- Email: [email protected]
Combinatorial Chemistry Online
Combinatorial Chemistry - An Online Journal 12 (2010) 29–31
Contents lists available at ScienceDirect
Combinatorial Chemistry - An Online Journal journal homepage: www.elsevier.com/locate/comche
Combinatorial Chemistry Online Volume 12, Issue 8, August 2010 N.K. Terrett Ensemble Therapeutics Corp., Cambridge, MA 02139, USA
1. Current literature highlights 1.1. A library approach to highly substituted indolizinones Halogenated heterocycles provide a rich source of chemical diversity to the medicinal chemist, especially with the rise in popularity and the scope of transition-metal catalysed cross-coupling technologies. Consequently, methods that allow the production of structurally complex functionalised heterocycles are in demand to provide starting materials for parallel synthesis. A recent publication describes the generation of a range of 2-iodoindolizinones which in turn were useful for diversity-oriented synthesis.1 A novel approach has been established to 2-iodoindolizinones based on a 5-endo-dig cyclisation and subsequent 1,2-migration, generating a range of 2-iodoindolizinones in excellent yield and under mild conditions. The importance of such compounds is underscored by activity of related structures such as indolizines in a CHTH2 receptor assay suggesting a possible utility for the treatment of inflammatory respiratory disease. The authors, suspecting that the related indolizinones have not been explored as pharmacophores, set out with the intent of generating a library based on this heterocyclic core. Using the previously published method, the authors generated diverse 2-iodoindolizinones (3) by nucleophilic attack of appropriate terminal acetylene anions onto 2-acypyridines (1) to generate the tertiary propargyl alcohols (2). Conversion to the 2-iodoindolizinones (3) occurred by a sequential iodocyclisation and 1,2-shift of the R1 group. The products 3 have two diversity positions, but the presence of the iodine allows introduction of a third element of diversity into the products 4 by a range of coupling chemistries. O R1 N
R2
Li
Three different palladium-catalysed chemistries were employed to diversify the third position and introduce the R3 substituent: Heck, Sonogashira and Suzuki-Miyaura coupling reactions. Methyl acrylate was employed as the reagent for the Heck chemistry, whereas for the Sonogashira reaction small sets of terminal acetylenes were used. Suzuki-Miyaura coupling employed a set of aromatic or olefinic boronic acids. Overall, good yields were observed with the Heck and Sonogashira couplings, but some of the Suzuki-Miyaura reactions proceeded in less than optimal yields. The products have been advanced to biochemical screening and some compounds have been demonstrated to kill cancer cells, although the mechanism has yet to be determined.
2. A summary of the papers in this month’s issue 2.1. Solid-phase synthesis Starting from resin-bound orthogonally protected lysine, the generation of 19-membered ring macro-heterocycles via intramolecular thioether formation has been described. The approach provides versatile synthetic routes toward the synthesis of libraries of macro-heterocycles in an attempt to establish lead drug candidates. The desired cyclic products were obtained in good yields and good purities.2 An efficient and low-cost protocol for the manual synthesis of Peptide Nucleic Acids (PNAs) has been reported. The protocol relies on coupling reactions carried out with 2.5 equiv of PNA monomers activated with HOBT/HBTU, in the presence of pyridine/NMM. The protocol has been tested on four PNA oligomers with a length ranging from 9 to 12 bases and a purine content up to 67%.3 2.2. Solution-phase synthesis
1
R1
No papers this month.
