63404-84-2Relevant academic research and scientific papers
N- vs O-alkylation in 2(1H)-quinolinone derivatives
Guo, Zhao-Xia,Cammidge, Andrew N.,McKillop, Alexander,Horwell, David C.
, p. 6999 - 7002 (1999)
N- vs O-alkylation reactions of 8-benzyloxy-2(1H)-quinolinone have been investigated using both classical and phase transfer conditions. The influence of reaction solvents/conditions was found to have a dramatic effect on selectivity, with opposite trends
Efficient visible light mediated synthesis of quinolin-2(1H)-ones from quinolineN-oxides
Bhuyan, Samuzal,Chhetri, Karan,Hossain, Jagir,Jana, Saibal,Mandal, Susanta,Roy, Biswajit Gopal
, p. 5049 - 5055 (2021/07/29)
Quinolin-2(1H)-ones are one of the important classes of compounds due to their prevalence in natural products and in pharmacologically useful compounds. Here we present an unconventional and hitherto unknown photocatalytic approach to their synthesis from easily available quinoline-N-oxides. This reagent free highly atom economical photocatalytic method, with low catalyst loading, high yield and no undesirable by-product, provides an efficient greener alternative to all conventional synthesis reported to date. The robustness of the methodology has been successfully demonstrated with easy scaling up to the gram scale.
PRMT5 INHIBITORS AND USES THEREOF
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Paragraph 0442-0443, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
Synthesis and evaluation of radioiodinated 1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging
Effendi, Nurmaya,Ogawa, Kazuma,Mishiro, Kenji,Takarada, Takeshi,Yamada, Daisuke,Kitamura, Yoji,Shiba, Kazuhiro,Maeda, Takehiko,Odani, Akira
, p. 5576 - 5585 (2017/10/06)
Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [125I]-1-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([125I]IIQP) and [125I]-N-3-iodobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([125I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [125I]IIQP and [125I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1 h after the injection of [125I]IIQP was significantly higher than that after the injection of [125I]IB-IQP. These results indicated that [125I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal/noise ratio.
Hydroxy-Substituted Heteroarylpiperazines: Novel Scaffolds for β-Arrestin-Biased D2R Agonists
M?nnel, Barbara,Dengler, Daniela,Shonberg, Jeremy,Hübner, Harald,M?ller, Dorothee,Gmeiner, Peter
supporting information, p. 4693 - 4713 (2017/06/13)
By means of a formal structural hybridization of the antipsychotic drug aripiprazole and the heterocyclic catecholamine surrogates present in the β2-adrenoceptor agonists procaterol and BI-167107 (4), we designed and synthesized a collection of novel hydroxy-substituted heteroarylpiperazines and heteroarylhomopiperazines with high dopamine D2 receptor (D2R) affinity. In contrast to the weak agonistic behavior of aripiprazole, these ligands are capable of effectively mimicking those interactions of dopamine and the D2R that are crucial for an active state, leading to the recruitment of β-arrestin-2. Interestingly, some ligands show considerably lower intrinsic activity in guanine nucleotide exchange experiments at D2R and consequently represent biased agonists favoring β-arrestin-2 recruitment over canonical G protein activation. The ligands' agonistic properties are substantially driven by the presence of an endocyclic H-bond donor.
Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists
Weichert, Dietmar,Stanek, Markus,Hübner, Harald,Gmeiner, Peter
, p. 2641 - 2653 (2016/06/08)
Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describ
Molecular determinants of biased Agonism at the dopamine D2 receptor
Weichert, Dietmar,Banerjee, Ashutosh,Hiller, Christine,Kling, Ralf C.,Hubner, Harald,Gmeiner, Peter
, p. 2703 - 2717 (2015/04/14)
The development of biased (functionally selective) ligands provides a formidable challenge in medicinal chemistry. In an effort to learn to design functionally selective molecular tools for the highly therapeutically relevant dopamine D2 receptor, we synthesized a collection of agonists based on structurally distinct head groups derived from canonical or atypical dopaminergic pharmacophores. The test compounds feature a long lipophilic appendage that was shown to mediate biased signaling. By employing functional assays and molecular dynamics simulations, we could show that atypical dopamine surrogates of type 1 and 2 promote biased signaling, while ligands built from classical dopaminergic head groups (type 3 and 4) typically elicit more balanced signaling profiles. Besides this, we found a strong influence of the stereochemistry of type 4 aminotetraline-derived agonists on functional selectivity at D2 receptors. Whereas the (S)-enantiomer behaved as a full agonist, the biased ligand (R)-4 induced poor G protein coupling but substantial β-arrestin recruitment.
Discovery of a novel class of imidazo[1,2-a ]pyridines with potent PDGFR activity and oral bioavailability
Hicken, Erik J.,Marmsater, Fred P.,Munson, Mark C.,Schlachter, Stephen T.,Robinson, John E.,Allen, Shelley,Burgess, Laurence E.,Delisle, Robert Kirk,Rizzi, James P.,Topalov, George T.,Zhao, Qian,Hicks, Julie M.,Kallan, Nicholas C.,Tarlton, Eugene,Allen, Andrew,Callejo, Michele,Cox, April,Rana, Sumeet,Klopfenstein, Nathalie,Woessner, Richard,Lyssikatos, Joseph P.
supporting information, p. 78 - 83 (2014/02/14)
The in silico construction of a PDGFRβ kinase homology model and ensuing medicinal chemistry guided by molecular modeling, led to the identification of potent, small molecule inhibitors of PDGFR. Subsequent exploration of structure-activity relationships
PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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Paragraph 00347, (2014/07/08)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AS RECEPTOR TYROSINE KINASE INHIBITORS
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Page/Page column 49-50; 57, (2008/12/04)
Compounds of Formula I: in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by class 3 and class 5 receptor tyrosine kinases. Particular compounds of this invention have also been found to be inhibitors of Pim-1.
