Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats

The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0–1.5 mM; up to 90 min) or vehicle. Of these metabolites, 3,5-DCPHA was the most potent nephrotoxicant, with 3,5-DCNB intermediate in nephrotoxic potential. 2-A-4,6-DCP and 3,5-DCAA were not cytotoxic. In separate experiments, 3,5-DCNB cytotoxicity was reduced by pretreating IKC with antioxidants and cytochrome P450, flavin monooxygenase and peroxidase inhibitors, while 3,5-DCPHA cytotoxicity was attenuated by two nucleophilic antioxidants (glutathione and N-acetyl-L-cysteine). Incubation of IKC with 3,5-DCA (0.5–1.0 mM, 90 min) produced only 3,5-DCAA and 3,5-DCNB as detectable metabolites. These data suggest that 3,5-DCNB and 3,5-DCPHA are potential nephrotoxic metabolites and may contribute to 3,5-DCA induced nephrotoxicity in vivo. In addition, the kidney can bioactivate 3,5-DCNB to toxic metabolites, and 3,5-DCPHA appears to generate reactive metabolites to contribute to 3,5-DCA nephrotoxicity. In vitro, N-oxidation of 3,5-DCA appears to be the primary mechanism of bioactivation of 3,5-DCA to nephrotoxic metabolites.     

抗氧抗铜剂1024的合成研究

以[β (3,5 二叔丁基 4 羟基苯基)丙酸甲酯、氯化亚砜、水合肼为原料,经水解、卤置换、胺酰化和缩合反应合成1024,讨论了各步反应条件对成品收率及质量的影响。最佳反应条件:①3,5 丙酸的合成:pH值1～3,干燥温度100～105℃;②3,5 丙酰氯合成:3,5 丙酸与氯化亚砜摩尔比为1∶1.3,重结晶温度0～7℃;③3,5 丙酰肼合成:反应时间24h,反应温度为室温;④1024合成:3,5 丙酰肼和3,5 丙酰氯的摩尔比为1∶1.3。1024总收率为67.4%,熔点223～227℃。     

3,5-二羟基戊苯的合成研究

以3,5-二甲氧基苯甲酸为原料,通过合成3,5-二甲氧基苯甲酸乙酯、3,5-二甲氧基苯甲酰胺、3,5-二甲氧基苯戊酮、3,5-二甲氧基戊苯等4种中间产物最终得到目标产物3,5-二羟基戊苯,总收率为70.10%、纯度为98.84%.     

有机中间产品3，5-二氯硝基苯合成条件的研究

研究了以2,6-二氯-4-硝基苯胺为原料,合成3,5-氯苯胺的中间体3,5-二氯硝基苯的工艺条件。通过实验讨论了硫酸用量、乙醇用量、反应温度、时间、催化剂等各种因素对产品产率的影响,确定了最佳合成条件。结果表明：在最佳合成条件下,得到的产品收率可达79．6％。     

3,5-二氧基苯甲酰哌嗪和均苯三甲酰氯界面聚合法制备复合纳滤膜

A new aromatic diamine,3,5-diaminobenzoylpiperazine (3,5-DABP),was synthesized from 3,5-diaminobenzoic acid and 1-formyl piperazine.The structure of 3,5-DABP was identified by FT-IR spectra and 1H NMR spectra.With 3,5-DABP as aqueous monomer and trimesoyl chloride (TMC) as organic monomer,thin film composite (TFC) nanofiltration membranes were prepared by interfacial polymerization technology.The salt rejection order of these TFC membranes is Na2SO4>MgSO4>MgCl2>NaCl.This sequence indicates that the membranes are negatively charged.     

Down-Regulation of Porcine Heart Diaphorase Reactivity by Trimanganese Hexakis(3,5-Diisopropylsalicylate), Mn(3)(3,5-DIPS)6, and Down-Regulation of Nitric Oxide Synthase Reactivity by Mn(3)(3,5-DIPS)(6) and Cu(II)(2)(3,5-DIPS)(4)