OH I2
N
R1
O
2.3. Scaffolds and synthons for combinatorial libraries R1
I
N 3
iodocyclisation/1,2-shif t R2
2
Pd-catalysed couplings
R2
E-mail: [email protected] doi:10.1016/j.comche.2010.07.001
O
N 4
No papers this month. R3
R2
2.4. Solid-phase supported reagents No papers this month.
30
N.K. Terrett / Combinatorial Chemistry - An Online Journal 12 (2010) 29–31
2.5. Novel resins, linkers and techniques A stable benzylazido-boronate ester has been presented as an example of a dual-functional linker that allows the synthetically valuable boronate motif to be clicked onto other molecules under mild conditions. The utility of the azido-boronate motif as a modular building block is demonstrated in the rapid synthesis of drug-like structures employing sequential catalytic azide–alkyne cycloaddition and Suzuki coupling reactions and can be used for the diversity-oriented synthesis of drug-like molecules.4 An analysis of in vitro human liver microsomal turnover assay results, from a large dataset of experimental compounds tested, has been described. Combined with an analysis of small substituents on known drugs and existing published results, a new set of 29 substituents was proposed to increase stability and probe SAR. A statistical analysis of in vitro human microsomal metabolic stability of small phenyl group substituents, led to improved design sets for parallel SAR exploration of a chemical series.5 2.6. Library applications A 270-membered library of trisubstituted ureas has been synthesised and evaluated for inhibition of soluble epoxide hydrolase. Library design and reagent selection was guided by the use of a pharmacophore model and synthesis of the array was enabled with a general solid-phase method.6 A series of phenyl piperidine a-sulphone hydroxamate derivatives has been prepared utilising a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats.7 In the next paper in this issue, the same authors report a series of N-aryl isonipecotamide a-sulphone hydroxamate derivatives prepared using a combination of solution-phase and resinbound library technologies, also targeted to generate potent and highly selective inhibitors of MMP-13.8 A novel series of [6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethyl]-dialkylamines have been discovered as potent CRF1R antagonists. The optimisation of binding affinity in the series by a parallel synthetic approach is discussed.9 The synthesis and biofilm inhibitory activity of a 30-member arylamide 2-aminoimidazole library against the three biofilm forming Gram-negative bacteria Escherichia coli, Psuedomonas aeruginosa, and Acinetobacter baumannii has been described. The most active compound identified inhibits the formation of E. coli biofilms with an IC50 of 5.2 lM and was observed to be non-toxic to planktonic growth, demonstrating that analogues based on an aryl framework are viable options as biofilm inhibitors within the 2aminoimidazole family.10 A novel class of hemagglutinin (HA) inhibitors has been identified based on ligand similarity search of known HA inhibitors. Parallel synthesis and further structural modifications resulted in 1phenyl-cyclopentanecarboxylic acid (4-cyano-phenyl)-methylamide as a potent and selective inhibitor to phylogenetic H1 influenza viruses with an EC50 of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.11 Head group analogues of the antibacterial and antiparasitic drug nitazoxanide (NTZ) have been reported. A library of 39 analogues was synthesised and assayed for their ability to suppress growth of Helicobacter pylori, Campylobacter jejuni, Clostridium difficile and inhibit NTZ target pyruvate:ferredoxin oxidoreductase.12 Lavendustin-mimetic small molecules modifying the linker – CH2–NH– with an 1,2,3-triazole ring have been synthesised via click chemistry. Two pharmacophoric fragments of lavendustin were varied in a library format to investigate chemical space and the auxophoric –CH2–NH– was altered to a 1,2,3-triazole for rapid
click conjugation. The small molecules were evaluated against HCT116 colon cancer and CCRF-CEM leukemia cell lines, and amongst 28 analogues produced, a 3-phenylpropyl ester inhibited CCRF-CEM leukemia cell growth with GI50 value of 0.9 lM.13 A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilising a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC50 values ranging from 0.0115 lM.14 Novel acrylic acid ethyl ester derivatives have been synthesised and evaluated as potential agents against Mycobacterium species. A versatile and efficient copper-catalysed coupling process was developed and used to prepare a library of substituted acrylic acid ethyl ester analogues. Minimum inhibitory