- Discovery and Mechanistic Study of Tailor-Made Quinoline Derivatives as Topoisomerase 1 Poison with Potent Anticancer Activity
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To overcome chemical limitations of camptothecin (CPT), we report design, synthesis, and validation of a quinoline-based novel class of topoisomerase 1 (Top1) inhibitors and establish that compound 28 (N-(3-(1H-imidazol-1-yl)propyl)-6-(4-methoxyphenyl)-3-(1,3,4-oxadiazol-2-yl)quinolin-4-amine) exhibits the highest potency in inhibiting human Top1 activity with an IC50 value of 29 ± 0.04 nM. Compound 28 traps Top1-DNA cleavage complexes (Top1ccs) both in the in vitro cleavage assays and in live cells. Point mutation of Top1-N722S fails to trap compound 28-induced Top1cc because of its inability to form a hydrogen bond with compound 28. Unlike CPT, compound 28 shows excellent plasma serum stability and is not a substrate of P-glycoprotein 1 (permeability glycoprotein) advancing its potential anticancer activity. Finally, we provide evidence that compound 28 overcomes the chemical instability of CPT in human breast adenocarcinoma cells through generation of persistent and less reversible Top1cc-induced DNA double-strand breaks as detected by γH2AX foci immunostaining after 5 h of drug removal.
- Kundu, Biswajit,Das, Subhendu K.,Paul Chowdhuri, Srijita,Pal, Sourav,Sarkar, Dipayan,Ghosh, Arijit,Mukherjee, Ayan,Bhattacharya, Debomita,Das, Benu Brata,Talukdar, Arindam
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Read Online
- Discovery of a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as PI3K/mTOR dual inhibitors
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Recently, the phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) have been considered as promising targets for the treatment of cancer. Herein, we synthesized a series of N-(5-(quinolin-6-yl)pyridin-3-yl)benzenesulfonamides as novel PI3K/mTOR dual inhibitors for cancer therapy. In the biological evaluation, compound 17e was identified as a potent PI3K/mTOR dual inhibitor, which significantly inhibit Class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level. Moreover, 17e display high potency against PC-3?cells (IC50?=?80?nM) in the anti-proliferative assay, and showed acceptable pharmacokinetic properties in?vivo.
- Zhang, Jiankang,Lv, Xiaoqing,Ma, Xiaodong,Hu, Yongzhou
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Read Online
- BICYCLIC HETEROCYCLIC COMPOUNDS USEFUL AS IRAK4 INHIBITORS
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Disclosed are compounds of Formula (I) or a salt or prodrug thereof, wherein: X is CR4a4a or N; Y is CR4b4b or N; Z is CR4d4d or N; provided that zero or 1 of X, Y, and Z is N; and R11, R22, R33, R4a4a, R4b4b, R4c4c, and R4d4d are define herein. Also disclosed are methods of using such compounds as modulators of IRAK4, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases, or in the treatment of cancer.
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Page/Page column 43-44
(2021/02/12)
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- BENZO[H][1,6] NAPHTHYRIDIN-2(1H)-ONES AS BMX INHIBITORS, FOR USE AGAINST CANCER
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The present invention provides a compound of formula (I) and its use in methods of treatment, including the treatment of cancer. The compound has the structure shown below where D is an acceptor group and -A-, -L-, R7 are as discussed in the ap
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Page/Page column 45; 48
(2020/12/29)
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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 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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- PAPD5 INHIBITORS AND METHODS OF USE THEREOF
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The present application provides compounds that are PAPD5 inhibitors and are useful in treating a variety of conditions such as cancer, telomere diseases, and aging-related and other degenerative disorders.
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(2020/11/03)
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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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Page/Page column 22; 40-41
(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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- 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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- The Identification of Potent, Selective, and Orally Available Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase: The Discovery of AZD0156 (8-{6-[3-(Dimethylamino)propoxy]pyridin-3-yl}-3-methyl-1-(tetrahydro-2 H-pyran-4-yl)-1,3-dihydro-2 H-imidazo[4,5- c]quinolin-2-one)
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ATM inhibitors, such as 7, have demonstrated the antitumor potential of ATM inhibition when combined with DNA double-strand break-inducing agents in mouse xenograft models. However, the properties of 7 result in a relatively high predicted clinically efficacious dose. In an attempt to minimize attrition during clinical development, we sought to identify ATM inhibitors with a low predicted clinical dose (50 mg) and focused on strategies to increase both ATM potency and predicted human pharmacokinetic half-life (predominantly through the increase of volume of distribution). These efforts resulted in the discovery of 64 (AZD0156), an exceptionally potent and selective inhibitor of ATM based on an imidazo[4,5-c]quinolin-2-one core. 64 has good preclinical phamacokinetics, a low predicted clinical dose, and a high maximum absorbable dose. 64 has been shown to potentiate the efficacy of the approved drugs irinotecan and olaparib in disease relevant mouse models and is currently undergoing clinical evaluation with these agents.
