- ACRIDIN-9-YL-AMINE, QUINOLIN-9-YL-AMINE, 1 -AMINO-9H-THIOXANTHENE-9-ONE AND BENZO[B][1,5]NAPHTHYRI DIN-10-YL-AMINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR TREATING CANCER
-
This disclosure provides a cridin-9-yl-amine, quinolin-9-yl-amine, 1- amino-9H-thioxanthene-9-one and benzo[b][l,5]naphthyridin-10- yl-amine derivatives and structurally related compounds for use as autophagy inhibitors for treating cancer. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 77 to 155; examples 1 to 22; compound A; compounds 1 to 21; tables 1 to 3).
- -
-
Paragraph 0333; 0337; 0354; 0358
(2021/07/17)
-
- The breaking beads approach for photocleavage from solid support
-
Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. Photocleavage from intact porous polystyrene beads is not optimal because light cannot penetrate into the beads and the surface area exposed to irradiation is limited. Thus, hazardous, technically challenging and expensive setups are used for photocleavage from intact beads. We developed a new concept in which grinding the beads during or prior to irradiation is employed as an essential part of the photocleavage process. By grinding the beads we are exposing more surface area to the light source, hence, photocleavage can be performed even using a simple benchtop LED setup. This approach proved very efficient for photocleavage of various model compounds including fully protected oligosaccharides.
- Alshanski, Israel,Bakhatan, Yasmeen,Grunhaus, Dana,Hurevich, Mattan
-
supporting information
p. 4183 - 4188
(2020/06/21)
-
- Synthetic method 6-amino-1-hexanol
-
The invention discloses a synthetic method 6-amino-1-hexanol. According to the synthetic method 6-amino-1-hexanol, chlorosulphonyl isocyanate and 1, 6-hexanediol are taken as main raw materials, one-pot method is adopted to synthesize 6-amino-1-hexanol. The synthesis route comprises following steps: 1, under the catalyst effect of a tertiary amine, chlorosulphonyl isocyanate and a primary alcoholare reacted to generate a Burgess reagent, 1, 6-hexanediol is added to generate an intermediate 6-hydroxyhexyl carbamic acid; and 2, the intermediate 6-hydroxyhexyl carbamic acid synthesized in step is subjected to projecting group removing directly without separation so as to obtain target product 6-amino-1-hexanol. The synthetic method is low in cost, simple in reaction conditions, few in reaction steps, short in time, and high in purity and yield of finished product 6-amino-1-hexanol.
- -
-
Paragraph 0031-0032; 0034-0035
(2019/10/23)
-
- ENDOSOMAL CLEAVABLE LINKERS
-
The present disclosure relates generally to cleavable linkers and uses thereof.
- -
-
Paragraph 00568
(2018/08/20)
-
- Toward aplyronine payloads for antibody-drug conjugates: Total synthesis of aplyronines A and D
-
The aplyronines are a family of antimitotic marine macrolides that disrupt cytoskeletal dynamics by dual targeting of both actin and tubulin. Given their picomolar cytotoxicity profile and unprecedented mode of action, the aplyronines represent an excellent candidate as a novel payload for the development of next-generation antibody-drug conjugates (ADCs) for cancer chemotherapy. Enabled by an improved second-generation synthesis of the macrolactone core 5, we have achieved the first total synthesis of the most potent congener aplyronine D together with a highly stereocontrolled synthesis of aplyronine A. To facilitate step economy, an adventurous site-selective esterification of the C7 hydroxyl group was performed to install the N,N,O-trimethylserine pharmacophore to directly afford aplyronines A and D. Toward the assembly of ADCs incorporating an aplyronine warhead, the C29-ester derivative 4 featuring an Fmoc-amino substituted linker attached to the actin-binding tail region was also prepared by adapting this flexible endgame.
- An?i?ek, Nika,Williams, Simon,Housden, Michael P.,Paterson, Ian
-
supporting information
p. 1343 - 1350
(2018/03/06)
-
- METHOD OF CONJUGATING OLIGOMERIC COMPOUNDS
-
Provided herein are solid phase methods for the synthesis of conjugated oligomeric compounds and intermediates used in such methods. In particular, the solid phase methods provide for addition of a phosphoramidite functionalized conjugate group to a solid support bound oligomeric compound. The methods also provide an increase in overall yield and a cost benefit over existing methods.