Purposes of this work were to examine the plausible down-regulation of porcine heart diaphorase (PHD) enzyme reactivity and nitric oxide synthase (NOS) enzyme reactivity by trimanganese hexakis(3,5-diisopropylsalicylate), [Mn(3)(3,5-DIPS)(6)] as well as dicopper tetrakis(3,5- diisopropylsalicylate, [Cu(II)(2)(3,5-DIPS)(4)] as a mechanistic accounting for their pharmacological activities.Porcine heart disease was found to oxidize 114 muM reduced nicotinamide-adenine- dinucleotide-'(3)-phosphate (NADPH) with a corresponding reduction of an equivalent concentration of 2,6-dichlorophenolindophenol (DCPIP). As reported for Cu(II)(2) (3,5-DIPS)(4), addition of Mn(3)(3,5-DIPS)(6) to this reaction mixture decreased the reduction of DCPIP without significantly affecting the oxidation of NADPH. The concentration of Mn(3)(3,5-DIPS)(6) that produced a 50% decrease in DCPIP reduction (IC(50)) was found to be 5muM. Mechanistically, this inhibition of DCPIP reduction with ongoing NADPH oxidation by PHD was found to be due to the ability of Mn(3)(3,5-DIPS)(6) to serve as a catalytic electron acceptor for reduced PHD as had been reported for Cu(II)(2)(3,5-DIPS)(4). This catalytic decrease in reduction of DCPIP by Mn(3)(3,5-DIPS)(6) was enhanced by the presence of a large concentration of DCPIP and decreased by the presence of a large concentration of NADPH, consistent with what had been observed for the activity of Cu(II)(2)(3,5-DIPS)(4)Oxidation of NADPH by PHD in the presence of Mn(3)(3,5-DIPS)(6) and the absence of DCPIP was linearly related to the concentration of added Mn(3)(3,5-DIPS)(6) through the concentration range of 2.4 muM to 38muM with a 50% recovery of NADPH oxidation by PHD at a concentration of 6 muM Mn(3)(3,5-DIPS)(6)Conversion of [(3)H] L-Arginine to [(3)H] L-Citrulline by purified rat brain nitric oxide synthase (NOS) was decreased in a concentrated related fashion with the addition of Mn(3)(3,5-DIPS)(6) as well as Cu(II)(2)(3,5-DIPS)(4) which is an extention of results reported earlier for Cu(II)(2)(3,5-DIPS)(4). The concentration of these two compounds required to produce a 50% decrease in L-Citrulline synthesis by NOS, which may be due to down-regulation of NOS, were 0.1 mM and 8muM respectively, consistent with the relative potencies of these two complexes in preventing the reduction of Cytochrome c by NOS.It is concluded that Mn(3)(3,5-DIPS)(6), as has been reported for Cu(II)(2) (3,5-DIPS)(4) , serves as an electron acceptor in down-regulating PHD and both of these complexes down-regulate rat brain NOS reactivity. A decrease in NO synthesis in animal models of seizure and radiation injury may account for the anticonvulsant, radioprotectant, and radiorecovery activities of Mn(3)(3,5-DIPS)(6) and Cu(II)(2)(3,5-DIPS)(4).     

3,5-二羟基苯甲酸转移加氢动力学

研究了3,5-二羟基苯甲酸(DHB)为原料采用催化转移加氢法合成3,5-二氧代环己烷羧酸(DOC)的过程,得到了以5％Pd／C为催化剂、甲酸钠为氢供体的3,5-二羟基苯甲酸转移加氢宏观反应动力学。研究发现,在实验条件下原料3,5-二羟基苯甲酸的反应级数为0,供体甲酸钠和催化剂分别为一级;当氢供体大量过量时,3,5-二羟基苯甲酸的吸附速率是反应的控速步骤,初步探讨了反应过程的机理。     

氨化法合成3,5-二甲基苯胺的工艺研究

在钯碳催化剂存在下,3,5-二甲基苯酚通过部分加氢再氨化,生成3,5-二甲基苯胺。3,5-二甲基苯酚的转化率为95％,3,5-二甲基苯胺的产率为52％。     

一种安全的合成3,5-双三氟甲基苯乙酮方法

以3,5-双三氟甲基苯胺为初始原料,利用浓硫酸为介质和亚硝酰硫酸作为重氮化试剂制备3,5-双三氟甲基苯胺重氮盐,再与乙醛肟反应合成3,5-双三氟甲基苯乙酮。该方法可以安全、高效地制备3,5-双三氟甲基苯乙酮。     

利用二氢吡啶光诱导芳香化反应合成3,5-二氰基-2，4，6-三甲基吡啶

3，5-二氰基-2，4，6-三甲基吡啶在新型光电功能材料的合成中有重要的应用价值．本文在CCl4中光照1，4-二氢-3，5-二氰基-2，4，6-三甲基吡啶，高产率地合成了3，5-二氰基．2，4，6-三甲基吡啶．     

