64892-53-1Relevant academic research and scientific papers
PYRIDAZINONES AND METHODS OF USE THEREOF
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Paragraph 0173; 0174, (2020/04/24)
Disclosed are compounds according to Formula (I), and related pharmaceutical compositions. Also disclosed are therapeutic methods, e.g., of treating kidney diseases, using the compounds of Formula (I).
PYRIDAZINONES AND METHODS OF USE THEREOF
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Page/Page column 59; 60, (2020/10/09)
Disclosed are therapeutic methods, e.g., of treating kidney diseases, using compounds of Formula (A) in combination with a second therapeutic agent.
KRAS G12C INHIBITORS
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Paragraph 0637-0638, (2019/05/24)
The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
KRAS G12C INHIBITORS
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Paragraph 0360, (2017/12/18)
The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
Synthesis of Heteroaryl-Substituted Pyrroles via the 1,3-Dipolar Cycloaddition of Unsymmetrical Münchnones and Nitrovinylheterocycles
Lopchuk, Justin M.,Song, Mia,Butler, Blythe,Gribble, Gordon W.
, p. 2776 - 2780 (2015/09/15)
A series of furanyl-, thiophenyl-, and pyrrolo-substituted pyrroles were prepared via the 1,3-dipolar cycloaddition of unsymmetrical münchnones and nitrovinylheterocycles. The regiochemical outcome of the furan and thiophene cycloadditions compares favorably to previously reported cycloadditions with β-nitrostyrene, while the nitrovinylpyrrole cycloadditions mirror the results observed with nitrovinylindole.
Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration
Meredith, Erik L.,Mainolfi, Nello,Poor, Stephen,Qiu, Yubin,Miranda, Karl,Powers, James,Liu, Donglei,Ma, Fupeng,Solovay, Catherine,Rao, Chang,Johnson, Leland,Ji, Nan,Artman, Gerald,Hardegger, Leo,Hanks, Shawn,Shen, Siyuan,Woolfenden, Amber,Fassbender, Elizabeth,Sivak, Jeremy M.,Zhang, Yiqin,Long, Debby,Cepeda, Rosemarie,Liu, Fang,Hosagrahara, Vinayak P.,Lee, Wendy,Tarsa, Peter,Anderson, Karen,Elliott, Jason,Jaffee, Bruce
, p. 9273 - 9285 (2015/12/23)
The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high-throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.
Enantioselective synthesis of α-secondary and α-tertiary piperazin-2- Ones and piperazines by catalytic asymmetric allylic alkylation
Korch, Katerina M.,Eidamshaus, Christian,Behenna, Douglas C.,Stoltz, Brian M.,Nam, Sangkil,Horne, David
supporting information, p. 179 - 183 (2015/02/05)
The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2- ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.
Selective N-alkylation of primary amines with R-NH2·HBr and alkyl bromides using a competitive deprotonation/protonation strategy
Bhattacharyya, Shubhankar,Pathak, Uma,Mathur, Sweta,Vishnoi, Subodh,Jain, Rajeev
, p. 18229 - 18233 (2014/05/20)
Monoalkylation of primary amines using amine hydrobromides and alkyl bromides has been carried out. Under controlled reaction conditions the reactant primary amine was selectively deprotonated and made available for reaction, while the newly generated secondary amine remained protonated, and did not participate in alkylation further. Reaction was carried out under mild reaction conditions and was applicable to a wide range of primary amines and alkyl bromides.
Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: From hit to clinic
Pizzonero, Mathieu,Dupont, Sonia,Babel, Marielle,Beaumont, Stéphane,Bienvenu, Natacha,Blanqué, Roland,Cherel, La?titia,Christophe, Thierry,Crescenzi, Benedetta,De Lemos, Elsa,Delerive, Philippe,Deprez, Pierre,De Vos, Steve,Djata, Fatoumata,Fletcher, Stephen,Kopiejewski, Sabrina,Lebraly, Christelle,Lefran?ois, Jean-Michel,Lavazais, Stéphanie,Manioc, Murielle,Nelles, Luc,Oste, Line,Polancec, Denis,Quénéhen, Vanessa,Soulas, Florilène,Triballeau, Nicolas,Van Der Aar, Ellen M.,Vandeghinste, Nick,Wakselman, Emanuelle,Brys, Reginald,Saniere, Laurent
, p. 10044 - 10057 (2015/02/05)
FFA2, also called GPR43, is a G-protein coupled receptor for short chain fatty acids which is involved in the mediation of inflammatory responses. A class of azetidines was developed as potent FFA2 antagonists. Multiparametric optimization of early hits with moderate potency and suboptimal ADME properties led to the identification of several compounds with nanomolar potency on the receptor combined with excellent pharmacokinetic (PK) parameters. The most advanced compound, 4-[[(R)-1-(benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid 99 (GLPG0974), is able to inhibit acetate-induced neutrophil migration strongly in vitro and demonstrated ability to inhibit a neutrophil-based pharmacodynamic (PD) marker, CD11b activation-specific epitope [AE], in a human whole blood assay. All together, these data supported the progression of 99 toward next phases, becoming the first FFA2 antagonist to reach the clinic.
P2X7 MODULATORS
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Paragraph 0491, (2014/09/30)
The present invention is directed to a compound of Formula (I) The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.
