cas 39859-36-4, 2-AMINO-5-BROMOBENZOPHENONE

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Design, Synthesis, and in vitro Biological Evaluation of 3,5-Dimethylisoxazole Derivatives as BRD4 Inhibitors
BRD4 has been identified as a potential target for blocking proliferation in a variety of cancer cell lines. In this study, 3,5-dimethylisoxazole derivatives were designed and synthesized with excellent stability in liver microsomes as potent BRD4 inhibitors, and were evaluated for their BRD4 inhibitory activities in vitro. Gratifyingly, compound 11 h [3-((1-(2,4-difluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-6-(3,5-dimethylisoxazol-4-yl)-4-phenyl-3,4-dihydroquinazolin-2(1H)-one] exhibited robust potency for BRD4(1) and BRD4(2) inhibition with IC50 values of 27.0 and 180 nm, respectively. Docking studies were performed to illustrate the strategy of modification and analyze the conformation in detail. Furthermore, compound 11 h was found to potently inhibit cell proliferation in the BRD4-sensitive cell lines HL-60 and MV4-11, with IC50 values of 0.120 and 0.09 μm, respectively. Compound 11 h was further demonstrated to downregulate c-Myc levels in HL-60 cells. In summary, these results suggest that compound 11 h is most likely a potential BRD4 inhibitor and is a lead compound for further investigations.
Li, Xiangyang,Zhang, Jian,Zhao, Leilei,Yang, Yifei,Zhang, Huibin,Zhou, Jinpei
p. 1363 - 1368
(2018)
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Identification of 3,5-Dimethylisoxazole Derivatives as BRD4 Inhibitors for the Treatment of Colorectal Cancer
Bromodomain-containing protein 4 (Brd4) plays a critical regulatory role in gene transcription that has been recently recognized as a promising strategy for cancer therapy. Based on the BRD4 protein containing two tandem bromodomain structures, BD1 and BD2, we designed and synthesized a series of 3,5-dimethylisoxazole derivative dimers targeting both bromodomains simultaneously to enhance protein binding potency. Among them, compound 22 significantly inhibited the proliferation of colorectal cancer cells HCT116 (IC50= 162 nM), with a 20-fold increase in antiproliferative activity compared to inhibitor 14. The results of WesternBlot showed that compound 22 could down-regulate c-MYC protein levels and up-regulate HEXIM1 expression and modulate apoptosis through intrinsic pathways. In addition, compound 22 exhibited outstanding antitumor efficacy in the CT-26 tumor mouse model with a tumor suppression rate of 56.1%. Taken together, 3,5-dimethylisoxazole derivative dimer 22 has remarkable protein inhibitory effect and antitumor activity in vitro and in vivo. A protein binding model of compound 22 is being further analyzed, which will facilitate the development of bivalent BRD4 inhibitors and probe the biological function of BRD4.
Yang, Yifei,Fang, Lincheng,Chen, Pan,Zhang, Huibin,Zhou, Jinpei
p. 2174 - 2181
(2020)
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Synthesis of substituted 2-pyridyl-4-phenylquinolines
The acid-catalyzed condensation of o-aminobenzophenones with aromatic acetyl derivatives, in a basic methanol/tetrahydrofuran medium, has been used to prepare a series of substituted 2-pyridyl-4-phenylquinolines. Derivatives having two aza binding sites can act as asymmetric bidendate ligands to complex transition metals such as ruthenium, osmium or iridium. All the compounds were characterized by elemental analysis, Ei or FAB (+) MS, 1H- and 13C-NMR spectroscopies. Complete assignments of the (1)H spectra were accomplished by using a combination of one- and two-dimensional NMR techniques.
Mamo, Antonino,Nicoletti, Salvatore,Tat, N. Cam
p. 618 - 627
(2002)
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Discovery of 3,5-dimethylisoxazole derivatives as novel, potent inhibitors for bromodomain and extraterminal domain (BET) family
Bromodomain and extra-terminal (BET) is a promising therapeutic target for various hematologic cancers. We used the BRD4 inhibitor compound 13 as a lead compound to develop a variety of compounds, and we introduced diverse groups into the position of the compound 13 orienting toward the ZA channel. A series of compounds (14–23, 38–41, 43, 47–49) bearing triazolopyridazine motif exhibited remarkable BRD4 protein inhibitory activities. Among them, compound 39 inhibited BRD4(BD1) protein with an IC50 of 0.003 μM was superior to lead compound 13. Meanwhile, compound 39 possess activity, IC50 = 2.1 μM, in antiproliferation activity against U266 cancer cells. On the other hand, compound 39 could arrest tumor cells into the G0/G1 phase and induce apoptosis, which was consistent with its results in inhibiting cell proliferation. Biological and biochemical data suggest that BRD4 protein might be a therapeutic target and that compound 39 is an excellent lead compound for further development.
Fang, Lincheng,Hu, Zhaoxue,Yang, Yifei,Chen, Pan,Zhou, Jinpei,Zhang, Huibin
(2021/04/15)

