- A novel versatile precursor suitable for 18F-radiolabeling via “click chemistry”
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As an effort to improve 18F-radiolabeling of biomolecules in method robustness and versatility, we report the synthesis and radiolabeling of a new azido precursor potentially useful for the so-called “click reaction,” in particular the ligand-free version of the copper(I)-catalyzed alkyne-azide cycloaddition. The new azido precursor may help to overcome problems sometimes exhibited by most of the currently used analogues, as it is safe to handle and it displays long-term chemical stability, thus facilitating the development of new radiolabeling procedures. Moreover, the formed 18F-labeled 1,2,3-triazole is potentially metabolically stable and could enhance the in vivo circulation time. The above azido precursor was successfully radiolabeled with 18F, with 51% radiochemical yield (nondecay-corrected). As a proof of concept, the 18F-labeled azide was then tested with a suitable alkyne functionalized aminoacid (l-propargylglycine), showing 94% of conversion, and a final radiochemical yield of 27% (>99% radiochemical purity), nondecay-corrected, with a total preparation time of 104?minutes.
- Lugato,Stucchi,Ciceri,Iannone,Turolla,Giuliano,Chinello,Todde,Ferraboschi
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Read Online
- New ferrocenyl P,O ligands with polar substituents
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A new ferrocenyl P,O ligand has been synthesized and successfully used in the Suzuki-Miyaura coupling reaction of phenylboronic acid with bromobenzene. Some analogues carrying charged (imidazolium) or neutral (monomethylether PEG 750, tetraethylbisphospho
- Audin, Catherine,Daran, Jean-Claude,Deydier, éric,Manoury, éric,Poli, Rinaldo
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Read Online
- Reaction of Diisobutylaluminum Borohydride, a Binary Hydride, with Selected Organic Compounds Containing Representative Functional Groups
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The binary hydride, diisobutylaluminum borohydride [(iBu)2AlBH4], synthesized from diisobutylaluminum hydride (DIBAL) and borane dimethyl sulfide (BMS) has shown great potential in reducing a variety of organic functional groups. This unique binary hydride, (iBu)2AlBH4, is readily synthesized, versatile, and simple to use. Aldehydes, ketones, esters, and epoxides are reduced very fast to the corresponding alcohols in essentially quantitative yields. This binary hydride can reduce tertiary amides rapidly to the corresponding amines at 25 °C in an efficient manner. Furthermore, nitriles are converted into the corresponding amines in essentially quantitative yields. These reactions occur under ambient conditions and are completed in an hour or less. The reduction products are isolated through a simple acid-base extraction and without the use of column chromatography. Further investigation showed that (iBu)2AlBH4 has the potential to be a selective hydride donor as shown through a series of competitive reactions. Similarities and differences between (iBu)2AlBH4, DIBAL, and BMS are discussed.
- Amberchan, Gabriella,Snelling, Rachel A.,Moya, Enrique,Landi, Madison,Lutz, Kyle,Gatihi, Roxanne,Singaram, Bakthan
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supporting information
p. 6207 - 6227
(2021/05/06)
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- PYRIDINE COMPOUND SUBSTITUTED WITH AZOLE
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The present invention provides a compound represented by formula [I] shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme. (in formula [I] above, the structure represented by formula [II] below: represents any of the structures represented by formula group [III] below: R1, R2, R3, and R4 independently represent a hydrogen atom, a fluorine atom, methyl, or the like, R5 represents any of the structures represented by formula group [IV]:
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Paragraph 0917; 1076
(2020/07/07)
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- Sustainable organophosphorus-catalysed Staudinger reduction
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A highly efficient and sustainable catalytic Staudinger reduction for the conversion of organic azides to amines in excellent yields has been developed. The reaction displays excellent functional group tolerance to functionalities that are otherwise prone to reduction, such as sulfones, esters, amides, ketones, nitriles, alkenes, and benzyl ethers. The green nature of the reaction is exemplified by the use of PMHS, CPME, and a lack of column chromatography.
