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1.
To identify new agents for the treatment of American cutaneous leishmaniasis, a series of eight 1,4‐bis(substituted benzalhydrazino)phthalazines was evaluated against Leishmania braziliensis and Leishmania mexicana parasites. These compounds represent a disubstituted version of the 1‐chloro‐4‐(monoaryl/heteroarylhydranizyl)phthalazine that exhibited a significant response against L. braziliensis according to our previous findings. Two disubstituted phthalazines 3b and 3f were identified as potential antileishmanial agents against L. braziliensis parasites, exhibiting a submicromolar IC50 response of 2.37 and 7.90 µM on the promastigote form, and of 1.82 and 4.56 µM against intracellular amastigotes, respectively. In particular, compound 3b showed interesting responses against amastigote isolates from reference, glucantime‐resistant and clinical human strains, which were by far superior to the biological response found for the glucantime drug. With regard to the toxicity results, both 3b and 3f exhibited moderate LD50 values against murine macrophages (BMDM), with good selectivity indexes on promastigotes and intracellular amastigotes of L. braziliensis. A comparison of biological response was established between the monosubstituted and disubstituted versions of these benzalhydrazino‐phthalazines. Easy synthetic procedure and significant response against amastigote strains including against resistant lines made compound 3b a potential candidate for further pharmacokinetic and in vivo experiments as antileishmanial agent, and as a platform for further structural optimization. Mechanism‐of‐action studies and molecular docking simulations discarded to inhibition of superoxide dismutase as possible mode of action. 相似文献
2.
γ‐Cyhalothrin ( 1a ), (S)‐cyano(3‐phenoxyphenyl)methyl (1R,3R)‐3‐[(1Z)‐2‐chloro‐3,3,3‐trifluoro‐1‐propenyl]‐2,2‐dimethylcyclopropanecarboxylate, is a single‐isomer, synthetic pyrethroid insecticide marketed by Pytech Chemicals GmbH, a joint venture between Dow AgroSciences and Cheminova A/S. As a part of the registration process there was a need to incorporate a carbon‐14 label into the cyclopropyl ring of this molecule. A high yielding radiochemical synthesis of γ‐cyhalothrin was developed from readily available carbon‐14 labeled N‐t‐Boc protected glycine. This seven step synthesis, followed by a preparative normal phase HPLC separation of diastereomers, provided 21.8 mCi of γ‐cyhalothrin‐1‐14C ( 1b ) with >98% radiochemical purity. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
3.
Pamela B. Lamb Charles J. McElhinny Todd Sninski Hunter Purdom F. Ivy Carroll Anita H. Lewin 《Journal of labelled compounds & radiopharmaceuticals》2009,52(11):457-462
High specific activity (+)‐amphetamine and (+)‐methamphetamine were prepared by reductive dechlorination of (S)‐(3′,5′‐dichlorophenyl)‐2‐propylazide and (S)‐2′6′‐dichloromethamphetamine, respectively. While the latter was readily obtained by resolution of racemic 2′6′‐dichloromethamphetamine using (+)‐dibenzoyltartaric acid, the analogous amphetamine resisted all efforts to resolve it. Hence, the required chiral precursor was prepared by stereospecific total synthesis following methodology that had been previously developed in our Laboratories. The tritium labeled compounds had specific activity 30.1 Ci/mmol and 38.3 Ci/mmol, respectively. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
4.
Synthesis of N‐(2‐diethylamino‐ethyl)‐4‐(4‐fluoro‐benzamido)‐2‐methoxybenzamide (desiodo‐MIP‐1145) by coupling technique and its radioiodination: a potential melanoma imaging agent
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H. Aglan S. A. Kandil A. F. EL‐Kafrawy U. Seddik 《Journal of labelled compounds & radiopharmaceuticals》2016,59(9):372-374
Radioiodinated MIP‐1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP‐1145 lacking the iodo‐substituent (desiodo‐MIP‐1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo‐MIP‐1145 by iodine‐125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [125I]MIP‐1145 was measured as 4.5. 相似文献
5.
