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Design, synthesis and evaluation of novel indole-2-carboxamides for growth inhibition of Mycobacterium tuberculosis and paediatric brain tumour cells
The omnipresent threat of tuberculosis (TB) and the scant treatment options thereof necessitate the development of new antitubercular agents, preferably working via a novel mechanism of action distinct from the current drugs. Various studies identified th
Alsayed, Shahinda S. R.,Lun, Shichun,Bailey, Anders W.,Suri, Amreena,Huang, Chiang-Ching,Mocerino, Mauro,Payne, Alan,Sredni, Simone Treiger,Bishai, William R.,Gunosewoyo, Hendra
p. 15497 - 15511
(2021)
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Liquid-phase synthesis of 2,3-dihydro-4-pyridones: One-pot three-component aza Diels-Alder reaction of Danishefsky's diene with aldehydes and PEG-supported amine
An efficient liquid-phase synthesis technique for the construction of 2,3-dihydro-4-pyridones on soluble polymer support has been developed, which utilized one-pot reaction of Danishefsky's diene with aldehydes and polymer-supported amine.
Guo, Hongchao,Ding, Kuiling
p. 7103 - 7106
(2003)
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Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
supporting information
p. 3791 - 3804
(2021/11/04)

Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase
To tackle leishmaniasis, search for efficient therapeutic drug targets should be pursued. Dihydrofolate reductase (DHFR) is considered as a key target for the treatment of leishmaniasis. In current study, we are interested in the design and synthesis of selective antifolates targeting DHFR from L. major. We focused on the development of new antifolates based on 3,4-dihydropyrimidine-2-one and 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine motif. Structure activity relationship (SAR) studies were performed on 4-phenyl ring of dihydropyrimidine (26–30) template. While for 5-(3,5-dimethoxybenzyl)pyrimidine-2,4-diamine, the impact of different amino acids (valine, tryptophan, phenylalanine, and glutamic acid) and two carbon linkers were explored (52–59). The synthesized compounds were assayed against LmDHFR. Compound 59 with the IC50 value of 0.10 μM appeared as potent inhibitors of L. major. Selectivity for parasite DHFR over human DHFR was also determined. Derivatives 55–59 demonstrated excellent selectivity for LmDHFR. Highest selectivity for LmDHFR was shown by compounds 56 (SI = 84.5) and 58 (SI = 87.5). Compounds Antileishmanial activity against L. major and L. donovani promastigotes was also performed. To explore the interaction pattern of the synthesized compounds with biological macromolecules, the docking studies were carried out against homology modelled LmDHFR and hDHFR targets.
Bibi, Maria,Qureshi, Naveeda Akhter,Sadiq, Abdul,Farooq, Umar,Hassan, Abbas,Shaheen, Nargis,Asghar, Irfa,Umer, Duaa,Ullah, Azmat,Khan, Farhan A.,Salman, Muhammad,Bibi, Ahtaram,Rashid, Umer
(2020/11/16)

Antiglioma Activity of Aryl and Amido-Aryl Acetamidine Derivatives Targeting iNOS: Synthesis and Biological Evaluation
Nitric oxide is an important inflammation mediator with a recognized role in the development of different cancers. Gliomas are primary tumors of the central nervous system with poor prognosis, and the expression of the inducible nitric oxide synthase correlates with the degree of malignancy, changes in vascular reactivity, and neo-angiogenesis. Therefore, targeting the nitric oxide biosynthesis appears as a potential strategy to impair glioma progression. In the present work a set of aryl and amido-aryl acetamidine derivatives were synthesized to obtain new potent and selective inducible nitric oxide synthase inhibitors with improved physicochemical parameters with respect to the previously published molecules. Compound 17 emerged as the most promising inhibitor and was evaluated on C6 rat glioma cell line, showing antiproliferative effects and high selectivity over astrocytes.
Maccallini, Cristina,Arias, Fabio,Gallorini, Marialucia,Amoia, Pasquale,Ammazzalorso, Alessandra,De Filippis, Barbara,Fantacuzzi, Marialuigia,Giampietro, Letizia,Cataldi, Amelia,Camacho, María Encarnación,Amoroso, Rosa
supporting information
p. 1470 - 1475
(2020/07/31)

Highly efficient chemoselective N-tert butoxycarbonylation of aliphatic/aromatic/heterocyclic amines using diphenylglycoluril as organocatalyst
An efficient approach for the Chemoselective N-tert-butoxycarbonylation of a variety of amines using diphenylglycoluril as organocatalyst has been described. For the first time, a plausible mechanism for the N-tert-butoxycarbonylation has been proposed using density functional theory (DFT) calculations supported by NMR studies. The reusability of the organocatalyst and observation of the desired N-Boc protected amines being formed without the formation of side products like urea, oxazolidinone, isocyanate, and N, N-di-Boc derivatives makes the present protocol desirable.
Awasthi, Amardeep,Mukherjee, Anagh,Singh, Mandeep,Rathee, Garima,Vanka, Kumar,Chandra, Ramesh
(2020/05/14)

