- Design, synthesis, and docking studies of New Torin2 analogs as potential ATR/mTOR kinase inhibitors
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Targeting DNA damage and response (DDR) pathway has become an attractive approach in cancer therapy. The key mediators involved in this pathway are ataxia telangiectasia-mutated kinase (ATM) and ataxia telangiectasia-mutated, Rad3-related kinase (ATR). These kinases induce cell cycle arrest in response to chemo- and radio-therapy and facilitate DNA repair via their major downstream targets. Targeting ATP-binding site of these kinases is currently under study. Torin2 is a second generation ATP competitive mTOR kinase inhibitor (EC50 = 250 pmol/L) with better pharmacokinetic profile. Torin2 also exhibits potent biochemical and cellular activity against ATM (EC50 = 28 nmol/L) and ATR (EC50 = 35 nmol/L) kinases. In this study, eight new Torin2 analogs were designed and synthesized through multistep synthesis. All the synthesized compounds were characterized by NMR and mass analysis. The newly synthesized analogs were evaluated for their anti-cancer activity via CellTiter-Glofi assay. Additionally, compounds 13 and 14 also showed significant inhibition for ATR and mTOR substrates, i.e., p-Chk1 Ser 317 and p70 S6K Thr 389, respectively. Compounds 13 and 14 displayed promising anti-cancer activity with HCT-116 cell lines in the preliminary study. Further, a comparative model of ATR kinase was generated using the SWISS-MODEL server and validated using PROCHECK, ProSA analysis. Synthesized compounds were docked into the ATP-binding site to understand the binding modes and for the rational design of new inhibitors.
- Shaik, Althaf,Bhakuni, Rashmi,Kirubakaran, Sivapriya
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- 3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities
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Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is
- Chen, Nan-Ying,Gu, Zi-Yu,Li, Xiao-Juan,Liao, Hao-Ran,Mo, Dong-Liang,Pan, Cheng-Xue,Su, Gui-Fa,Yuan, Jing-Mei,Zhang, Guo-Hai
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- Antiparasitic Lead Discovery: Toward Optimization of a Chemotype with Activity Against Multiple Protozoan Parasites
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Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis present a significant burden across the developing world. Existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. Previously
- Devine, William,Thomas, Sarah M.,Erath, Jessey,Bachovchin, Kelly A.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Sciotti, Richard J.,Mensa-Wilmot, Kojo,Pollastri, Michael P.
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- Discovery of novel quinoline-based mTOR inhibitors via introducing intra-molecular hydrogen bonding scaffold (iMHBS): The design, synthesis and biological evaluation
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A series of quinoline derivatives featuring the novelty of introducing intra-molecular hydrogen bonding scaffold (iMHBS) were designed, synthesized and biologically evaluated for their mTOR inhibitory activity, as well as anti-proliferative efficacies aga
- Ma, Xiaodong,Lv, Xiaoqing,Qiu, Ni,Yang, Bo,He, Qiaojun,Hu, Yongzhou
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- Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights
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Aurora kinases (AURKs) were identified as promising druggable targets for targeted cancer therapy. Aiming at the development of novel chemotype of dual AURKA/B inhibitors, herein we report the design and synthesis of three series of 4-anilinoquinoline derivatives bearing a sulfonamide moiety (5a-d, 9a-d and 11a-d). The percent inhibition of AURKA/B was determined for all target quinolines, then compounds showed more than 50percent inhibition on either of the enzymes, were evaluated further for their IC50 on the corresponding enzyme. In particular, compound 9d displayed potent AURKA/B inhibitory activities with IC50 of 0.93 and 0.09 μM, respectively. Also, 9d emerged as the most efficient anti-proliferative analogue in the US-NCI anticancer assay toward the NCI 60 cell lines panel, with broad spectrum activity against different cell lines from diverse cancer subpanels. Docking studies, confirmed that, the sulfonamide SO2 oxygen was involved in a hydrogen bond with Lys162 and Lys122 in AURKA and AURKB, respectively, whereas, the sulfonamide NH could catch hydrogen bond interaction with the surrounding amino acid residues Lys141, Glu260, and Asn261 in AURKA and Lys101, Glu177, and Asp234 in AURKB. Furthermore, N1 nitrogen of the quinoline scaffold formed an essential hydrogen bond with the hinge region key amino acids Ala213 and Ala173 in AURKA and AURKB, respectively.