concentration assays indicated that two of these compounds have greater in vitro activity against Mycobacterium smegmatis than rifampin, one of the current, first-line anti-mycobacterial chemotherapeutic agents.15 CuI-catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) ‘click chemistry’ was used to assemble a library of 21 a-d- and b-d-glucopyranosyl triazoles, which were assessed as potential glycosidase inhibitors. In the course of this work, different reactivities of isomeric a- and b-glucopyranosyl azides under CuAAC conditions were noted. The triazole library was assayed for inhibition of sweet almond b-glucosidase (GH1) and yeast a-glucosidase (GH13), which led to the identification of a set of glucosidase inhibitors effective in the 100 lM range.16 References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
Kim K, Kim I. J Comb Chem 2010;12(3):379–82. Derbel S et al. Tetrahedron Lett 2010;51(28):3607–9. Avitabile C et al. Tetrahedron Lett 2010;51(29):3716–8. White JR et al. Tetrahedron Lett 2010;51(30):3913–7. Dossetter AG. Bioorg Med Chem 2010;18(12):4405–14. Kowalski JA et al. Bioorg Med Chem Lett 2010;20(12):3703–7. Kolodziej SA et al. Bioorg Med Chem Lett 2010;20(12):3557–60. Kolodziej SA et al. Bioorg Med Chem Lett 2010;20(12):3561–4. Zuev D et al. Bioorg Med Chem Lett 2010;20(12):3669–74. Bunders CA et al. Bioorg Med Chem Lett 2010;20(12):3797–800. Tang G et al. Bioorg Med Chem Lett 2010;20(12):3507–10. Ballard TE et al. Bioorg Med Chem Lett 2010;20(12):3537–9. Yoon J, Ryu J-S. Bioorg Med Chem Lett 2010;20(13):3930–5. Khan MTH et al. Bioorg Med Chem 2010;18(12):4317–27. Kabir MS et al. Bioorg Med Chem 2010;18(12):4178–86. Dedola S et al. Carbohydr Res 2010;345(9):1123–34.
Further reading Papers on combinatorial chemistry or solid-phase synthesis from other journals Niralwad KS, Shingate BB, Shingare MS. Solid-phase synthesis of 2-arylbenzothiazole using silica sulfuric acid under microwave irradiation. Bulletin of the Korean Chemical Society 2010;31(4):981–3. Upert G, Merten CA, Wennemers H. Nanoliter plates – versatile tools for the screening of split-and-mix libraries on-bead and o-bead. Chemical Communications (Cambridge, United Kingdom) 2010;46(13):2209–11. Frei R, Blackwell HE. Small molecule macroarray construction via palladiummediated carbon–carbon bond-forming reactions: highly efficient synthesis and screening of stilbene arrays. Chemistry – A European Journal 2010;16(9):2692–5. Cornaggia C, Pasini D. Tagging molecules with linear polymers: biocatalytic transformation of substrates anchored on soluble macromolecules. Combinatorial Chemistry & High Throughput Screening 2010;13(1):45–53. Liu Z, Myers MC, Shah PP, Beavers MP, Benedetti PA, Diamond SL, et al. Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitors. Combinatorial Chemistry & High Throughput Screening 2010;13(4):337–51. Townsend J, Do A, Lehman A, Dixon S, Sanii B, Lam KS. 3-Nitro-tyrosine as an internal quencher of autofluorescence enhances the compatibility of fluorescence based screening of OBOC combinatorial libraries. Combinatorial Chemistry & High Throughput Screening 2010;13(5):422–9. Gozalbes R, Carbajo RJ, Pineda-Lucena A. Contributions of computational chemistry and biophysical techniques to fragment-based drug discovery. Current Medicinal Chemistry 2010;17(17):1769–94.
N.K. Terrett / Combinatorial Chemistry - An Online Journal 12 (2010) 29–31 Akella LB, DeCaprio D. Cheminformatics approaches to analyze diversity in compound screening libraries. Current Opinion in Chemical Biology 2010;14(3):325–30. Welsch ME, Snyder SA, Stockwell BR. Privileged scaolds for library design and drug discovery. Current Opinion in Chemical Biology 2010;14(3):347–61. Biggs-Houck JE, Younai A, Shaw JT. Recent advances in multicomponent reactions for diversity-oriented synthesis. Current Opinion in Chemical Biology 2010;14(3): 371–82. Vendrell M, Lee J-S, Chang Y-T. Diversity-oriented fluorescence library approaches for probe discovery and development. Current Opinion in Chemical Biology 2010;14(3):383–9. Park J-W, Jun C-H. Transition-metal-catalyzed immobilization of organic functional groups onto solid supports through vinylsilane coupling reactions. Journal of the American Chemical Society 2010;132(21):7268–9. Cho S, Choi J, Kim A, Lee Y, Kwon Y-U. Efficient solid-phase synthesis of a series of cyclic and linear peptoid-dexamethasone conjugates for the cell permeability studies. Journal of Combinatorial Chemistry 2010;12(3):321–6. Wu H, Xie X, Liu G. Parallel solution phase synthesis of 3,6,7-4(3H)-quinazolinones and evaluation of their antitumor activities against human cancer. Journal of Combinatorial Chemistry 2010;12(3):346–55.