- Lenstra, Danny C.,Lenting, Peter E.,Mecinovi?, Jasmin
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supporting information
p. 4418 - 4422
(2018/10/17)
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- Discovery of novel 3-(hydroxyalkoxy)-2-alkylchromen-4-one analogs as interleukin-5 inhibitors
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A series of novel chromen-4-one analogs 9a-d and 10a-u was designed, synthesized and evaluated for their IL-5 inhibitory activity. Most of the chromen-4-one analogs showed strong inhibitory activity in low micro molar potency. Among them, 5-(cyclohexylmet
- Boggu, Pulla Reddy,Venkateswararao, Eeda,Manickam, Manoj,Kim, Youngsoo,Jung, Sang-Hun
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p. 290 - 304
(2017/08/14)
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- NOVEL 3-(4(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, METHOD OF PREPARING SAME AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING METABOLIC DISEASE INCLUDING SAME AS EFFECTIVE INGREDIENT
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The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.
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Paragraph 0247-0249
(2016/02/18)
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- Synthesis of dihydropyrimidine α,μ3-diketobutanoic acid derivatives targeting HIV integrase
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The synthesis and antiviral evaluation of a series of dihydropyrimidinone and thiopyrimidine derivatives bearing aryl α,γ-diketobutanoic acid moiety are described using the Biginelli multicomponent reaction as key step. The most active among 20 synthesized novel compounds were 4c, 4d and 5b, which possess nanomolar HIV-1 integrase (IN) stand transfer (ST) inhibition activities. In order to understand their mode of interactions within the IN active site, we docked all the compounds into the previously reported X-ray crystal structure of IN. We observed that compounds 4c, 4d and 5b occupied an area close to the two catalytic Mg2+ ions surrounded by their chelating triad (E221, D128 and D185), DC16, Y212 and the β-diketo acid moiety of 4c, 4d and 5b chelating Mg2+. As those compounds lack anti-HIV activities in cell, their prodrugs were synthetized. The prodrug 4c′ exhibited an anti-HIV activity of 0.19 μM in primary human lymphocytes with some cytotoxicity. All together, these results indicate that the new analogs potentially interact within the catalytic site with highly conserved residues important for IN catalytic activity.
- Sari, Ozkan,Roy, Vincent,Métifiot, Mathieu,Marchand, Christophe,Pommier, Yves,Bourg, Stéphane,Bonnet, Pascal,Schinazi, Raymond F.,Agrofoglio, Luigi A.
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p. 127 - 138
(2015/10/28)
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- THERAPEUTIC INHIBITORY COMPOUNDS
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The invention provides compounds of Formula I and Formula II: A-B-C-D-E-F-G-J (I) C-D-E-F-G-J (II) wherein A, B, C, D, E, F, G, and J have any of the values defined in the specification, and salts thereof. The compounds are useful for inhibiting plasma kallikrein, and for treating a disease or condition in an animal where inhibition of plasma kallikrein is indicated.
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Page/Page column 196
(2015/07/16)
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- Polyvinylpyrrolidone-bromine complex: An efficient polymeric reagent for selective preparation of benzyl bromides in the presence of hexamethyldisilane
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Benzylic bromides were conveniently obtained in high yields via the reaction of the corresponding alcohols with crosslinked polyvinylpyrrolidone- bromine complex (PVPP-Br2)/hexamethyldisilane in chloroform at reflux condition. Selective conversion of benzyl alcohol to benzyl bromide in the presence of primary aliphatic alcohols, e.g. 2-phenylethanol was also achieved.
- Mokhtary, Masoud,Lakouraj, Moslem M.
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p. 305 - 309
(2012/10/29)
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- LABELING COMPOUND FOR PET
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A labeling compound of the present invention includes a structure represented by formula (1) wherein X1 is 11CH3, CH218F, CF218F, 18F, 76Br or 124/sup
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Page/Page column 26-27
(2012/05/20)
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- COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE
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The present invention relates to pyrazine and pyridine compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I wherein the variables are as defined herein.