- Abdelgawad, Mohamed A.,Al-Sanea, Mohammad M.,Alharbi, Khalid S.,Ali Farahat, Ibrahim,Alzarea, Abdulaziz I.,Alzarea, Sami I.,Bakr, Rania B,El Kerdawy, Ahmed M.,Eldehna, Wagdy M.,Elkamhawy, Ahmed,Elshemy, Heba A. H.,Joo Roh, Eun,Lee, Kyeong,Paik, Sora,Syed Nasir Abbas, Bukhari
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- Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues
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Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinolone (BSTFA 1% TMCS) followed by equimolar amount addition of 1,3-dioxolane, chlorotrimethylsilane and KI, at room temperature. The acyclonucleosides 2a-l were obtained in 40-77% yields. The esters 2a-j and 2l were subsequently converted into the corresponding hydroxyacids 3 in 40-70% yields. Attempts of hydrolysis of 2k produced only a mixture of degradation products. Antiviral activity of 2 and 3 on HSV-1 virus infection was assessed by the virus yield assay. Except for compounds 2i and 3e, the acyclonucleosides were found to reduce the virus yield by 70-99% at the concentration of 50 μM, being the acids, in general, more effective inhibitors than their corresponding esters. Compounds 3j and 2d exhibited antiviral activity against HSV-1 virus with EC50 of 0.7 ± 0.04 and 0.8 ± 0.09 μM, respectively. Both compounds were not toxic towards the Vero cell line.
- Lucero, Bianca D'A.,Gomes, Claudia Regina B.,Frugulhetti, Izabel Christina De P.P.,Faro, Leticia V.,Alvarenga, Lise,De Souza, Maria Cecilia B.V.,De Souza, Thiago M.L.,Ferreira, Vitor F.
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- Indolo[3,2-c]quinoline G-quadruplex stabilizers: A structural analysis of binding to the human telomeric G-quadruplex
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A library of 5-methylindolo[3,2-c]quinolones (IQc) with various substitution patterns of alkyldiamine side chains were evaluated for G-quadruplex (G4) binding mode and efficiency. Fluorescence resonance energy transfer melting assays showed that IQcs with a positive charge in the heteroaromatic nucleus and two weakly basic side chains are potent and selective human telomeric (HT) and gene promoter G4 stabilizers. Spectroscopic studies with HT G4 as a model showed that an IQc stabilizing complex involves the binding of two IQc molecules (2,9-bis{[3-(diethylamino)propyl]amino}-5-methyl-11H-indolo[3,2-c]quinolin-5-ium chloride, 3 d) per G4 unit, in two non-independent but equivalent binding sites. Molecular dynamics studies suggest that end-stacking of 3 d induces a conformational rearrangement in the G4 structure, driving the binding of a second 3 d ligand to a G4 groove. Modeling studies also suggest that 3 d, with two three-carbon side chains, has the appropriate geometry to participate in direct or water-mediated hydrogen bonding to the phosphate backbone and/or G4 loops, assisted by the terminal nitrogen atoms of the side chains. Additionally, antiproliferative studies showed that IQc compounds 2 d (2-{[3-(diethylamino)propyl]amino}-5-methyl-11H-indolo[3,2-c]quinolin-5-ium chloride) and 3 d are 7- to 12-fold more selective for human malignant cell lines than for nonmalignant fibroblasts.
- Lavrado, Jo?o,Ohnmacht, Stephan A.,Correia, Isabel,Leit?o, Clara,Pisco, Sílvia,Gunaratnam, Mekala,Moreira, Rui,Neidle, Stephen,Santos, Daniel J.V.A. Dos,Paulo, Alexandra
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- Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline scaffold
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Background. CDK8/CycC complex has kinase activity towards the carboxyterminal domain of RNA polymerase II, and contributes to the regulation of transcription via association with the mediator complex. Different human malignancies, mainly colorectal and gastric cancers, were produced as a result of overexpression of CDK8/CycC in the mediator complex. Therefore, CDK8/CycC complex represents as a cancer oncogene and it has become a potential target for developing CDK8/CycC modulators. Methods. A series of nine 4-phenylaminoquinoline scaffold-based compounds 5a-i was synthesized, and biologically evaluated as potential CDK8/CycC complex inhibitors. Results. The scaffold substituent effects on the intrinsic inhibitory activity toward CDK8/CycC complex are addressed trying to present a novel outlook of CDK8/CycC Complex inhibitors with 4-phenylaminoquinoline scaffold in cancer therapy. The secondary benzenesulfonamide analogues proved to be the most potent compounds in suppressing CDK8/CycC enzyme, whereas, their primary benzenesulfonamide analogues showed inferior activity. Moreover, the benzene reversed sulfonamide analogues were totally inactive. Discussion. The titled scaffold showed promising inhibitory activity data and there is a crucial role of un/substituted sulfonamido group for CDK8/CycC complex inhibitory activity. Compound 5d showed submicromolar potency against CDK8/CycC (IC50 = 0.639 μM) and it can be used for further investigations and to design another larger library of phenylaminoquinoline scaffold-based analogues in order to establish detailed SARs.