S. De Bruyne T. L. Boos L. wyffels J. L. Goeman K. C. Rice F. De Vos 《Journal of labelled compounds & radiopharmaceuticals》2009,52(8):304-311
Dopamine transporter (DAT) neuroimaging is a useful tool in Parkinson's disease diagnosis, staging and follow‐up providing information on the integrity of the dopaminergic neurotransmitter system in vivo. 4‐(2‐(Bis(4‐fluorophenyl)methoxy)ethyl)‐1‐(4‐iodobenzyl)piperidine (7) has nanomolar affinity for DAT and better selectivity over the other monoamine transporters compared with the existing SPECT radioligands for DAT. The aim of this study was to synthesize and evaluate [123I]‐7 as an in vivo tracer for DAT. The tributylstannyl precursor was synthesized with an overall yield of 25%. [123I]‐7 was synthesized by electrophilic destannylation with a yield of 40±10%. Radiochemical purity appeared to be >98%, whereas specific activity was at least 667 GBq/µmol. Biodistribution studies in mice showed brain uptake of 0.96±0.53%ID/g at 30 s post injection (p.i.) and 0.26±0.02%ID/g at 3 h p.i. High blood activity was observed at all time points. Pretreatment with Cyclosporin A raised brain uptake indicating that [123I]‐7 is transported by P‐glycoprotein (P‐gp) pumps. In rats, regional brain distribution of [123I]‐7 was not in agreement with DAT distribution. These results indicate that [123I]‐7 is not suitable for mapping DAT in vivo but could be a useful tracer for the P‐gp transporter. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
6.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(9):557-569
Derivatives of nido‐carborate have potential use in tumour targeting as hydrophilic boron‐rich compounds for boron neutron capture therapy (BNCT) and as pendant groups for attachment of radiohalogens to tumour‐seeking molecules. For this purpose, functionalized derivatives of nido‐carborates that can be conjugated to biomolecules should be synthesized and evaluated. In this study, racemic 1 , 7‐(3′‐ammoniopropyl)‐7,8‐dicarba‐nido‐undecaborate(‐1) (acronym ANC ) was obtained by degradation of the corresponding aminopropyl‐o‐carborane, which was synthesized in three steps from 1‐tert‐butyldimethylsilyl‐2‐(3‐bromopropyl)‐o‐carborane, with sodium hydroxide in absolute ethanol. The racemate 1 was radioiodinated (125 I ) using the Chloramine‐T method. Radio‐TLC results showed that radiolabelling with 125 I was achieved in a yield greater than 95%. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2006,49(8):699-705
We report here a facile synthesis of (RS) methyl‐2‐([2′‐14C]4,6‐dimethoxypyrimidin‐2′‐yloxy)‐2‐phenyl [1‐14C]ethanoate under microwave irradiation. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
10.
《Journal of labelled compounds & radiopharmaceuticals》2002,45(1):19-28
Unprotected deoxyadenosine 1 was treated with an excess of phosphorus acid and stoichiometric proportions of N, N′‐di‐p‐tolylcarbodiimide in anhydrous pyridine to give deoxyadenosine‐5′‐monophosphite 2 . The latter was activated with trimethylsilyl chloride followed by sulphurisation with elemental 35S (specific activity>1000 Ci/mmol) in toluene solution to give deoxyadenosine‐5′‐(35S)‐thiomonophosphate [dAMP(35S)] 3 . Enzymatic conversion of deoxyadenosine‐5′‐(35S)‐thiomonophosphate to Sp‐deoxyadenosine‐5′‐(α‐35S)‐thiotriphosphate [Sp‐dATP (α‐35S)] 5 was carried out following a standard reaction protocol. Copyright © 2001 John Wiley & Sons, Ltd. 相似文献
11.
Sandip J. Wagh Raghunath Chowdhury Sulekha Mukhopadhyay Sunil K. Ghosh 《Journal of labelled compounds & radiopharmaceuticals》2013,56(13):649-654
Deuterium‐labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl‐d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)‐N‐(2‐pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2O combination with high yield and isotopic purity. The 5,5‐dideutero‐4‐dimethyl(phenyl)silyl‐6‐undecyl‐tetrahydropyran‐2‐one was obtained from the adduct of methyl‐d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran‐2‐one is the precursor for geminal 2H2‐labeled (+)‐4‐hydroxy‐6‐undecyl‐tetrahydropyran‐2‐one, an advanced intermediate for gem‐dideutero (–)‐tetrahydrolipstatin and (+)‐δ‐hexadecanolide syntheses. 相似文献
12.
Jixia Yang Gongzheng Zhang Zhaoyang Wang Zhanxiong Xiao Hongliang Wen 《Journal of labelled compounds & radiopharmaceuticals》2019,62(14):920-924
Parkinson disease (PD) is a neurodegenerative disorder characterized by the accumulation of α‐synuclein into Lewy bodies. 3‐Benzylidine‐indolin‐2‐one represents a class of compounds, which are known to inhibit the accumulation of α‐synuclein. In this paper, we report the synthesis of [13C] and [15N] labelled 1‐benzyl‐(Z)‐3‐(benzylidene)indolin‐2‐one from commercially available [13C2]‐chloroacetic acid and [15N]‐aniline in five steps. The product will be used to study its metabolites in human liver microsomes by liquid chromatography‐tandem mass spectrometry. 相似文献
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Thomas Bourdier Christopher J. R. Fookes Tien Q. Pham Ivan Greguric Andrew Katsifis 《Journal of labelled compounds & radiopharmaceuticals》2008,51(11):369-373
The F‐18 labelled methionine derivative S‐(2‐[18F]fluoroethyl)‐L‐homocysteine ([18F]FEHCys) was prepared by a one‐pot two‐step synthesis via the protected S‐(2‐bromoethyl)‐L‐homocysteine 1 and S‐(2‐chloroethyl)‐L‐homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 100°C compared with the chloro‐analogue (22% at 100°C in 30 min). However, [18F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
14.