Benzothiazole compounds and medical application
The invention discloses a benzothiazole compound and medical application thereof, particularly relates to a benzothiazole compound shown as a formula I and medical application thereof, and especiallyrelates to application of the benzothiazole compound serving as a USP7C-terminal structural domain regulating agent in medicines for preventing and treating myelodysplastic syndromes and malignant tumors. The benzothiazole compound shown in the formula I or the pharmaceutically acceptable salt or solvate of the benzothiazole compound has strong binding force with USP7C-terminal protein; and the protein level of DNMT1 in tumor cells can be reduced, so that the compound can be applied to the preparation of USP7 regulators, has a remarkable anti-tumor cell proliferation effect, and can be used for preparing medicines for preventing or treating myelodysplastic syndrome and malignant tumors.
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Paragraph 0095; 0099-0100

(2020/10/21)

INHIBITORS OF CYCLIN-DEPENDENT KINASES
Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00443

(2020/01/24)

Aqueous Flow Hydroxycarbonylation of Aryl Halides Catalyzed by an Amphiphilic Polymer-Supported Palladium-Diphenylphosphine Catalyst
An aqueous continuous-flow reaction system is developed for the palladium-catalyzed hydroxycarbonylation of aryl halides. Flow hydroxycarbonylation of aryl halides in aqueous solution proceeds efficiently in a flow reactor containing a palladium-diphenylphosphine complex immobilized on an amphiphilic polystyrene-poly(ethylene glycol) resin to give the corresponding benzoic acids in excellent yields.
Osako, Takao,Kaiser, Reinhard,Torii, Kaoru,Uozumi, Yasuhiro
p. 961 - 966
(2019/05/10)

From alkylarenes to anilines via site-directed carbon–carbon amination
Anilines are fundamental motifs in various chemical contexts, and are widely used in the industrial production of fine chemicals, polymers, agrochemicals and pharmaceuticals. A recent development for the synthesis of anilines uses the primary amination of C–H bonds in electron-rich arenes. However, there are limitations to this strategy: the amination of electron-deficient arenes remains a challenging task and the amination of electron-rich arenes has a limited control over regioselectivity—the formation of meta-aminated products is especially difficult. Here we report a site-directed C–C bond primary amination of simple and readily available alkylarenes or benzyl alcohols for the direct and efficient preparation of anilines. This chemistry involves a novel C–C bond transformation and offers a versatile protocol for the synthesis of substituted anilines. The use of O2 as an environmentally benign oxidant is demonstrated, and studies on model compounds suggest that this method may also be used for the depolymerization of lignin.
Liu, Jianzhong,Qiu, Xu,Huang, Xiaoqiang,Luo, Xiao,Zhang, Cheng,Wei, Jialiang,Pan, Jun,Liang, Yujie,Zhu, Yuchao,Qin, Qixue,Song, Song,Jiao, Ning
p. 71 - 77
(2018/11/10)

Polyvalent Diazonium Polymers Provide Efficient Protection of Oncolytic Adenovirus Enadenotucirev from Neutralizing Antibodies while Maintaining Biological Activity in Vitro and in Vivo
Oncolytic viruses offer many advantages for cancer therapy when administered directly to confined solid tumors. However, the systemic delivery of these viruses is problematic because of the host immune response, undesired interactions with blood components, and inherent targeting to the liver. Efficacy of systemically administered viruses has been improved by masking viral surface proteins with polymeric materials resulting in modulation of viral pharmacokinetic profile and accumulation in tumors in vivo. Here we describe a new class of polyvalent reactive polymer based on poly(N-(2-hydroxypropyl)methacrylamide) (polyHPMA) with diazonium reactive groups and their application in the modification of the chimeric group B oncolytic virus enadenotucirev (EnAd). A series of six copolymers with different chain lengths and density of reactive groups was synthesized and used to coat EnAd. Polymer coating was found to be extremely efficient with concentrations as low as 1 mg/mL resulting in complete (>99%) ablation of neutralizing antibody binding. Coating efficiency was found to be dependent on both chain length and reactive group density. Coated viruses were found to have reduced transfection activity both in vitro and in vivo, with greater protection against neutralizing antibodies resulting in lower transgene production. However, in the presence of neutralizing antibodies, some in vivo transgene expression was maintained for coated virus compared to the uncoated control. The decrease in transgene expression was found not to be solely due to lower cellular uptake but due to reduced unpackaging of the virus within the cells and reduced replication, indicating that the polymer coating does not cause permanent inactivation of the virus. These data suggest that virus activity may be modulated by the appropriate design of coating polymers while retaining protection against neutralizing antibodies.
Francini, Nora,Cochrane, Daniel,Illingworth, Sam,Purdie, Laura,Mantovani, Giuseppe,Fisher, Kerry,Seymour, Leonard W.,Spain, Sebastian G.,Alexander, Cameron
p. 1244 - 1257
(2019/05/11)