- Pike, Kurt G.,Barlaam, Bernard,Cadogan, Elaine,Campbell, Andrew,Chen, Yingxue,Colclough, Nicola,Davies, Nichola L.,De-Almeida, Camila,Degorce, Sebastien L.,Didelot, Myriam,Dishington, Allan,Ducray, Richard,Durant, Stephen T.,Hassall, Lorraine A.,Holmes, Jane,Hughes, Gareth D.,Macfaul, Philip A.,Mulholland, Keith R.,McGuire, Thomas M.,Ouvry, Gilles,Pass, Martin,Robb, Graeme,Stratton, Natalie,Wang, Zhenhua,Wilson, Joanne,Zhai, Baochang,Zhao, Kang,Al-Huniti, Nidal
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p. 3823 - 3841
(2018/05/14)
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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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- Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
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The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour efficacy of cytotoxic chemotherapeutic agents. In the search for new Chk1 inhibitors, a congeneric series of 2-aryl-2 H-pyrazolo[4,3-c]quinolin-3-one (PQ) was evaluated by in-vitro and in-silico approaches for the first time. A total of 30 PQ structures were synthesised in good to excellent yields using conventional or microwave heating, highlighting that 14 of them are new chemical entities. Noteworthy, in this preliminary study two compounds 4e2 and 4h2 have shown a modest but significant reduction in the basal activity of the Chk1 kinase. Starting from these preliminary results, we have designed the second generation of analogous in this class and further studies are in progress in our laboratories.
- Malvacio, Ivana,Cuzzolin, Alberto,Sturlese, Mattia,Vera, D. Mariano A.,Moyano, E. Laura,Moro, Stefano
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p. 171 - 183
(2017/12/26)
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- Identification of 3-amidoquinoline derivatives as PI3K/mTOR dual inhibitors with potential for cancer therapy
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A new series of 3-amidoquinoline derivatives were designed, synthesized and evaluated as PI3K/mTOR dual inhibitors. Among them, five compounds showed potent PI3Kα inhibitory activities (IC50 50 1 μM). The representative compound 15a can significantly inhibit other class I PI3Ks, mTOR and phosphorylation of pAkt(Ser473) at low nanomolar level, suggesting that 15a was a potent PI3K/mTOR dual inhibitor. Moreover, 15a displayed favorable pharmacokinetic properties in vivo.
- Zhang, Jiankang,Ma, Xiaodong,Lv, Xiaoqing,Li, Ming,Zhao, Yanmei,Liu, Guoqiang,Zhan, Shuyu
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p. 2342 - 2350
(2017/01/21)
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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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- 8-[6-[3-(AMINO)PROPOXY]-3-PYRIDYL]-1 -ISOPROPYL-IMIDAZO[4,5-C]QUINOLIN-2-ONE DERIVATIVES AS SELECTIVE MODULATORS OF ATAXIA TELANGIECTASIA MUTATED (ATM) KINASE FOR THE TREATMENT OF CANCER
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The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where Rl, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also discloses the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
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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): (I) and pharmaceutically acceptable salts thereof, where R1, R2, R3 and R4 have any of the meanings defined herein. The specification also relates
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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 x, R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
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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 4-fluoropiperidin-1-yl or 3-fluoropyrrolidin-1-yl and R2 is methyl or hydro; the use of compounds of Formula (I) or pharmaceutically acceptable salts thereof to treat or prevent ATM mediated disease, including cancer; pharmaceutical compositions comprising substituted imidazo[4,5- c]quinolin-2-one compounds or pharmaceutically acceptable salts thereof; kits comprising compounds of Formula (I) or pharmaceutically acceptable salts thereof; methods of manufacture of compounds of Formula (I) or pharmaceutically acceptable salts thereof; and intermediates useful in such manufacture.
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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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- 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 0148; 0149; 0150
(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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- 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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p. 7585 - 7596
(2015/12/18)
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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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- PI3 KINASE/mTOR DUAL INHIBITOR
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The present invention provides an imidazo[4,5-c]quinolin-2-one compound, or a pharmaceutically acceptable salt thereof, that inhibits both PI3K and mTOR and, therefore, is useful in the treatment of cancer.
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(2012/07/28)
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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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p. 1448 - 1452
(2011/04/24)
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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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Page/Page column 33-34
(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 22-23
(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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Page/Page column 13-14
(2009/06/27)
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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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- NOVEL CHEMICAL COMPOUNDS
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This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with hYAK3 activity.
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Page/Page column 47
(2010/11/25)
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- Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors
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Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1′ group. Select compounds were found to be effective in in vivo models of arthritis.
- Zask,Gu,Albright,Du,Hogan,Levin,Chen,Killar,Sung,DiJoseph,Sharr,Roth,Skala,Jin,Cowling,Mohler,Barone,Black,March,Skotnicki
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p. 1487 - 1490
(2007/10/03)
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