3,5-双(4-氨基苯氧基)苯甲酸的合成及其聚酰亚胺薄膜的性能研究

合成3,5-双(4-氨基苯氧基)苯甲酸(35BAPBA)。其方法为3,5-二羟基苯甲酸(35DHBA)和对氯硝基苯(PCNB)通过缩合反应,合成得到了3,5-双(4-硝基苯氧基)苯甲酸(35BNPBA);然后,进一步还原,得到3,5-双(4-氨基苯氧基)苯甲酸(35BAPBA),基于35BAPBA单体,制得多种结构的含羧基芳香族聚酰亚胺薄膜,并对这些薄膜的性能进行研究。制得的3,5-双(4-氨基苯氧基)苯甲酸(35BAPBA)的熔点为245.8℃,且纯度高。各类薄膜的透过率均可达80%以上,具有良好的紫外吸收性能;吸水性均小于3%,具有优异的疏水性能;其拉伸强度在15~56MPa之间。     

3,5-二甲氧苯基己基酮的合成

以3,5-二甲氧基苯甲酰胺为原料,经氰化反应,格式反应合成大麻隆的重要中间体-3,5-二甲氧苯基己基酮。较佳的合成工艺条件为:(1)腈基化反应:以0.2 mol 3,5-二甲氧基苯甲酰胺为基准,滴加时间2 h,质量分数(NaOH)=50%,溶剂为氯仿,相转移催化剂为TEBA,反应收率为74.39%;(2)格式反应:以0.25 mol 3,5-二甲氧基苯甲腈为基准,正溴己烷格氏试剂四氢呋喃溶液与3,5-二甲氧基苯甲腈的摩尔比为1.5∶1,回流时间为12 h,反应收率为92.1%。两步反应总收率为68.5%。通过熔点,沸点,1H NMR确证目标产物的化学结构。     

Synthesis and Field Tests of Possible Minor Components of the Sex Pheromone of Prionus californicus

Earlier work has shown that adult male Prionus californicus Motschulsky (Coleoptera: Cerambycidae) are attracted to the female-produced compound (3R,5S)-3,5-dimethyldodecanoic acid, and to a synthetic mixture of the four stereoisomers of 3,5-dimethyldodecanoic acid. Here, we report the results of field trials that tested whether or not three structurally related compounds (methyl 3,5-dimethyldodecanoate, 3,5-dimethyltridecanoic acid, and 3,5-dimethylpentadecanoic acid), present in extracts of virgin females, are attractive, and whether or not they influence attraction to 3,5-dimethyldodecanoic acid. In a trial with single components, only traps baited with the acid or its methyl ester captured more beetles than did control traps; catches to the acid were five times higher than to the methyl ester. Another trial, excluding 3,5-dimethyldodecanoic acid, confirmed the activity of the methyl ester. Finally, addition of the three compounds to 3,5-dimethyldodecanoic acid, in the ratio found in extracts from female beetles, gave a catch similar to that of traps baited with 3,5-dimethyldodecanoic acid alone. Consequently, the function of these minor compounds remains undetermined.     

HIV病毒抑制剂中间体3,5-二羟基戊苯(olivetol)的新合成方法

以工业级的3,5-二甲氧基苯甲酸为起始原料,与L iH于室温下在四氢呋喃中反应5 h生成3,5-二甲氧基苯甲酸锂(Ⅰ),不需精制,直接与正丁基锂在冰浴中进行酰化反应制得3,5-二甲氧基苯戊酮(Ⅱ),收率85.06%;进而在210℃以下通过乌尔夫-黄鸣龙反应将Ⅱ还原为3,5-二甲氧基戊苯(Ⅲ),Ⅲ与熔融的吡啶盐酸盐在200℃回流2 h,脱甲基制得目标产物3,5-二羟基戊苯(Ⅳ),总收率为60.90%,质量分数为98.22%。利用IR1、HNMR、GC、HLPC-MS等分析手段对各步产物进行了表征。结果表明:该文所提出合成路线是可行的,具有工艺简单、收率高等特点,优于目前所报道的其他合成路线。目前正在进行放大实验。     

