- Alkenyl Isocyanide Conjugate Additions: A Rapid Route to γ-Carbolines
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Isocyanides are exceptional building blocks, the wide deployment of which in multicomponent and metal-insertion reactions belies their limited availability. The first conjugate addition/alkylation to alkenyl isocyanides is described, which addresses this deficiency. An array of organolithiums, magnesiates, enolates, and metalated nitriles add conjugately to β- and β,β-disubstituted arylsulfonyl alkenyl isocyanides to rapidly assemble diverse isocyanide scaffolds. The intermediate metalated isocyanides are efficiently trapped with electrophiles to generate substituted isocyanides incorporating contiguous tri- and tetra-substituted centers. The substituted isocyanides are ideally functionalized for elaboration into synthetic targets as illustrated by the three-step synthesis of γ-carboline N-methyl ingenine B.
- Chepyshev, Sergiy V.,Lujan-Montelongo, J. Armando,Chao, Allen,Fleming, Fraser F.
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- HETEROCYCLIC COMPOUNDS USED AS FGFR INHIBITORS
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The present invention relates to a heterocyclic compound, a pharmaceutical composition containing the same, a preparation method thereof, and use thereof as a fibroblast growth factor receptor (FGFR) inhibitor. The compound is a heterocyclic compound as shown in Formula I, or a pharmaceutically acceptable salt, prodrug, solvent compound, polymorph, isomer or stable isotopic derivative thereof. The present invention further relates to use of the compound for the treatment or prevention of related diseases which are FGFR-mediated such as cancer, and a method for applying the compound to treat said diseases.
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Paragraph 0171-0173
(2019/05/24)
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- A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor
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The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure-activity relationship (SAR) studies led to the identification of compound 12b with a ~450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.
- Borsari, Chiara,Rageot, Denise,Dall'Asen, Alix,Bohnacker, Thomas,Melone, Anna,Sele, Alexander M.,Jackson, Eileen,Langlois, Jean-Baptiste,Beaufils, Florent,Hebeisen, Paul,Fabbro, Doriano,Hillmann, Petra,Wymann, Matthias P.
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p. 8609 - 8630
(2019/10/16)
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- NEW THIENOPYRIMIDINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R12, X, A and n are as defined in the description.
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- Two new approaches towards the synthesis of annomontine using Pictet-Spengler and aza-Diels-Alder reactions
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Two new routes were established for the synthesis of biologically active natural product annomontine utilizing Pictet-Spengler and aza-Diels-Alder reactions as key steps.
- Naik, Nilesh H.,Sikder, Arun K.,Kusurkar, Radhika S.
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supporting information
p. 3715 - 3717
(2013/07/05)
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- AMINO-HETEROARYL DERIVATIVES AS HCN BLOCKERS
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The invention relates to amino-heteroaryl derivatives having the general Formula I or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of these derivatives for the treatment of pain, such as neuropathic pain or inflammatory pain.
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Page/Page column 23
(2011/07/09)
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- 8-SUBSTITUTED 2-(BENZIMIDAZOLYL)PURINE DERIVATIVES FOR IMMUNOSUPPRESSION
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The present invention provides novel purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the general formula I:
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Page/Page column 17
(2008/06/13)
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- 8-HETEROARYLPURINE MNK2 INHIBITORS FOR TREATING METABOLIC DISORDERS
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This invention relates to 8-Heteroarylpurine Mnk2 Inhibitors which are useful for the treatment and prevention of metabolic disorders such as obesity and diabetes.
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Page/Page column 36-37
(2010/11/28)
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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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- Oxazoles for treating cytokine mediated diseases
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This invention relates to the novel oxazole compounds of Formula (I) and novel pharmaceutical compositions comprising a compound of Formula (I) and a pharmaceutically acceptable diluent or carrier. This invention also relates to a method of inhibiting cytokines and the treatment of cytokine mediated diseases, in mammals, thereby by administration of an effective amount of a compound according to Formula (I).
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- Pyrimidinylimidazole inhibitors of CSBP/P38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes
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Pyrimidine analogs of the pyridinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2- methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinase from P450 inhibition for this series and furthermore achieves an increase in oral activity.
- Adams, Jerry L.,Boehm, Jeffrey C.,Kassis, Shouki,Gorycki, Peter D.,Webb, Edward F.,Hall, Ralph,Sorenson, Margaret,Lee, John C.,Ayrton, Andrew,Griswold, Don E.,Gallagher, Timothy F.
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p. 3111 - 3116
(2007/10/03)
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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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- 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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- 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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