Zebrafish (Danio rerio) were fed a diet containing a mixture of 11 structurally diverse brominated flame retardants (BFRs) at nominal concentrations of either 1 or 100 nmol/g for up to 42 days, followed by an elimination period of 14 days. Uptake rates and elimination constants for five of the BFRs were calculated from measurements of their concentrations in the male fish during the exposure and elimination phases. Observed uptake efficiencies were highest for 2,4,4'-tribromodiphenyl ether (BDE 28) and 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) and were lowest for decabromodiphenyl ether (BDE 209). Estimated half-lives for TBECH and 2,4,6-tribromophenol were short (<2 d). Four BFR metabolites were identified in the fish: 2,2',3,4',5',6-Hexabromodiphenyl ether (BDE 149), 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE 154), 2,4,6-tribromoanisole, and 1,2,4,5-hexabromobenzene. These metabolites were still present in the zebrafish after the 14 day elimination period.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Consider drug therapy for pulmonary edema ... . Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatic hydrocarbons and related compounds/
/ALTERNATIVE and IN VITRO TESTS/ ... /This/ study assessed the potential effects of nineteen brominated diphenyl ethers (BDEs), five hydroxylated BDEs (OH-BDEs), one methoxylated BDE (CH(3)O-BDE), tetrabromobisphenol-A (TBBPA), its dibromopropane ether derivative (TBBPA-DBPE), and the brominated phenols/anisols 2,4,6-tribromophenol (TBP), 4-bromophenol (4BP) and 2,4,6-tribromoanisole (TBA) on the catalytic activity of the steroidogenic enzyme aromatase (CYP19) in H295R human adrenocortical carcinoma cells. Effects were studied in the concentration range from 0.5 to 7.5 uM; exposures were for 24 hr. Both 6-OH-BDE47 and 6-OH-BDE99 showed an inhibitory effect on aromatase activity at concentrations > 2.5 uM and > 5 uM, respectively. However, 6-OH-BDE47 also caused a statistically significant increase in cytotoxicity (based on mitochondrial MTT reduction and lactate dehydrogenase-leakage [LDH]) at concentrations > 2.5 uM that could explain in part the apparent inhibitory effect on aromatase activity. Compared to 6-OH-BDE47, the methoxy analog (6-CH(3)O-BDE47) did not elicit a cytotoxic effect, whereas significant inhibition of aromatase remained. TBP caused a concentration-dependent induction of aromatase activity between 0.5 and 7.5 uM (with a maximum of 3.8-fold induction at 7.5 uM). This induction was not observed when a OH- group replaced the CH(3)O- group or when bromine atoms adjacent to this OH- group were absent ...
/OTHER TOXICITY INFORMATION/ ... Synthetic 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1) and 2,4,6-tribromoanisole (TBA) were available in pure form ... Q1 was negative by established test systems for the determination of ethoxyresorufin-O-deethylase (EROD) induction and by sulforhodamine B assay. EROD induction potency was at least 10-7 times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). At a relatively high concentration (20 uM), Q1 inhibited specific binding of 2 nM (3H)TCDD to the in vitro-expressed human aryl hydrocarbon receptor (AHR) by 18%; lower concentrations showed no effect. Molecular modeling showed that Q1 is nonplanar, consistent with its relatively modest affinity as an AHR ligand. When tested for cell-growth inhibitory/cytocidal activity in human tumor cells, Q1 was only marginally, if at all, active with an IC(50) value > 50 uM compared with five to ten times lower IC(50) values for potent cytotoxins tested in the test system used. Furthermore, standard pesticide tests on insecticidal, herbicidal, and fungicidal activity did not provide any significant activity at highest concentrations. For TBA, the results in all tests were comparable with Q1 ...
Efficient Method for Demethylation of Aryl Methyl Ether Using Aliquat-336
摘要：
A rapid method for selective cleavage of aryl methylethers can be achieved in the presence of a protic acid and a catalytic amount of phase-transfer catalyst (Aliquat-336). Aliquat-336 accelerates the rate of reaction and affords the corresponding phenols in excellent to good yields on a wide variety of substrates. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.]
