Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. (1/409)Transcription of the prostate-specific antigen (PSA) gene escapes regulation by androgens in advanced prostate cancer. To determine the molecular mechanism(s) of androgen-independent regulation of the PSA gene, the possibility that the androgen receptor (AR) is activated in the absence of androgen by stimulation of protein kinase A (PKA) was investigated. Activation of PKA by forskolin resulted in elevated expression of the PSA gene in androgen-depleted LNCaP cells, an effect that was blocked by the antiandrogen, bicalutamide. Further evidence that induction of PSA gene expression was dependent on AR was obtained from experiments using PC3 cells devoid of AR. Neither PSA, PB, nor ARR3 androgen-responsive reporters could be induced by activation of PKA in the absence of transfected AR. In addition, when nuclear AR from forskolin-treated LNCaP cells was incubated with oligonucleotides encoding an androgen response element of the PSA promoter and examined by electromobility shift assay, an increase in AR-androgen response element complex formation was observed. Lastly, cotransfection of an expression vector for a chimeric protein encoding the amino-terminal domain of the human AR linked to Gal4 and a 5xGal4UAS reporter gene construct resulted in activation of the amino-terminal domain of the AR by stimulation of PKA activity. These results demonstrate androgen-independent induction of PSA gene expression in prostate cancer cells by an AR-dependent pathway. (+info)
Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers. (2/409)This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC. (+info)
Histochemically reactive zinc in plaques of the Swedish mutant beta-amyloid precursor protein transgenic mice. (3/409)Endogenous metals such as zinc may contribute to beta-amyloid (Abeta) aggregation and hence the plaque formation. In the present study, we examined brains of four Swedish mutant amyloid precursor protein (APP) transgenic mice at 12 months of age for histochemically reactive zinc in the plaques. Here, we report that all the Congo red (+) mature plaques contained chelatable zinc, as demonstrated by staining with the zinc-specific fluorescent dye 6-methoxy-8-quinolyl-para-toluenesulfonamide (TSQ). On the other hand, Congo red (-) preamyloid Abeta deposits were not stained with TSQ. Interestingly, although cerebellum contained similar degree of preamyloid Abeta deposits as cerebral cortex, it was completely devoid of Congo red- or TSQ-stained mature plaques. Although zinc from plaques was only slowly and partially removed by a specific zinc remover, dithizone, treatment of brain sections with heparinase-III, which degrades heparan sulfate proteoglycan (HSPG), another major constituent of plaques, greatly fastened the zinc removal with dithizone. The present study has demonstrated the presence of histochemically reactive zinc in plaques, but not preamyloid Abeta deposits, of the Swedish mutant APP transgenic mice. Because preamyloid Abeta deposits fail to develop into congophilic plaques in cerebellum where synaptic vesicle zinc is deficient, the synaptic zinc may be a necessary element in the plaque formation. In holding zinc inside plaques, HSPG may contribute in addition to Abeta. (+info)
Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. (4/409)The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment. (+info)
Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system. (5/409)Advanced prostate cancer is treated by androgen ablation and/or androgen receptor (AR) antagonists. In order to investigate the mechanisms relevant to the development of therapy-resistant tumours, we established a new tumour model which closely resembles the situation in patients who receive androgen ablation therapy. Androgen-sensitive LNCaP cells were kept in androgen-depleted medium for 87 passages. The new LNCaP cell subline established in this manner, LNCaP-abl, displayed a hypersensitive biphasic proliferative response to androgen until passage 75. Maximal proliferation of LNCaP-abl cells was achieved at 0.001 nM of the synthetic androgen methyltrienolone (R1881), whereas 0.01 nM of this compound induced the same effect in parental cells. At later passages (> 75), androgen exerted an inhibitory effect on growth of LNCaP-abl cells. The non-steroidal anti-androgen bicalutamide stimulated proliferation of LNCaP-abl cells. AR protein expression in LNCaP-abl cells increased approximately fourfold. The basal AR transcriptional activity was 30-fold higher in LNCaP-abl than in LNCaP cells. R1881 stimulated reporter gene activity in LNCaP-abl cells even at 0.01 nM, whereas 0.1 nM of R1881 was needed for induction of the same level of reporter gene activity in LNCaP cells. Bicalutamide that acts as a pure antagonist in parental LNCaP cells showed agonistic effects on AR transactivation activity in LNCaP-abl cells and was not able to block the effects of androgen in these cells. The non-steroidal AR blocker hydroxyflutamide exerted stimulatory effects on AR activity in both LNCaP and LNCaP-abl cells; however, the induction of reporter gene activity by hydroxyflutamide was 2.4- to 4-fold higher in the LNCaP-abl subline. The changes in AR activity were associated neither with a new alteration in AR cDNA sequence nor with amplification of the AR gene. Growth of LNCaP-abl xenografts in nude mice was stimulated by bicalutamide and repressed by testosterone. In conclusion, our results show for the first time that the nonsteroidal anti-androgen bicalutamide acquires agonistic properties during long-term androgen ablation. These findings may have repercussions on the natural course of prostate cancer with androgen deprivation and on strategies of therapeutic intervention. (+info)
