- Synthesis and Studies of Potential Inhibitors of CD73 Based on a Triazole Scaffold
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The ecto-5′-nucleotidase CD73 is involved in the production of immunosuppressive adenosine in the tumoral microenvironment and recently became a validated target in immuno-oncology. To avoid formation of CD73-produced adenosine, several series of potential inhibitors of the target enzyme based on a triazole scaffold were synthetized and evaluated on recombinant purified hCD73 and in cell-based assays.
- Braka, Abdenour,Chaloin, Laurent,Cros-Perrial, Emeline,Grosjean, Félix,Jordheim, Lars Petter,Mathé, Christophe,Peyrottes, Suzanne,Uttaro, Jean-Pierre
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supporting information
(2021/12/14)
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- Iron-Catalyzed β-Alkylation of Alcohols
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β-Branched alkylated alcohols have been prepared in good yields using a double-hydrogen autotransfer strategy in the presence of our diaminocyclopentadienone iron tricarbonyl complex Fe1. The alkylation of some 2-arylethanol derivatives was successfully addressed with benzylic alcohols and methanol as alkylating reagents under mild conditions. Deuterium labeling experiments suggested that both alcohols (2-arylethanol and either methanol or benzyl alcohol) served as hydrogen donors in this cascade process.
- Bettoni, Leó,Gaillard, Sylvain,Renaud, Jean-Luc
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supporting information
p. 8404 - 8408
(2019/10/16)
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- PIPECOLIC ESTERS FOR INHIBITION OF THE PROTEASOME
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The present disclosure relates to chemical compounds that modulate proteasome activity, pharmaceutical compositions containing such compounds, and use of these compounds and compositions for the treatment of disorders of uncontrolled cellular proliferation such as, for example, a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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Paragraph 00274; 00275
(2019/08/26)
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- A concise approach to anthraquinone-xanthone heterodimers
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A synthetic approach to anthraquinone-xanthone heterodimers is described. The route to the pentacyclic core features an efficient assembly of a benzocycloheptenone via a new intramolecular oxidative arylation of an enol ether and a Hauser-Kraus annulation-aldol reaction sequence to access the characteristic bicyclo[3.2.2]nonene motif. Acremoxanthone A is synthesized in 10 steps from commercially available material to demonstrate the application of this approach.
- Holmbo, Stephen D.,Pronin, Sergey V.
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supporting information
p. 5065 - 5068
(2018/04/24)
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- Highly sulphated cellulose: a versatile, reusable and selective desilylating agent for deprotection of alcoholic TBDMS ethers
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A mild, efficient and rapid protocol was developed for the deprotection of alcoholic TBDMS ethers using a recyclable, eco-friendly highly sulphated cellulose sulphate acid catalyst in methanol. This acid catalyst selectively cleaves alcoholic TBDMS ethers in bis-TBDMS ethers containing both alcoholic and phenolic TBDMS ether moieties.
- Dachavaram, Soma Shekar,Penthala, Narsimha R.,Calahan, Julie L.,Munson, Eric J.,Crooks, Peter A.
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p. 6057 - 6062
(2018/09/06)
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- Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate
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Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogu
- Takubo, Keita,Furutsu, Kazunori,Ide, Takafumi,Nemoto, Hiroyuki,Ueda, Yuko,Tsujikawa, Kazutake,Ikawa, Takashi,Yoshimitsu, Takehiko,Akai, Shuji
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p. 1562 - 1576
(2016/04/05)
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- Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity
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Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.