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Page/Page column 76
(2011/12/02)
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- Novel Spiropiperidine Compounds
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A compound of the formula: or a pharmaceutically acceptable salt thereof as well as a pharmaceutical composition, and a method for treating diabetes.
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Page/Page column 11
(2011/05/03)
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- Synthesis and structure-activity relationships of azamacrocyclic C-X-C chemokine receptor 4 antagonists: Analogues containing a single azamacrocyclic ring are potent inhibitors of T-cell tropic (X4) HIV-1 replication
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Bis-tetraazamacrocycles such as the bicyclam AMD3100 (1) are a class of potent and selective anti-HIV-1 agents that inhibit virus replication by binding to the chemokine receptor CXCR4, the coreceptor for entry of X4 viruses. By sequential replacement and/or deletion of the amino groups within the azamacrocyclic ring systems, we have determined the minimum structural features required for potent antiviral activity in this class of compounds. All eight amino groups are not required for activity, the critical amino groups on a per ring basis are nonidentical, and the overall charge at physiological pHcan be reduced without compromising potency. This approach led to the identification of several single ring azamacrocyclic analogues such as AMD3465 (3d), 36, and 40, which exhibit EC50's against the cytopathic effects of HIV-1 of 9.0, 1.0, and 4.0 nM, respectively, antiviral potencies that are comparable to 1 (EC50 against HIV-1 of 4.0 nM). More importantly, however, the key structural elements of 1 required for antiviral activitymay facilitate the design of nonmacrocyclic CXCR4 antagonists suitable for HIV treatment via oral administration. 2009 American Chemical Society.
- Bridger, Gary J.,Skerlj, Renato T.,Hernandez-Abad, Pedro E.,Bogucki, David E.,Wang, Zhongren,Zhou, Yuanxi,Nan, Susan,Boehringer, Eva M.,Wilson, Trevor,Crawford, Jason,Metz, Markus,Hatse, Sigrid,Princen, Katrien,De Clercq, Erik,Schols, Dominique
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supporting information; experimental part
p. 1250 - 1260
(2010/08/07)
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- PROCESS FOR THE PREPARATION OF PIPERAZINE BENZOTHIAZOLES
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The present invention discloses a process for the preparation of compounds of formula (I) where the groups and symbols are as defined in the description, said process comprising a) reacting a benzothiazol-2-ylacetonitrile bearing group R1 with
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Page/Page column 12-14
(2008/12/08)
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- A synthetic method for diversification of the P1′ substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1′ binding pockets of leucine aminopeptidases
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A novel, general, and versatile method of diversification of the P1′ position in phosphinic pseudodipeptides, presumable inhibitors of proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1′ modified phosphinic dipeptides, inhibitors of cytosolic leucine aminopeptidase, through computer-aided design basing on the structure of homophenylalanyl-phenylalanine analogue (hPheP[CH2]Phe) bound in the enzyme active site as a lead structure. In this approach novel interactions between inhibitor P1′ fragment and the S1′ region of the enzyme, particularly hydrogen bonding involving Asn330 and Asp332 enzyme residues, were predicted. The details of the design, synthesis, and activity evaluation toward cytosolic leucine aminopeptidase and aminopeptidase N are discussed. Although the potency of the lead compound has not been improved, marked selectivity of the synthesized inhibitors toward both studied enzymes was observed.
- Vassiliou, Stamatia,Xeilari, Metaxia,Yiotakis, Athanasios,Grembecka, Jolanta,Pawelczak, Malgorzata,Kafarski, Pawel,Mucha, Artur
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p. 3187 - 3200
(2008/02/07)
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- NITROSATED GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (1) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.
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Page/Page column 102
(2008/06/13)
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- Methods to modulate conditions mediated by the CXCR4 receptor
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The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV- or FIV-infected ce
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- Synthesis of new AB2 monomers for polymerization to hyperbranched polymers by 1,3-dipolar cycloaddition
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A number of AB2 monomers containing either one azide and two acetylene functions or vice versa have been prepared. Upon polymerization, these compounds were found to give rise to hyperbranched oligomers as detected by NMR spectroscopy. However, the formation of high-molecular-weight polymers could not be proven by GPC analysis. Crosslinking was found to be a major drawback of this approach to hyperbranched polymers. Two examples of the interesting situation in which the polymerization already starts during the introduction of the polymerizable group are described.