Design and synthesis of selective CYP1B1 inhibitor via dearomatization of α-naphthoflavone
Selective cytochrome P450 (CYP) 1B1 inhibition has potential as an anticancer strategy that is unrepresented in the current clinical arena. For development of a selective inhibitor, we focused on the complexity caused by sp3-hybridized carbons and synthesized a series of benzo[h]chromone derivatives linked to a non-aromatic B-ring using α-naphthoflavone (ANF) as the lead compound. Ring structure comparison suggested compound 37 as a suitable cyclohexyl-core with improved solubility. Structural evolution of 37 produced the azide-containing cis-49a, which had good properties in three important respects: (1) selectivity for CYP1B1 over CYP1A1 and CYP1A2 (120-times and 150-times, respectively), (2) greater inhibitory potency of >2 times that of ANF, and (3) improved solubility. The corresponding aromatic B-ring compound 59a showed low selectivity and poor solubility. To elucidate the binding mode, we performed X-ray crystal structure analysis, which revealed the interaction mode and explained the subtype selectivity of cis-49a.
Kubo, Makoto,Yamamoto, Keiko,Itoh, Toshimasa
p. 285 - 304
(2019/01/04)

INHIBITORS OF CYCLIN-DEPENDENT KINASES
Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
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Paragraph 00352

(2019/11/19)

ARYL-BIPYRIDINE AMINE DERIVATIVES AS PHOSPHATIDYLINOSITOL PHOSPHATE KINASE INHIBITORS
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula (I): wherein A, X, Y, Z, Q, R1, R2, R3, R4, R5, and n are described herein.
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Paragraph 0691

(2019/07/13)

AMINOPYRIDINE DERIVATIVES AS PHOSPHATIDYLINOSITOL PHOSPHATE KINASE INHIBITORS
The invention relates to inhibitors of PI5P4K inhibitors useful in the treatment of cancers, neurodegenerative diseases, inflammatory disorders, and metabolic diseases, having the Formula: (I) where A, B, R1, X1, X2, and W are described herein.
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Paragraph 0667

(2019/07/13)

MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF
Selective mTOR inhibitors of formulas (I)-(III), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from abnormal cell growth, functions, or behaviors mediated by an mTOR kinase and/or one or more PI3K enzyme, are provided. Such diseases and disorder include cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
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(2018/04/11)

Visible-Light-Driven Carboxylation of Aryl Halides by the Combined Use of Palladium and Photoredox Catalysts
A highly useful, visible-light-driven carboxylation of aryl bromides and chlorides with CO2 was realized using a combination of Pd(OAc)2 as a carboxylation catalyst and Ir(ppy)2(dtbpy)(PF6) as a photoredox catalyst. This carboxylation reaction proceeded in high yields under 1 atm of CO2 with a variety of functionalized aryl bromides and chlorides without the necessity of using stoichiometric metallic reductants.
Shimomaki, Katsuya,Murata, Kei,Martin, Ruben,Iwasawa, Nobuharu
supporting information
p. 9467 - 9470
(2017/07/24)

Structural Optimization of 4-Chlorobenzoylpiperidine Derivatives for the Development of Potent, Reversible, and Selective Monoacylglycerol Lipase (MAGL) Inhibitors
Monoacylglycerol lipase (MAGL) inhibitors are considered potential therapeutic agents for a variety of pathological conditions, including several types of cancer. Many MAGL inhibitors are reported in literature; however, most of them showed an irreversible mechanism of action, which caused important side effects. The use of reversible MAGL inhibitors has been only partially investigated so far, mainly because of the lack of compounds with good MAGL reversible inhibition properties. In this study, starting from the (4-(4-chlorobenzoyl)piperidin-1-yl)(4-methoxyphenyl)methanone (CL6a) lead compound that showed a reversible mechanism of MAGL inhibition (Ki = 8.6 μM), we started its structural optimization and we developed a new potent and selective MAGL inhibitor (17b, Ki = 0.65 μM). Furthermore, modeling studies suggested that the binding interactions of this compound replace a structural water molecule reproducing its H-bonds in the MAGL binding site, thus identifying a new key anchoring point for the development of new MAGL inhibitors.
Granchi, Carlotta,Rizzolio, Flavio,Palazzolo, Stefano,Carmignani, Sara,MacChia, Marco,Saccomanni, Giuseppe,Manera, Clementina,Martinelli, Adriano,Minutolo, Filippo,Tuccinardi, Tiziano
p. 10299 - 10314
(2016/12/07)

