- The base-free van Leusen reaction of cyclic imines on water: Synthesis of N-fused imidazo 6,11-dihydro β-carboline derivatives
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Construction of imidazoles has been demonstrated on water under base-free conditions. The reaction of dihydro β-carboline imines and p-toluenesulfonylmethyl isocyanides furnished the corresponding substituted N-fused imidazo 6,11-dihydro β-carboline derivatives in very good yields under ambient conditions. The use of deuterium oxide (D2O) as a solvent enabled the incorporation of deuterium isotopes in the imidazole ring.
- Satyam, Killari,Murugesh,Suresh, Surisetti
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supporting information
p. 5234 - 5238
(2019/06/07)
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- Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor
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As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-?-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-κB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38α. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.
- Divakaran, Anand,Talluri, Siva K.,Ayoub, Alex M.,Mishra, Neeraj K.,Cui, Huarui,Widen, John C.,Berndt, Norbert,Zhu, Jin-Yi,Carlson, Angela S.,Topczewski, Joseph J.,Schonbrunn, Ernst K.,Harki, Daniel A.,Pomerantz, William C. K.
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supporting information
p. 9316 - 9334
(2018/10/24)
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- 1,3-DIARYL-SUBSTITUTED HETEROCYCLIC PESTICIDES
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Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein Q is and Z1, Z2, J1, J2, M, R1a, R1b, R2a, R2b, R2c, R2d, R14/su
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Page/Page column 40
(2013/12/03)
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- 4-SUBSTITUTED-6-ISOPROPYL-BENZENE-1,3-DIOL COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain 4-substituted-6-isopropyl-benzene 1,3-diol compounds (referred to herein as IBD compounds), which, inter alia, inhibit heat shock protein 90 (HSP90) function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HSP90 function, and in the treatment of diseases and conditions that are mediated by HSP90, that are ameliorated by the inhibition of HSP90 function, etc., including proliferative conditions such as cancer, etc.
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Page/Page column 137
(2009/06/27)
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- Novel substituted imidazole compounds
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Novel 1,4,5 substituted imidazole compounds and compositions for use in therapy as CSBP/p38 kinase inhibitors.
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- Isonitrile intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of isonitrile compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Imine intermediates for the preparation of trisubstituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of iminc compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Formamide intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of formamide compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Substituted imidazole compounds
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The present invention relates to novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as CSBP/p38 inhibitors.
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- Process for making pyridyl and pyrimidine substituted imidazole compounds
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1,4,5,-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Cycloalkyl substituted imidazoles
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy.
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- Substituted imidazole compounds
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Substituted imidazole compounds
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This invention relates to a novel group of imidazole compounds, processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and pharmaceutical compositions for use in such therapy.
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- Cycloalkyl substituted imidazoles
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy.
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- Substituted imidazole compounds
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Imidazole compounds and compositions
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Substituted imidazole compounds
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Imidazole compounds, compositions and use
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Compounds
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Imidazole compounds, use and process of making
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Pyridyl imidazole compounds and compositions
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Novel 1, 4, 5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- 1-Substituted 4-aryl-5-pyridinylimidazoles: A new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency
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A series of 1-alkyl- or -aryl-4-aryl-5-pyridinylimidazoles (A) were prepared and tested for their ability to bind to a recently discovered protein kinase termed CSBP and to inhibit lipopolysaccharide (LPS)-stimulated TNF production in mice. The kinase, CS
- Boehm, Jeffrey C.,Smietana, Juanita M.,Sorenson, Margaret E.,Garigipati, Ravi S.,Gallagher, Timothy F.,Sheldrake, Peter L.,Bradbeer, Jeremy,Badger, Alison M.,Laydon, Jeffrey T.,Lee, John C.,Hillegass, Leonard M.,Griswold, Donald E.,Breton, John J.,Chabot-Fletcher, Marie C.,Adams, Jerry L.
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p. 3929 - 3937
(2007/10/03)
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- An efficient method for the synthesis of substituted TosMIC precursors
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Substituted tosylmethyl isocyanides (TosMICs) are useful reagents for which no general method of preparation is available. We describe here a high-yielding method for the synthesis of substituted tosylmethyl formamides, which are readily converted to the corresponding isocyanides.
- Sisko, Joseph,Mellinger, Mark,Sheldrake, Peter W.,Baine, Neil H.
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p. 8113 - 8116
(2007/10/03)
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