31
Shaterian HR, Honarmand M, Oveisi AR. Multicomponent synthesis of 3,5-diaryl-2,6dicyanoanilines under thermal solvent-free conditions. Monatshefte fuer Chemie 2010;141(5):557–60. Bhat VT, Caniard AM, Luksch T, Brenk R, Campopiano DJ, Greaney MF. Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry. Nature Chemistry 2010;2(6):490–7. Wu J-J, Cao S, Liu N-J, Shen L, Yu J-L, Zhang J, et al. A general strategy for construction of a difluoromethyl compound library and its application in synthesis of pseudopeptides bearing a terminal difluoromethyl group. Organic & Biomolecular Chemistry 2010;8(10):2386–91. Besenius P, Cormack PAG, Ludlow RF, Otto S, Sherrington DC. Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor. Organic & Biomolecular Chemistry 2010;8(10):2414–8. Shih H-W, Chen K-T, Chen S-K, Huang C-Y, Cheng T-JR, Ma C, et al. Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors. Organic & Biomolecular Chemistry 2010;8(11):2586–93. Huang Z, Derksen DJ, Vederas JC. Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides. Organic Letters 2010;12(10):2282–5.
Contents lists available at ScienceDirect
Combinatorial Chemistry - An Online Journal journal homepage: www.elsevier.com/locate/comche
Combinatorial Chemistry Online Volume 12, Issue 8, August 2010 N.K. Terrett Ensemble Therapeutics Corp., Cambridge, MA 02139, USA
1. Current literature highlights 1.1. A library approach to highly substituted indolizinones Halogenated heterocycles provide a rich source of chemical diversity to the medicinal chemist, especially with the rise in popularity and the scope of transition-metal catalysed cross-coupling technologies. Consequently, methods that allow the production of structurally complex functionalised heterocycles are in demand to provide starting materials for parallel synthesis. A recent publication describes the generation of a range of 2-iodoindolizinones which in turn were useful for diversity-oriented synthesis.1 A novel approach has been established to 2-iodoindolizinones based on a 5-endo-dig cyclisation and subsequent 1,2-migration, generating a range of 2-iodoindolizinones in excellent yield and under mild conditions. The importance of such compounds is underscored by activity of related structures such as indolizines in a CHTH2 receptor assay suggesting a possible utility for the treatment of inflammatory respiratory disease. The authors, suspecting that the related indolizinones have not been explored as pharmacophores, set out with the intent of generating a library based on this heterocyclic core. Using the previously published method, the authors generated diverse 2-iodoindolizinones (3) by nucleophilic attack of appropriate terminal acetylene anions onto 2-acypyridines (1) to generate the tertiary propargyl alcohols (2). Conversion to the 2-iodoindolizinones (3) occurred by a sequential iodocyclisation and 1,2-shift of the R1 group. The products 3 have two diversity positions, but the presence of the iodine allows introduction of a third element of diversity into the products 4 by a range of coupling chemistries. O R1 N
R2
Li
Three different palladium-catalysed chemistries were employed to diversify the third position and introduce the R3 substituent: Heck, Sonogashira and Suzuki-Miyaura coupling reactions. Methyl acrylate was employed as the reagent for the Heck chemistry, whereas for the Sonogashira reaction small sets of terminal acetylenes were used. Suzuki-Miyaura coupling employed a set of aromatic or olefinic boronic acids. Overall, good yields were observed with the Heck and Sonogashira couplings, but some of the Suzuki-Miyaura reactions proceeded in less than optimal yields. The products have been advanced to biochemical screening and some compounds have been demonstrated to kill cancer cells, although the mechanism has yet to be determined.
