- Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors
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An interesting enzyme of the endocannabinoid system is monoacylglycerol lipase (MAGL). This enzyme, which metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG), has attracted great interest due to its involvement in several physiological and pathological processes, such as cancer progression. Experimental evidences highlighted some drawbacks associated with the use of irreversible MAGL inhibitors in vivo, therefore the research field concerning reversible inhibitors is rapidly growing. In the present manuscript, the class of benzoylpiperidine-based MAGL inhibitors was further expanded and optimized. Enzymatic assays identified some compounds in the low nanomolar range and steered molecular dynamics simulations predicted the dissociation itinerary of one of the best compounds from the enzyme, confirming the observed structure-activity relationship. Biological evaluation, including assays in intact U937 cells and competitive activity-based protein profiling experiments in mouse brain membranes, confirmed the selectivity of the selected compounds for MAGL versus other components of the endocannabinoid system. An antiproliferative ability in a panel of cancer cell lines highlighted their potential as potential anticancer agents. Future studies on the potential use of these compounds in the clinical setting are also supported by the inhibition of cell growth observed both in cancer organoids derived from high grade serous ovarian cancer patients and in pancreatic ductal adenocarcinoma primary cells, which showed genetic and histological features very similar to the primary tumors.
- Granchi, Carlotta,Bononi, Giulia,Ferrisi, Rebecca,Gori, Eleonora,Mantini, Giulia,Glasmacher, Sandra,Poli, Giulio,Palazzolo, Stefano,Caligiuri, Isabella,Rizzolio, Flavio,Canzonieri, Vincenzo,Perin, Tiziana,Gertsch, Jürg,Sodi, Andrea,Giovannetti, Elisa,Macchia, Marco,Minutolo, Filippo,Tuccinardi, Tiziano,Chicca, Andrea
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- Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy
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Bromodomain-containing protein 4 (BRD4) is an attractive epigenetic target in human cancers. Inhibiting the phosphorylation of BRD4 by casein kinase 2 (CK2) is a potential strategy to overcome drug resistance in cancer therapy. The present study describes the synthesis of multiple BRD4–CK2 dual inhibitors based on rational drug design, structure–activity relationship, and in vitro and in vivo evaluations, and 44e was identified to possess potent and balanced activities against BRD4 (IC50 = 180 nM) and CK2 (IC50 = 230 nM). In vitro experiments show that 44e could inhibit the proliferation and induce apoptosis and autophagy-associated cell death of MDA-MB-231 and MDA-MB-468 cells. In two in vivo xenograft mouse models, 44e displays potent anticancer activity without obvious toxicities. Taken together, we successfully synthesized the first highly effective BRD4–CK2 dual inhibitor, which is expected to be an attractive therapeutic strategy for triple-negative breast cancer (TNBC).
- Chen, Juncheng,Chiang, Cheng-Ming,He, Gu,Liu, Bo,Liu, Jie,Ouyang, Liang,Tang, Pan,Wang, Guan,Yang, Chengcan,Ye, Tinghong,Zhang, Jifa,Zhang, Jin,Zou, Ling
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p. 18025 - 18053
(2022/01/03)
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- Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease
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Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC50 = 51.1 nM; GSK-3β: IC50 = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
- Yao, Hong,Uras, Giuseppe,Zhang, Pengfei,Xu, Shengtao,Yin, Ying,Liu, Jie,Qin, Shuai,Li, Xinuo,Allen, Stephanie,Bai, Renren,Gong, Qi,Zhang, Haiyan,Zhu, Zheying,Xu, Jinyi
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p. 7483 - 7506
(2021/06/28)
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- Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles
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Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound 12d, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 μL/min/mg (human) and 33.2 μL/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment. Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 μL/min/mg; rat, 33.2 μL/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.
- Han, Sheng,Sang, Yali,Wu, Yan,Tao, Yuan,Pannecouque, Christophe,De Clercq, Erik,Zhuang, Chunlin,Chen, Fen-Er
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- On the Synthesis and Reactivity of 2,3-Dihydropyrrolo[1,2- a ]quinazolin-5(1 H)-ones
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An improved, scalable synthetic route to the quinazolinone natural product 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one is reported. The applicability of this method to analogue synthesis and the synthesis of related natural products is explored. Finally, reactivity of the scaffold to a variety of electrophilic reagents, generating products stereoselectively, is reported.