NOVEL CELL METABOLISM MODULATING COMPOUNDS AND USES THEREOF
A class of compounds that bind to fatty acid binding protein (FABP4) and modulate adipocyte metabolism to drive enhanced glucose utilization, as well as pharmaceutical compositions comprising the class of compounds, in combination with a pharmaceutically acceptable diluent or carrier, and optionally, further in combination with a therapeutically active agent, and the use of these compounds in medicine and for the preparation of a medicament in the treatment of disorders acting on the FABP4.
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(2021/07/31)

IRIDIUM COMPLEX COMPOUND
An iridium complex compound represented by formula (5). Provided is an iridium complex compound that is useful as a material for a light-emitting layer of an organic electroluminescent element, has a narrow half-width of the emission spectrum thereof, has high solubility in a solvent, and has a short wavelength that is not too long and is suitable as a red-light-emitting material. where in formula (5), Ir represents an iridium atom. X represents a bidentate ligand. m represents an integer of 1 to 3. R1 to R22 each independently represent a hydrogen atom or a substituent. Adjacent substituents are optionally bonded together to form a ring. At least one of R13, R17, R18, and R22 represents a substituent other than a hydrogen atom.
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Paragraph 0295; 0296

(2021/10/22)

Ir(iii)-Catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling for the synthesis of N-H indoles
Herein, an iridium(iii)-catalysed electrooxidative intramolecular dehydrogenative C-H/N-H coupling of unprotected 2-alkenyl anilines is described. The developed method allows the synthesis of a variety of 3-substituted N-H indole scaffolds under undivided electrolytic conditions. Mechanistic studies suggest that the reaction proceeds through the electro-oxidation induced reductive elimination pathway.
Chang, Sukbok,Kim, Dongwook,Kim, Youyoung
supporting information
p. 12309 - 12312
(2021/12/07)

Synthesis of 1-Amino-2,2,2-trifluoroalkylphosphonates from Alkene-Tethered Trifluoroacetimidoyl Chlorides
The reaction of alkene-tethered trifluoroacetimidoyl chlorides with trialkyl phosphites furnishes 1-amino-2,2,2-trifluoroalkylphosphonates. The products were generated in moderate to good yields, and the scalability of this process was showcased. Partial hydrolysis of the phosphonate moiety was achieved. The cyclization is proposed to occur via formation of an imidoyl phosphonate intermediate that becomes susceptible to nucleophilic attack at nitrogen through the strong electron-withdrawing groups at the imidoyl carbon.
Rodríguez, José F.,Zhang, Anji,Arora, Ramon,Lautens, Mark
supporting information
p. 7540 - 7544
(2021/10/12)

Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin
High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.
Abdelkafi, Hajer,Michau, Aurélien,Pons, Valérie,Ngadjeua, Flora,Clerget, Alexandra,Ait Ouarab, Lilia,Buisson, David-Alexandre,Montoir, David,Caramelle, Lucie,Gillet, Daniel,Barbier, Julien,Cintrat, Jean-Christophe
p. 8114 - 8133
(2020/09/21)

Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide
BRD4 has emerged as an attractive target for anticancer therapy. However, BRD4 inhibitors treatment leads to BRD4 protein accumulation, together with the reversible nature of inhibitors binding to BRD4, which may limit the efficacy of BRD4 inhibitors. To address these problems, a protein degradation strategy based on the proteolysis targeting chimera (PROTAC) technology has been developed to target BRD4 recently. Herein, we present our design, synthesis and biological evaluation of a new class of PROTAC BRD4 degraders, which were based on a potent dihydroquinazolinone-based BRD4 inhibitor compound 6 and lenalidomide/pomalidomide as ligand for E3 ligase cereblon. Gratifyingly, several compounds showed excellent inhibitory activity against BRD4, and high anti-proliferative potency against human monocyte lymphoma cell line THP-1. Especially, compound 21 (BRD4 BD1, IC50 = 41.8 nM) achieved a submicromolar IC50 value of 0.81 μM in inhibiting the growth of THP-1 cell line, and was 4 times more potent than compound 6. Moreover, the mechanism study established that 21 could effectively induce the degradation of BRD4 protein and suppression of c-Myc. All of these results suggested that 21 was an efficacious BRD4 degrader for further investigation.
Zhang, Fangqing,Wu, Zhenwei,Chen, Pan,Zhang, Jian,Wang, Tao,Zhou, Jinpei,Zhang, Huibin
(2019/12/24)