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-
Page/Page column 39
(2018/04/21)
-
- Method for synthesis of reactive conjugate clusters
-
Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.
- -
-
Page/Page column 79-80
(2018/11/10)
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- METHOD FOR PREPARING 6-AMINOHEXYL LACTOSIDE-NOTA CONJUGATE
-
The present invention provides a method for preparing a 6-aminohexyl lactoside-NOTA conjugate. The preparation method comprises brominating perbenzoylated lactose with hydrobromic acid; glycosylating 6-azidohexanol to obtain 6-azidohexyl perbenzoyl lactoside; and deprotecting this precursor in two steps to obtain 6-aminohexyl lactoside and conjugating 6-aminohexyl lactoside to NCS-benzyl-NODA GA (i.e. 2,2′-(7-(1-carboxy-4-((4-isothiocyanate benzyl) amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl) diacetic acid) in triethyl amine as an alkaline solvent, to obtain a 6-aminohexyl lactoside-NCS-benzyl-NODA GA conjugate. In this novel preparation method, no deglycosylated side product is produced, such that the yield is considerably increased to 46%. Therefore, the method is suitable for future massive production since the requirement for repeated preparations for massive production is reduced, and the impurities produced in the previously scaled-up preparation process are not present.
- -
-
Paragraph 0046; 0047; 0048; 0049
(2017/07/14)
-
- Orthoester in Cyclodehydration of Carbamate-Protected Amino Alcohols under Acidic Conditions
-
The first acid-promoted reaction system to form azaheterocycles from N -carbamate-protected amino alcohols is described. The reaction involves the activation of the hydroxyl group via the use of orthoesters. Despite the reduced nucleophilicity of carbamate nitrogen, this reaction system provides several types of pyrrolidines and piperidines in good to high yields. Using this protocol, prolinol derivatives can also be synthesized from carbamate-protected amino diols with regio- and stereoselectivity.
- Park, Heemin,Kwon, Yongseok,Shin, Jae Eui,Kim, Woo-Jung,Hwang, Soonho,Lee, Seokwoo,Kim, Sanghee
-
supporting information
p. 2761 - 2767
(2017/06/13)
-
- Metal-free one-pot α-carboxylation of primary alcohols
-
An efficient metal-free procedure for the formal α-carboxylation of primary alcohols has been developed. The method involves a one-pot oxidation/Passerini/hydrolysis sequence and provides access to α-hydroxy acids bearing a broad range of functional groups. A minor modification to the reaction conditions extends the range of accessible products to α-hydroxy esters.
- Van Der Heijden, Gydo,Kraakman, Jasper,Biemolt, Jasper,Ruijter, Eelco,Orru, Romano V. A.
-
supporting information
p. 9716 - 9719
(2016/10/31)
-
- Comprehensive Structure-Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes
-
The comprehensive structure-activity relationships of triantennary GalNAc conjugated ASOs for enhancing potency via ASGR mediated delivery to hepatocytes is reported. Seventeen GalNAc clusters were assembled from six distinct scaffolds and attached to ASOs. The resulting ASO conjugates were evaluated in ASGR binding assays, in primary hepatocytes, and in mice. Five structurally distinct GalNAc clusters were chosen for more extensive evaluation using ASOs targeting SRB-1, A1AT, FXI, TTR, and ApoC III mRNAs. GalNAc-ASO conjugates exhibited excellent potencies (ED50 0.5-2 mg/kg) for reducing the targeted mRNAs and proteins. This work culminated in the identification of a simplified tris-based GalNAc cluster (THA-GN3), which can be efficiently assembled using readily available starting materials and conjugated to ASOs using a solution phase conjugation strategy. GalNAc-ASO conjugates thus represent a viable approach for enhancing potency of ASO drugs in the clinic without adding significant complexity or cost to existing protocols for manufacturing oligonucleotide drugs.
- Prakash, Thazha P.,Yu, Jinghua,Migawa, Michael T.,Kinberger, Garth A.,Wan, W. Brad,?stergaard, Michael E.,Carty, Recaldo L.,Vasquez, Guillermo,Low, Audrey,Chappell, Alfred,Schmidt, Karsten,Aghajan, Mariam,Crosby, Jeff,Murray, Heather M.,Booten, Sheri L.,Hsiao, Jill,Soriano, Armand,MacHemer, Todd,Cauntay, Patrick,Burel, Sebastien A.,Murray, Susan F.,Gaus, Hans,Graham, Mark J.,Swayze, Eric E.,Seth, Punit P.