Heterogenization of chiral mono oxazoline ligands by grafting onto mesoporous silica MCM-41 and their application in copper-catalyzed asymmetric allylic oxidation of cyclic olefins
A series of chiral 4-oxazolinylaniline ligands 8 were conveniently synthesized on a gram scale from inexpensive and commercially available 4-aminobenzoic acid in four steps. The obtained organic chiral ligands have been covalently grafted onto ordered mesoporous silicas MCM-41 and the resulting inorganic–organic hybrid materials have been characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA), powder X-ray diffraction, BET and BJH nitrogen adsorption–desorption methods, energy-dispersive X-ray spectroscopy (EDX), CHN analysis, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR). The catalytic and induced asymmetric effects of the chiral copper (I) complexes of these new chiral supported heterogeneous catalysts on the asymmetric allylic oxidation of cycloolefins were investigated under different conditions. Reactions using the catalyst exhibited moderate to good enantioselectivities, up to 80%, and good yields, up to 95% better than the corresponding homogeneous reaction. The catalyst could be recovered easily and reused five times without remarkable loss of reactivity, yield, or enantioselectivity. This is, to the best of our knowledge, the first heterogenization of chiral 4-oxazolinylaniline ligands on an inorganic (silica) surface and their application as a heterogeneous catalyst in the asymmetric Kharash–Sosnovsky reaction.
Samadi, Saadi,Jadidi, Khosrow,Khanmohammadi, Behnam,Tavakoli, Niloofar
p. 344 - 353
(2016/07/06)

CYSTOBACTAMIDES
The present invention provides cystobactamides of formula (I) and the use thereof for the treatment or prophylaxis of bacterial infections:
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Paragraph 0466; 0467; 0468; 0469; 0470; 0471; 0472

(2016/06/13)

OXAZOLIDINONE DERIVATIVES AS PPAR LIGANDS
The present invention relates to a family of differently substituted oxazolidinones and to the pharmaceutically acceptable salts, esters, prodrugs, tautomers, solvates and hydrates thereof, which show affinity for the alpha and gamma subtypes of the perox
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Paragraph 0148

(2016/06/28)

Aerobic flow oxidation of alcohols in water catalyzed by platinum nanoparticles dispersed in an amphiphilic polymer
We have developed a technique for the aqueous aerobic flow oxidation of alcohols in a continuous-flow reactor containing platinum nanoparticles dispersed on an amphiphilic polystyrene-poly(ethylene glycol) resin (ARP-Pt). Various primary and secondary alcohols including aliphatic, aromatic and heteroaromatic alcohols were efficiently oxidized within 73 seconds in a flowing aqueous system at 100-120°C under 40-70 bar of the system pressure to give the corresponding carboxylic acids and ketones, respectively, in up to 99% yield. Benzaldehydes could be also prepared selectively from benzyl alcohols by conducting the flow oxidation under the standard conditions in the presence of triethylamine. Moreover, a practical gram-scale synthesis of surfactants was realized in the aqueous aerobic continuous flow oxidation for 36-116 hours. This aerobic flow oxidation system provides a safe, clean, green, rapid and efficient practical method for oxidizing alcohols.
Osako, Takao,Torii, Kaoru,Uozumi, Yasuhiro
p. 2647 - 2654
(2015/02/05)

Synthesis and biological evaluation of 2,4-diaminopyrimidines as selective Aurora A kinase inhibitors
The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Here we synthesized 15 2,4-diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 1/4M. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for anticancer activity.
Qin, Wen-Wen,Sang, Chun-Yan,Zhang, Lin-Lin,Wei, Wei,Tian, Heng-Zhi,Liu, Huan-Xiang,Chen, Shi-Wu,Hui, Ling
p. 174 - 184
(2015/03/31)

Novel Oxazolidinone-Based Peroxisome Proliferator Activated Receptor Agonists: Molecular Modeling, Synthesis, and Biological Evaluation
(Figure Presented). A series of new peroxisome proliferator activated receptors (PPARs) chiral ligands have been designed following the accepted three-module structure comprising a polar head, linker, and hydrophobic tail. The majority of the ligands inco
Fresno,Macías-González,Torres-Zaguirre,Romero-Cuevas,Sanz-Camacho,Elguero,Pavón,Rodríguez De Fonseca,Goya,Pérez-Fernández
p. 6639 - 6652
(2015/09/07)

DITHIOLAN-3-YLPENTANOATE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR THE TREATMENT OF PAIN
The disclosure herein provides 1-carbamoyloxyethyl 5-(1,2-dithiolan-3-yl)pentanoate derivatives of formula I, formula II and formula III. The disclosure also provides a method of synthesizing the compound of formula I, formula II and formula III. The compound of formula I, formula II and formula III or its pharmaceutical acceptable salts, as well as polymorphs, solvates, and hydrates, thereof may be formulated as pharmaceutical composition. The pharmaceutical composition of compound of formula I, formula II and formula III or the final compound of formula I, formula II or formula III may be formulated for non-invasive peroral, topical (example transdermal), enteral, transmucosal, targeted delivery, sustained release delivery, delayed release, pulsed release and parenteral methods. Such compositions may be used to treat chronic pain manifested with chronic diseases or its associated complications.
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Page/Page column 20; 24

(2015/09/23)

