155837-14-2Relevant articles and documents
MENIN INHIBITORS AND METHODS OF USE FOR TREATING CANCER
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Paragraph 00489-00490, (2021/10/15)
The present disclosure provides compounds represented by Formula (I): or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, Rc, Rd, L1, R2 B, Q and E are as defined as set forth in
MACROCYCLIC COMPOUNDS AS KINASES INHIBITORS AND USES THEREOF
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Page/Page column 51, (2021/10/15)
The present disclosure describes kinases (ALK, ROS1, and TRK) inhibitors and their uses. The pharmaceutical compositions comprising such kinase inhibitors and methods of using them for treating cancer, infectious diseases, and other disorders are also des
PIPERIDINE COMPOUNDS AS MENIN INHIBITORS
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Paragraph 000315-000316; 000524-000525, (2021/04/10)
The present disclosure provides compounds represented by Formula (la): and the pharmaceutically acceptable salts thereof, wherein R1a, R1b, R1c, R2, R3, L, M and G are as defined as set forth in the specification. The present disclosure also provides compounds of Formula la for use to treat a condition or disorder responsive to menin inhibition such as cancer.
MENIN INHIBITORS AND METHODS OF USE FOR TREATING CANCER
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Paragraph 00551-00553, (2021/10/15)
The present disclosure provides compounds represented by Formula (I), or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, Rc, Rd, V, Q, T, n, p, q, r and s are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat cancer or any other disease, condition, or disorder that is responsive to inhibition of menin.
FGFR INHIBITORS FOR THE TREATMENT OF CANCER
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Paragraph 00195; 00197, (2020/08/28)
The disclosure provides novel FGFR inhibitors based on the pyridinylpyrimidine. The disclosure includes inhibitors with broad inhibitory activity against all FGFR isoforms, and inhibitors with selective inhibition against FGFR4. These novel pyridinylpyrimidine-based FGFR inhibitors, or their derivatives, have strong potential to be used to treat cancer.
SMALL MOLECULE MENIN INHIBITORS
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Paragraph 0310, (2020/05/15)
The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein R1a, R1b, R1c, E, G, and Q are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat cancer or any other disease, condition, or disorder that is responsive to inhibition of menin.
ADENOSINE RECEPTOR AGONISTS
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Paragraph 0136-0137, (2020/10/09)
The present invention relates to compounds of Formula (I) for use in the treatment of nervous system disorders and pain, wherein Formula (I) is: formula(I) or a pharmaceutically acceptable salt or isomer thereof, wherein R is defined herein. The compounds are selective A1 adenosine receptor agonists with preferential action in the nervous system, with spared cardiovascular system and respiratory effects. The invention also relates to pharmaceutical compositions comprising the compounds.
Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein-Protein Interaction
Aguilar, Angelo,Zheng, Ke,Xu, Tianfeng,Xu, Shilin,Huang, Liyue,Fernandez-Salas, Ester,Liu, Liu,Bernard, Denzil,Harvey, Kaitlin P.,Foster, Caroline,McEachern, Donna,Stuckey, Jeanne,Chinnaswamy, Krishnapriya,Delproposto, James,Kampf, Jeff W.,Wang, Shaomeng
, p. 6015 - 6034 (2019/07/03)
Inhibition of the menin-mixed lineage leukemia (MLL) protein-protein interaction is a promising new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein our structure-based design, synthesis, and evaluation of a new class of small-molecule inhibitors of the menin-MLL interaction (hereafter called menin inhibitors). Our efforts have resulted in the discovery of highly potent menin inhibitors, as exemplified by compound 42 (M-89). M-89 binds to menin with a Kd value of 1.4 nM and effectively engages cellular menin protein at low nanomolar concentrations. M-89 inhibits cell growth in the MV4;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC50 values of 25 and 55 nM, respectively, and demonstrates >100-fold selectivity over the HL-60 leukemia cell line lacking MLL fusion. The determination of a co-crystal structure of M-89 in a complex with menin provides the structural basis for their high-affinity interaction. Further optimization of M-89 may lead to a new class of therapy for the treatment of MLL leukemia.
INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
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Paragraph 252, (2019/08/08)
The present invention provides, inter alia, compounds having the structures of formulas described herein; pharmaceutically acceptable salts, solvates, hydrates, tautomers, and isotopic forms thereof; and compositions (e.g., pharmaceutical compositions and kits) containing one or more of the foregoing. Also provided are methods of administering and uses involving the compounds and/or pharmaceutical compositions for treating or preventing disease. The disease can be a proliferative disease, such as a cancer (e.g., a blood cancer (e.g., a leukemia or lymphoma), a brain cancer, a breast cancer, melanoma, multiple myeloma, or an ovarian cancer) a benign neoplasm, pathologic angiogenesis, or a fibrotic disease. While no aspect of the invention is limited by the biological events that may transpire, administering a compound or other composition described herein may selectively inhibit the aberrant expression or activity of cyclin-dependent kinase 7 (CDK7) and, thereby, induce cellular apoptosis and/or inhibit the transcription of disease-related genes in the patient (or in a biological sample).
COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS
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Paragraph 00787; 00788; 00789; 00790; 001600; 001601; 001602, (2019/01/10)
The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.