Deoxygenative Arylation of Carboxylic Acids by Aryl Migration
An unprecedented deoxygenative arylation of aromatic carboxylic acids has been achieved, allowing the construction of an enhanced library of unsymmetrical diaryl ketones. The synergistic photoredox catalysis and phosphoranyl radical chemistry allows for precise cleavage of a stronger C?O bond and formation of a weaker C?C bond by 1,5-aryl migration under mild reaction conditions. This new protocol is independent of substrate redox-potential, electronic, and substituent effects. It affords a general and promising access to 60 examples of synthetically versatile o-amino and o-hydroxy diaryl ketones under redox-neutral conditions. Furthermore, it also brings one concise route to the total synthesis of quinolone alkaloid, (±)-yaequinolone A2, and a viridicatin derivative in satisfying yields.
Ruzi, Rehanguli,Ma, Junyang,Yuan, Xiang-Ai,Wang, Wenliang,Wang, Shanshan,Zhang, Muliang,Dai, Jie,Xie, Jin,Zhu, Chengjian
p. 12724 - 12729
(2019/11/05)

Palladium-Catalyzed Cascade Reductive and Carbonylative Cyclization of Ortho-Iodo-Tethered Methylenecyclopropanes (MCPs) Using N-Formylsaccharin as CO Source
A palladium-catalyzed reductive and carbonylative cyclization of ortho-iodo-tethered methylenecyclopropanes (MCPs) using N-formylsaccharin as CO source has been developed, affording the desired indanone derivatives in moderate to good yields with high regio- and stereoselectivity and good functional group compatibility.
Fan, Xing,Shi, Min,Wei, Yin
supporting information
p. 5677 - 5683
(2019/11/16)

Retro-1-oligonucleotide conjugates. Synthesis and biological evaluation
Addition of small molecule Retro-1 has been described to enhance antisense and splice switching oligonucleotides. With the aim of assessing the effect of covalently linking Retro-1 to the biologically active oligonucleotide, three different derivatives of Retro-1 were prepared that incorporated a phosphoramidite group, a thiol or a 1,3-diene, respectively. Retro-1–oligonucleotide conjugates were assembled both on-resin (coupling of the phosphoramidite) and from reactions in solution (Michael-type thiol-maleimide reaction and Diels-Alder cycloaddition). Splice switching assays with the resulting conjugates showed that they were active but that they provided little advantage over the unconjugated oligonucleotide in the well-known HeLa Luc705 reporter system.
Agramunt, Jordi,Pedroso, Enrique,Kreda, Silvia M.,Juliano, Rudolph L.,Grandas, Anna
(2019/02/10)

Cascade Amination/Cyclization/Aromatization Process for the Rapid Construction of [2,3-c]Dihydrocarbazoles and [2,3-c]Carbazoles
An intramolecular cascade amination/cyclization/aromatization reaction of functionalized alkylidenecyclopropanes has been developed in the presence of silver acetate, affording a variety of [2,3-c]dihydrocarbazoles and [2,3-c]carbazoles in moderate to excellent yields. The mechanistic investigations revealed that this cascade reaction proceeds through a radical initiated process. Moreover, further transformations for the synthesis of eustifoline-D and an OLED exhibit a potential synthetic utility of this method.
Fan, Xing,Yu, Liu-Zhu,Wei, Yin,Shi, Min
p. 4476 - 4479
(2017/09/11)

Single-Step Synthesis of 3-Iodoquinolines from 2-Aminophenyl Ketones through a Regioselective (6-endo-dig) Electrophilic Cyclization
A highly facile single-step synthetic approach to 3-iodoquinolines has been developed for the first time from readily available 2-aminobenzophenones and terminal alkynes. The reaction involves the nucleophilic addition of terminal alkynes to 2-aminobenzophenones followed by a regioselective iodocyclization (6-endo-dig) to furnish 2,4-disubstituted 3-iodoquinolines in high yields. In general, 2,4-diaryl-substituted products were isolated without the need for column chromatography.
Yaragorla, Srinivasarao,Pareek, Abhishek,Dada, Ravikrishna,Saini, Pyare Lal
supporting information
p. 4600 - 4608
(2017/08/30)

Bromodomain protein divalent inhibitors and preparation method and applications thereof
The invention relates to divalent dihydro quinazolinone compounds shown as a general formula (I) and pharmaceutically acceptable salts, hydrates or prodrugs thereof. The compounds have a good antitumor activity when serving as bromodomain protein divalent inhibitors. The invention also relates to a preparation method of the compounds, medicinal preparations containing the compounds and applications of the compounds and the medicinal compositions to treating tumors.
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Paragraph 0107-0109

(2017/09/02)