-
p. 2718 - 2733
(2016/04/10)
-
- UBA5 INHIBITORS
-
The present disclosure relates to compounds of the Formula (I), which are UBA5 inhibitors.
- -
-
Paragraph 00125
(2015/12/18)
-
- Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds
-
The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds. Strong as an ox: The highly chemoselective aerobic oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has been achieved by using 2-azaadamantane N-oxyl (AZADO)/copper catalysis. This catalytic system oxidizes not only alcohols with tertiary amino groups but also those with secondary and primary amines in good to high yield at ambient temperature in air. bpy=2,2-bipyridyl, DMAP=4-(N,N-dimethylamino)pyridine.
- Sasano, Yusuke,Nagasawa, Shota,Yamazaki, Mai,Shibuya, Masatoshi,Park, Jaiwook,Iwabuchi, Yoshiharu
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supporting information
p. 3236 - 3240
(2014/04/03)
-
- PRECURSOR USED FOR LABELING HEPATORCYTE RECEPTOR AND CONTAINING TRISACCHARIDE AND DIAMIDE DEMERCAPTIDE LIGAND, METHOD FOR PREPARING THE SAME, RADIOTRACER AND PHARMACEUTICAL COMPOSITION OF THE SAME
-
A precursor used for labeling hepatocyte receptors and applied to radiotracers for imaging or pharmaceutical compositions for liver cancers is revealed. The precursor is a bifunctional compound. The bifunctional group includes a trisaccharide structure an
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-
Paragraph 0092; 0093; 0094; 0095
(2014/02/16)
-
- Further characterization of a putative serine protease contributing to the γ-secretase cleavage of β-amyloid precursor protein
-
The 3-alkoxy-7-amino-4-chloro-isocoumarins JLK-6 and JLK-2 have been shown to markedly reduce the production of Amyloid β-peptide (Aβ) by Amyloid-β Precursor Protein (APP) expressing HEK293 cells by affecting the γ-secretase cleavage of APP, with no effect on the cleavage of the Notch receptor. This suggested that these compounds do not directly inhibit the presenilin-dependent γ-secretase complex but more likely interfere with an upstream target involved in γ-secretase-associated pathway. The mechanism of action of these compounds is unknown and there are high fundamental and therapeutical interests to unravel their target. Isocoumarin compounds were previously shown to behave as potent mechanism-based irreversible inhibitors of serine proteases, suggesting that the JLK-directed target could belong to such enzyme family. To get further insight into structure-activity relationships and to develop more potent isocoumarin derivatives, we have synthesized and evaluated a series of isocoumarin analogues with modifications at positions 3, 4 and 7. In particular, the 7-amino group was substituted with either acyl, urethane, alkyl or aryl groups, which could represent additional interaction sites. Altogether, the results highlighted the essential integrity of the 3-alkoxy-7-amino-4-chloro-isocoumarin scaffold for Aβ-lowering activity and supported the involvement of a serine protease, or may be more generally, a serine hydrolase. The newly reported 7-N-alkyl series produced the most active compounds with an IC50 between 10 and 30 μM. Finally, we also explored peptide boronates, a series of reversible serine protease inhibitors, previously shown to also lower cellular Aβ production. The presented data suggested they could act on the same target or interfere with the same pathway as isocoumarins derivatives.
- Peuchmaur, Marine,Lacour, Marie-Agnes,Sevalle, Jean,Lisowski, Vincent,Touati-Jallabe, Youness,Rodier, Fabien,Martinez, Jean,Checler, Frederic,Hernandez, Jean-Francois
-
p. 1018 - 1029
(2013/03/14)
-
- 18F-FBHGal for asialoglycoprotein receptor imaging in a hepatic fibrosis mouse model
-
Quantification of the expression of asialoglycoprotein receptor (ASGPR), which is located on the hepatocyte membrane with high-affinity for galactose residues, can help assess ASGPR-related liver diseases. A hepatic fibrosis mouse model with lower asialoglycoprotein receptor expression was established by dimethylnitrosamine (DMN) administration. This study developed and demonstrated that 4-18F-fluoro-N-(6-((3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl)oxy)hexyl)benzamide (18F-FBHGal), a new 18F-labeled monovalent galactose derivative, is an asialoglycoprotein receptor (ASGPR)-specific PET probe in a normal and a hepatic fibrosis mouse models. Immunoassay exhibited a linear correlation between the accumulation of GalH-FITC, a fluorescent surrogate of FBHGal, and the amount of ASGPR. A significant reduction in HepG2 cellular uptake (P 18F-FBHGal in fibrosis liver (14.84 ± 1.10 %ID/g) was appreciably decreased compared with that in normal liver (20.50 ± 1.51 %ID/g, P 1/2α, T1/2β, AUC and Cl) derived from microPET images revealed prolonged systemic circulation of 18F-FBHGal in hepatic fibrosis mice compared to that in normal mice. The findings in biological characterizations suggest that 18F-FBHGal is a feasible agent for PET imaging of hepatic fibrosis in mice and may provide new insights into ASGPR-related liver dysfunction.