申请人：The Provost, Fellows, Foundation Scholars, & the other Members of Board, of the College of the Holy
公开号：US20150018566A1
公开（公告）日：2015-01-15
The invention provides combretastatin A-4 like compounds that are modified to have enhanced tubulin binding activity and in some embodiments the ability to promote accumulation in the vasculature undergoing angiogenesis (homing activity). The compounds are based on the combretastatin A-4 skeletal structure having a tubulin-binding pharmacophore comprising two fused rings (A and B rings) in which the B ring is substituted with (a) an aromatic ring structure (C ring) and (b) a second substituent/functional group that comes off the B ring. The aromatic ring structure is typically a six membered ring phenolic or aniline structure, or may also be a fused ring structure such as a substituted or unsubstituted naphthalene. The second substituent on the B ring may for example be a substituent which has been found to provide enhanced tubulin binding activity (for example a carbonyl group), or may be a substituent that facilitates functionalisation of the B ring (for example an hydroxyl or amine group), or it may be a binding agent for a target that is preferentially expressed on vasculature undergoing angiogenesis, and not expressed on quiescent vasculature.
Zwitterionic-Salt-Catalyzed Site-Selective Monobromination of Arenes
作者：Xiaodong Xiong、Fei Tan、Ying-Yeung Yeung
DOI：10.1021/acs.orglett.7b01899
日期：2017.8.18
A zwitterionic-salt-catalyzed electrophilic monobromination of arenes with high regioselectivity has been developed. Under mild reaction conditions, a wide range of monobrominated aromaticcompounds can be obtained in excellent yields. The reaction can be operated using an extremely low catalyst loading (0.05 mol %) with the inexpensive brominating agent N-bromosuccinimide. The versatility of this
STRAIGHTFORWARD ENTRY TO 7-AZABICYCLO[2.2.1]HEPTANE-1-CARBONITRILES AND SUBSEQUENT SYNTHESIS OF EPIBATIDINE ANALOGUES
申请人：STEVENS Christian
公开号：US20090275616A1
公开（公告）日：2009-11-05
The present invention relates to a group of substituted-7-azabicyclo-[2.2.1]heptyl derivatives with biological activity. The present invention also relates to synthetic methods for producing said substituted-7-azabicyclo-[2.2.1]heptyl derivatives. The present invention also relates to certain intermediates for producing such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as a synthetic method for producing such intermediates. The present invention also relates to pharmaceutical compositions comprising such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as their use as medicaments for the treatment of diseases mediated by a Nicotinic Acetylcholine Receptor or a receptor being a member of the Neurotransmitter-gated Ion Channel Superfamily, such as pain, Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy and nicotine addiction.
Regioselective Bromine/Magnesium Exchange for the Selective Functionalization of Polyhalogenated Arenes and Heterocycles
作者：Alexandre Desaintjean、Tobias Haupt、Leonie J. Bole、Neil R. Judge、Eva Hevia、Paul Knochel
DOI：10.1002/anie.202012496
日期：2021.1.18
toluene enables efficient and regioselective Br/Mg exchanges with various dibromo‐arenes and ‐heteroarenes under mild reaction conditions and provides bromo‐substituted magnesium reagents. Assessing the role of Lewis donor additives in these reactions revealed that N,N,N′,N′′,N′′‐pentamethyldiethylenetriamine (PMDTA) finely tunes the regioselectivity of the Br/Mg exchange on dibromo‐pyridines and quinolines
Selective bromination of polyenes by 2,4,4,6-tetrabromocyclohexa-2,5-dienone
作者：Tadahiro Kato、Isao Ichinose
DOI：10.1039/p19800001051
日期：——
4,6-Tetrabromocyclohexa-2,5-dienone (TBCO) liberates bromoniumion when treated with polyenes to form brominated products. The results of the reaction of TBCO with simple olefins are presented. The analogous bromo-ketones, 4-bromo-2,4,6-trichloro- and 2,4,6-tribromo-4-methyl-cyclohexa-2,5-dienone, (4) and (5) respectively, afford the same products (3a), (6), and (7) when treated with geranyl cyanide
当用多烯处理形成溴化产物时，2,4,4,6-四溴环己基-2,5-二烯酮（TBCO）释放出溴离子。给出了TBCO与简单烯烃的反应结果。类似的溴代酮（4-溴-2,4,6-三氯-和2,4,6-三溴-4-甲基-环己-2,5-二烯酮）（4）和（5）分别提供相同的产品（3a），（6）和（7）用香叶基氰化物（1; R = CN）处理时。有证据表明二溴化物（3a）的形成可能是由于顺序反应。在十六烷基三甲基溴化铵的存在下，TBCO是在非常温和的条件下对多烯进行选择性溴化的极好试剂。