Novel heterocyclic compounds and organic light-emitting diode including the same
The present invention relates to an organic heterocyclic compound represented by any one of chemical formulas [A], [B] and [C], and an organic light-emitting diode comprising the same. The chemical formulas [A], [B] and [C] are each the same as defined in the detailed description of the invention. An objective of the present invention is to provide a novel heterocyclic compound having a long lifetime and low voltage driving characteristics and having excellent luminous efficiency.COPYRIGHT KIPO 2018
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Paragraph 0395-0401

(2018/02/28)

Chemoselective double annulation of two different isocyanides: Rapid access to trifluoromethylated indole-fused heterocycles
An unprecedented chemoselective double annulation of α-trifluoromethylated isocyanides with o-acylaryl isocyanides has been developed. This new reaction provides a rapid, efficient, and complete atom-economic strategy for the synthesis of trifluoromethylated oxadiazino[3,2-α]indoles in a single operation from readily available starting materials. Isocyanide insertion into C=O double bonds is disclosed for the first time as indicated by the results of 18O-labeling experiment. A mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides, followed by indole-2,3-epoxide formation and rearrangement.
Gao, Yuelei,Hu, Zhongyan,Dong, Jinhuan,Liu, Jun,Xu, Xianxiu
supporting information
p. 5292 - 5295
(2017/11/06)

Chemoselective generation of acyl phosphates, acylium ion equivalents, from carboxylic acids and an organophosphate ester in the presence of a Br?nsted acid
We describe the chemoselective conversion of carboxylic acids to functional aromatic ketones promoted by a tailored organophosphate ester in the presence of a Br?nsted acid. The protonated phosphate ester reacts with the carboxylic acid to form acyl phosphate, which reacts with benzenes to give aromatic ketones, probably through the acylium ion or its equivalent. The reaction time is short even at room temperature, and the reaction is compatible with various other functional groups, including amines, olefins, esters, amides and nitriles.
Sumita, Akinari,Otani, Yuko,Ohwada, Tomohiko
supporting information
p. 1482 - 1485
(2017/02/05)

COMPOUNDS WHICH HAVE A PROTECTIVE ACTIVITY WITH RESPECT TO THE ACTION OF TOXINS AND OF VIRUSES WITH AN INTRACELLULAR MODE OF ACTION
The subject matter of the present invention is novel families of compounds which are aromatic amine, imine, aminoadamantane and benzodiazepine derivatives, medicaments comprising same and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as, for example, ricin, and of viruses that use the internalization pathway for infecting cells.
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Paragraph 0339

(2016/04/19)

Preparation method of triazole derivatives and application of triazole derivatives as drugs
The invention relates to a preparation method of triazole derivatives and medical application of the triazole derivatives. The invention particularly relates to triazole derivatives disclosed as general formula (I) and pharmaceutical salts thereof or a pharmaceutical composition containing the triazole derivatives or pharmaceutical salts thereof, and a preparation method thereof, and further relates to application of the triazole derivatives and pharmaceutical salts thereof or pharmaceutical composition containing the triazole derivatives and pharmaceutical salts thereof as a BET inhibitor in treating multiple tumors.
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Paragraph 0064; 0065; 0066; 0067; 0068; 0069

(2016/10/17)

Synthesis, Chiral Separation, Absolute Configuration Assignment, and Biological Activity of Enantiomers of Retro-1 as Potent Inhibitors of Shiga Toxin
The Shiga toxin (Stx) family is composed of related protein toxins produced by the bacteria Shigella dysenteriae and certain pathogenic strains of E.coli. No effective therapies for Stx intoxication have been developed yet. However, inhibitors that act on the intracellular trafficking of these toxins may provide new options for the development of therapeutic strategies. This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of Retro-1, a compound active against Stx and other such protein toxins. Retro-1 works by inhibiting retrograde transport of these toxins inside cells. In vitro experiments proved that the configuration of the stereocenter at position 5 is not crucial for the activity of this compound. X-ray diffraction data revealed (S)-Retro-1 to be slightly more active than (R)-Retro-1.
Abdelkafi, Hajer,Michau, Aurélien,Clerget, Alexandra,Buisson, David-Alexandre,Johannes, Ludger,Gillet, Daniel,Barbier, Julien,Cintrat, Jean-Christophe
supporting information
p. 1153 - 1156
(2015/07/07)

Palladium-catalyzed direct addition of 2-Aminobenzonitriles to sodium arylsulfinates: Synthesis of o-Aminobenzophenones
The first example of the palladium-catalyzed synthesis of o-Aminobenzophenones in moderate to excellent yields via a direct addition of sodium arylsulfinates to unprotected 2-Aminobenzonitriles was reported. A plausible mechanism for the formation of o-Aminobenzophenones involving desulfination and addition reactions was proposed. The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, the method represents a convenient and practical strategy for synthesis of o-Aminobenzophenones.
Chen, Jiuxi,Li, Jianjun,Su, Weike
p. 6439 - 6449
(2014/06/10)

