133560-57-3Relevant academic research and scientific papers
Palladium-catalyzed phosphonylation of pyrazoles substituted by electron-withdrawing groups
Huang, Qi,Tran, Ga?l,Gomez Pardo, Domingo,Tsuchiya, Tomoki,Hillebrand, Stefan,Vors, Jean-Pierre,Cossy, Janine
, p. 7250 - 7259 (2015)
Abstract A series of bromopyrazoles substituted by electron-withdrawing groups such as an ester, a trifluoromethyl group or a cyano group was involved in Pd-catalyzed phosphonylation. Moderate to good yields were obtained in the corresponding phosphonylat
N-(1H-IMIDAZOL-2-YL)BENZAMIDE COMPOUND AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME AS ACTIVE INGREDIENT
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Page/Page column 33, (2021/04/10)
N-(1H-imidazol-2-yl)benzamide compound of formula (I), or a pharmaceutically acceptable salt, a prodrug, a solvate, or a stereoisomer thereof which is a novel compound exhibiting excellent inhibitory activity against IRAK-4, can be used without side effects for efficient prevention and treatment of diseases mediated by IRAK-4 receptors, particularly autoimmune diseases or lymphomas.
Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies
Barlaam, Bernard,Casella, Robert,Cidado, Justin,Cook, Calum,De Savi, Chris,Dishington, Allan,Donald, Craig S.,Drew, Lisa,Ferguson, Andrew D.,Ferguson, Douglas,Glossop, Steve,Grebe, Tyler,Gu, Chungang,Hande, Sudhir,Hawkins, Janet,Hird, Alexander W.,Holmes, Jane,Horstick, James,Jiang, Yun,Lamb, Michelle L.,McGuire, Thomas M.,Moore, Jane E.,O'Connell, Nichole,Pike, Andy,Pike, Kurt G.,Proia, Theresa,Roberts, Bryan,San Martin, Maryann,Sarkar, Ujjal,Shao, Wenlin,Stead, Darren,Sumner, Neil,Thakur, Kumar,Vasbinder, Melissa M.,Varnes, Jeffrey G.,Wang, Jianyan,Wang, Lei,Wu, Dedong,Wu, Liangwei,Yang, Bin,Yao, Tieguang
supporting information, p. 15564 - 15590 (2021/01/09)
A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after intravenous administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated effective dose. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematological cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is currently in clinical trials for the treatment of hematological malignancies.
BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION
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Paragraph 00197; 00198; 00199, (2018/09/02)
The present invention relates to bis-heteroaryl compounds of formula (I), pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
Synthesis of (5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol-3-yl)methanamine
Bai, Zhong-Gang,Qi, Hui,Zhang, Qun-Zheng,Ma, Yu,Pan, Qing,Zhang, Xun-Li
, p. 1923 - 1930 (2017/10/24)
This short paper reports the development of a new method for the synthesis of (5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)methanamine. Pyrazole was initially protected with an N-SEM protective group, followed by alkylation at C-5 position with 1-bromo-3-chloropropane. Following SEM deprotection, the intramolecular ring was closed and then a bromine atom (Br) was introduced with N-bromosuccinimide (NBS) by electrophilic aromatic substitution (SEAr), forming 3-bromo-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole. The Br group was subsequently converted into aldehyde group, then into oxime. The final step of hydrogenation resulted in the desired product. The overall yield through the 8-step reaction process was found to be 29.4%. The intermediates and final product were identified by HPLC-MS and 1H NMR. This development provides a novel synthetic route to the formation of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole skeleton.
Chemical Compounds
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Paragraph 1218, (2017/01/19)
Provided are a series of novel pyridine or pyrimidine derivatives which inhibit CDK9 and may be useful for the treatment of hyperproliferative diseases. In particular the compounds are of use in the treatment of proliferative disease such as cancer including hematological malignancies such as acute myeloid leukemia, multiple myeloma, chronic lymphocytic leukemia, diffuse large B cell lymphoma, Burkitt's lymphoma, follicular lymphoma and solid tumors such as breast cancer, lung cancer, neuroblastoma and colon cancer.
Negishi cross-coupling enabled synthesis of novel NAD+-dependent DNA ligase inhibitors and SAR development
Murphy-Benenato, Kerry E.,Gingipalli, Lakshmaiah,Boriack-Sjodin, P. Ann,Martinez-Botella, Gabriel,Carcanague, Dan,Eyermann, Charles J.,Gowravaram, Madhu,Harang, Jenna,Hale, Michael R.,Ioannidis, Georgine,Jahic, Harris,Johnstone, Michele,Kutschke, Amy,Laganas, Valerie A.,Loch, James T.,Miller, Matthew D.,Oguto, Herbert,Patel, Sahil Joe
, p. 5172 - 5177 (2015/11/09)
Two novel compounds, pyridopyrimidines (1) and naphthyridines (2) were identified as potent inhibitors of bacterial NAD+-dependent DNA ligase (Lig) A in a fragment screening. SAR was guided by molecular modeling and X-ray crystallography. It was observed that the diaminonitrile pharmacophore made a key interaction with the ligase enzyme, specifically residues Glu114, Lys291, and Leu117. Synthetic challenges limited opportunities for diversification of the naphthyridine core, therefore most of the SAR was focused on a pyridopyrimidine scaffold. The initial diversification at R1 improved both enzyme and cell potency. Further SAR developed at the R2 position using the Negishi cross-coupling reaction provided several compounds, among these compounds 22g showed good enzyme potency and cellular potency.
6-SUBSTITUTED-3H-1,3-BENZOTHIAZOL-2-ONE COMPOUNDS AS TARP-GAMMA 8 DEPENDENT AMPA RECEPTOR ANTAGONISTS
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Page/Page column 18, (2016/01/29)
A TARP ?8 dependant AMPA receptor antagonist of the formula: wherein X is CH or N; A is; and R1 is as defined herein; its pharmaceutically acceptable salts, uses, and methods for its preparation are described.
Synthesis of functionalized cyanopyrazoles via magnesium bases
Dishington, Allan,Feron, J. Lyman,Gill, Kathryn,Graham, Mark A.,Hollingsworth, Ian,Pink, Jennifer H.,Roberts, Andrew,Simpson, Iain,Tatton, Matthew
supporting information, p. 6120 - 6123 (2015/02/19)
4-Alkyl- and 4-H-pyrazoles were sequentially metalated using TMPMgCl·LiCl, and their reaction with electrophiles afforded 3-aryl-4-alkyl-5-cyanopyrazoles.
Palladium-catalyzed phosphonylation: Synthesis of C3-, C4-, and C5-phosphonylated pyrazoles
Tran, Gael,Pardo, Domingo Gomez,Tsuchiya, Tomoki,Hillebrand, Stefan,Vors, Jean-Pierre,Cossy, Janine
supporting information, p. 5550 - 5553 (2013/11/19)
A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a gre