- Segaoula, Zacharie,Leclercq, Julien,Verones, Valérie,Flouquet, Nathalie,Lecoeur, Marie,Ach, Lionel,Renault, Nicolas,Barczyk, Amélie,Melnyk, Patricia,Berthelot, Pascal,Thuru, Xavier,Lebegue, Nicolas
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p. 8422 - 8440
(2016/10/03)
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- α-Alkylidene-γ-butyrolactone synthesis via one-pot C-H insertion/olefination: substrate scope and the total synthesis of (±)-cedarmycins A and B
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Abstract A system for the synthesis of α-alkylidene-γ-butyrolactones via a one-pot C-H insertion/olefination sequence is described. The process is based on the rhodium catalysed C-H insertion reaction of α-diazo-α-(diethoxyphosphoryl)acetates. The mild reaction conditions, operational simplicity and ready availability of starting materials are all key features. A wide range of successful reaction systems are reported (41 examples) highlighting the generality of the method. The application of this method in the total synthesis of the natural products (±)-cedarmycins A and B is also described.
- Lloyd, Matthew G.,D'Acunto, Mariantonietta,Taylor, Richard J.K.,Unsworth, William P.
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p. 7107 - 7123
(2015/02/19)
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- METHOD FOR MANUFACTURING ALCOHOL BY HYDROGENATION OF CARBOXYLIC ACID COMPOUND AND ESTER COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for obtaining alcohol by hydrogenation of carboxylic acid compound efficiently by using a homogeneous system catalyst, especially a method for obtaining alcohol by hydrogenation of various carboxylic acid compound and ester compound by the homogeneous system catalyst efficiently even under alleviation condition. SOLUTION: A carboxylic acid compound and/or an ester compound is hydrogenated in a presence of a rhenium complex represented by ReXmYnZp, where X is a halogen atom, Y is same or different and each a ligand containing one or more phosphorus atom, Z is a ligand other than X and Y, m is an integer of 1 to 6, p is an integer of 0 to 2 and the sum of m, n and p is an integer of 2 to 6, and a specific alkali metal salt. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0117; 0118; 0127; 0129; 0131
(2016/10/10)
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- Synthesis of salidroside analogues and their ability of DPPH radical scavenging activity
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Salidroside is a phenylpropanoid glycoside isolated from Rhodiolarosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 22 novel glycosides have been synthesized and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenge activity of each glycoside has been evaluated. 2-(3,4,5-Trihydroxyphenyl)ethyl β-D-galactopyranoside and 3-(3,4,5-trihydroxyphenyl)propyl β-D-glucopyranoside exhibit significant activity prior to salidroside and Vitamin C with EC50 values of 35.85 μM and 36.71 μM, respectively. The results indicate that the phenolic hydroxyl group of these compounds is important for radical scavenging activity and phenyl ring substitution by electron-donating substituents lead to increased antioxidant activity.
- Zheng, Cheng,Guo, Yibing,Meng, Ying,Dou, Sufeng,Shao, Jian,Yang, Yumin
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p. 654 - 664
(2013/07/11)
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- Design, synthesis, and biological evaluation of the first podophyllotoxin analogues as potential vascular-disrupting agents
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We designed and synthesized two novel series of azapodo-phyllotoxin analogues as potential antivascular agents. A linker was inserted between the trimethoxyphenyl ring E and the tetracyclic ABCD moiety of the 4-aza-1,2-didehydropodophyllotoxins. In the first series, the linker enables free rotation between the two moieties; in the second series, conformational restriction of the E nucleus was considered. We have identified several new compounds with inhibitory activity toward tubulin polymerization similar to that of CA-4 and colchicine, while displaying low cytotoxic activity against normal and/or cancer cells. An aminologue and a methylenic analogue were shown to disrupt endothelial cell cords on Matrigel at subtoxic concentrations, and an original assay of drug washout allowed us to demonstrate the rapid reversibility of this effect. These two new analogues are promising leads for the development of vascular-disrupting agents in the podophyllotoxin series.