General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as an efficient catalyst
A simple, rapid and solvent-free protocol is described for the chemo-selective transformation of amines to tert-butyloxycarbonyl protected derivatives (NHBoc) using Boc2O and imidazolium trifluoroacetate protic ionic liquid (5-20 mol%). Unwanted side products such as isocyanate, urea or N,N-di-Boc were not detected. The scope of the protection strategy was successfully explored for substrate alcohols, phenols and thiol at elevated temperatures. Optically pure amino acids, amino acid esters and amino alcohols were efficiently converted to the corresponding N-Boc protected derivatives in excellent yields without racemization at the chiral center. The distinct advantages of this method are: operational simplicity, cleaner reaction, high selectivity, excellent yield, rapid reaction convergence, easy preparation and recyclability of the catalyst.
Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Maiti, Dilip K.
p. 24544 - 24550
(2014/07/07)

NEW CYCLOHEXYL AND QUINUCLIDINYL CARBAMATE DERIVATIVES HAVING BETA2 ADRENERGIC AGONIST AND M3 MUSCARINIC ANTAGONIST ACTIVITY
The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.
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Page/Page column 134

(2014/07/08)

Structure-activity relationships for vitamin D3-based aromatic a-ring analogues as hedgehog pathway inhibitors
A structure-activity relationship study for a series of vitamin D3-based (VD3) analogues that incorporate aromatic A-ring mimics with varying functionality has provided key insight into scaffold features that result in potent, selective Hedgehog (Hh) pathway inhibition. Three analogue subclasses containing (1) a single substitution at the ortho or para position of the aromatic A-ring, (2) a heteroaryl or biaryl moiety, or (3) multiple substituents on the aromatic A-ring were prepared and evaluated. Aromatic A-ring mimics incorporating either single or multiple hydrophilic moieties on a six-membered ring inhibited the Hh pathway in both Hh-dependent mouse embryonic fibroblasts and cultured cancer cells (IC50 values 0.74-10 μM). Preliminary studies were conducted to probe the cellular mechanisms through which VD3 and 5, the most active analogue, inhibit Hh signaling. These studies suggested that the anti-Hh activity of VD3 is primarily attributed to the vitamin D receptor, whereas 5 affects Hh inhibition through a separate mechanism.
Deberardinis, Albert M.,Madden, Daniel J.,Banerjee, Upasana,Sail, Vibhavari,Raccuia, Daniel S.,De Carlo, Daniel,Lemieux, Steven M.,Meares, Adam,Hadden, M. Kyle
p. 3724 - 3736
(2014/05/20)

A design strategy for small molecule-based targeted MRI contrast agents: Their application for detection of atherosclerotic plaques
Gadolinium(III) ion (Gd3+) complexes are widely used as contrast agents in magnetic resonance imaging (MRI), and many attempts have been made to couple them to sensor moieties in order to visualize biological phenomena of interest inside the bo
Iwaki, Shimpei,Hokamura, Kazuya,Ogawa, Mikako,Takehara, Yasuo,Muramatsu, Yasuaki,Yamane, Takehiro,Hirabayashi, Kazuhisa,Morimoto, Yuji,Hagisawa, Kohsuke,Nakahara, Kazuhide,Mineno, Tomoko,Terai, Takuya,Komatsu, Toru,Ueno, Tasuku,Tamura, Keita,Adachi, Yusuke,Hirata, Yasunobu,Arita, Makoto,Arai, Hiroyuki,Umemura, Kazuo,Nagano, Tetsuo,Hanaoka, Kenjiro
supporting information
p. 8611 - 8618
(2015/01/09)

Synthesis and biological activities of novel pleuromutilin derivatives with a substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors
A series of novel pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by the agar dilution method and Oxford cup assay. The majority of the tested compounds displayed moderate antibacterial activities. Importantly, the three compounds with amino or tertiary amine groups in their side chains, 11, 13b, and 15c, were the most active antibacterial agents. Docking experiments carried out on the peptidyl transferase center (PTC) of 23S rRNA proved that there is a reasonable direct correlation between the binding free energy (ΔGb, kcal/mol) and the antibacterial activity. Moreover, the pharmacokinetic profiles of 11 and 15c in rat were characterized by moderate clearance and oral bioavailability.
Shang, Ruofeng,Pu, Xiuying,Xu, Ximing,Xin, Zhijun,Zhang, Chao,Guo, Wenzhu,Liu, Yu,Liang, Jianping
p. 5664 - 5678
(2014/08/05)