- Kao, Hao-Wen,Chen, Chuan-Lin,Chang, Wen-Yi,Chen, Jenn-Tzong,Lin, Wuu-Jyh,Liu, Ren-Shyan,Wang, Hsin-Ell
-
p. 912 - 921
(2013/03/28)
-
- NOVEL AZAPEPTIDE OR AZAPEPTIDOMIMETIC COMPOUNDS INHIBITING BCRP AND/OR P-GP
-
The present invention relates to compounds of azapeptide or azapeptidomimetic type of formula (I): in which R1, R2, R3, X1, X2, X3, X4 and Y are as defined in claim 1, to pharmaceutical compositions containing them and to such compounds as adjuvant for an anticancer or anti-infectious medicament.
- -
-
Page/Page column 14
(2012/01/15)
-
- Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein- mediated multidrug efflux: Design, synthesis, characterization and biological evaluation
-
Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.
- Zeinyeh, Wael,Mahiout, Zahia,Radix, Sylvie,Lomberget, Thierry,Dumoulin, Axel,Barret, Roland,Grenot, Catherine,Rocheblave, Luc,Walchshofer, Nadia,Matera, Eva-Laure,Dumontet, Charles
-
p. 1177 - 1191,15
(2020/08/20)
-
- BIFUNCTIONAL COMPOUND WITH MONOSACCHARIDE AND N2S2 LIGAND, AND PREPARATION AND USE THEREOF
-
A bifunctional compound with a monosaccharide and a N2S2 ligand, and more particularly, a bifunctional compound with a N2S2 ligand and aminohexylacetyl galactosamine (ah-GalNAc4) is provided. A method for preparing the bifunctional compound with a monosaccharide and a N2S2 ligand is also provided, including activating a carboxyl group in an organic ligand, reacting the activated carboxyl group with a galactopyranoside through amidation, and then hydrolyzing. The bifunctional compound of the present invention is widely useful in nuclear medicine for preparation of liver imaging agents for assisting in correct diagnosis of diseases.
- -
-
Page/Page column 7
(2012/01/15)
-
- Oxidative photoredox catalysis: Mild and selective deprotection of PMB ethers mediated by visible light
-
Herein we report an advancement in the application of visible light photoredox catalysts in the oxidation of electron-rich arenes resulting in the selective deprotection of para-methoxybenzyl (PMB) ethers. This method is highlighted by excellent functional group tolerance, protecting group orthogonality, mild reaction conditions and avoidance of stoichiometric redox byproducts.
- Tucker, Joseph W.,Narayanam, Jagan M. R.,Shah, Pinkey S.,Stephenson, Corey R. J.
-
supporting information; experimental part
p. 5040 - 5042
(2011/06/10)
-
- Aminoluciferins as functional bioluminogenic substrates of firefly luciferase
-
Firefly luciferase is widely used as a reporter gene in assays to study gene expression, gene delivery, and so on because of its extremely high signal-to-noise ratio. The availability of a range of bioluminogenic substrates would greatly extend the applicability of the luciferin-luciferase system. Herein, we describe a design concept for functional bioluminogenic substrates based on the aminoluciferin (AL) scaffold, together with a convenient, high-yield method for synthesizing N-alkylated ALs. We confirmed the usefulness of ALs as bioluminogenic substrates by synthesizing three probes. The first was a conjugate of AL with glutamate, Glu-AL. When Glu-AL, the first membrane-impermeable bioluminogenic substrate of luciferases, was applied to cells transfected with luciferase, luminescence was not observed; that is, by using Glu-AL, we can distinguish between intracellular and extracellular events. The second was Cy5-AL, which consisted of Cy5, a near-infrared (NIR) cyanine fluorescent dye, and AL, and emitted NIR light. When Cy5-AL reacted with luciferase, luminescence derived from Cy5 was observed as a result of bioluminescence resonance energy transfer (BRET) from AL to Cy5. The NIR emission wavelength would allow a signal to be observed from deeper tissues in bioluminescence in vivo imaging. The third was biotin-DEVD-AL (DEVD=the amino acid sequence Asp-Glu-Val-Asp), which employed a caspase-3 substrate peptide as a switch to control the accessibility of the substrate to luciferase, and could detect the activity of caspase-3 in a time-dependent manner. This generalized design strategy should be applicable to other proteases. Our results indicate that the AL scaffold is appropriate for a range of functional luminophores and represents a useful alternative substrate to luciferin.