Equilibrium in the hydrolysis and synthesis of cannabimimetic anandamide demonstrated by a purified enzyme. (6/409)Anandamide, an endogenous ligand for cannabinoid receptors, loses its biological activities when it is hydrolyzed to arachidonic acid and ethanolamine by anandamide amidohydrolase. We overexpressed a recombinant rat enzyme with a hexahistidine tag in a baculovirus-insect cell expression system, and purified the enzyme with the aid of a Ni-charged resin to a specific activity as high as 5.7 micromol/min/mg protein. The purified recombinant enzyme catalyzed not only the hydrolysis of anandamide and palmitoylethanolamide, but also their reverse synthetic reactions. In order to attain an equilibrium of the anandamide hydrolysis and its reverse reaction within 10 min, we utilized a large amount of the purified enzyme. The equilibrium constant ([arachidonic acid][ethanolamine])/([anandamide][water]) was calculated as 4x10(-3) (37 degrees C, pH 9.0). These experimental results with a purified enzyme preparation quantitatively confirmed the reversibility of the enzyme reaction previously observed with crude enzyme preparations. (+info)
Enzymes as reagents in peptide synthesis: enzymatic removal of amine protecting groups. (7/409)A model system is described for the enzymatic deprotection of suitably masked amino groups during stepwise peptide synthesis. Nitrophenyl esters of amino acids, N-protected with trypsin-labile benzyloxycarbonylarginyl groups, were prepared as crystalline, analytically pure picrate salts in a standardized procedure. These intermediates were shown to react with amino compounds to form the expected peptide linkages. A pair of diasteriomeric peptides prepared in this way and featuring benzyloxycarbonylarginyl-L-, AND -D-glutaminyl sequences, respectively, were subjected to tryptic digestion. In both cases, a specific cleavage of the arginyl bond was achieved; however, the peptide containing the L-glutaminyl residue was deprotected much more rapidly than its diasteriomer containing the D-glutaminyl residue. The hydrolysis of the former isomer was not noticeably impeded by the presence of the latter. The results of these studies suggest that C-activated amino-acid derivatives, N-protected with trypsin-labile groups, are readily prepared in convenient form and that the peptide derivatives prepared from these intermediates are readily freed of their amino-protecting groups under mild, aqueous conditions with a potentially useful degree of stereospecificity. Theoretical implications of this first enzyme-catalyzed step in the repetitive cycle of peptide elaboration are discussed along with the procedural advantages implicit in the alternation of strongly and weakly basic groups in the protected and unprotected peptide intermediates, respectively. (+info)
Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study. (8/409)PURPOSE: To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. PATIENTS AND METHODS: Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. RESULTS: A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. CONCLUSION: Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL. (+info)
Tosyl compounds are organic compounds that contain the tosyl group (p-toluenesulfonyl, -SO2C6H4CH3) as a substituent. The tosyl group is a protecting group or a good leaving group in organic reactions. Tosyl compounds are often prepared by reacting alcohols or amines with p-toluenesulfonyl chloride (TsCl) in the presence of a base.
The general formula for a tosyl compound can be represented as R-OTs, where R represents an organic group such as an alkyl, aryl, or heteroaryl group. Tosyl compounds are widely used in organic synthesis due to their versatility and reactivity.
Tosyl phenylalanyl chloromethyl ketone
Strychnine total synthesis
List of MeSH codes (D02)
Inactivation and pharmacological properties of sqKv1A homotetramers in Xenopus oocytes cannot account for behavior of the squid...
Tosylhydrazone - Wikipedia
Registration Dossier - ECHA
Three-dimensional structure-activity relationships of nonsteroidal ligands in complex with androgen receptor ligand-binding...
Advanced Search Results - Public Health Image Library(PHIL)
Figures and data in Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit...
CCCC 1958, Volume 23, Issue 4, Abstracts pp. 759-765, Articles by the same authors | Collection of Czechoslovak Chemical...
Adelaide Research & Scholarship: Changes in distribution of labile zinc in mouse spermatozoa during maturation in the...
Cme carbodiimide. Medical search
N-alpha-Tosyl-L-lysine chloromethyl ketone hydrochloride | Inhibitor | COX | Proteasome | TargetMol
Additional COVID-19 Sanitization Supplies Archives | ProcureNet
Targeting the pro-survival side-effects of androgen-deprivation therapy in prostate cancer. - Nuffield Department of Surgical...