- Sutherell, Charlotte L.,Ley, Steven V.
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supporting information
p. 135 - 144
(2016/12/24)
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- The therapeutic compound, use and related method (by machine translation)
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PROBLEM TO BE SOLVED: To provide a pharmaceutical composition containing a compound or its salt which prevents or treats a central nervous system disease in which integration dysfunction syndrome and agnosia are enumerated as exemplary disorders.SOLUTION: The pharmaceutical composition includes the compound or its salt represented by chemical formula (A) which modulates striatal-enriched protein tyrosine phosphatase (STEP).
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-
Paragraph 1096; 1097
(2017/06/29)
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- Optimization of substituted imidazobenzodiazepines as novel asthma treatments
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We describe the synthesis of analogs of XHE-III-74, a selective α4β3γ2 GABAAR ligand, shown to relax airway smooth muscle ex vivo and reduce airway hyperresponsiveness in a murine asthma model. To improve properties of this compound as an asthma therapeutic, a series of analogs with a deuterated methoxy group in place of methoxy group at C-8 position was evaluated for isotope effects in preclinical assays; including microsomal stability, cytotoxicity, and sensorimotor impairment. The deuterated compounds were equally or more metabolically stable than the corresponding non-deuterated analogs and increased sensorimotor impairment was observed for some deuterated compounds. Thioesters were more cytotoxic in comparison to other carboxylic acid derivatives of this compound series. The most promising compound 16 identified from the in vitro screens also strongly inhibited smooth muscle constriction in ex vivo guinea pig tracheal rings. Smooth muscle relaxation, determined by reduction of airway hyperresponsiveness with a murine ovalbumin sensitized and challenged model, showed that 16 was efficacious at low methacholine concentrations. However, this effect was limited due to suboptimal pharmacokinetics of 16. Based on these findings, further analogs of XHE-III-74 will be investigated to improve in vivo metabolic stability while retaining the efficacy at lung tissues involved in asthma pathology.
- Jahan, Rajwana,Stephen, Michael Rajesh,Forkuo, Gloria S.,Kodali, Revathi,Guthrie, Margaret L.,Nieman, Amanda N.,Yuan, Nina Y.,Zahn, Nicolas M.,Poe, Michael M.,Li, Guanguan,Yu, Olivia B.,Yocum, Gene T.,Emala, Charles W.,Stafford, Douglas C.,Cook, James M.,Arnold, Leggy A.
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p. 550 - 560
(2016/12/09)
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- Identification of a Water-Soluble Indirubin Derivative as Potent Inhibitor of Insulin-like Growth Factor 1 Receptor through Structural Modification of the Parent Natural Molecule
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Indirubins have been identified as potent ATP-competitive protein kinase inhibitors. Structural modifications in the 5-and 3′-position have been extensively investigated, but the impact of substituents in 5′-position is not equally well-studied. Here, we report the synthesis of new indirubin 3′-and 5′-derivatives in the search of water-soluble indirubins by introducing basic centers. Antiproliferative activity of all compounds in tumor cells was evaluated along with kinase inhibition of selected compounds. The results show the 3′-position to tolerate large substituents without compromising activity, whereas bulk and rigid substituents in 5′-position appear unfavorable. Screening molecular targets of water-soluble 3′-oxime ethers revealed 6ha as preferential inhibitor of insulin-like growth factor 1 receptor (IGF-1R) in a panel of 22 protein kinases and in cells. Consistently, 6ha inhibited tumor cell growth in the NCI 60 cell line panel and induced apoptosis. The results indicate that the 5′-position provides limited space for chemical modifications and identify 6ha as a potent water-soluble indirubin-based IGF-1R inhibitor.