DIHYDROQUINAZOLINONE ANALOGUES AS BRD4 INHIBITORS
The present invention encompasses compounds of general formula (I) wherein the groups R1 to R4 and A1 to A5 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
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(2014/10/15)

DIHYDROQUINAZOLINONE ANALOGUES
The present invention encompasses compounds of general formula (I) wherein the groups R1 to R4 and A1 to A5 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.
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Paragraph 0141-0143

(2014/10/16)

METHODS AND COMPOSITIONS FOR INHIBITION OF BROMODOMAIN-CONTAINING PROTEINS
The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.
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(2014/10/15)

Palladium-catalyzed direct addition of arylboronic acids to 2-aminobenzonitrile derivatives: Synthesis, biological evaluation and in silico analysis of 2-aminobenzophenones, 7-benzoyl-2-oxoindolines, and 7-benzoylindoles
A palladium-catalyzed direct addition of arylboronic acids to unprotected 2-aminobenzonitriles has been developed, leading to a wide range of 2-aminobenzophenones with moderate to excellent yields. The transformation has broad scope and high functional group tolerance. Moreover, 2-oxoindoline-7-carbonitrile and indole-7-carbonitrile were applicable to this process for the construction of 7-benzoyl-2-oxoindolines and 7-benzoylindoles, respectively. Among the compounds examined, compound 4e possessed the most potent anticancer activity against H446 and HGC-27 in vitro, with IC50 values of 0.02 μmol L-1 and 0.09 μmol L-1, respectively, while compound 4a showed the best potent anticancer activity against SGC-7901 with an IC50 value of 0.01 μmol L-1. Furthermore, we also performed in silico molecular docking calculations to investigate the interaction mode and binding affinity between the examined compounds and their tubulin target. This journal is
Chen, Jiuxi,Ye, Leping,Su, Weike
supporting information
p. 8204 - 8211
(2015/01/08)

Discovery of potent, selective, and orally bioavailable quinoline-based dipeptidyl peptidase IV inhibitors targeting Lys554
Dipeptidyl peptidase IV (DPP-4) inhibition is a validated therapeutic option for type 2 diabetes, exhibiting multiple antidiabetic effects with little or no risk of hypoglycemia. In our studies involving non-covalent DPP-4 inhibitors, a novel series of quinoline-based inhibitors were designed based on the co-crystal structure of isoquinolone 2 in complex with DPP-4 to target the side chain of Lys554. Synthesis and evaluation of designed compounds revealed 1-[3-(aminomethyl)-4-(4-methylphenyl)-2-(2-methylpropyl)quinolin-6-yl] piperazine-2,5-dione (1) as a potent, selective, and orally active DPP-4 inhibitor (IC50 = 1.3 nM) with long-lasting ex vivo activity in dogs and excellent antihyperglycemic effects in rats. A docking study of compound 1 revealed a hydrogen-bonding interaction with the side chain of Lys554, suggesting this residue as a potential target site useful for enhancing DPP-4 inhibition.
Maezaki, Hironobu,Banno, Yoshihiro,Miyamoto, Yasufumi,Moritou, Yuusuke,Asakawa, Tomoko,Kataoka, Osamu,Takeuchi, Koji,Suzuki, Nobuhiro,Ikedo, Koji,Kosaka, Takuo,Sasaki, Masako,Tsubotani, Shigetoshi,Tani, Akiyoshi,Funami, Miyuki,Yamamoto, Yoshio,Tawada, Michiko,Aertgeerts, Kathleen,Yano, Jason,Oi, Satoru
p. 4482 - 4498
(2011/09/19)

Metal-free intramolecular oxidative decarboxylative amination of primary α-amino acids with product selectivity
A novel metal-free intramolecular oxidative decarboxylative coupling of primary α-amino acids with 2-aminobenzoketones under mild and neutral conditions was developed. Different quinazolines can be selectively obtained by various oxidants.
Yan, Yizhe,Wang, Zhiyong
supporting information; experimental part
p. 9513 - 9515
(2011/10/01)

Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: Discovery, synthesis, and characterization of their binding mode by protein crystallography
Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei, the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution complex between a noncovalent ligand and this enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes a conformational change to create a new subpocket which is occupied by an aryl group on the ligand. Therefore, the inhibitor, in effect, creates its own small binding pocket within the otherwise large, solvent exposed active site. The TryR-ligand structure was subsequently used to guide the synthesis of inhibitors, including analogues that challenged the induced subpocket. This resulted in the development of inhibitors with improved potency against both TryR and T. brucei parasites in a whole cell assay.
Patterson, Stephen,Alphey, Magnus S.,Jones, Deuan C.,Shanks, Emma J.,Street, Ian P.,Frearson, Julie A.,Wyatt, Paul G.,Gilbert, Ian H.,Fairlamb, Alan H.
supporting information; experimental part
p. 6514 - 6530
(2011/12/02)