Sample Final Exam - Biology LibreTexts
Ring-opening of N-tosyl aziridines by sulphur-stabilized nucleophiles - Lancaster EPrints
Pesquisa | Biblioteca Virtual em Saúde - BRASIL
Taming tosyl azide: the development of a scalable continuous diazo transfer process
IUCr) A thio-phene-based aza-cryptand Mannich base: 18,24-bis--(p-tolyl-sulfonamido)-2,5,8,11,21-penta-oxa-15,27-di-thia-18,24...
US Patent for Hydrazone substituted penems Patent (Patent # 4,559,333 issued December 17, 1985) - Justia Patents Search
Tosyl Isocyanate - Product Ingredients
Critical Role of Protease-activated Receptor 2 Activation by Mast Cell Tryptase in the Development of Postoperative Pain |...
Indian Patents. 210046:NOVEL BORONATE ESTERS
ICMAB - Synthesis of Globular Precursors
One Step Ecofriendly and Metal-Free Introduction of N,N-Bisallyl Amino and N-substituted 2,5-dihydropyrrole Moieties from...
WHO EMRO | Detection of influenza B viruses with reduced sensitivity to neuraminidase inhibitor in Morocco during 2014/15...
BJOC - Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides
Vitamin-B12-photokatalysierte Dicarbofunktionalisierung von Bromoalkenen - Thieme Chemistry - Georg Thieme Verlag KG
Sciencemadness Discussion Board - Preparation of methyl tosylate, safe methylating agent - Powered by XMB 1.9.11
- Using this powerful method it is possible to access bioactive compounds. (wikipedia.org)
- link A New Protocol for the In Situ Generation of Aromatic, Heteroaromatic, and Unsaturated Diazo Compounds and Its Application in Catalytic and Asymmetric Epoxidation of Carbonyl Compounds. (wikipedia.org)
- doi:10.1002/ejoc.200400700 Catalytic Cyclopropanation of Alkenes Using Diazo Compounds Generated in Situ. (wikipedia.org)
- The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. (ucc.ie)
- The invention also relates to methods of using antibodies and antibody-drug conjugate compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions. (justia.com)
- c) protecting the compound of formula V with ArB(0H)2 to give a compound of formula VI, where Ar is unsubstituted or substituted aryl or heteroaryl, G is tetrahydropyranyl, tert-butyldimethyl silyl or trityl and R3 is alkyl from 1 to 8 carbons, ( f) deprotection of the compound of formula VI using mild acid catalyst to give a compound of formula II. (allindianpatents.com)
- The compound of formula II is oxidized to a compound of formula VIII, where R3 is alkyl from 1 to 8 carbons, aryl or aralkyi and Ar is unsubstituted or substituted aryl or heteroaryl using pyridinium chioro chromate or DMSO/oxalyl chloride. (allindianpatents.com)
- This group of compounds includes amino acids and fatty acids. (lookformedical.com)
- Tosyl Isocyanate is the synthetic and aromatic silane compound with an isocyanate group, that confroms to the formula: C 8 H 7 NO 3 S. (productingredients.com)
- Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. (ucc.ie)
- Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. (ucc.ie)
- For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. (ucc.ie)
- These led to new terminal groups (chloro, bromo, and tosyl leaving groups, organic acid, and azide) that permitted ester production, click chemistry, and oxonium ring opening to be performed as examples of reactions that demonstrate the wide possibilities of the globular icosahedral carboranes to produce new dendritic or dendrimer-like structures. (icmab.es)
- Polyanionic species were obtained in high yield through the ring-opening reaction of cyclic oxonium compound [3,3′-Co(8-C4H8O2-1,2-C2B9H10)(1′,2′-C2B9H11)] by using terminal hydroxyl groups as nucleophiles. (icmab.es)
- Experimental and Theoretical Analysis of the Thiol-Promoted Fragmentation of 2-Halo-3-tosyl-oxanorbornadienes. (us.es)
- The present invention relates to optically active dihydroxy hexanoate derivatives of formula IIa and more particularly to compounds of formula II which are useful intermediates for the synthesis of HMG-CoA enzyme inhibitors like atorvastatin, cerivastatin, rosuvastatin, pitavastatin, fluvastatin. (allindianpatents.com)
- The synthesis of the ribo - trihydroxy sugar derivative starting from diacetone-D-glucose led to the formation of an inseparable 1:1 mixture of the required compound and its C-3 epimer, i.e., 4- C- hydroxymethyl-1,2- O -isopropylidene-α-D-xylofuranose  . (beilstein-journals.org)
- Professor Gryko said: "We demonstrated that nature native cobalt complex - vitamin B12 - and light as the source of energy can facilitate the synthesis of complex and valuable organic compounds, including pyrrolidines and piperidines. (thieme.de)
- Organic compounds having this functional group can be accessed by reaction of an aldehyde or ketone with tosylhydrazine. (wikipedia.org)