- Cheng, Xinlai,Merz, Karl-Heinz,Vatter, Sandra,Zeller, Jochen,Muehlbeyer, Stephan,Thommet, Andrea,Christ, Jochen,W?lfl, Stefan,Eisenbrand, Gerhard
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p. 4949 - 4962
(2017/06/28)
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- QUINAZOLINE-2,4(1H,3H)-DIONE DERIVATIVES AS TRCP5 MODULATORS FOR THE TREATMENT OF NEUROPSYCHIATRY DISORDERS
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This invention relates to novel Quinazoline-2,4(1H,3H)-dione derivatives of Formula (I): and their use as TRPC5 modulators, pharmaceutical compositions containing the same, and methods of using the same as agents for the treatment of TRPC5 receptor mediated disorders or conditions. R1, R2, R3 and R4 have meanings given in the description.
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Page/Page column 40
(2016/02/29)
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- Concise Synthesis of Dictyoquinazol A via a Dimerisation-Cyclocondensation Sequence
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A two-step total synthesis of the neuroprotective alkaloid, dictyoquinazol A, has been achieved. The brevity of this synthesis was enabled by exploiting the hidden symmetry of the target molecule. Several structural analogues were also prepared using a similar strategy. These results provide a platform for future structure-activity relationship studies in the quest for a novel treatment for stroke.
- Wangsahardja, Jonatan,Marcolin, Gabriella M.,Lizarme, Yuvixza,Morris, Jonathan C.,Hunter, Luke
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supporting information
p. 1237 - 1240
(2016/05/10)
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- THERAPEUTIC COMPOUNDS AND RELATED METHODS OF USE
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Methods of treating disorders using compounds that modulate striatal-enriched tyrosine phosphatase (STEP) are described herein. Exemplary disorders include schizophrenia and cognitive deficit.
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Paragraph 1495
(2015/11/16)
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- A facile method for the synthesis of Betrixaban
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A facile method for the synthesis of N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide (Betrixaban) from 5-methoxy-2-nitrobenzoic acid is achieved by reduction, acylation, chlorination, acylation and the formation of the amidine. A dechlorinated impurity is avoided in this method. Using tetrahydrofuran as the solvent in the four steps makes its recovery easier. The total yield of the target compound is about 40% and this method is suitable for large-scale production.
- Li, Jianye,Chen, Ligong,Yan, Xilong,Li, Yang,Wei, Daiyan,Wang, Donghua
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p. 524 - 526
(2015/11/27)
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- QUINAZOLINEDIONES AS TANKYRASE INHIBITORS
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This invention relates to the use of quinazolinediones for the modulation, notably the inhibition of the activity of tankyrases (TNKS1 and TNKS2). Suitably, the present invention relates to the use of quinazolinediones in the treatment of cancer, fibrosis and other hyperproliferative diseases through this mechanism.
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Page/Page column 63
(2014/01/07)
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- Catalysis and mechanistic studies of ruthenium and osmium on synthesis of anthranilic acids
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Ruthenium, osmium and ruthenium + osmium catalyzed synthetic methodology was developed for the synthesis of anthranilic acids from indoles in good to excellent yields using bromamine-B in alkaline acetonitrile-water (1:1) at 313 K. Detailed catalysis studies of ruthenium, osmium and the mixture of both were carried out for the synthetic reactions. The positive synergistic catalytic activity of Ru(III) + Os(VIII) was observed to a large extent with the activity greater than the sum of their separate catalytic activities. Detailed kinetic and mechanistic investigations for each catalyzed reactions were carried out. The kinetic pattern and mechanistic picture of each catalyzed reaction were found to be different for each catalyst and to obey the underlying rate laws: rate = k[BAB]t[Indole][Ru(III)]x[OH-] y rate = k[BAB]t[Indole][Os(VIII)][OH-] y rate = k[BAB]t[Indole]o[Ru(III) + Os(VIII)][OH-]y where, x, y Os(VIII) > Ru(III). This trend may be attributed to the different d-electronic configuration of the catalysts. The proposed mechanisms and the rigorous kinetic models derived give results that fit well with the experimental data in each catalyzed reaction. Copyright
- Karthikeyan,Jagadeesh, Rajenahally V.,Sree Sandhya,Puttaswamy,Nithya,Kumar, S. Senthil,Bhagat
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experimental part
p. 34 - 46
(2011/09/16)
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- Bromamine-B/PdCl2 is an efficient system for the synthesis of anthranilic acids from indoles and indigos
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A convenient method has been developed for the conversion of indoles and indigos into anthranilic acids in good to excellent yields using a bromamine-B/PdCl2 system. The general process utilizes our efficient method for the oxidation of indoles and indigos in alkaline (pH 12) acetonitrile/water (1:1) at 60°C. Copyright Taylor & Francis Group, LLC.