2. A summary of the papers in this month’s issue 2.1. Solid-phase synthesis Starting from resin-bound orthogonally protected lysine, the generation of 19-membered ring macro-heterocycles via intramolecular thioether formation has been described. The approach provides versatile synthetic routes toward the synthesis of libraries of macro-heterocycles in an attempt to establish lead drug candidates. The desired cyclic products were obtained in good yields and good purities.2 An efficient and low-cost protocol for the manual synthesis of Peptide Nucleic Acids (PNAs) has been reported. The protocol relies on coupling reactions carried out with 2.5 equiv of PNA monomers activated with HOBT/HBTU, in the presence of pyridine/NMM. The protocol has been tested on four PNA oligomers with a length ranging from 9 to 12 bases and a purine content up to 67%.3 2.2. Solution-phase synthesis
1
R1
No papers this month.
OH I2
N
R1
O
2.3. Scaffolds and synthons for combinatorial libraries R1
I
N 3
iodocyclisation/1,2-shif t R2
2
Pd-catalysed couplings
R2
E-mail: [email protected] doi:10.1016/j.comche.2010.07.001
O
N 4
No papers this month. R3
R2
2.4. Solid-phase supported reagents No papers this month.
30
N.K. Terrett / Combinatorial Chemistry - An Online Journal 12 (2010) 29–31
2.5. Novel resins, linkers and techniques A stable benzylazido-boronate ester has been presented as an example of a dual-functional linker that allows the synthetically valuable boronate motif to be clicked onto other molecules under mild conditions. The utility of the azido-boronate motif as a modular building block is demonstrated in the rapid synthesis of drug-like structures employing sequential catalytic azide–alkyne cycloaddition and Suzuki coupling reactions and can be used for the diversity-oriented synthesis of drug-like molecules.4 An analysis of in vitro human liver microsomal turnover assay results, from a large dataset of experimental compounds tested, has been described. Combined with an analysis of small substituents on known drugs and existing published results, a new set of 29 substituents was proposed to increase stability and probe SAR. A statistical analysis of in vitro human microsomal metabolic stability of small phenyl group substituents, led to improved design sets for parallel SAR exploration of a chemical series.5 2.6. Library applications A 270-membered library of trisubstituted ureas has been synthesised and evaluated for inhibition of soluble epoxide hydrolase. Library design and reagent selection was guided by the use of a pharmacophore model and synthesis of the array was enabled with a general solid-phase method.6 A series of phenyl piperidine a-sulphone hydroxamate derivatives has been prepared utilising a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats.7 In the next paper in this issue, the same authors report a series of N-aryl isonipecotamide a-sulphone hydroxamate derivatives prepared using a combination of solution-phase and resinbound library technologies, also targeted to generate potent and highly selective inhibitors of MMP-13.8 A novel series of [6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethyl]-dialkylamines have been discovered as potent CRF1R antagonists. The optimisation of binding affinity in the series by a parallel synthetic approach is discussed.9 The synthesis and biofilm inhibitory activity of a 30-member arylamide 2-aminoimidazole library against the three biofilm forming Gram-negative bacteria Escherichia coli, Psuedomonas aeruginosa, and Acinetobacter baumannii has been described. The most active compound identified inhibits the formation of E. coli biofilms with an IC50 of 5.2 lM and was observed to be non-toxic to planktonic growth, demonstrating that analogues based on an aryl framework are viable options