A simple and efficient approach to the synthesis of 2-phenylquinazolines via sp3 C-H functionalization
(Figure presented) A facile and novel approach to the synthesis of 2-phenylquinazolines was developed via a tandem reaction following sp 3 C-H functionalization. Twenty-five examples of 2-phenylquinazolines were obtained from easily available 2-aminobenzophenones and benzylic amines with good to excellent yields.
Zhang, Jintang,Zhu, Dapeng,Yu, Chenmin,Wan, Changfeng,Wang, Zhiyong
supporting information; experimental part
p. 2841 - 2843
(2010/09/04)

A novel and efficient methodology for the construction of quinazolines based on supported copper oxide nanoparticles
A series of quinazolines were synthesized from 2-aminobenzophenones and benzylic amines in good to excellent yields by employing a new heterogeneous catalyst based on the copper oxide nanoparticles supported on kaolin.
Zhang, Jintang,Yu, Chenmin,Wang, Sujing,Wan, Changfeng,Wang, Zhiyong
supporting information; experimental part
p. 5244 - 5246
(2010/09/05)

QUINOLINE, NAPHTHALENE AND CONFORMATIONALLY CONSTRAINED QUINOLINE OR NAPHTHALENE DERIVATES AS ANTI-MYCOBACTERIAL AGENTS
The invention relates to a compound of general formula I, II, III, IV V VI, VII, VIII, IX, X or a tautomer and the stereochemically isomeric forms thereof or pharmaceutically acceptable salts thereof, a N-oxide form thereof or a pro-drug thereof. The compound is usable as a medicament for the treatment of mycobacterial disease
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(2009/08/16)

Bakers' yeast-catalyzed reductive cleavage of 3-aryl-2,1-benzisoxazoles and its quaternary salts: An efficient green synthesis of 2-aminobenzophenones
3-Aryl-2,1-benzisoxazoles and its salts underwent reductive cleavage of the N-O bond leading to 2-aminobenzophenones with bakers' yeast under non-fermenting conditions in aqueous media. The procedure gives excellent yields of 2-alkylamino- and 2-aminobenzophenones.
Lekhok, Kushal C.,Prajapati, Dipak,Boruah, Ramesh C.,Mazumder, Sharbani,Borah, Tarun C.
experimental part
p. 1183 - 1187
(2011/10/01)

Rational modification of a candidate cancer drug for use against chagas disease
Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14a-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.
Kraus, James M.,Verlinde, Christophe L. M. J.,Karimi, Mandana,Lepesheva, Galina I.,Gelb, Michael H.,Buckner, Frederick S.
experimental part
p. 1639 - 1647
(2010/01/07)

Simple catalyst-free regio- and chemoselective monobromination of aromatics using NBS in polyethylene glycol
NBS in polyethylene glycol has been efficiently utilized for regio- and chemoselective bromination of activated aromatics at room temperature to form the corresponding bromo products in excellent yields. Copyright Taylor & Francis Group, LLC.
Venkateswarlu, Katta,Suneel, Kanaparthy,Das, Biswanath,Reddy, Kuravallapalli Nagabhushana,Reddy, Thummala Sreenivasulu
experimental part
p. 215 - 219
(2009/04/07)

New vistas in quinoline synthesis
The gold-catalyzed Friedlander reaction was applied to the condensation of 2-aminoarylketones with β-keto-esters, β-diketones, β-keto-amides, and β-keto-sulfones to afford a diverse range of 2,3,4-trisubstituted quinolines in 3-82% yield. The seven-membered rings 1,3-cycloheptadione and azepane-2,4-dione reacted smoothly in 75% yield. An alternative procedure for the synthesis of 3-(methanesulfonyl)quinolines was developed and provided an entry into late stage manipulation of the 4-position of these quinolines. The requisite 2-aminoarylketones for the Friedlander reaction were prepared in one pot by modified Sugasawa reaction using gallium(III) chloride and boron(III) chloride in 12-54% yield.
Atechian, Sarkis,Nock, Nadine,Norcross, Roger D.,Ratni, Hassen,Thomas, Andrew W.,Verron, Julien,Masciadri, Raffaello
p. 2811 - 2823
(2007/10/03)