Discovery of a series of hydroximic acid derivatives as potent histone deacetylase inhibitors
To develop potent histone deacetylase inhibitors as antitumor agents, structural modification was performed. The synthesized molecules were tested by enzymatic inhibition assay and anti-proliferation assay. Several molecules show improved activities in the enzymatic inhibition assay. However, in the MTT assays, all these derived molecules have limited performance compared with SAHA. The IC50 values of molecule ((S)-N-(6-(hydroxyamino)-6-oxohexyl)-4-(3-(2-oxo-1-phenyl-2-((3-(trifluoromethyl)phenyl)amino)ethyl)ureido)benzamide, L8) which has the best enzymatic inhibition activity (with an IC50 value of 11.7nm and 967nm against Hela nucleus extract and HDAC8, respectively) were calculated compared with SAHA. Molecular docking was performed to predict the binding mode of molecule L8 in the active site of HDAC2 and HDAC8. Hydrophobic interaction, chelate binding, electrostatic attraction and H-bond interaction in combination make contribution to the ligand-receptor interactions.
Zhang, Lei,Wang, Xuejian,Li, Xiaoguang,Zhang, Lihui,Xu, Wenfang
p. 582 - 589
(2014/08/05)

Design, synthesis and biological evaluation of 4′-demethyl-4-deoxypodophyllotoxin derivatives as novel tubulin and histone deacetylase dual inhibitors
A new class of 4′-demethyl-4-deoxypodophyllotoxin derivatives has been designed and synthesized as tubulin-HDAC dual inhibitors. Biological evaluation of these hybrids included the inhibitory activity of HDAC, in vitro cell cycle analysis in HCT-116 cells as well as cytotoxicity against two cancer cell lines (A549 and HCT116). The distance and angle between the HDAC capping group and the zinc binding group were systematically varied. Compounds 14a and 14c showed most potent dual inhibitory activity and powerful antiproliferative activity on HCT116 and A549 cell lines. This journal is
Zhang, Xuan,Zhang, Jie,Su, Mingbo,Zhou, Yubo,Chen, Yi,Li, Jia,Lu, Wei
p. 40444 - 40448
(2014/12/11)

Synthesis and antibacterial evaluation of novel pleuromutilin derivatives
A series of novel pleuromutilin derivatives possessing thioether moiety has been synthesized via acylation reaction under mild conditions. Their in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae were tested by agar dilution method and Oxford cup assay. Among the 17 compounds screened, 14-O-[(4-methoxybenzamide-2- methylpropane-2-yl) thioacetate] mutilin 4i, 14-O-[(2-aminobenzamide-2- methylpropane-2-yl) thioacetate] mutilin 5a and 14-O-[(4-aminobenzamide-2- methylpropane-2-yl) thioacetate] mutilin 5c were resulted as most active antibacterial agents.
Shang, Ruofeng,Liu, Yu,Xin, Zhijun,Guo, Wenzhu,Guo, Zhiting,Hao, Baocheng,Jianping, Liang
p. 231 - 238
(2013/07/27)

Palladium-catalyzed synthesis of aromatic carboxylic acids with silacarboxylic acids
Aryl iodides and bromides were easily converted to their corresponding aromatic carboxylic acids via a Pd-catalyzed carbonylation reaction using silacarboxylic acids as an in situ source of carbon monoxide. The reaction conditions were compatible with a wide range of functional groups, and with the aryl iodides, the carbonylation was complete within minutes. The method was adapted to the double and selective isotope labeling of tamibarotene.
Friis, Stig D.,Andersen, Thomas L.,Skrydstrup, Troels
supporting information
p. 1378 - 1381
(2013/04/24)

SURFACE ENHANCED RAMAN SPECTROSCOPY (SERS) COMPOUNDS AND METHODS OF THEIR PREPARATION
A compound for detecting an analyte using Surface Enhanced Raman Spectroscopy (SERS) and a method of forming the compound is provided. The compound has Formula I: wherein W is selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group; each Y independently is NR1R2, wherein R1 and R2 are independently selected from the group consisting of H and C1-C6 alkyl, or R1 and R2 combine to form together with the nitrogen to which they are attached a heterocyclic group with 4 to 5 carbon atoms, is used to denote a single or a double bond, and Z is NH, NH2, NH—(C═O)—(CH2)n—SH, wherein n=1 to 10, or or a tautomer or stereoisomer thereof, or a salt thereof. A method and device for detecting an analyte using Surface Enhanced Raman Spectroscopy (SERS) is also provided.
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(2012/06/01)

Direct peptide bioconjugation/PEGylation at tyrosine with linear and branched polymeric diazonium salts
Direct polymer conjugation at peptide tyrosine residues is described. In this study Tyr residues of both leucine enkephalin and salmon calcitonin (sCT) were targeted using appropriate diazonium salt-terminated linear monomethoxy poly(ethylene glycol)s (mPEGs) and poly(mPEG) methacrylate prepared by atom transfer radical polymerization. Judicious choice of the reaction conditions-pH, stoichiometry, and chemical structure of diazonium salt-led to a high degree of site-specificity in the conjugation reaction, even in the presence of competitive peptide amino acid targets such as histidine, lysines, and N-terminal amine. In vitro studies showed that conjugation of mPEG 2000 to sCT did not affect the peptide's ability to increase intracellular cAMP induced in T47D human breast cancer cells bearing sCT receptors. Preliminary in vivo investigation showed preserved ability to reduce [Ca2+] plasma levels by mPEG2000-sCT conjugate in rat animal models.
Jones, Mathew W.,Mantovani, Giuseppe,Blindauer, Claudia A.,Ryan, Sinead M.,Wang, Xuexuan,Brayden, David J.,Haddleton, David M.
supporting information; experimental part
p. 7406 - 7413
(2012/06/16)

