77716-11-1Relevant articles and documents
NOVEL BENZODIAZEPINE DERIVATIVES
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Page/Page column 141, (2010/08/18)
The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
Guanine-Containing DNA Minor-Groove binders
Pulido, Daniel,Sanchez, Albert,Robles, Jordi,Pedroso, Enrique,Grandas, Anna
experimental part, p. 1398 - 1406 (2009/08/07)
Solid-phase procedures have been used to prepare six di-pyrrole-containing DNA ligands that combine (guanin-9-yl)-acetyl, (guanin-7-yl)acetyl or acetyl moieties at the N-terminal end and two lysines or a (dimethylamino)propyl group at the C terminus. Inspection of their DNA-stabilizing properties by UV-monitored thermal denaturation experiments showed that the ligand incorporating the (guanin-9-yl)acetyl group and the (dimethylamino)propyl tail had the highest duplex-stabilizing effects. Wiley-VCH Verlag GmbH & Co, KGaA.
2’-DEOXYGUANOSINE HYBRID COMPOUND CONTAINING PYRROLE AMIDE TETRAMER, METHOD OF PRODUCING THE SAME AND PRODUCTION INTERMEDIATE THEREFOR
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Page/Page column 18-19, (2010/11/26)
It is intended to provide an MGB polyamide hybrid compound which has a function of recognizing a base sequence useful in gene therapy, is efficacious in synthesizing an oligomer and has a high stability. An MGB polyamide hybrid compound represented by the following formula (38) which is characterized by being a pyrrole amide tetramer prepared by introducing a 1-methylpyrrole-2-carbonyl group as a substitute for the N-terminal formyl group in the existing case.
Synthesis of DNA-sequence-selective hairpin polyamide platinum complexes
Taleb, Robin I.,Jaramillo, David,Wheate, Niai J.,Aldrich-Wright, Janice R.
, p. 3177 - 3186 (2008/02/05)
Two DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing pyrrole and imidazole heterocyclic rings, have been synthesised by different methods. A six-ring complex, selective for (A/T)GGG-(A/T) DNA sequences, was made by using solid-phase synthesis, whilst an eight-ring complex, selective for (A/ T)CCTG(A/T) DNA sequences, was made by utilising standard wet chemistry. Solid-phase synthesis resulted in a significantly higher yield, required less purification and is more efficient than the wet synthesis; as such, it is the preferred method for further work. The metal complexes were characterised by 1H and 195Pt NMR spectroscopy and ESI mass spectrometry. The two compounds provide a foundation for the synthesis of more complex molecules containing multiple hairpins and/or platinum groups.
Synthesis of distamycin a polyamides targeting G-quadruplex DNA
Moore, Michael J. B.,Cuenca, Francisco,Searcey, Mark,Neidle, Stephen
, p. 3479 - 3488 (2008/09/17)
A number of amide-linked oligopyrroles based on distamycin molecules have been synthesized by solid-state methods, and their interactions with a human intramolecular G-quadruplex have been measured by a melting procedure. Several of these molecules show an enhanced ratio of quadruplex vs. duplex DNA binding compared to distamycin itself, including one with a 2,5-disubstituted pyrrole group. Quadruplex affinity increases with the number of pyrrole groups, and it is suggested that this is consistent with a mixed groove/G-quartet stacking binding mode. The Royal Society of Chemistry 2006.
Synthesis of N-methylpyrrole and N-methylimidazole amino acids suitable for solid-phase synthesis
Jaramillo, David,Liu, Qi,Aldrich-Wright, Janice,Tor, Yitzhak
, p. 8151 - 8153 (2007/10/03)
New and higher yielding synthetic routes to N-protected N-methylpyrrole and N-methylimidazole amino acids are introduced to circumvent difficulties associated with established schemes. Key steps in each synthesis include copper-mediated cross-coupling reaction to directly install a carbamate-protected 4-amine in the N-methylpyrrole derivative and effective nitration followed by a one-pot reduction/Boc protection of the amine in the synthesis of the N-Me-imidazole amino acid.
Charged compounds comprising a nucleic acid binding moiety and uses therefor
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, (2008/06/13)
Charged compounds are provided that comprise one or more regions of localized positive charge, compositions comprising such compounds, methods of synthesizing such compounds, methods of screening such compounds to identify those having anti-infective activity, and methods of using such compounds to prevent or inhibit infections. These compounds, and compositions containing them, have multiple applications, including use in human and animal medicine and in agriculture.
Method for the synthesis of pyrrole and imidazole carboxamides on a solid support
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, (2008/06/13)
The present invention describes a novel method for the solid phase synthesis of polyamides containing imidazole and pyrrole carboxamides. The polyamides are prepared on a solid support from aromatic carboxylic acids and aromatic amines with high stepwise coupling yields (>99%), providing milligram quantities of highly pure polyamides. The present invention also describes the synthesis of analogs of the natural products Netropsin and Distamycin A, two antiviral antibiotics. The present invention also describes a novel method for the solid phase synthesis of imidazole and pyrrole carboxamide polyamide-oligonucleotide conjugates. This methodology will greatly increase both the complexity and quantity of minor-groove binding polyamides and minor-groove binding polyamide-oligonucleotide conjugates which can be synthesized and tested.
Complex formation between dsDNA and pyrrole imidazole polyamides
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, (2008/06/13)
Methods and compositions are provided for forming complexes between dsDNA and oligomers of heterocycles, aliphatic amino acids, particularly omega-amino acids, and a polar end group. By appropriate choice of target sequences and composition of the oligomers, complexes are obtained with low dissociation constants. The formation of complexes can be used for identification of specific dsDNA sequences, for inhibiting gene transcription, and as a therapeutic for inhibiting proliferation of undesired cells or expression of undesired genes.
Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids
Baird, Eldon E.,Dervan, Peter B.
, p. 6141 - 6146 (2007/10/03)
The solid phase synthesis of sequence specific DNA binding polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids is described. Two monomer building blocks, Boc-Py-OBt ester and Boc-Im acid, are prepared on a 50 g scale without column chromatography. Using commercially available Boc-β-alanine-Pam resin, cycling protocols were optimized to afford high stepwise coupling yields (>99%). Deprotection by aminolysis affords up to 100 mg quantities of polyamide. Solid phase methodology increases both the number and complexity of minor groove binding polyamides which can be synthesized and analyzed with regard to DNA binding affinity and sequence specificity. The solid phase synthesis of a representative eight-residue polyamide is reported.