as biofilm inhibitors within the 2aminoimidazole family.10 A novel class of hemagglutinin (HA) inhibitors has been identified based on ligand similarity search of known HA inhibitors. Parallel synthesis and further structural modifications resulted in 1phenyl-cyclopentanecarboxylic acid (4-cyano-phenyl)-methylamide as a potent and selective inhibitor to phylogenetic H1 influenza viruses with an EC50 of 98 nM against H1N1 A/Weiss/43 strain and over 1000-fold selectivity against host MDCK cells.11 Head group analogues of the antibacterial and antiparasitic drug nitazoxanide (NTZ) have been reported. A library of 39 analogues was synthesised and assayed for their ability to suppress growth of Helicobacter pylori, Campylobacter jejuni, Clostridium difficile and inhibit NTZ target pyruvate:ferredoxin oxidoreductase.12 Lavendustin-mimetic small molecules modifying the linker – CH2–NH– with an 1,2,3-triazole ring have been synthesised via click chemistry. Two pharmacophoric fragments of lavendustin were varied in a library format to investigate chemical space and the auxophoric –CH2–NH– was altered to a 1,2,3-triazole for rapid
click conjugation. The small molecules were evaluated against HCT116 colon cancer and CCRF-CEM leukemia cell lines, and amongst 28 analogues produced, a 3-phenylpropyl ester inhibited CCRF-CEM leukemia cell growth with GI50 value of 0.9 lM.13 A combinatorial series of novel quinazolin-4(3H)-ones were synthesised and their structures were established based on spectroscopic data (IR, NMR, EI-MS, and FAB-MS). The compounds were tested for inhibition of the zinc metalloproteinase thermolysin (TLN) utilising a chemical array-based approach. Some of the compounds were found to inhibit TLN, with IC50 values ranging from 0.0115 lM.14 Novel acrylic acid ethyl ester derivatives have been synthesised and evaluated as potential agents against Mycobacterium species. A versatile and efficient copper-catalysed coupling process was developed and used to prepare a library of substituted acrylic acid ethyl ester analogues. Minimum inhibitory concentration assays indicated that two of these compounds have greater in vitro activity against Mycobacterium smegmatis than rifampin, one of the current, first-line anti-mycobacterial chemotherapeutic agents.15 CuI-catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) ‘click chemistry’ was used to assemble a library of 21 a-d- and b-d-glucopyranosyl triazoles, which were assessed as potential glycosidase inhibitors. In the course of this work, different reactivities of isomeric a- and b-glucopyranosyl azides under CuAAC conditions were noted. The triazole library was assayed for inhibition of sweet almond b-glucosidase (GH1) and yeast a-glucosidase (GH13), which led to the identification of a set of glucosidase inhibitors effective in the 100 lM range.16 References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.
Kim K, Kim I. J Comb Chem 2010;12(3):379–82. Derbel S et al. Tetrahedron Lett 2010;51(28):3607–9. Avitabile C et al. Tetrahedron Lett 2010;51(29):3716–8. White JR et al. Tetrahedron Lett 2010;51(30):3913–7. Dossetter AG. Bioorg Med Chem 2010;18(12):4405–14. Kowalski JA et al. Bioorg Med Chem Lett 2010;20(12):3703–7. Kolodziej SA et al. Bioorg Med Chem Lett 2010;20(12):3557–60. Kolodziej SA et al. Bioorg Med Chem Lett 2010;20(12):3561–4. Zuev D et al. Bioorg Med Chem Lett 2010;20(12):3669–74. Bunders CA et al. Bioorg Med Chem Lett 2010;20(12):3797–800. Tang G et al. Bioorg Med Chem Lett 2010;20(12):3507–10. Ballard TE et al. Bioorg Med Chem Lett 2010;20(12):3537–9. Yoon J, Ryu J-S. Bioorg Med Chem Lett 2010;20(13):3930–5. Khan MTH et al. Bioorg Med Chem 2010;18(12):4317–27. Kabir MS et al. Bioorg Med Chem 2010;18(12):4178–86. Dedola S et al. Carbohydr Res 2010;345(9):1123–34.