《Journal of labelled compounds & radiopharmaceuticals》2002,45(5):371-377
14C‐Labelled N‐(2‐chloro‐3,4‐dimethoxybenzylideneamino)guanidinium acetate has been synthesized as a part of a four‐step procedure which involved decarboxylation of 2‐chloro‐3,4‐dimethoxybenzoic acid by Pb(OAc)4 to give 2‐chloro‐3,4‐dimethoxy‐1‐iodobenzene, followed by a selective lithiation at the iodine position and electrophilic substitution with N,N‐dimethylformamide [α‐14C] and final reaction with aminoguanidine bicarbonate. The specific activity was 59 mCi/mmol and the overall yield 49%. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
15.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(5):323-330
2‐[14C]‐N‐(6‐Chloro‐9H‐pyrido [3,4‐b]indol‐8‐yl)‐3‐pyridinecarboxamide (9A , also referred to as [14C]‐PS‐1145) was synthesized from [14C]‐paraformaldehyde in five steps in an overall radiochemical yield of 15%. The key intermediate 1‐[14C]‐6‐chloro‐1,2,3,4‐tetrahydro‐β‐carboline was obtained by Pictet–Spengler cyclization of chlorotryptamine with [14C]‐paraformaldehyde. Similar reactions were conducted with tryptamine to address the generality of the methodology. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2005,48(8):621-627
N‐[1‐(4‐chlorophenyl)‐1H‐pyrrol‐2‐yl‐13C4‐methyleneamino]guanidinium acetate has been synthesized by a four‐step procedure. This involved reduction of the Weinreb amide N,N′‐dimethyl‐N,N′‐dimethyloxybutane‐1,4‐diamide‐1,2,3,4‐13C4 by Dibal‐H to give the corresponding unstable dialdehyde which is reacted in situ with 4‐chloroaniline to form 1‐(4‐chlorophenyl)‐1H‐pyrrole‐13C4. This pyrrole analogue underwent a Vilsmeyer acylation with POCl3/DMF followed by final reaction with aminoguanidine bicarbonate to produce the desired labelled compound with 99% atom 13C. By using DMF [α‐14C] a radio‐labelled analogue was synthesized with a specific activity of 60 mCi/mmol. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
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Neha Agre Mariam Degani Antima Gupta Sanjib Bhakta Mukti Kanta Ray 《Archiv der Pharmazie》2019,352(9)
5‐Substituted‐6‐acetyl‐2‐amino‐7‐methyl‐5,8‐dihydropyrido[2,3‐d]pyrimidin‐4(3H)‐one derivatives were synthesized and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium aurum, Escherichia coli, and Staphylococcus aureus as well as a human monocyte‐derived macrophage (THP‐1), and murine macrophage (RAW 264.7) cell lines to assess their antibacterial and cytotoxic potential, respectively. The compounds showed activity in the range of 1.95–125 µg/ml against M. tuberculosis but showed no activity against M. aurum, E. coli, and S. aureus, indicating selectivity towards slow‐growing mycobacterial pathogens. The compounds exhibited very low to no cytotoxicity up to 500 µg/ml concentration against eukaryotic cell lines. The most potent molecule, 2l , showed a minimum inhibitory concentration of 1.95 µg/ml against M. tuberculosis H37Rv and a selectivity index of >250 against both the eukaryotic cell lines. Furthermore, 2l showed moderate inhibition of whole‐cell mycobacterial drug‐efflux pumps when compared to verapamil, a known potent inhibitor of efflux pumps. Thus, derivative 2l was identified as an antituberculosis hit molecule, which could be used to yield more potent lead molecules. 相似文献
19.
《Journal of labelled compounds & radiopharmaceuticals》2004,47(13):935-945
Pure 3‐L ‐chlorotyrosine‐[ring‐13C6] is prepared by chlorination of the 5‐oxazolidinone of L ‐tyrosine‐[ring‐13C6] with SO2Cl2 in CH3COOH‐Et2O and successive one‐pot regeneration of the protected aminoacidic functions by BCl3 in dichloromethane. Copyright © 2004 John Wiley & Sons, Ltd. 相似文献
20.
Pradeep K. Sharma Min He Leo J. Romanczyk Jr Hagen Schroeter 《Journal of labelled compounds & radiopharmaceuticals》2010,53(10):605-612
The first synthesis of doubly labeled, [2‐13C, 4‐13C]‐(2R,3S)‐catechin 15 and [2‐13C, 4‐13C]‐(2R,3R)‐epicatechin 18 starting from labeled 2‐hydroxy‐4, 6‐bis(benzyloxy)acetophenone 3 and labeled 3, 4‐bis(benzyloxy)‐benzaldehyde 7 are described. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献