- Al-Sanea, Mohammad M.
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- BICYCLE TOPOISOMERASE I INHIBITING COMPOUNDS, PROCESS FOR PREPARATION AND USE THEREOF
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The invention described herein relates to the compounds of Formula I for treating diseases and disorders for which inhibition or modulation of the topoisomerase I enzyme produces a physiologically beneficial response, in particular for the treatment of breast cancer. Also provided is the process of preparing compounds of Formula I.
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(2019/12/25)
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- Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors
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Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with KIs in the range of 0.966–9.091 μM, whereas hCA II in the range of 0.083–3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (KI = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.
- Al-Sanea, Mohammad M.,Elkamhawy, Ahmed,Paik, Sora,Bua, Silvia,Ha Lee, So,Abdelgawad, Mohamed A.,Roh, Eun Joo,Eldehna, Wagdy M.,Supuran, Claudiu T.
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p. 1457 - 1464
(2019/08/26)
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- Synthesis and pharmacological evaluation of pyrazolo[4,3-c]quinolinones as high affinity GABAA-R ligands and potential anxiolytics
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The synthesis, in vitro ligand binding study and in vivo Elevated Plus Maze test (EPM) of a series of pyrazolo[4,3-c]quinolin-3-ones (PQs) are reported. Multistep synthesis of PQs started from anilines and diethyl 2-(ethoxymethylene)malonate to give the q
- López Rivilli, Marisa J.,Turina, Anahí V.,Bignante, Elena A.,Molina, Victor H.,Perillo, María A.,Bri?on, Margarita C.,Moyano, Elizabeth L.
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p. 3967 - 3974
(2018/06/29)
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- IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER
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The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1 is tetrahydropyran-3-yl or 3,3-dimethyltetrahydropyran-4-yl; R2 is methyl or hydro; R3 is hydro or fl
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(2017/10/06)
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- FUSED QUINOLINE COMPUNDS AS PI3K/MTOR INHIBITORS
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The present invention relates to the compounds of formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with cancers associated with protein kin
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Page/Page column 16
(2017/02/09)
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- 6-bromo-4-chloroquinoline preparation method
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The invention discloses a 6-bromo-4-chloroquinoline preparation method. 4-bromaniline, ethyl propiolate, phosphorus trichloride and the like are used as raw materials to obtain a target product 6-bromo-4-chloroquinoline through three-step reaction. The 6-bromo-4-chloroquinoline preparation method is convenient and simple in operation and environment friendly, the comprehensive yield is 70% or above and remarkably increased as compared with existing yield which is 26-42%, existing medicine production cost is sharply reduced, and the 6-bromo-4-chloroquinoline preparation method is suitable for industrial mass production.
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Paragraph 0061; 0062; 0063; 0064
(2017/03/28)
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- Synthesis of Fused Pyrimidinone and Quinolone Derivatives in an Automated High-Temperature and High-Pressure Flow Reactor
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Fused pyrimidinone and quinolone derivatives that are of potential interest to pharmaceutical research were synthesized within minutes in up to 96% yield in an automated Phoenix high-temperature and high-pressure continuous flow reactor. Heterocyclic scaffolds that are either hard to synthesize or require multisteps are readily accessible using a common set of reaction conditions. The use of low-boiling solvents along with the high conversions of these reactions allowed for facile workup and isolation. The methods reported herein are highly amenable for fast and efficient heterocycle synthesis as well as compound scale-ups.
- Tsoung, Jennifer,Bogdan, Andrew R.,Kantor, Stanislaw,Wang, Ying,Charaschanya, Manwika,Djuric, Stevan W.
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p. 1073 - 1084
(2018/06/18)
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- Fused ring compound and preparation method, application and intermediate compound thereof
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The invention relates to a fused ring compound and a preparation method, application and intermediate compound thereof. The fused ring compound can be used as an inhibitor of phosphatidylinositol 3-kinase.