Further reading Papers on combinatorial chemistry or solid-phase synthesis from other journals Niralwad KS, Shingate BB, Shingare MS. Solid-phase synthesis of 2-arylbenzothiazole using silica sulfuric acid under microwave irradiation. Bulletin of the Korean Chemical Society 2010;31(4):981–3. Upert G, Merten CA, Wennemers H. Nanoliter plates – versatile tools for the screening of split-and-mix libraries on-bead and o-bead. Chemical Communications (Cambridge, United Kingdom) 2010;46(13):2209–11. Frei R, Blackwell HE. Small molecule macroarray construction via palladiummediated carbon–carbon bond-forming reactions: highly efficient synthesis and screening of stilbene arrays. Chemistry – A European Journal 2010;16(9):2692–5. Cornaggia C, Pasini D. Tagging molecules with linear polymers: biocatalytic transformation of substrates anchored on soluble macromolecules. Combinatorial Chemistry & High Throughput Screening 2010;13(1):45–53. Liu Z, Myers MC, Shah PP, Beavers MP, Benedetti PA, Diamond SL, et al. Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitors. Combinatorial Chemistry & High Throughput Screening 2010;13(4):337–51. Townsend J, Do A, Lehman A, Dixon S, Sanii B, Lam KS. 3-Nitro-tyrosine as an internal quencher of autofluorescence enhances the compatibility of fluorescence based screening of OBOC combinatorial libraries. Combinatorial Chemistry & High Throughput Screening 2010;13(5):422–9. Gozalbes R, Carbajo RJ, Pineda-Lucena A. Contributions of computational chemistry and biophysical techniques to fragment-based drug discovery. Current Medicinal Chemistry 2010;17(17):1769–94.
N.K. Terrett / Combinatorial Chemistry - An Online Journal 12 (2010) 29–31 Akella LB, DeCaprio D. Cheminformatics approaches to analyze diversity in compound screening libraries. Current Opinion in Chemical Biology 2010;14(3):325–30. Welsch ME, Snyder SA, Stockwell BR. Privileged scaolds for library design and drug discovery. Current Opinion in Chemical Biology 2010;14(3):347–61. Biggs-Houck JE, Younai A, Shaw JT. Recent advances in multicomponent reactions for diversity-oriented synthesis. Current Opinion in Chemical Biology 2010;14(3): 371–82. Vendrell M, Lee J-S, Chang Y-T. Diversity-oriented fluorescence library approaches for probe discovery and development. Current Opinion in Chemical Biology 2010;14(3):383–9. Park J-W, Jun C-H. Transition-metal-catalyzed immobilization of organic functional groups onto solid supports through vinylsilane coupling reactions. Journal of the American Chemical Society 2010;132(21):7268–9. Cho S, Choi J, Kim A, Lee Y, Kwon Y-U. Efficient solid-phase synthesis of a series of cyclic and linear peptoid-dexamethasone conjugates for the cell permeability studies. Journal of Combinatorial Chemistry 2010;12(3):321–6. Wu H, Xie X, Liu G. Parallel solution phase synthesis of 3,6,7-4(3H)-quinazolinones and evaluation of their antitumor activities against human cancer. Journal of Combinatorial Chemistry 2010;12(3):346–55.
31
Shaterian HR, Honarmand M, Oveisi AR. Multicomponent synthesis of 3,5-diaryl-2,6dicyanoanilines under thermal solvent-free conditions. Monatshefte fuer Chemie 2010;141(5):557–60. Bhat VT, Caniard AM, Luksch T, Brenk R, Campopiano DJ, Greaney MF. Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry. Nature Chemistry 2010;2(6):490–7. Wu J-J, Cao S, Liu N-J, Shen L, Yu J-L, Zhang J, et al. A general strategy for construction of a difluoromethyl compound library and its application in synthesis of pseudopeptides bearing a terminal difluoromethyl group. Organic & Biomolecular Chemistry 2010;8(10):2386–91. Besenius P, Cormack PAG, Ludlow RF, Otto S, Sherrington DC. Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor. Organic & Biomolecular Chemistry 2010;8(10):2414–8. Shih H-W, Chen K-T, Chen S-K, Huang C-Y, Cheng T-JR, Ma C, et al. Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors. Organic & Biomolecular Chemistry 2010;8(11):2586–93. Huang Z, Derksen DJ, Vederas JC. Preparation and use of cysteine orthoesters for solid-supported synthesis of peptides. Organic Letters 2010;12(10):2282–5.