Synthesis and photophysics of new donor-acceptor copolymers based on fluorene and phenylquinolines
The synthesis and photophysics of two new donor-acceptor conjugated A-B type copolymers based on conjugated 2,6-disubstitued-4-phenyl-quinoline and 2-substitued-4-phenyl-quinoline, and 9,9-dialkyl-fluorene linked through the 1,4 and 1,3,5 phenyl rings via the Friedlnder condensation and Suzuki coupling reaction are presented. The band gap energy of the polymers 1 and 2 measured from the thin films were 430nm and 380nm corresponding to 2.88eV and 3.26eV, respectively. The photoluminescence (PL) spectra of the thin films of the polymers 1 and 2 showed maximum peaks at 427 and 397nm corresponding to the deep blue and UV ranges respectively. The red shift of the polymer 1 relative to the polymer 2 can be accounted for by the increased conjugation length because the quinoline unit is oriented to include the phenyl ring in the backbone of polymer 1. Both polymers have similar trends of irreversible oxidation. The ionization energy of polymers 1 and 2 were measured by cyclic voltammetry (CV) and were found to be 5.60 and 5.65eV, respectively.
Siemssen, Brent,Kim, Ki-Won,Kim, Min-Sook,Kim, Byung-Soo,Cho, Seong-Jin,Park, Dong-Kyu,Woo, Hyung-Suk,Kwon, Tae-Woo
p. 159 - 167
(2007/10/03)

Quinolines as allosteric enhancers of the GABAB receptors
The present invention relates to compounds of formula I wherein R1 to R6 are as described herein, which compounds are active at the GABAB receptor and can be used for the preparation of medicaments useful in the treatment of CNS disorders comprising anxiety and depression.
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Page/Page column 11

(2008/06/13)

An efficient, rapid and regioselective nuclear bromination of aromatics and heteroaromatics with NBS using sulfonic-acid-functionalized silica as a heterogeneous recyclable catalyst
A simple, efficient and rapid method has been developed for high-yielding regioselective nuclear monobromination of aromatic and heteroaromatic compounds using NBS in the presence of sulfonic-acid-functionalized silica at room temperature. The catalyst works under heterogeneous conditions and can be recycled.
Das, Biswanath,Venkateswarlu, Katta,Krishnaiah, Maddeboina,Holla, Harish
p. 8693 - 8697
(2007/10/03)

Preparation of 2-arninpbenzophenones and polysubstituted quinolines through Sml2 promoted reductive cleavage of 3-aryl-2,1-benzisoxazoles
Promoted by SmI2, 3-aryl-2,1-benzisoxazoles underwent reductive cleavage of the N - O bond leading to 2-aminobenzophenones in high yields upon protonation. Otherwise, if ketones with active methylene group were added to the reaction mixture prior to protonation, the desired poly substituted quinolines could be obtained under mild conditions in a one-pot manner.
Fan, Xuesen,Zhang, Xinying,Zhang, Yongmin
p. 637 - 643
(2007/10/03)

QUINOLINONE DERIVATIVES AS INHIBITORS OF C-FMS KINASE
The invention is directed to compounds of Formulae I and II: (I) (II) wherein R1, R2, R3, R5, R6, Y1, Y2, Y3, Y4 and X are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.
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Page/Page column 58

(2010/02/10)

Bis-aryl sulfonamides
Compounds are provided that act as potent antagonists of chemokine receptors. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of chemokine receptor-mediated diseases, and as controls in assays for the identification of chemokine antagonists.
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(2008/06/13)

Sulfonyl-containing 2,3-diarylindole compounds, methods for making same, and methods of use thereof
The present invention relates to sulfonyl-containing 2,3-diarylindole, especially to new compounds of general Formula, to a preparation method for their preparation, to pharmaceutical compositions containing said compound, and to the medical use thereof in the treatment of diseases relating to the inhibition of cyclooxygenase-2 (COX-2).
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Page/Page column 15

(2010/02/06)

Synthesis and biological evaluation of substituted 2-sulfonyl-phenyl-3-phenyl-indoles: A new series of selective COX-2 inhibitors
A new series of substituted 2-sulfonyphenyl-3-phenyl-indole derivatives were synthesized and evaluated for their ability to inhibit COX-2 and COX-1enzymes. Most of the compounds synthesized were found to be highly potent and selective inhibitors of COX-2. This work led to the discovery of 2-aminosulfonylphenyl-3-phenyl-indole 5a which possesses higher activity and selectivity for COX-2 than Celecoxib both in vitro and in vivo.
Hu, Wenhui,Guo, Zongru,Chu, Fengming,Bai, Aiping,Yi, Xiang,Cheng, Guifang,Li, Jing
p. 1153 - 1160
(2007/10/03)