- Labruere, Raphael,Gautier, Benoit,Testud, Marlene,Seguin, Johanne,Lenoir, Christine,Desbene-Finck, Stephanie,Helissey, Philippe,Garbay, Christiane,Chabot, Guy G.,Vidal, Michel,Giorgi-Renault, Sylviane
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scheme or table
p. 2016 - 2025
(2011/12/15)
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- Asymmetric synthesis of antimicrotubule biaryl hybrids of allocolchicine and steganacin
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The asymmetric synthesis of novel axially chiral hiaryl compounds 5 a-f containing a seven- or eight-memhered heterocyclic medium ring is described. These molecules can he considered to he structural hybrids of allocolchicine- and sleganacin-lype natural products. The synthesis featured an atropo-diastereoselective biaryl Suzuki coupling in which a benzylic stereocenter efficiently transferred its stereochemical information to the biaryl axis. The coupling conditions were optimized. and two biphenylphosphane ligands (DavePhos and S-Phos) were found to give Ihe highest yields and diastereoselectivities. A three-element stereochemical model was proposed to explain the observed diastereoselectivities. In a second key step, the medium ring of the target molecules was formed by a stercoselective SN1-type cyclodehydration that probably involved a configurationally stable carbocationic intermediate, as supported by calculations. Alternatively. S N2-type cyclizations were employed on the same Suzuki coupling products to give the target molecules in a stereodivergent or stereoconvergent manner. These cyclization methods furnished the target hybrid analogues 5 a-f with ee values above 94%. All analogues were evaluated as antimicrotubule agents and against a panel of cancer-cell lines using colchicine (1) and N-acetylcolchinol (3) as references. Promising activities were found for R,a R-configured compounds 5 a, b and 5 f; in particular, ethyl analogue 5 b showed a twofold antimicrotubule activity relative to colchicine.
- Joncour, Agnes,Decor, Anne,Liu, Jian-Miao,Tran Huu Dau, Marie-Elise,Baudoin, Olivier
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p. 5450 - 5465
(2008/03/12)
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- Highly efficient ligands for dihydrofolate reductase from Cryptosporidium hominis and Toxoplasma gondii inspired by structural analysis
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The search for effective therapeutics for cryptosporidiosis and toxoplasmosis has led to the discovery of novel inhibitors of dihydrofolate reductase (DHFR) that possess high ligand efficiency: compounds with high potency and low molecular weight. Detaile
- Pelphrey, Phillip M.,Popov, Veljko M.,Joska, Tammy M.,Beierlein, Jennifer M.,Bolstad, Erin S. D.,Fillingham, Yale A.,Wright, Dennis L.,Anderson, Amy C.
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p. 940 - 950
(2007/10/03)
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- Biaryl axis as a stereochemical relay for the enantioselective synthesis of antimicrotubule agents
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(Chemical Equation Presented) Return to sender: A biaryl configuration that is controlled by a benzylic stereocenter in an atropo-selective Suzuki coupling in turn controls the stereocenter configuration in an SN1-type dehydrative cyclization performed at low temperature. Promising antimicrotubule biaryls of high optical purity are obtained in this manner. TFA = trifluoroacetic acid, pin = pinacolato.
- Joncour, Agnes,Decor, Anne,Thoret, Sylviane,Chiaroni, Angele,Baudoin, Olivier
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p. 4149 - 4152
(2007/10/03)
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- Reductive cleavage of acetals and ketals with 9-borabicyclo[3.3.1]nonane
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The reductive cleavage of benzaldehyde acetals and acetophenone ketals with the air-stable crystalline 9-borabicyclo[3.3.1]-nonane dimer provides monobenzylated ether derivatives of diols and 1,2-oxygen-transposed β-phenethyl alcohols, respectively. The boron moiety is effectively recovered through simple procedures which involve convenient air-stable reagents and boron byproducts. The process is particularly selective for 1,3-diols giving the more substituted monobenzyl ether derivatives exclusively. With acetophenone ketals both reduction and elimination occur, permitting 9-BBN-H to hydroborate the resulting styrene to produce 1,2-oxygen-transposed β-phenethyl alcohols cleanly. Potential applications of this new process were illustrated with the synthesis of the hallucinogen, mescaline, and the analgesic, ibufenac.
- Soderquist, John A.,Kock, Iveliz,Estrella, Maria E.
