50720-12-2Relevant articles and documents
Regioselective Amination or Alkoxylation of Halogenated Amino-, Thio- or Alkoxypyridines via Pyridyne Intermediates
Djukanovic, Dimitrije,Heinz, Benjamin,Idriess, Mohamed,Knochel, Paul,Martin, Benjamin,Siemens, Fiona
, (2021/11/26)
The treatment of 3-halopyridines (Cl, Br) bearing an R-substituent in position 2 (R = OEt, NEt2, N-piperidyl, or SEt) or in position 5 (R = OMe, OEt, SEt, NMe2, NEt2, or aryl) with KHMDS and an amine at 25 C for 12 hours in THF provided regioselectively 3
SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
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Paragraph 1793-1795, (2015/12/23)
The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR1 (R1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH2), and at least one of ring B and ring C has substituent(s), provided that N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.
BCR-ABL TYROSINE-KINASE LIGANDS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
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Paragraph 00634; 00643; 00644, (2015/07/23)
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. invivo) to form a multimer (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding sites on a Bcr-Abl tyrosine kinase.
Aurora Kinase Modulators and Method of Use
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Paragraph 0314, (2014/11/27)
The present invention relates to chemical compounds having a general formula I wherein A1-8, D′, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.
Synthesis of novel 7-substituted pyrido[2′,3′:4,5]furo[3,2-d] pyrimidin-4-amines and their N-aryl analogues and evaluation of their inhibitory activity against Ser/Thr kinases
Deau, Emmanuel,Loidreau, Yvonnick,Marchand, Pascal,Nourrisson, Marie-Renee,Loaec, Nadege,Meijer, Laurent,Levacher, Vincent,Besson, Thierry
, p. 6784 - 6788 (2014/01/06)
The efficient synthesis of 7-substituted pyrido[2′,3′:4,5] furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2- carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki-Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1δ/ε, CLK1, DYRK1A, GSK3α/β). Compound 35 showed the best inhibitory activity with an IC50 value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases.
Highly fluorescent M2L4 molecular capsules with anthracene shells
Li, Zhiou,Kishi, Norifumi,Hasegawa, Kimiko,Akita, Munetaka,Yoshizawa, Michito
supporting information; experimental part, p. 8605 - 8607 (2011/09/14)
M2L4 molecular capsules self-assembled from M(ii) ions (where M = Zn, Ni, and Pd) and bent bidentate ligands constructed from anthracene fluorophores. The Ni(ii) and Zn(ii) capsules exhibited weak to strong blue emission unlike traditional Pd(ii) cages and capsules. The Royal Society of Chemistry 2011.
TRI-CYCLIC PYRAZOLOPYRIDINE KINASE INHIBITORS
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Page/Page column 47, (2010/12/18)
The present invention relates to compounds useful as inhibitors of P13K, particularly of P13Kgamma. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of several diseases, such as cancer and autoimmune diseases.
A convenient route to functionalized 3-amino-6-bromofuro[3,2-b]pyridine-2-carboxamides
Bretéché, Anne,Marchand, Pascal,Nourrisson, Marie-Renée,De Nanteuil, Guillaume,Duflos, Muriel
experimental part, p. 4490 - 4494 (2010/07/06)
An efficient synthesis of 3-amino-6-bromofuro[3,2-b]pyridine-2-carboxamides is described via the formation of 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile. Functionalization of the amino group at position 3 of the heterocycle will be discussed.
Characterization of nicotinamidases: Steady state kinetic parameters, classwide inhibition by nicotinaldehydes, and catalytic mechanism
French, Jarrod B.,Cen, Yana,Vrablik, Tracy L.,Xu, Ping,Allen, Eleanor,Hanna-Rose, Wendy,Sauve, Anthony A.
experimental part, p. 10421 - 10439 (2011/10/07)
Nicotinamidases are metabolic enzymes that hydrolyze nicotinamide to nicotinic acid. These enzymes are widely distributed across biology, with examples found encoded in the genomes of Mycobacteria, Archaea, Eubacteria, Protozoa, yeast, and invertebrates, but there are none found in mammals. Although recent structural work has improved our understanding of these enzymes, their catalytic mechanism is still not well understood. Recent data show that nicotinamidases are required for the growth and virulence of several pathogenic microbes. The enzymes of Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans regulate life span in their respective organisms, consistent with proposed roles in the regulation of NAD+ metabolism and organismal aging. In this work, the steady state kinetic parameters of nicotinamidase enzymes from C. elegans, Sa. cerevisiae, Streptococcus pneumoniae (a pathogen responsible for human pneumonia), Borrelia burgdorferi (the pathogen that causes Lyme disease), and Plasmodium falciparum (responsible for most human malaria) are reported. Nicotinamidases are generally efficient catalysts with steady state kcat values typically exceeding 1 s -1. The Km values for nicotinamide are low and in the range of 2 -110 μM. Nicotinaldehyde was determined to be a potent competitive inhibitor of these enzymes, binding in the low micromolar to low nanomolar range for all nicotinamidases tested. A variety of nicotinaldehyde derivatives were synthesized and evaluated as inhibitors in kinetic assays. Inhibitions are consistent with reaction of the universally conserved catalytic Cys on each enzyme with the aldehyde carbonyl carbon to form a thiohemiacetal complex that is stabilized by a conserved oxyanion hole. The S. pneumoniae nicotinamidase can catalyze exchange of 18O into the carboxy oxygens of nicotinic acid with H218O. The collected data, along with kinetic analysis of several mutants, allowed us to propose a catalytic mechanism that explains nicotinamidase and nicotinic acid 18O exchange chemistry for the S. pneumoniae enzyme involving key catalytic residues, a catalytic transition metal ion, and the intermediacy of a thioester intermediate.
CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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Page/Page column 60, (2010/04/03)
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