- Kumar, C. Vinod,Shivananda,Raju, C. Nagu,Jagadeesh
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experimental part
p. 3480 - 3487
(2011/02/22)
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- Novel agents for preventing and treating disorders involving modulation of the RyR receptors
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The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells. Such disorders and diseases include, by way of example only, cardiac disorders and diseases, skeletal muscular disorders and diseases, cognitive disorders and diseases, malignant hyperthermia, diabetes, and sudden infant death syndrome. Cardiac disorder and diseases include, but are not limited to, irregular heartbeat disorders and diseases; exercise-induced irregular heartbeat disorders and diseases; sudden cardiac death; exercise-induced sudden cardiac death; congestive heart failure; chronic obstructive pulmonary disease; and high blood pressure. Irregular heartbeat disorders and diseases include and exercise-induced irregular heartbeat disorders and diseases include, but are not limited to, atrial and ventricular arrhythmia; atrial and ventricular fibrillation; atrial and ventricular tachyarrhythmia; atrial and ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia (CPVT); and exercise-induced variants thereof. Skeletal muscular disorder and diseases include, but are not limited to, skeletal muscle fatigue, exercise-induced skeletal muscle fatigue, muscular dystrophy, bladder disorders, and incontinence. Cognitive disorders and diseases include, but are not limited to, Alzheimer's Disease, forms of memory loss, and age-dependent memory loss.
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Page/Page column 34
(2008/06/13)
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- Novel anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof
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The present invention provides methods for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject. The present invention further provides methods for treating and preventing atrial and ventricular cardiac arrhythmias, heart failure, and exercise-induced sudden cardiac death in a subject. Additionally, the present invention provides use of JTV-519 in a method for limiting or preventing a decrease in the level of RyR2-bound FKBP12.6 in a subject who has, or is a candidate for, atrial fibrillation. Also provided are uses of 1,4-benzothiazepine derivatives in methods for treating and preventing atrial and ventricular cardiac arrhythmias and heart failure in a subject, and for preventing exercise-induced sudden cardiac death. The present invention also provides methods for identifying agents for use in treating and preventing atrial fibrillation and heart failure, and agents identified by these methods.
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Page/Page column 37
(2008/06/13)
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- A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): Its application to the synthesis of key intermediates for anti-malarial agents
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A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2- dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.
- Theeraladanon, Chumpol,Arisawa, Mitsuhiro,Nishida, Atsushi,Nakagawa, Masako
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p. 3017 - 3035
(2007/10/03)
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- 1H-IMIDAZO[4,5-c]QUINOLINE DERIVATIVES IN THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES
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The invention relates to the use of imidazoquinolines and salts thereof in the treatment of protein kinase dependent diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases, imidazoquinolines for use in the treatment of protein kinase dependent diseases, a method of treatment against said diseases, comprising administering the imidazoloquinolines to a warm-blooded animal, especially a human, pharmaceutical preparations comprising an imidazoquinoline, especially for the treatment of a protein kinase dependent disease, novel imidazoquinolines, and a process for the preparation of the novel imidazoquinolines.
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Page/Page column 64
(2008/06/13)
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- Studies in search of diazepam-insensitive subtype selective agents for GABA/Bz receptors
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In search of more selective ligands for "diazepam-insensitive" (DI) GABA receptors (i.e. receptors containing either an α4 or α6 subunit), a series of 3- and 8-substituted 6-oxo-imidazo [1,5a] [1,4]-benzodiazepines were synthesized and evaluated in vitro on recombinant human GABAA (receptor) subtypes to study their structure activity relationships. In agreement with previous findings,1,2 it was found the size of ring-D exerted a marked influence on the binding affinity at all receptor subtypes. Based on this finding, the most DI selective ligands in vitro [CM-D45 (10) and XHeIII-74 (37)] have been synthesized.
- Li, Xiaoyan,Ma, Chunrong,He, Xiaohui,Yu, Jianming,Han, Dongmei,Zhang, Chunchun,Atack, John R.,Cook, James M.