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p. 1076 - 1079
(2012/12/23)
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- Novel benzopyridothiadiazepines as potential active antitumor agents
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The synthesis of novel thiadiazepine derivatives, that could be considered as constraint analogues of E-7010, are reported. These molecules were evaluated for their antiproliferative activity toward the murine L1210 leukemia cell line. Flow cytometric studies performed on L1210 cells with the most cytotoxic compounds showed an accumulation of the cells in the G2/M phases of the cell cycle with a significant percentage of tetraploid cells (8N DNA content). Submicromolar cytotoxicities were observed with compounds 2b, 4b, 4e, 4g, and 4i. Two of them, compounds 2b and 4b, were found to be potent inhibitors of tubulin polymerization with IC50 of respectively 3.8 and 2.4 μM compared to 2.4 μM for desoxypodophyllotoxin. A 4-methoxyphenylethyl substitution on the pyridinyl nitrogen of the benzopyridothiadiazepine was found to be essential for the antiproliferative activity. The in vitro activities of compounds 2b and 4b make benzopyridothiadiazepine dioxides a promising new class of tubulin binders which warrant further in vivo evaluation.
- Lebegue, Nicolas,Gallet, Sebastien,Flouquet, Nathalie,Carato, Pascal,Pfeiffer, Bruno,Renard, Pierre,Léonce, Stéphane,Pierré, Alain,Chavatte, Philippe,Berthelot, Pascal
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p. 7363 - 7373
(2007/10/03)
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- Regiochemical control of the catalytic asymmetric hydroboration of 1,2-diarylalkenes
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The hydroboration of stilbenes and related disubstituted alkenes catalysed by QUINAP complexes may proceed with high enantio- and regioselectivity; rhodium and indium catalysts give the same product regioisomer but opposite enantiomers. The Royal Society
- Black, Antonia,Brown, John M.,Pichont, Christophe
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p. 5284 - 5286
(2007/10/03)
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- Development of novel reactions using hypervalent iodine(III) reagents: Total synthesis of sulfur-containing pyrroloiminoquinone marine product, (±)-makaluvamine F
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Novel and efficient intramolecular nucleophilic substitution reactions of phenol ethers using activated hypervalent iodine species have been developed and their application to the total synthesis of strongly cytotoxic makaluvamine F (1), a member of sulfur-containing pyrroloiminoquinone marine products, is described.
- Kita, Yasuyuki,Egi, Masahiro,Takada, Takeshi,Tohma, Hirofumi
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p. 885 - 897
(2007/10/03)
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- 2,4-diamino-6,7-dihydro-5?-cyclopentacf|pyrimidine analogues of trimethoprim as inhibitors of pneumocystis carinii and toxoplasma gondii dihydrofolate reductase
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Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl)alkyl]-6,7-dihydro5.ff- cyclopenta[rf]pyrimidines 15a-c were synthesized as analogues of trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii, Toxoplasma gondii,
- Rosowsky, Andre,Papoulis, Andrew T.,Queener, Sherry F.
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p. 913 - 918
(2007/10/03)
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- LEWIS X DERIVATIVE AND PROCESS FOR PRODUCING THE SAME
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A novel oligosaccharide derivative having a cell adhesion inhibitory activity and represented by structural formula (I).
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- Synthesis and action on the central nervous system of mescaline analogues containing piperazine or homopiperazine rings
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Structural juxtaposition of the 3,4,5-trimethoxyphenyl group is the same molecule with a piperazine or homopiperazine ring has been realized in a series of mescaline analogues (I-IV) as part of an investigation into the pharmacological properties of the seven-membered perhydro-1,4-diazepines (homopiperazines). The analogous six-membered piperazines were synthesized and tested as reference substances to determine whether the seven-membered ring conveyed special properties. A variety of pharmacological tests of action on the CNS showed that replacement of the amino group in mescaline by the heterocycles significantly alters the biological activity. In particular, both the piperazine and the homopiperazine derivatives displayed sedative activity to about the same extent.
- Majchrzak,Kotelko,Guryn,Lambert,Szadowska,Kowalczyk
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p. 304 - 306
(2007/10/02)
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