structures of sildenafil, tadalafil and vardenafil.
Scheme 62: Short route to imidazotriazinones.
Scheme 63: Alternative route towards vardenafils core imidazotriazinone (6.95).
Scheme 64: Bayer’s approach to the vardenafil core.
Scheme 65: Large scale synthesis of vardenafil.
Scheme 66: Mode of action of temozolomide (6.105) as methylating agent.
Scheme 67: Different routes to temozolomide.
Scheme 68: Safer route towards temozolomide.
Figure 21: Some unreported heterocyclic scaffolds in top market drugs.
The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels
- Jiayang Li,
- Yi Kuang,
- Junfeng Shi,
- Yuan Gao,
- Jie Zhou and
- Bing Xu
Beilstein J. Org. Chem. 2013, 9, 908–917, doi:10.3762/bjoc.9.104
- Jiayang Li Yi Kuang Junfeng Shi Yuan Gao Jie Zhou Bing Xu Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA 10.3762/bjoc.9.104 Abstract Here we report supramolecular hydrogelators made of nonsteroidal anti-inflammatory drugs (NSAID) and small peptides. The
- covalent linkage of Phe–Phe and NSAIDs results in conjugates that self-assemble in water to form molecular nanofibers as the matrices of hydrogels. When the NSAID is naproxen (1), the resultant hydrogelator 1a forms a hydrogel at a critical concentration (cgc) of 0.2 wt % at pH 7.0. Hydrogelator 1a, also
- -delivery; hydrogel; multifunctional; nanofibers; NSAID; self-assembly; supramolecular; topical use; Introduction This article reports the design, synthesis, and characterization of hydrogelators made of non-steroidal anti-inflammatory drugs (NSAID) and small peptides for the development of multifunctional
Graphical Abstract
Scheme 1: The structures of the NSAIDs and peptides explored as the building blocks of hydrogelators in this ...
Scheme 2: The synthetic route of the naproxen-containing hydrogelators and the corresponding precursors: (i) ...
Figure 1: Optical images of the hydrogels formed by (A) 1a (0.8 wt %, pH 7.0); (B) 1b (0.8 wt %, pH 4.0); (C) ...
Figure 2: The TEM images of the matrices of the hydrogels formed by (A) 1a (0.8 wt %, pH 7.0); (B) 1b (0.8 wt...
Figure 3: Recovery of the storage moduli of the gels formed by 0.8 wt % of 1a at pH 7.0 and 1.5 wt % of 1d fo...
Figure 4: The IC50 values of 1a, 1c and 1d incubated with HeLa cells after 72 h.