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p. 504 - 537
(2007/10/03)
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- Ring-substituted 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides with similar patterns of cytotoxicity to the dual topo I/II inhibitor DACA
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A series of ring-substituted analogues of the topoisomerase inhibitor 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides was prepared and evaluated. The compounds were prepared by Pfitzinger reaction of the appropriate isatin-7-carboxylic acids and 1-indanones, followed by selective thermal decarboxylation of the resulting tetracyclic diacids, subsequent oxidation of the methylene group with alkaline permanganate under carefully controlled conditions, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were evaluated in a panel of cell lines in culture. The largest increases in cytotoxicity (five to tenfold) were shown by 4-substituted analogues, with the 4-Cl derivative having an IC50 of 8nM against the Lewis lung carcinoma. Copyright (C) 1999 Elsevier Science Ltd.
- Deady, Leslie W.,Desneves, Jose,Kaye, Anthony J.,Thompson, Michelle,Finlay, Graeme J.,Baguley, Bruce C.,Denny, William A.
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p. 2801 - 2809
(2007/10/03)
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- Optional site selectivity in the metalation of o- and p-anisidine through matching of reagents with neighboring groups
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N-Protected o- and p-anisidines (2- and 4-methoxyanilines) undergo a hydrogen/metal exchange at the position adjacent to either the oxygen or nitrogen atom depending on what organometalic base is employed. These synthetically useful findings support previous views about neighboring group/reagent interactions.
- Maggi, Raimondo,Schlosser, Manfred
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p. 5430 - 5434
(2007/10/03)
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- Cyclization of N-butyl-4-pentenylaminyl: Implications for the cyclization of alkenylaminyl radicals
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The utility of arenesulfenamides as aminyl radical precursors has been clearly demonstrated. The cyclization of N-butyl-4-pentenylaminyl is shown to be a slow and irreversible process that is accelerated significantly by small amounts of bis(tributyltin) oxide.
- Maxwell, Brendan J.,Tsanaktsidis, John
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p. 4276 - 4283
(2007/10/03)
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- Structure-activity relationships of a series of substituted benzamides: Potent D2/5-HT2 antagonists and 5-HT1a agonists as neuroleptic agents
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A series of substituted (4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide derivatives was prepared and evaluated as potential atypical antipsychotic agents. The target compounds were readily prepared from their benzoyl chloride, benzoic acid, or isatoic anhydride precursors, and they were evaluated in vitro for their ability to bind to dopamine D2, serotonin 5-HT2, and serotonin 5-HT1a receptors. To assess the potential antipsychotic activity of these compounds, we investigated their ability to inhibit the apomorphine-induced climbing response in mice. Selected compounds were evaluated further to determine their side-effect potentials. Structure-activity relationships of both mono- and polysubstituted benzamides are discussed herein. While several analogues had potent in vitro and in vivo activities indicative of potential atypical antipsychotic activity, anthranilamide 77 (1192U90) demonstrated a superior pharmacological profile. As a result of this investigation, 1192U90 (2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)benzamide hydrochloride) was selected for further evaluation and is currently in phase I clinical trials as a potential atypical antipsychotic agent.
- Norman, Mark H.,Rigdon, Greg C.,Hall, William R.,Navas III, Frank
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p. 1172 - 1188
(2007/10/03)
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- Multisubstituted 1-hydroxy-9-acridones with anticancer activity
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The present invention provides a compound having the structure: STR1 The present invention also provides a method for synthesizing a compound having the above-identified structure as well as the intermediate compounds produced according to that method. The present invention further provides a pharmaceutical composition comprising the above compounds. Lastly, the present invention provides a method of inhibiting growth of tumor cells.
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- The synthesis of a novel series of substituted 2-phenyl-4H-3,1- benzoxazin-4-ones
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Following initial studies on a substituted 2-[3-methylphenyl]-4H-3,1- benzoxazin-4-one showing some cytotoxic activity, the synthesis of a novel series of 2-phenyl substituted 4H-3,1-benzoxazin-4-ones is reported herein.
- Pavlidis,Perry
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p. 533 - 548
(2007/10/02)
-