- Takakura, Hideo,Kojima, Ryosuke,Urano, Yasuteru,Terai, Takuya,Hanaoka, Kenjiro,Nagano, Tetsuo
-
experimental part
p. 1800 - 1810
(2011/12/16)
-
- A tetranuclear-zinc-cluster-catalyzed practical and versatile deprotection of acetates and benzoates
-
A new catalytic deacylation of acetates and benzoates through transesterification with methanol was developed (see scheme). Reactions with various acidand nucleophile-sensitive functional groups proceeded efficiently in the presence of a catalytic amount of the tetranuclear zinc cluster. The present catalysis is applicable to less-reactive tertiary acetates, the deacylation of which is difficult to achieve by transesterification with other catalysts.
- Iwasaki, Takanori,Agura, Kazushi,Maegawa, Yusuke,Hayashi, Yukiko,Ohshima, Takashi,Mashima, Kazushi
-
scheme or table
p. 11567 - 11571
(2010/11/24)
-
- Synthesis and application of a 2-[(4-fluorophenyl)-sulfonyl]ethoxy carbonyl (Fsec) protected glycosyl donor in carbohydrate chemistry
-
The 2-[(4-fluorophenyl)sulfonyl]ethoxy carbonyl (Fsec) group for protection of hydroxyl groups has been designed, synthesized, and evaluated. Fsec-Cl was readily prepared in 91% yield over three steps and subsequently used to protect 4-fluorobenzyl alcohol in high yield. The Fsec group was cleaved from the resulting model compound under mild basic conditions e.g., 20% piperidine in DMF and was stable under acidic conditions, e.g., neat acetic acid. The Fsec group was used to protect the unreactive 4-OH in a galactose building block that was later used in the synthesis of 6-aminohexyl galabioside.
- Spjut, Sara,Qian, Weixing,Elofsson, Mikael
-
experimental part
p. 5708 - 5720
(2010/12/24)
-
- Design, synthesis and evaluation of progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux
-
Steroidal bivalent ligands were designed on the basis of the described closer proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of seven progesterone-adenine hybrids were described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone.
- Zeinyeh, Wa?l,Alameh, Ghina,Radix, Sylvie,Grenot, Catherine,Dumontet, Charles,Walchshofer, Nadia
-
scheme or table
p. 3165 - 3168
(2010/09/05)
-
- Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells
-
In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics.
- Aspland, Simon E.,Ballatore, Carlo,Castillo, Rosario,Desharnais, Joel,Eustaquio, Trisha,Goelet, Philip,Guo, Zijian,Li, Qing,Nelson, David,Sun, Chengzao,Castellino, Angelo J.,Newman, Michael J.