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Paragraph 0144; 0145
(2016/10/17)
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- FUSED QUINOLINE COMPUNDS AS PI3K, mTOR INHIBITORS
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(Formula I), The present invention relates to the compounds of formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with cancers associated wit
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(2016/02/05)
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- IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER
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The specification generally relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, where Q, R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of imidazo[4,5- c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating ATM kinase mediated disease, including cancer, using such compounds and salts.
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(2015/11/27)
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- Design, synthesis and biological evaluation of novel 4-alkynyl-quinoline derivatives as PI3K/mTOR dual inhibitors
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Abstract A novel series of 4-alkynyl-quinoline derivatives were designed, synthesized and biologically evaluated for their PI3Kα inhibitory activities and anti-proliferative effects against two cancer cell lines PC-3 and HCT-116. Most of them showed potent PI3Kα inhibitory activities with IC50 values at low nanomolar level and good to excellent anti-proliferative effects against both cell lines. Among them, compound 15d, the most potent one, was selected for further biological evaluation. As a result, 15d displayed strong inhibitory activity against other class I PI3K isoforms (PI3Kβ, PI3Kγ and PI3Kδ) and mTOR with an acceptable kinase selectivity profile. Moreover, the western blot assay indicated that the phosphorylation of Akt, another downstream effector of PI3K, can be remarkably suppressed by 15d at cellular level. All these experimental results suggested that 15d is a potent PI3K/mTOR dual inhibitor and could serve as a promising lead compound for the development of anticancer agents.
- Lv, Xiaoqing,Ying, Huazhou,Ma, Xiaodong,Qiu, Ni,Wu, Peng,Yang, Bo,Hu, Yongzhou
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- AGENTS FOR USE IN THE TREATMENT OF CARDIOVASCULAR AND INFLAMMATORY DISEASES STRUCTURALLY BASED ON 4(1 H)-QUINOLONE
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The present invention provides a compound of formula I, a tautomer thereof, or a pharmaceutically acceptable salt or N-oxide thereof for use in the treatment or prevention of a cardiovascular disease or of an inflammatory disease or condition:
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Page/Page column 64; 65
(2016/01/01)
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- 4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: Synthesis, biological evaluation and docking studies
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In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3- carboxamide derivatives as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 μM) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.
- Liu, Peng,Niu, Yan,Wang, Chao,Sun, Qi,Zhai, Yaya,Yu, Jiapei,Sun, Jing,Xu, Fengrong,Yan, Gang,Huang, Wenjie,Liang, Lei,Xu, Ping
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p. 413 - 421
(2014/05/06)
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- Molecular design, synthesis and biological evaluation of 1,4-dihydro-4-oxoquinoline ribonucleosides as TcGAPDH inhibitors with trypanocidal activity
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The 1,4-dihydro-4-oxoquinoline ribonucleoside, Neq135, is the first low micromolar trypanosomatidae inhibitor to show good ligand efficiency (0.28 kcal mol-1 atom-1) and good ligand lipophilicity efficiency (0.37 kcal mol-1/sup
- Soares, Fabyana A.,Sesti-Costa, Renata,Da Silva, Jo?o Santana,De Souza, Maria Cecília B.V.,Ferreira, Vitor F.,Da C. Santos, Fernanda,Monteiro, Patricia A.U.,Leit?o, Andrei,Montanari, Carlos A.
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supporting information
p. 4597 - 4601
(2013/08/15)
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- Synthesis of substituted-4-oxo-1, 4-dihydro-3-[1-oxo-2-hydrazino-3-{p- toluenesulfon}]quinoline derivatives and their biological activity against bacterial infections
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We have synthesized a series of quinolone and fluoroquinolones derivatives substituted with p-tosyl group. All these compounds were screened as antibacterial and datas were compared with reference marketed drug viz.; Ciprofloxacin & Norfloxacin.
- Srivatava,Kumar
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p. 507 - 511
(2013/11/06)
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- Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1
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The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1- [(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC 50 values of 0.4 ± 0.2 μM (3f) and 0.2 ± 0.005 μM (3g) and selectivity index values (SI) of 6240 and 14675, respectively.
- Faro, Leticia V.,De Almeida, Jessica M.,Cirne-Santos, Claudio C.,Giongo, Viveca A.,Castello-Branco, Luis R.,Oliveira, Ingrid De B.,Barbosa, Juliana E.F.,Cunha, Anna C.,Ferreira, Vitor F.,De Souza, Marcos C.,Paixao, Izabel C.N.P.,De Souza, Maria Cecilia B.V.
