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Search for "Erlotinib" in Full Text gives 4 result(s) in Beilstein Journal of Organic Chemistry.
Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents
- Rodolfo H. V. Nishimura,
- Thiago dos Santos,
- Valter E. Murie,
- Luciana C. Furtado,
- Leticia V. Costa-Lotufo and
- Giuliano C. Clososki
Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206
- apoptosis [7]. Figure 1 highlights the structures of three EGFR inhibitors approved by the United States Food and Drug Administration (FDA) and one known tubulin inhibitor: erlotinib (1), gefitinib (2), lapatinib (3), and MPC-6827 – verubulin (4) [5][7]. Given that 4-anilinoquinazolines are potential
- control. We also investigated the potency of erlotinib hydrochloride, gefitinib, and verubulin against T98G cells, which were the most sensitive to the novel 4-anilinoquinazolines (Figure S2 in Supporting Information File 1). Compared to the reference drug, doxorubicin, derivative 10b showed promising
- ). The EGFR inhibitor drugs bearing the 4-anilinoquinazoline moiety did not show potent cytotoxic activity against T98G cells (21.3 µM for erlotinib, and 37.8 µM for gefitinib). However, the tubulin polymerization inhibitor (verubulin), which contains 4-anilinoquinazoline in its chemical structure, was
Graphical Abstract
Figure 1: Some antitumor agents containing the 4-anilinoquinazoline moiety.
Scheme 1: Examples of N-arylation reactions using 4-chloroquinazolines as substrates.
Scheme 2: Synthesis of verubulin analog.
Scheme 3: Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a and 8b. Conditions: a) NBS, CH3CN, 30 min, 25 ...
Scheme 4: N-Arylation reactions using ortho-, meta-, and para-substituted primary anilines of type 14 followe...
Scheme 5: N-Arylation reactions using 4-chloroquinazoline (16) and 4-chloro-2-methylquinazoline (17) to achie...
Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs
- Jongwoo Son
Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122
- constitute an important structural modality in small-molecule drugs, such as levonorgestrel (birth control drug), efavirenz (HIV/AIDS treatment), and erlotinib (anticancer). Although step-economical C–H alkynylations have been investigated with 4d and 5d transition metals, 3d metal-catalyzed late-stage C–H
Graphical Abstract
Scheme 1: Mn-catalyzed late-stage fluorination of sclareolide (1) and complex steroid 3.
Figure 1: Proposed reaction mechanism of C–H fluorination by a manganese porphyrin catalyst.
Scheme 2: Late-stage radiofluorination of biologically active complex molecules.
Figure 2: Proposed mechanism of C–H radiofluorination.
Scheme 3: Late-stage C–H azidation of bioactive molecules. a1.5 mol % of Mn(TMP)Cl (5) was used. bMethyl acet...
Figure 3: Proposed reaction mechanism of manganese-catalyzed C–H azidation.
Scheme 4: Mn-catalyzed late-stage C–H azidation of bioactive molecules via electrophotocatalysis. a2.5 mol % ...
Figure 4: Proposed reaction mechanism of electrophotocatalytic azidation.
Scheme 5: Manganaelectro-catalyzed late-stage azidation of bioactive molecules.
Figure 5: Proposed reaction pathway of manganaelectro-catalyzed late-stage C–H azidation.
Scheme 6: Mn-catalyzed late-stage amination of bioactive molecules. a3 Å MS were used. Protonation with HBF4⋅...
Figure 6: Proposed mechanism of manganese-catalyzed C–H amination.
Scheme 7: Mn-catalyzed C–H methylation of heterocyclic scaffolds commonly found in small-molecule drugs. aDAS...
Scheme 8: Examples of late-stage C–H methylation of bioactive molecules. aDAST activation. bFor insoluble sub...
Scheme 9: A) Mn-catalyzed late-stage C–H alkynylation of peptides. B) Intramolecular late-stage alkynylative ...
Figure 7: Proposed reaction mechanism of Mn(I)-catalyzed C–H alkynylation.
Scheme 10: Late-stage Mn-catalyzed C–H allylation of peptides and bioactive motifs.
Scheme 11: Intramolecular C–H allylative cyclic peptide formation.
Scheme 12: Late-stage C–H glycosylation of tryptophan analogues.
Scheme 13: Late-stage C–H glycosylation of tryptophan-containing peptides.
Scheme 14: Late-stage C–H alkenylation of tryptophan-containing peptides.
Scheme 15: A) Late-stage C–H macrocyclization of tryptophan-containing peptides and B) traceless removal of py...
Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions
- Andrea Caporale,
- Stefano Tartaggia,
- Andrea Castellin and
- Ottorino De Lucchi
Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36
- bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described. Keywords: alkynes; decarboxylative couplings; Erlotinib; palladium; propiolic acid; Introduction The Sonogashira coupling reaction of aryl or alkenyl halides with
- Sonogashira coupling reactions have found many applications in the synthesis of pharmaceutical substances. During the investigation about a possible alternative preparation of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol (2a) to improve a key-step in the synthesis of Erlotinib, an important anticancer
- been optimized for the synthesis of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol, which has never been prepared through a Cu-free coupling process and which is also a pharmaceutical intermediate for Erlotinib. The present work provides also a more detailed description about the coupling process and a more
Graphical Abstract
Scheme 1: Conventional (from the left) and decarboxylative (from the right) Pd-catalyzed Sonogashira coupling...
Scheme 2: Protection of propiolic acid with acetone.
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
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.