Chemical conversions of 8,18-disubstituted derivatives of 6,16-diphenyl-1,2,3,11,12,13-hexahydrodibenzo[g,o]-4,14-dioxa-1,5,11, 15-tetraazacyclohexadecine-2,12-diones
The chemical properties of 8,18-disubstituted 6,16-diphenyl-1,2,3,11,12,13-tetrahydrodibenzo[g,o]-4,14-dioxa-1,5,11, 15-tetraazahexadecine-2,12-diones have been studied, including their interaction with N-nucleophiles (hydroxylamine, hydrazine, semicarbazide, and thiosemicarbazide), acidic and alkaline hydrolysis, and methylation. A hypothesis has been made from analysis of the mass spectral data of the thiosemicarbazide on the preferred existence of 6-substituted 4-phenylquinazoline-2-carbaldehydes in the gas phase as the linear tautomer.
Kulikov,Pavlovsky,Mazepa,Andronati
p. 485 - 492
(2007/10/03)

CCR9 INHIBITORS AND METHODS OF USE THEREOF
The invention relates to compounds represented by Structural Formula I, which can bind to CCR9 receptors and block the binding of a ligand (e.g., TECK) to the receptors. The invention also relates to a method of inhibiting a function of CCR9, and to the use compounds represented by Structural Formula I in research, therapeutic, prophylactic and diagnostic methods.
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Page 56-57

(2008/06/13)

Cyclic regimens using quinazolinone and benzoxazine derivatives
This invention relates to cyclic combination therapies utilizing, in combination with progestins, estrogens, or both, compounds which are progesterone receptor antagonists of the general structure: wherein: R1and R2are H, CORA, or NRBCORA, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or heterocyclic; or R1and R2fuse to form 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RAis H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RBis H or alkyl; R3is H, OH, NH2, CORCor alkyl, alkenyl, or alkynyl; RCis H, alkyl, aryl, alkoxy, or aminoalkyl; R4is H, halogen, CN, NO2, alkyl, alkynyl, alkoxy, amino or aminoalkyl; R5is benzene or 5- or 6-membered heterocyclic ring; R6is H or alkyl; G1is O, NR7, or CR7R8; G2is CO or CR7R8; provided that when G1is O, G2is CR7R8, and G1and G2cannot both be CR7R8; R7and R8are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof. These methods may be used for contraception or treatment and/or prevention of secondary amenorrhea, dysfunctional bleeding, uterine leiomyomata, endometriosis; polycystic ovary syndrome, carcinomas and adenocarcinomas of the endometrium, ovary, breast, colon, prostate, or minimization of side effects or cyclic menstrual bleeding. Additional uses of the invention include stimulation of food intake.
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(2008/06/13)

Quinazolinone and benzoxazine derivatives as progesterone receptor modulators
This invention provides compounds which are agonists and antagonists of the progesterone receptor having the general structure: wherein: R1and R2are independently selected from H, CORA, or NRBCORA, or optionally substituted alkyl, alkenyl, alknyl, cycloalklyl, aryl, or heterocyclic moieties; or R1and R2are fused to form: 3 to 8 membered spirocyclic alkyl, alkenyl or heterocyclic rings; RAis H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl groups; RBis H, C1to C3alkyl, or substituted C1to C3alkyl; R3is H, OH, NH2, CORCor optionally substituted alkyl, alkenyl, or alkynyl; RCis H or optionally substituted alkyl, aryl, alkoxy, or aminoalkyl; R4is H, halogen, CN, NO2, or optionally substituted alkyl, alkynyl, alkoxy, amino or aminoalkyl; R5is an optionally substituted benzene or five or six membered ring with 1, 2, or 3 heteroatoms selected from O, S, SO, SO2or NR6; R6is H or C1to C3alkyl; G1is O, NR7, or CR7R8; G2is CO, CS, or CR7R8; provided that when G1is O, G2is CR7R8, and G1and G2cannot both be CR7R8; R7and R8are H or an optionally substituted alkyl, aryl, or heterocyclic moiety; or pharmaceutically acceptable salt thereof, and methods using these compounds in mammals as agonists or antagonists of the progesterone receptor.
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Example 17

(2010/11/29)

Water promoted iodotrimethyl silane reactions: Reductive cleavage of isoxazolidines and 2,1-benzisoxazoles to γ-amino alcohols and o-aminobenzophenones
Water promoted iodotrimethyl silane [ITMS] reductively cleaved isoxazolidines and 2,1-benzisoxazoles to γ-amino alcohols and o-aminobenzophenones respectively at shorter times and in higher yields at room temperature.
Boruah, Monalisa,Konwar, Dilip
p. 601 - 603
(2007/10/03)

SmI2-mediated facile one-pot preparation of 2,4-diarylquinolines from 3-aryl-2,1-benzisoxazoles
On treatment with SmI2, 3-aryl-2,1-benzisoxazoles undergo reductive cleavage of the N-O bond leading to 2-aminobenzophenones in high yields upon protonation. If aryl methyl ketones are added to the reaction mixture prior to protonation, the desired 2,4-diarylquinolines can be obtained in moderate yields under mild conditions.
Fan, Xuesen,Zhang, Yongmin
p. 7001 - 7003
(2007/10/03)