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scheme or table
p. 5055 - 5058
(2012/08/28)
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- Synthesis and anticancer activities of some novel 2-(benzo[d]thiazol-2-yl)- 8-substituted-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones
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A series of 2-(benzo[d]thiazol-2-yl)-8-substituted-2H-pyrazolo[4,3-c] quinolin-3(5H)-ones (3a-g) have been synthesized and evaluated for their in vitro antiproliferative activities against four human cancer cell lines: MDA-MB-435 (breast), HL-60 (leukemia), HCT-8 (colon) and SF-295 (central nervous system). The results showed that the compounds 3b (2-(benzo[d]thiazol-2-yl)-8- methyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one) and 3c (2-(benzo[d]thiazol-2-yl)-8- bromo-2H-pyrazolo[4,3-c]quinolin-3(5H)-one) exhibited good cytotoxicity for three cell lines with IC50 values lower than 5 μg/mL. Analysis of theoretical toxicity risks have shown medium tumorigenic and irritant risks related to 3b and 3c in contrast to doxorubicin, the positive control.
- Reis, Raísa Da R.,Azevedo, Elisa C.,De Souza, Maria Cecília B.V.,Ferreira, Vitor Francisco,Montenegro, Raquel C.,Araújo, Ana Jérsia,Pessoa, Cláudia,Costa-Lotufo, Letícia V.,De Moraes, Manoel O.,Filho, José D.B.M.,De Souza, Alessandra M.T.,De Carvalho, Natasha C.,Castro, Helena C.,Rodrigues, Carlos R.,Vasconcelos, Thatyana R.A.
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experimental part
p. 1448 - 1452
(2011/04/24)
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- Use of 2-[18F]fluoroethylazide for the Staudinger ligation - Preparation and characterisation of GABAA receptor binding 4-quinolones
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The labelling reagent 2-[18F]fluoroethylazide was used in a traceless Staudinger ligation. This reaction was employed to obtain the GABAA receptor binding 6-benzyl-4-oxo-1,4-dihydro-quinoline-3- carboxylic acid (2-[18F]flu
- Gaeta, Alessandra,Woodcraft, John,Plant, Stuart,Goggi, Julian,Jones, Paul,Battle, Mark,Trigg, William,Luthra, Sajinder K.,Glaser, Matthias
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supporting information; experimental part
p. 4649 - 4652
(2010/10/02)
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- An alternative approach toward 2-aryl-2H-pyrazolo[4,3-c]-quinolin-3-ones by a multistep synthesis
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A series of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones derivatives 6 and 7 was conveniently prepared. A multistep synthesis was carried out starting from dichloro- and bromoanilines (1a-b) and diethyl 2-(ethoxymethylene)malonate using a slightly modified Go
- López Rivilli, Marisa J.,Moyano, Elizabeth L.,Yranzo, Gloria I.
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supporting information; experimental part
p. 478 - 481
(2010/10/02)
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- SUBSTITUTED QUINOLINES FOR USE AS VEGF INHIBITORS
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A compound of formula (I), as well as pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising a therapeutically effective amount of the compounds. The compound is useful in treatment of cancer, diabetic retinopathy, age-related macular degeneration, inflammation, stroke, ischemic myocardium, atherosclerosis, macular edema and psoriasis.
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(2010/12/18)
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- DERIVATIVES OF QUINOLINE-3-CARBOXYLIC ACID AND THEIR MEDICAL USE
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A compound of formula (I) as well as pharmaceutically acceptable salts thereof and pharmaceutical compositions comprising a therapeutically effective amount of the compounds. The compounds are useful in treatment of cancer, diabetic retinopathy, age-related macular degeneration, inflammation, stroke, ischemic myocardium, atherosclerosis, macular edema or psoriasis.
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Page/Page column 22
(2010/12/18)
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- COMPOUNDS AND METHODS
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A compound of formula (I) as well as pharmaceutically acceptable salts thereof. A pharmaceutical composition comprising a therapeutically effective amount of the compound. The compound is useful for the treatment of cancer, diabetic retinopathy, age-relat
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(2009/06/27)
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- IMAGING AGENTS
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The invention relates to compounds of formula (I), or a salt or solvate thereof which comprise a detectable label. The compounds have use as radioligands for the GABAA receptor.
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(2009/05/29)
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- COMPOUNDS, USE AND METHODS
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A quinoline-3-carboxyderivative of formula (I), a method for preparing it and use ofthe derivativein therapy, in particular for the treatment and prevention of cell proliferative disorders or cell differentiation disorders.