-
p. 5194 - 5198
(2008/02/02)
-
- SMALL MOLECULE COMPOSITIONS AND METHODS FOR INCREASING DRUG EFFICIENCY USING COMPOSITIONS THEREOF
-
In certain embodiments, provided herein are compositions and methods for increasing drug efficiency. The conjugates provided are in certain embodiments, for compositions and methods in treatment of variety of diseases and have the formula 1: D - L - S (1)
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Page/Page column 116
(2008/06/13)
-
- Toward Efficient Zn(II)-Based Artificial Nucleases
-
A series of cis-cis-triaminocyclohexane Zn(II) complex-anthraquinone intercalator conjugates, designed in such a way to allow their easy synthesis and modification, have been investigated as hydrolytic cleaving agents for plasmid DNA. The ligand structure
- Boseggia, Elisa,Gatos, Maddalena,Lucatello, Lorena,Mancin, Fabrizio,Moro, Stefano,Palumbo, Manlio,Sissi, Claudia,Tecilla, Paolo,Tonellato, Umberto,Zagotto, Giuseppe
-
p. 4543 - 4549
(2007/10/03)
-
- Poly(ethylene glycol)-supported copper(II) triazacyclononane: An efficient, recoverable, and recyclable catalyst for the cleavage of a phosphodiester
-
The triazacyclononane macrocycle has been linked to the soluble polymer monomethoxy poly(ethylene) glycol and its copper(II) complex efficiently catalyzes the hydrolysis of a model phosphodiester. The catalyst, easily recovered from the water solution, sh
- Bonora, Gian Maria,Drioli, Sara,Felluga, Fulvia,Mancin, Fabrizio,Rossi, Paola,Scrimin, Paolo,Tecilla, Paolo
-
p. 535 - 538
(2007/10/03)
-
- Aryl sulfonamides and sulfamide derivatives and uses thereof
-
This invention is directed to novel aryl sulfonamide and sulfamide compounds which bind selectively to and inhibit the activity of the human Y5 receptor. This invention is also related to uses of these compounds for the treatment of feeding disorders such
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-
-
- ERYTHROMYCIN A 9-0-OXIME DERIVATIVES ENDOWED WITH ANTIBIOTIC ACTIVITY
-
PCT No. PCT/EP95/04815 Sec. 371 Date May 16, 1997 Sec. 102(e) Date May 16, 1997 PCT Filed Dec. 7, 1995 PCT Pub. No. WO96/18633 PCT Pub. Date Jun. 20, 1996Erythromycin 9-oxime derivatives wherein a phenyl or heterocylic group is attached indirectly to the 9-position of erythromycin A through an alkylene diamine bridging member. These compounds exhibit broad spectrum antibiotic activity.
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-
-
- Polyvalent polymers for the treatment of rotavirus infection
-
The present invention includes polymerizable monomers comprising a fucoside moiety. In one embodiment, the monomer has a polymerizable functional group, such as an olefinic bond, to which the fucoside moiety is attached by a spacer group, for example, an alkylene group, or an alkylene group wherein one or more carbon atoms are substituted by heteroatoms, such as oxygen, nitrogen or sulfur atoms. The present invention also includes polymers comprising one or more fucoside moieties, such as pendant fucoside moieties, which can inhibit or prevent rotavirus infection in a mammal. Such a polymer can comprise, for example, a monomer of the present invention. The polymer can be a homopolymer or a copolymer, and can have, for example, a polyacrylamide, polyacrylate or polystyrene backbone. In another embodiment, the present invention comprises a method for treating a rotavirus infection in a mammal, for example, a human, by administering to the mammal a therapeutically effective amount of a polymer comprising one or more glycoside moieties, such as pendant glycoside moieties. The glycoside moieties can be, for example, fucoside moieties or sialic acid moieties. The polymer can be a homopolymer or a co-polymer. In one embodiment, the polymer is a copolymer comprising a glycoside-bearing monomer and a hydrophobic monomer. In another embodiment, the polymer to be administered comprises two or more different glycoside-bearing monomers.
- -
-
-
- Chemical synthesis of globotriose and galabiose: Relative stabilities of their complexes with Escherichia coli Shiga-like toxin-1 as determined by denaturation-titration with guanidinium chloride
-
Globotriose [α-D-Gal-(1→4)-β-D-Gal-(1→4)-D-Glc] is the carbohydrate moiety of the globotriosyl ceramide (Gb3), also known as the germinal centre B-cell differentiation antigen CD77, a glycolipid present on the plasma membrane of certain mammalian cells. In Gb3, globotriose functions as the cell-surface receptor for Shiga toxin and for the Shiga-like toxins (verocytotoxins). Here we report the chemical synthesis of globotriose and the corresponding terminal disaccharide, galabiose [α-D-Gal-(1→4)-β-D-Gal]. Globotriose and galabiose are attached via a linker to CNBr-activated Sepharose to generate affinity matrices that permit the one-step purification of recombinant Shiga-like toxin-1 from crude E. coli homogenates. Toxin is released from either of the immobilised saccharides by elution with 6 M guanidinium chloride. After dilution of the denaturant, the released toxin had full catalytic activity. Denaturation-titration experiments show that the bound toxin is released from galabiose-Sepharose at 2.3 M guanidinium chloride, while its release from globotriose-Sepharose requires a higher concentration of 4.8 M. These results indicate that the glucose component of globotriose contributes ~2.6 kcal mol-1 to the binding energy relative to galabiose.
