193148-60-6Relevant articles and documents
The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain
Brown, Alan D.,Bagal, Sharan K.,Blackwell, Paul,Blakemore, David C.,Brown, Bruce,Bungay, Peter J.,Corless, Martin,Crawforth, James,Fengas, David,Fenwick, David R.,Gray, Victoria,Kemp, Mark,Klute, Wolfgang,Malet Sanz, Laia,Miller, Duncan,Murata, Yoshihisa,Payne, C. Elizabeth,Skerratt, Sarah,Stevens, Edward B.,Warmus, Joseph S.
supporting information, p. 230 - 239 (2018/12/11)
The voltage gated sodium channel NaV1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole NaV1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.
Continuous flow synthesis of β-amino acids from α-amino acids via Arndt-Eistert homologation
Pinho, Vagner D.,Gutmann, Bernhard,Kappe, C. Oliver
, p. 37419 - 37422 (2014/12/09)
A fully continuous four step process for the preparation of β-amino acids from their corresponding α-amino acids utilizing the Arndt-Eistert homologation approach is described. the Partner Organisations 2014.
Synthesis of N-urethane protected α-aminoalkyl-α-cyanomethyl ketones; Application to the synthesis of 3-substituted 5-amino-1H-pyrazole tethered peptidomimetics
Sharnabai,Nagendra,Sureshbabu, Vommina V.
scheme or table, p. 1913 - 1918 (2012/09/25)
The preparation of N-protected amino/peptide α-cyanomethyl ketones through cyanation of the corresponding α-bromomethyl ketones is described. The utility of the resulting α-cyanomethyl ketones in the synthesis of 3-substituted-5-amino-1H-pyrazoles has also been demonstrated. In both steps a wide range of N-protected amino/peptide acids has been employed and the products are obtained in good yield. The enantiomeric purity of both the α-cyanomethyl ketones and pyrazoles were confirmed by chiral HPLC analysis of the corresponding Z-protected d- and l-Ala-OH as model substrates. The synthesis of peptide pyrazolecarboxamides is also delineated. Georg Thieme Verlag Stuttgart · New York.
CuI-promoted one-pot synthesis of N-boc protected β-ketotriazole amino acids: Application in the synthesis of new class of dipeptidomimetics
Vishwanathaa,Narendra,Sureshbabu, Vommina V.
, p. 308 - 314 (2012/07/17)
One-pot click chemistry of Nα-Boc-bromomethylketones, NaN3 and propiolic acid affords N-Boc protected 1,4- disubstituted 1,2,3-β-ketotriazole acids in good to excellent yield. The use of CuI as catalyst and DMSO as solvent leads the click react
Enantiospecific synthesis of pyridinones as versatile intermediates toward asymmetric piperidines
Gouault, Nicolas,Le Roch, Myriam,Cheignon, Adele,Uriac, Philippe,David, Michele
scheme or table, p. 4371 - 4373 (2011/10/08)
The enantiospecific syntheses of pyridinones from amino acids via a gold-catalyzed strategy are reported. Excellent stereocontrol was observed during the cyclization. This approach provides a straightforward tool for further synthetic applications toward
Synthesis of cyclo-β-tripeptides and their biological in vitro evaluation as antiproliferatives against the growth of human cancer cell lines
Gademann, Karl,Seebach, Dieter
, p. 2924 - 2937 (2007/10/03)
A number of cyclo-β-tripeptides and their linear precursors were subjected to primary biological evaluation for cancer-cell growth inhibition (one-dose, three-cell essay), and the five most active ones were then tested in the anti-tumor screen of the National Cancer Institute (Bethesda, USA) with 60 human cancer cell lines. Growth inhibition values GI50 in the one-digit micromolar, and in one case in the nanomolar range were obtained. The effects show selectivities for certain types of cancer cells and for certain cell lines within these types; the screen includes leukemia, non-small-cell lung, colon, and central-nervous-system (CNS) cancer, melanoma, ovarian, renal, prostate, and breast cancer cell lines. The synthesis and full characterization of two new cyclo-β-peptides, (β3-HSer(OBn))3 (11) and (β3-HMet)3 (12) are described. Other cyclo-β-peptides included in this investigation are (βAsp(Bn))3 (13), (β-HGlu(Bn))3 (14), and (β-HAla)3 (16), compounds which had been previously prepared by us. Strongest activities were measured with the cyclo-β-peptides bearing benzyl-ester or benzyl-ether groups in the side chains. The cytotoxic activity of the compounds included in this investigation is much lower (LC50 > 100 μM) than their antiproliferative activity (GI50).