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(2008/12/04)
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- Controlled derivatization of polyhalogenated quinolines utilizing selective cross-coupling reactions
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Straightforward procedures for the derivatization of tri- and tetrahalogenated quinolines utilizing sequential selective Pd-catalyzed cross-coupling reactions are described. Taking advantage of intrinsic halide reactivity, substrate control, and appropria
- Brad Nolt,Zhao, Zhijian,Wolkenberg, Scott E.
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p. 3137 - 3141
(2008/09/20)
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- Investigations on the 4-quinolone-3-carboxylic acid motif. 2. Synthesis and structure-activity relationship of potent and selective cannabinoid-2 receptor agonists endowed with analgesic activity in vivo
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Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and
- Pasquini, Serena,Botta, Lorenzo,Semeraro, Teresa,Mugnaini, Claudia,Ligresti, Alessia,Palazzo, Enza,Maione, Sabatino,Di Marzo, Vincenzo,Corelli, Federico
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supporting information; experimental part
p. 5075 - 5084
(2009/07/25)
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- Thiazolinone 4-monosubstituted quinolines
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Thiazolinone monosubstituted quinoline derivatives where the quinoline ring is mono-substituted at the 4 positions which derivatives demonstrates CDK1 antiproliferative activity and are useful as anti-cancer agents.
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(2010/10/20)
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- 4-Quinolone derivatives: High-affinity ligands at the benzodiazepine site of brain GABAA receptors. Synthesis, pharmacology, and pharmacophore modeling
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The 3-ethoxycarbonyl-4-quinolone compound 1 has previously been identified via a database search as an interesting lead compound for ligand binding at the benzodiazepine site of GABAA receptors (Kahnberg et al. J. Mol. Graphics Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead compound yielded a number of high-affinity ligands for the benzodiazepine site including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of the compounds have been tested on the α1β 2γ2S and α3β 2γ2S GABAA receptor subtypes, and two of the compounds (5 and 19) display selectivity for α1-versus α3-containing receptors by a factor of 22 and 27, respectively. This selectivity for α1β2γ2S is in the same range as that for the well-known α1 subunit selective compound zolpidem.
- Lager, Erik,Andersson, Pierre,Nilsson, Jakob,Pettersson, Ingrid,Nielsen, Elsebet ?stergaard,Nielsen, Mogens,Sterner, Olov,Liljefors, Tommy
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p. 2526 - 2533
(2007/10/03)
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- Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2
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Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitors-3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC 50 = 0.3 μM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (9) (IC50 = 1 μM), are ATP competitive (Ki values are 0.06 and 0.28 μM, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.
- Golub, Andriy G.,Yakovenko, Olexander Ya.,Bdzhola, Volodymyr G.,Sapelkin, Vladislav M.,Zien, Piotr,Yarmoluk, Sergiy M.
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p. 6443 - 6450
(2007/10/03)
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- Design, synthesis, and biological evaluation of novel 4-hydro-quinoline-3- carboxamide derivatives as an immunomodulator
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A series of novel quinoline-3-carboxamide derivatives were synthesized and evaluated for their immunomodulatory activity. The compounds were tested in vitro for effects on spleen lymphocyte proliferation and TNF-α production by macrophage. Three compounds showed immunomodulatory profiles similar to and more potent than those of linomide and FR137316 and were selected for further pharmacological studies in vivo.
- He, Jun-Feng,Yun, Liu-Hong,Yang, Ri-Fang,Xiao, Zhi-Yong,Cheng, Jun-Ping,Zhou, Wen-Xia,Zhang, Yong-Xiang
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p. 2980 - 2985
(2007/10/03)
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- 4-HYDROXYQUINOLINE-3-CARBOXAMIDES AND HYDRAZIDES AS ANTIVIRAL AGENTS
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The present invention provides 4-hydroxyquinoline-3-carboxamide and hydrazide compounds of formula I These compounds are useful to treat or prevent the herpesviral infections, particularly, human cytomegaloviral infection.
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Page/Page column 63
(2010/02/13)
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- Microwave assisted Gould-Jacob reaction: Synthesis of 4-quinolones under solvent free conditions
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A single step Gould-Jacob reaction between aromatic amines and diethyl ethoxymethylenemalonates (EMME) for the synthesis of 4-quinolones under solvent free microwave irradiation has been carried out and compared with classical heating.
- Dave, Chaitanya G.,Joshipura, Hardik M.
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p. 650 - 652
(2007/10/03)
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