Synthesis of benzoic acids and polybenzamides containing tertiary alkylamino functionality
The high-yielding and easily scalable synthesis of a number of benzoic acids bearing a tertiary alkylamino functionality has been achieved. The flexible synthesis began from readily available aminobenzoic acids or terephthaloyl chloride and requires almost no chromatography. Coupling of the synthesised amino acids to a range of substituted anilines was achieved when utilizing a specific combination of DIC, HOBt and DMAP.
Khan, Gul Shahzada,Dickson, Benjamin D.,Barker, David
experimental part
p. 1790 - 1801
(2012/03/11)

Microwave assisted mild, rapid, solvent-less, and catalyst-free chemoselective N-tert-butyloxycarbonylation of amines
Microwave assisted simple, rapid, solventless, and catalyst-free chemoselective method for the protection of amino group in aromatic, aliphatic, heterocyclic, aralkyl amines, phenyl hydrazine, and amino acid esters in good to excellent isolated yield (83-98%) in short reaction time (2-12 min) has been reported.
Dighe, Satish N.,Jadhav, Hemant R.
p. 5803 - 5806
(2012/10/29)

Novel folate-hydroxamate based antimetabolites: Synthesis and biological evaluation
A set of hydroxamate derivatives of folic acid and methotrexate (MTX) was synthesized and evaluated for the inhibitory activity against histone deacetylase (HDAC) and dihydrofolate reductase (DHFR), two enzymes overexpressed in metastasizing tumors. The s
Carrasco, Marta P.,Enyedy, Eva A.,Krupenko, Natalia I.,Krupenko, Sergey A.,Nuti, Elisa,Tuccinardi, Tiziano,Santamaria, Salvatore,Rossello, Armando,Martinelli, Adriano,Santos, M. Amelia
experimental part
p. 265 - 274
(2012/06/01)

COMPOUNDS AND METHODS FOR TREATING RESPIRATORY DISEASES
Described herein are compounds and compositions, and methods for using the compounds and compositions, for treating respiratory diseases and illness, such as severe acute respiratory syndrome (SARS).
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(2011/11/12)

SELECTIVE HDAC INHIBITORS
This disclosure is related to compounds having the structure (I) wherein Ar1, Ar2, R1 - R6, Z, m, n, o, and p are defined herein. This disclosure also relates to pharmaceutical compositions comprising the above compounds and methods for their use.
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Page/Page column 79

(2011/12/04)

Guanidine hydrochloride as an organocatalyst for N-Boc protection of amino groups
A simple and efficient method for the chemoselective N-Boc protection of the amine moiety in a variety of compounds is described using di-tert-butyl dicarbonate and guanidine hydrochloride as an organocatalyst in ethanol at 35-40°C. Selective mono-N-Boc protection of diamines and chemoselective protection of hydroxylamines without formation of any side products is achieved. Amino acids and peptides are N-Boc protected efficiently in excellent yields under convenient reaction conditions.
Jahani, Fatemeh,Tajbakhsh, Mahmood,Golchoubian, Hamid,Khaksar, Samad
supporting information; experimental part
p. 1260 - 1264
(2011/04/15)

Novel Compounds for the Treatment of Diseases Associated with Amyloid or Amyloid-Like Proteins
The present invention relates to novel compounds that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.
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(2011/11/30)

Pteridine-sulfonamide conjugates as dual inhibitors of carbonic anhydrases and dihydrofolate reductase with potential antitumor activity
Recent evidences suggest that cancer treatment based on combination of cytostatic and conventional chemostatic therapeutics, which are usually cytotoxic, can provide an improved curative option. On the sequence of our previous work on methotrexate (MTX) derivatives, we have developed and evaluated novel MTX analogues, containing a pteridine moiety conjugated with benzenesulfonamide derivatives, thus endowed with the potential capacity for dual inhibition of dihydrofolate reductase (DHFR) and carbonic anhydrases (CA). These enzymes are often overexpressed in tumors and are involved in two unrelated cellular pathways, important for tumor survival and progression. Their simultaneous inhibition may turn beneficial in terms of enhanced antitumor activity. Herein we report the design and synthesis of several diaminopteridine-benzenesulfonamide and -benzenesulfonate conjugates, differing in the nature and size of the spacer group between the two key moieties. The inhibition studies performed on a set of CAs and DHFR, revealed the activities in the low nanomolar and low micromolar ranges of concentration, respectively. Some inhibitors showed selectivity for the tumor-related CA (isozyme IX). Cell proliferation assays using two tumor cell lines (the non-small cell lung carcinoma, A549, and prostate carcinoma, PC-3) showed activities only in the millimolar range. Nevertheless, this fact points out the need of improving the cell intake properties of these new compounds, since the general inhibitory profiles revealed their potential as anticancer agents.
Marques, Sergio M.,Enyedy, Eva A.,Supuran, Claudiu T.,Krupenko, Natalia I.,Krupenko, Sergey A.,Amelia Santos
experimental part
p. 5081 - 5089
(2010/09/05)