- Mueller, Dieter,Vic, Gabin,Critchley, Peter,Crout, David H. G.,Lea, Nicholas,Roberts, Lynne,Lord, J. Michael
-
p. 2287 - 2294
(2007/10/03)
-
- 4-SUBSTITUTED 2-AMINOALK-3-ENOIC ACIDS
-
Substituted 2-aminoalk-3-enoic acid derivative of formula I STR1 wherein R 1 is an aliphatic hydrocarbon radical that is substituted by optionally acylated or aliphatically or araliphatically etherified hydroxy, by halogen, by optionally acylated and/or aliphatically substituted amino or by an aza-, diaza-, azoxa-or oxa-cycloaliphatic radical, or is an oxacycloaliphatic hydrocarbon radical bonded via a carbon atom, or is an optionally aliphatically N-substituted or N-acylated azacycloaliphatic hydrocarbon radical, and R. sub.2 is free or esterified carboxy, and their salts exhibit NMDA-antagonistic properties and are useful as active ingredients of anticonvulsive medicaments.
- -
-
-
- DNA-directed alkylating agents. 5. Acridinecarboxamide derivatives of (1,2-diaminoethane)dichloroplatinum(II)
-
A series of acridine-2- and -4-carboxamide-linked analogues of PtenCl2 has been prepared and evaluated for biological activity against several tumor cell lines in vitro and in vivo. The platinum complexes were generally more cytotoxic than the
- Lee,Palmer,Baguley,Chin,McFadyen,Wickham,Thorsbourne-Palmer,Wakelin,Denny
-
p. 2983 - 2987
(2007/10/02)
-
- Oxime esters as acylating agents in the aminolysis reaction. A simple and chemoselective method for the preparation of amides from amino alcohols
-
Oxime esters, such as acetone O-alkanoyl-, O-alkenoyl- or O-benzyloxycarbonyloximes, react with amines under extremely mild conditions to give the corresponding amides in very good yield. When amino alcohols are used a total chemoselectivity is observed.
- Fernandez,Menendez,Gotor
-
p. 713 - 716
(2007/10/02)
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- Synthesis of a lactosamine-type trisaccharide: 6-(bromoacetamido)-hexyl 2-O(4-O-β-D-galactopyranosyl-2-acetamido2-deoxy-β-D-glucopyranosyl)-α-D-mannopyranoside, designed to affinity label the leukoagglutinin sugar binding site
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We descibe the synthesis of a D-lactosamine-type trisaccharide, 6-(bromoacetamido)-hexyl 2-O-(4-O-β-D-galactopyranosyl-2-acetamido-2-(deoxy-β-D-glucopyranosyl)-α-D-mannopyranoside (18), designed for affinity labelling the Phaseolus vulgaris leukoagglutini
- Ammann, Helene,Dupuis, Gilles
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p. 1651 - 1655
(2007/10/02)
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- Ligand analog-irreversible enzyme inhibitor conjugates
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The present invention encompasses a method for determining ligands in test samples comprising intermixing with the test sample a ligand analog-irreversible enzyme inhibitor conjugate and a binding protein bindable to the ligand and the ligand analog-irreversible enzyme inhibitor conjugate and wherein the amount of ligand analog-irreversible enzyme inhibitor conjugate bound by the binding protein is related to the amount of ligand in the test sample, said binding protein inactivating the irreversible enzyme inhibitor when bound to the ligand analog portion of the conjugate; intermixing an enzyme which is irreversibly inhibited by the ligand analog-irreversible enzyme inhibitor conjugate unbound by the binding protein; and intermixing substrate to the enzyme and monitoring the enzyme substrate reaction. The invention also includes ligand analog-irreversible enzyme inhibitor conjugates useful as reagents in practicing the method. Methods and reagents of the present are particularly useful in determining drugs, hormones, and the like in biological fluids.
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- 1-Substituted glycopyranosides
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The invention disclosed herein relates to novel 1-deoxy-glycopyranosides, preferably 1-deoxy-D-mannopyranosides, having in the 1-position of the pyranoside ring an ω-aminoalkylthio, ω-aminoalkyloxy or ω-aminoalkanoylamino substituent; and to novel process
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