- Smet, Mario,Metten, Kris,Dehaen, Wim
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p. 1097 - 1108
(2007/10/03)
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- Antiviral compounds
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The present invention is drawn to novel antiviral compounds, pharmaceutical compositions and their use. More specifically this invention is drawn to derivatives of monocyclic polyamines which have activity in standard tests against HIV-infected cells as w
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- C602- chemistry: C60 adducts bearing two ester, carbonyl, or alcohol groups
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(Matrix presented) Reactions of activated halo compounds XCH2-A (X = Br, I; A = ester, ketone) with C602- anion give rise to C60(CH2-A)2 adducts (major products) along with unexpected metha
- Allard, Emmanuel,Delaunay, Jacques,Cousseau, Jack
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p. 2239 - 2242
(2007/10/03)
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- BENZYLIDENE RHODANINES
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This invention provides novel benzylidene rhodanines which are useful as agents in treating or preventing conditions associated with . beta.-amyloid peptide. This invention further provides methods of treating or preventing Alzheimer's Disease which comprises administering to a mammal in need thereof an effective amount of one or more of the benzylidene rhodanines of the present invention.
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- α-Dicarbonyls as 'non-charged' arginine-directed affinity labels. Novel synthetic routes to α-dicarbonyl analogs of the pp60(c-src) SH2 domain-targeted phosphopeptide Ac-Tyr(OPO3H2)-Glu-Glu-Ile-Glu
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The phosphopeptide 1 is a potent inhibitor of pp60(c-src) SH2 domain mediated phosphoprotein interactions (IC50 ≤ 0.5 μM), but lacks cell permeability. The syntheses of its less charged analogs 2 and 3 are described, in which the arginine-binding phosphate group has been substituted with uncharged α-dicarbonyl moieties. The chemistry described here may be of general use for the synthesis of other α-dicarbonyl compounds.
- Mehrotra, Mukund M.,Sternbach, Daniel D.,Rodriguez, Marc,Charifson, Paul,Berman, Judd
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p. 1941 - 1946
(2007/10/03)
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- Imidazole angiotensin II antagonists incorporating a substituted benzyl element
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Substituted imidazoles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. STR1
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- ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED PYRIDOIMIDAZOLYL RING
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Substituted heterocycles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I are useful as angiotensin II antagonists. STR1
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- QUINOLINE ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED BENZYL ELEMENT
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Substituted quinolines and azaquinolines (1,5-naphthridines) attached through an oxymethylene bridge to novel substituted phenyl derivatives of the Formula I, are useful as angiotensin II antagonists. STR1
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- A New Synthetic Method for Oligo(phenylenevinylenes) Terminated with Porphyrins
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A facile, high-yield synthesis of oligo(phenylenevinylenes) terminated with porphyrins via the Ramberg-Backlund reaction is reported.
- Ono, Noboru,Tomita, Hiroaki,Maruyama, Kazuhiro
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p. 2453 - 2456
(2007/10/02)
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- Synthesis of 4-phosphono- and of 4-(phosphonomethyl)-dl-phenylalanine, two analogues of O-phosphotyrosine
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:4-Phosphono-DL-phenylalanine 1 was synthetized from 4-bromo-DL-phenylalanine or from 4-(bromomethyl)-bromobenzene ; 4-(phosphonomethyl)-DL-phenylalanine 14 was prepared from methyl p-toluate. The interest of these phosphonic analogues arises from their possible interference in the metabolism of O-phosphotyrosine.
- Bayle-Lacoste, Mireille,Moulines, Jean,Collignon, Noel,Boumekouez, Abdelkader,De Tinguy-Moreaud, Eliane,Neuzil, Eugene
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p. 7793 - 7802
(2007/10/18)
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