- Hydrolysis is the reverse reaction of formation with regeneration of the carbonyl compound. (wikipedia.org)
- Following a literature procedure, we synthesized gram amounts of 1 from N-tosyl aniline, Scheme 1.three Initial evaluation of the reaction in between ynesulfonamide 1 and benzoyl chloride showed that copper(I) salts have been superior more than each zinc and palladium complexes typically made use of in alkynylation reactions. (adenosine-receptor.com)
- The Bischler-Napieralski reaction of N-(5-benzyloxy-3, 4-dimethoxyphenethyl)-3-(3-ethoxycarbonyl-4-methoxyphenyl) propionamide (XX) also gave a mixture of 3, 4-dihydroisoquinolines which was derived to the 1, 2, 3, 4-tetrahydroisoquinolines and separated into 8-hydroxy (XXIV) and 6-hydroxy (XXV) compounds. (go.jp)
- The Mitsunobu Reaction allows the conversion of primary and secondary alcohols to esters, phenyl ethers, thioethers and various other compounds. (organic-chemistry.org)
- The mol-ecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. (iucr.org)
- A tosylhydrazone in organic chemistry is a functional group with the general structure RR'C=N-NH-Ts where Ts is a tosyl group. (wikipedia.org)
- EP 0 319 847 describes a process for the preparation of compounds of formula 1 starting from L-Malic acid. (allindianpatents.com)
- We studied the three-dimensional quantitative structure-activity relationships (3D QSAR) of 70 structurally and functionally diverse androgen receptor (AR) binding compounds using the comparative molecular similarity indices analysis (CoMSIA) method. (nih.gov)
- A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. (lookformedical.com)
- What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol? (targetmol.com)
- Perhaps the etherifed poly(ethylene glycols) can be used as solvents for Grignard reactions since they are close analogs to ethyl ether, are known to coordinate well with metal ions, and are at the very least totally inert to Grignard compounds. (thevespiary.org)
- The large separation of the two tosyl rings influences the geometry of the macrocyclic cavity by ensuring that the thio-phene rings and therefore the O and N atoms do not lie in the same plane. (iucr.org)
- They are sweet-tasting compounds that are used as chemical intermediates and plant growth stimulants. (lookformedical.com)
- The computational chemistry in combination with mass spectrometry allows comprises several chemical events which may occur during the ionization and dissociation of a particular compound, through appropriated descriptors, for instance, gas-phase basicity, proton affinities, electron affinities and proton transfers. (fapesp.br)
- Organic compounds containing the carboxy group (-COOH). (lookformedical.com)
- Recently, the group of Professor Dorota Gryko (Polish Academy of Sciences, Warsaw, Poland) described the vitamin B12-photocatalyzed cyclization of N -tosyl amines carrying an ω-bromoalkyl and an allyl group, which occurs with subsequent C- dicarbofunctionalization in the presence of acrylic acid derivatives or acrylonitrile, leading to the corresponding cyclic amines. (thieme.de)
- Mol-ecules of the title compound, C 15 H 16 O 5 S, are composed of a 3,5-di-meth-oxy-phenyl moiety substituted with a toluene-4-sulfonate group. (iucr.org)
- The title compound, C 34 H 42 N 2 O 9 S 4 , is composed of two thio-phene rings bridged by an -O-(CH 2 ) 2 -O-(CH 2 ) 2 -O- chain and a tri-substitued diamine with pendent tosyl rings. (iucr.org)
- In the asymmetric unit of the title compound there is one independent mol-ecule. (iucr.org)
- The crystal packing of the title compound, viewed along the c axis. (iucr.org)
- The title compound was placed in small portions until a saturated solution was obtained. (iucr.org)
- Nevertheless, the results will be combined with pka values obtained from computational methods in order to suggest the reactivity of compounds in solution. (fapesp.br)
- The disadvantages of this process are that a stereo selective reduction using a costly ruthenium-BINAP catalyst in employed and the desired compound of formula 1 is obtained in six steps. (allindianpatents.com)
- The 3.4-dihvdroxv hutanoir arid derivative is then functionalized into compounds of formula I involving a multiple number of steps. (allindianpatents.com)
- With both receptors present in the same cell, the selectivity or nonselectivity of a variety of compounds that would affect PAR 1 and/or PAR 2 could be efficiently evaluated in a single experiment. (aspetjournals.org)
- The Grignard reacts with the most availible substance, which is usually the starting compound, and not wit the end product. (thevespiary.org)