Convenient and simple homologation of Nα-urethane protected α-amino acids to their β-homologues with concomitant o-nitrophenylesters formation
Ananda,Gopi,Suresh Babu
, p. 790 - 795 (2007/10/03)
The Wolff rearrangement of α-aminodiazoketones derived from Nα-urethane protected α-amino acids in presence of o-nitrophenol catalyzed by silver acetate at low temperature is described. The potential utility of the well-known ketene intermediat
Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease
Ogilvie,Yoakim,Do,Hache,Lagace,Naud,O'Meara,Deziel
, p. 1521 - 1531 (2007/10/03)
A series of monobactam inhibitors of HCMV (N(o)) protease bearing a heterocycle linked by a methylene group at C-4 is described. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole were found to be active in a plaque reduction assay. Furthermore, 2-benzothiazole derivatives were shown to inhibit the HCMV protease activity inside cells by using a cell transfection assay, indicating that their antiviral activity in the plaque reduction assay could be attributed to protease inhibition. Copyright (C) 1999 Elsevier Science Ltd.
Direct synthesis of N-protected β-amino dimethylhydroxamates: Application to the solid-phase synthesis of a peptide incorporating a new amide bond surrogate ψ[CH2CH2NH]
Limal, David,Quesnel, Anne,Briand, Jean-Paul
, p. 4239 - 4242 (2007/10/03)
A rapid and efficient one-step synthesis of N-protected β-amino dimethylhydroxamates starting from diazo ketones is reported. A Fmoc- protected β-amino aldehyde obtained by reduction of its corresponding dimethylhydroxamate was incorporated during solid p
Linear and cyclic β3-oligopeptides with functionalised side-chains (-CH2OBn, -CO2Bn, -CH2CH2CO2Bn) derived from serine and from aspartic and glutamic acid
Matthews, Jennifer L.,Gademann, Karl,Jaun, Bernhard,Seebach, Dieter
, p. 3331 - 3340 (2007/10/03)
The natural β-amino acid derivative Boc-Asp(β-OH)-OBn, as well as Boc-β-HGlu(OBn)-OH and Boc-β-HSer(OBn)-OH (prepared from appropriately protected glutamic acid and serine, respectively, by Arndt-Eistert homologation), were employed as building blocks for the synthesis of linear (11-20) and cyclic (21-23) β-oligopeptides consisting of two to six β-amino acids [using trichloroethyl (TCE) ester groups for C-terminal protection and pentafluorophenyl-ester activation for macrocyclisation]. While the linear derivatives are soluble enough for reactions and structural investigations in solution, the cyclo-β-tri- and -hexapeptides are not (according to FT-IR measurements they form networks of hydrogen bonds, perhaps consisting of so-called nanotubes). The CD spectra of the Boc-OTCE-protected (19) and of the unprotected (20) β-hexapeptides [β-Asp(OBn)-β-HGlu(OBn)-β-HSer(OBn)]2 differ drastically, and only the unprotected form shows the familiar pattern of a negative Cotton effect between 210 and 220 nm (indicative of a 314 helix). An NMR analysis in methanol of the β-hexapeptide 20 with free termini reveals the presence of a single, central, left-handed helix turn (14-membered hydrogen-bonded ring). The results are discussed and compared with those obtained previously for analogous β-peptides carrying non-functionalised side chains.
