156353-01-4Relevant academic research and scientific papers
Non-substrate based, small molecule inhibitors of the human isoprenylcysteine carboxyl methyltransferase
Butler, Kyle V.,Bohn, Kelsey,Hrycyna, Christine A.,Jin, Jian
, p. 1016 - 1021 (2016)
Activating mutations of human K-Ras proteins are among the most common oncogenic mutations, present in approximately 30% of all human cancers. Posttranslational modifications to K-Ras guide it to the plasma membrane and disruption of this localization inhibits the growth of Ras-driven cancers. The human isoprenylcysteine carboxyl methyltransferase (hIcmt) enzyme catalyzes the final α-carboxyl methylesterification of the C-terminal farnesyl cysteine of K-Ras, which is necessary for its proper localization. Thus, hIcmt inhibition is a regarded as a promising cancer therapy. A high quality inhibitor of hIcmt with in vivo activity would advance hIcmt research and drug development. Herein, Wwe report the results of a screen for small molecule hIcmt inhibitors in a library of molecules that were not hIcmt substrate analogs. The lead compound identified by this screen (1) was modified to remove chemical liabilities and to increase potency. The most potent resulting compound (5) inhibited hIcmt in vitro with low micromolar potency (IC50 = 1.5 ± 0.2 μM) and was kinetically characterized as a competitive inhibitor for prenylated substrates and a non-competitive inhibitor for the cofactor and methyl donor S-adenosylmethionine (SAM). These inhibitors offer important structure activity relationships for the future development of hIcmt inhibitors with in vivo activity.
Derivatives of Napabucasin and pharmaceutical application thereof
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, (2021/08/07)
The invention relates to derivatives of Napabucasin, and a pharmaceutical application thereof. The structure of the derivatives conforms to the general formula (I), and the water solubility of most of the compounds is obviously higher than that of Napabucasin. The compounds and pharmaceutically acceptable salts thereof can be used for preparing antitumor drugs, and the cell inhibition activity of most of the compounds is obviously superior to that of Napabucasin. Meanwhile, experiments show that the compounds have extremely high helicobacter pylori and fungal activity resistance and can be used for preparing drugs for resisting helicobacter pylori and fungal infection.
INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE
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Paragraph 0417-0418, (2021/09/04)
Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.
BICYCLIC KETONE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 45; 46; 259, (2019/02/02)
The invention provides novel compounds having the general formula (I): (I) wherein R1, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.
TRICYCLIC COMPOUND FOR BROMODOMAIN-CONTAINING PROTEIN INHIBITOR AND PREPARATION, PHARMACEUTICAL COMPOSITION, AND APPLICATION THEREOF
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Paragraph 0372; 0373, (2019/01/04)
The present applicationpresent application relates to a compound represented by Formula (III) or a pharmaceutically acceptable salt, solvent compound, active metabolite, crystal polymorph, ester, isomer, or prodrug thereof. The application further provides a pharmaceutical composition comprising the compound represented by Formula (III) and a use thereof for preparing a bromodomain inhibitor for preventing or treating various diseases, such as inflammation and cancer, related to the bromodomain.
Copper(I)-Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α-Hydroxyboronates
Kubota, Koji,Osaki, Shun,Jin, Mingoo,Ito, Hajime
supporting information, p. 6646 - 6650 (2017/05/29)
A new method was developed for the first catalytic enantioselective borylation of aliphatic ketones. A variety of substrates reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene complex catalyst to furnish optically active tertiary α-hydroxyboronates with moderate to high enantioselectivities (up to 94 % ee). Notably, the product could be converted into the chiral tertiary alcohol derivative using a stereospecific boron functionalization process. The theoretical study of the mechanism for the enantioselectivity is also described.
COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF BROMODOMAIN-CONTAINING PROTEINS
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Paragraph 00236-00237, (2017/03/21)
The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.
AGENT FOR TREATING AND/OR PREVENTING SLEEP DISORDER
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Paragraph 0742, (2017/08/26)
no abstract published
SUBSTITUTED 5-METHYL-[1, 2, 4] TRIAZOLO [1,5-A) PYRIMIDIN-2-AMINE COMPOUNDS AS PDE2 INHIBITORS
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Page/Page column 63, (2016/06/01)
The invention provides a chemical entity of Formula (I): (I), wherein R1, R2, R3, and R4, have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by PDE2 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma- dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training; and treating peripheral disorders, including hematological, cardiovascular, gastroenterological, and dermatological disorders.
NOVEL TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
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Paragraph 0491; 0492; 0775, (2016/07/27)
The present invention is directed to tricyclic compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