Combinatorial synthesis of a triphenylmethine library and their application in the development of Surface Enhanced Raman Scattering (SERS) probes
The first synthesis of a triphenylmethine (TM) library of compounds and screening of their Surface Enhanced Raman Scattering (SERS) capability was carried out to identify novel Raman reporters with high sensitivity. We identified three novel SERS reporters (B2, B7, and C7) with higher signal intensity than that of commonly used crystal violet (CV). These reporters may find potential applications in developing sensitive SERS based biosensors.
Cho, Sung Ju,Ahn, Young-Hoon,Maiti, Kaustabh Kumar,Dinish,Fu, Chit Yaw,Thoniyot, Praveen,Olivo, Malini,Chang, Young-Tae
supporting information; experimental part
p. 722 - 724
(2010/06/12)

Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome - Coronavirus papain-like protease
We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure - activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 μM; antiviral EC50 = 6 μM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 μM) and the most potent SARS antiviral activity (EC50 = 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.
Ghosh, Arun K.,Takayama, Jun,Aubin, Yoann,Ratia, Kiira,Chaudhuri, Rima,Baez, Yahira,Sleeman, Katrina,Coughlin, Melissa,Nichols, Daniel B.,Mulhearn, Debbie C.,Prabhakar, Bellur S.,Baker, Susan C.,Johnson, Michael E.,Mesecar, Andrew D.
experimental part
p. 5228 - 5240
(2010/03/04)

HETEROCYCLIC COMPOUNDS AND USES THEREOF
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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(2009/01/20)

N-tert-Butoxycarbonylation of amines using H3PW12O40 as an efficient heterogeneous and recyclable catalyst
The commercially available heteropoly acid H3PW12O40 (0.5 mol %) is a very efficient and environmentally benign catalyst for N-tert-butoxycarbonylation of amines (primary, secondary) with di-tert-butyl dicarbonate at room temperature in short reaction times (10 min). No competitive side products such as isocyanates, ureas, N,N-di-tert-butoxycarbonyls, O-Boc and oxazolidinones were observed. Chiral α-amino alcohols and esters afforded the corresponding N-Boc derivatives chemoselectively in excellent yields.
Heydari, Akbar,Shiroodi, Roohollah Kazem,Hamadi, Hossein,Esfandyari, Maryam,Pourayoubi, Mehrdad
p. 5865 - 5868
(2008/02/09)

An efficient approach to the synthesis of water-soluble cyanine dyes using poly(ethylene glycol) as a soluble support
An efficient synthesis approach to unsymmetrical water-soluble cyanine dyes has been established. Loading and activation of sulfoindolenium to poly(ethylene glycol) (PEG) have been achieved via a simple strategy. Cyanine dyes are released by the attack of heterocyclic carbon nucleophile and the cleavage of PEG-bound hemicyanine. The efficient approach delivers cyanine dyes in high purity without the nontrivial chromatographic separation.
Jiang, Lin-Ling,Dou, Li-Fang,Li, Bao-Lin
p. 5825 - 5829
(2008/02/09)

Rhodium(I)-catalyzed carboxylation of aryl- and alkenylboronic esters with CO2
When the esters of arylboronic acids with 2,2-dimethylpropan-1,3-diol were treated with a catalytic amount of [Rh(OH)(cod)]2 in the presence of 1,3-bis(diphenylphosphino)propane and CsF in dioxane at 60 °C under carbon dioxide atmosphere, the benzoic acid derivatives were obtained in good yields. Reactions of alkenylboronic esters also proceeded under similar conditions to give α,β-unsaturated carboxylic acids. As these boronic esters are now easily available through coupling or direct borylation reactions, this method would be a useful method for the preparation of various functionalized aryl- and alkenyl-carboxylic acids. Copyright
Ukai, Kazutoshi,Aoki, Masao,Takaya, Jun,Iwasawa, Nobuharu
p. 8706 - 8707
(2007/10/03)

NOVEL HETEROCYCLIC AMIDE DERIVATIVES HAVING DIHYDROOROTATE DEHYDROGENASE INHIBITING ACTIVITY
Novel heterocyclic amide derivatives having pharmacological effects, that is, compounds represented by the general formula (1) or salts thereof: (1) wherein X1-X2 is S-CH2 or the like; R1 is alkyl or the like; p is 0 to 7; R2 is hydrogen, alkyl, or the like; R3 is hydrogen, alkyl, or the like; Y1-Y2 is CH=CH or the like; R4 is halogeno, alkyl, or the like; q is 0 to 4; and R5 is halogeno, hydrogen, alkyl, or the like.
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(2010/10/20)