- N2-substituted alkoxy aromatic cyclo-2-aminopyrimidine derivative and application thereof
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The invention provides an N2-substituted alkoxy aromatic cyclo-2-aminopyrimidine derivative and application thereof. The N2-substituted alkoxy aromatic cyclo-2-aminopyrimidine derivative comprises anoptical isomer and pharmaceutically acceptable salt thereof. Preliminary pharmacodynamic indication shows that the compound disclosed by the invention has FLT3 inhibitory activity, wherein the proliferation inhibition activity is realized on various leukemia cell strains; moreover, the derivative is effective for multiple mutations of AML, such as internal tandem repeat mutation of a near-membranestructural domain and D835 point mutation of an activated ring in a kinase structural domain and almost has no inhibition effect on c-KIT. The derivative can overcome drug resistance brought by clinical point mutation, can reduce toxic and side effects of bone marrow inhibition, and can be applied to preparation of antitumor drugs. The general structural formula of the derivative is shown in thespecification.
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Paragraph 0055-0056; 0077-0078
(2020/09/20)
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- Synthesis of tetracyclic heterocompounds as selective estrogen receptor modulators. Part 1. Process development for scale-up of 2,5,8-substituted 5,11 -dihydrochromeno[4,3-c]chromene derivatives
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Unsymmetrical benzopyranobenzopyran compounds are novel selective estrogen receptor modulators (SERMs). A reproducible and nonchromatographic process was developed to prepare multihundred gram quantities of 5-(4-(2-(piperidin-1-yl) ethoxy)-phenyl)-5,11-di
- Li, Xun,Reuman, Michael,Russell, Ronald K.,Adams, Richard,Ma, Robert,Beish, Sandra,Branum, Shawn,Youells, Scott,Roberts, Jerry,Jain, Nareshkumar,Kanojia, Ramesh,Sui, Zhihua
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p. 414 - 421
(2012/12/31)
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- Synthesis of tetracyclic heterocompounds as selective estrogen receptor modulators. Part 2. Process improvement for scale-up of 2,5,8-substituted 11,12-dihydro-5H-6,13-dioxabenzo[3,4]cyclohepta-[1,2-a]naphthalene derivatives
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An improved, reproducible nonchromatographic process for scale-up synthesis of 2,5,8-substituted 11,12-dihydro-5H-6,13-dioxabenzo[3,4]cyclohepta[1,2-a] naphthalene derivatives as selective estrogen receptor modulators (SERMs) is described. The titled comp
- Li, Xun,Reuman, Michael,Russell, Ronald K.,Youells, Scott,Beish, Sandra,Hu, Zhiyong,Branum, Shawn,Jain, Nareshkumar,Sui, Zhihua
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p. 731 - 738
(2012/12/29)
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- TREATMENT OF HYPERPROLIFERATIVE DISEASES WITH N-OXIDES OF ESTROGEN RECEPTOR MODULATORS
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The invention relates to N-oxides of tamoxifen analogs having activity for treating hyperproliferative disorders. Pharmaceutical compositions comprising therapeutically effective amount of an N-oxide of an estrogen receptor modulator, or a pharmaceuticall
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Page/Page column 62; 65
(2008/06/13)
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- Differential response of estrogen receptor subtypes to 1,3-diarylindene and 2,3-diarylindene ligands
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Estrogen receptors (ERs) control transcription of genes important for normal human development and reproduction. The signaling networks are complex, and there is a need for a molecular level understanding of the roles of receptor subtypes ERα and ERβ in normal physiology and as therapeutic targets. We synthesized two series of ER ligands, based on a common indene scaffold, in an attempt to develop compounds that can selectively modulate ER-mediated transcription. The 3-ethyl-1,2-diarylindenes, utilizing an amide linker for the 1-aryl extension, bind weakly to the ERs. The 2,3-diarylindenes bind with high affinity to the ER subtypes and demonstrate a range of different biological activities, both in transcriptional reporter gene assays and inhibition of estradiol-stimulated proliferation of MCF-7 cells. Several ligands differentiate between ERα and ERβ subtypes at an estrogen response element (ERE), displaying various levels of partial to full agonist activity at ERα, while antagonizing estradiol action at ERβ.
- Clegg, Nicola J.,Paruthiyil, Sreenivasan,Leitman, Dale C.,Scanlan, Thomas S.
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p. 5989 - 6003
(2007/10/03)
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- Method for preparing oestrogen derivatives
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A process for the preparation of compounds of formula (I) in which R1, R2, R3 and n are defined as indicated in the description, use of said compounds as intermediates for the preparation of estrogen derivatives as well as the intermediates of this process.
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Page/Page column 6
(2010/02/08)
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- The synthesis of 17α-Methyl-11β-arylestradiol: Large-scale application of the cerium (III)-mediated alkylation of a ketone
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17α-Methyl-11lβ-arylestradiol (17α-methyl-11β-(4-(2-(1-piperidinyl)ethoxy)phenyl)estra-1,3,5 (10)-triene-3,17β-diol) is a new molecule developed by Aventis Pharma for the treatment of osteoporosis. It was produced on the pilot plant scale from the norster
- Larkin, John Patrick,Wehrey, Christian,Boffelli, Philippe,Lagraulet, Henri,Lemaitre, Guy,Nedelec, Alban,Prat, Denis
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- Novel Compounds
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The invention relates to heteroaromatic carboxamides of formula (I), wherein A, R1, R2 and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
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- Non-steroidal estrogen receptor ligands
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Novel non-steroidal estrogen receptor ligands and methods of synthesis are disclosed. The novel molecules are intended for use in therapeutic preparations for the treatment of estrogen receptor related disease states. The compounds specified are tetra-cyc
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- 2H-1-benzopyran derivatives, processes for their preparation and pharmaceutical compositions thereof
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2H-1-benzopyran derivatives, processes for their preparation and use thereof for the preparation of pharmaceutical compositions for the prevention and treatment of postmenopausal pathologies.
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- Triarylpyrazoles with basic side chains: Development of pyrazole-based estrogen receptor antagonists
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Recently, we developed a novel triaryl-substituted pyrazole ligand system that has high affinity for the estrogen receptor (ER) (Fink, B. E.; Mortenson, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205). Subsequent wor
- Stauffer, Shaun R.,Huang, Ying R.,Aron, Zachary D.,Coletta, Christopher J.,Sun, Jun,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.
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p. 151 - 161
(2007/10/03)
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