4-氨基-3,5-二氯-6-氟吡啶-2-酚的合成及机理探讨

在由3,5-二氯-2,4,6-三氟吡啶经氨取代、羟基取代得到4-氨基-3,5-二氯-6-氟吡啶-2-酚的过程中,我们发现4-氨基-3,5-二氯-2,6-二氟吡啶和2-氨基-3,5-二氯-4,6-二氟吡啶均可以转化为4-氨基-3,5-二氯-6-氟吡啶-2-酚,且收率和产物纯度均较高,我们对机理进行探讨,提出该现象的原因是在碱性水溶液中存在2-羟基吡啶的酮-醇异构互变。     

HIV病毒抑制剂中间体5-戊基间苯二酚的合成

以3,5-二甲氧基苯甲酸为起始原料,与LiH在室温下反应5h生成苯甲酸盐,生成的盐再与正丁基锂进行酰化反应得到3,5-二甲氧基苯戊酮,进而在210℃以下进行乌尔夫-黄鸣龙反应将酮还原,生成3,5-二甲氧基戊苯,所得产物与吡啶盐酸盐熔融,于200℃回流2h,脱甲基制得5-戊基间苯二酚,总收率达60.9%,纯度≥98%。     

Physisorption vs grafting of aryldiazonium salts onto iron: A corrosion study

The possible involvement of an adsorption step in the course of the electrografting of aryldiazonium salts is tested by investigating the effect of 3,5-dimethylbenzenediazonium and of 2,6-dimethyl benzene diazonium salts (respectively 3,5- and 2,6-DMBD) on the corrosion of iron. In the case of 3,5-DMBD, the grafting is confirmed by infra red reflection absorption spectroscopy (IRRAS). Polarization curves of iron modified electrodes show increased protection against corrosion, particularly in the presence of 3,5-DMBD in the corrosion medium. Conversely, in the presence of 2,6-DMBD, whose radical does not attach onto the iron surface, no inhibition is observed. This indicates that, besides the absence of grafting, there is no physical adsorption of diazoniums onto iron prior to the grafting reaction, in contrast with graphene and carbon nanotubes.     

3,5-二羟基苯甲酸甲酯催化加氢制备3,5-二羟基甲苯

研究了用于3,5-二羟基苯甲酸甲酯加氢反应的催化剂,得到具有良好活性和选择性的CuO-ZnO催化剂。实验结果表明：采用Cu∶Zn原子比为1∶2、还原温度为200℃的CuO-ZnO催化剂,在反应温度200℃和压力9MPa条件下,反应时间1.6h,3,5-二羟基苯甲酸甲酯的转化率为100%,3,5-二羟基甲苯的收率达到87.4%。加氢反应历程的研究结果表明,3,5-二羟基甲苯的苯环易被加氢,生成带基团的环己烷系列副产物,使其收率下降,控制反应时间是提高反应收率的一个重要因素。     

Calcium(II)(3) (3,5-Diisopropylsalicylate)(6)(H(2)O)(6) Activates Nitric Oxide Synthase: An Accounting for its Action in Decreasing Platelet Aggregation

Purposes of these studies were first; to determine whether or not Calcium(II)(3) (3,5- diisopropylsalicylate)(6)(H(2)O)(6) [Ca(II)(3)(3,5-DIPS)(6)], a lipophilic calcium complex, could decrease activated-platelet aggregation, and second; to determine whether or not it is plausible that Ca(II)(3)(3,5-DIPS)(6) decreases activated-platelet aggregation by facilitating the synthesis of Nitric Oxide (NO) by Nitric Oxide Synthase (NOS). The influence of Ca(II)(3)(3,5-DIPS)(6) on the initial rate of activated-platelet aggregation was determined by measuring the decrease in rate of increase in transmission at 550 nm for a suspension of Thrombin-CaCl(2) activated platelets following the addition of 0, 50, 100, 250, or 500 muM Ca(II)(3)(3,5-DIPS)(6). To establish that the Ca(lI)(3)(3,5- DIPS)(6)-mediated decrease in aggregation was due to activation of NOS, the effect of L-NMMA, an inhibitor of NOS, on the inhibition of platelet aggregation by Ca(II)(3)(3,5-DIPS)(6) was determined using a suspension of activated platelets contaimng 0 or 250 muM Ca(II)(3)(3,5-DIPS)(6) without or with 1 mM L-NMMA. An in vitro Bovine Brain NOS reaction mixture, containing CaCl(2) for the activation of Phosphodiesterase-3' ,5'-Cyclic Nucleotide Activator required for the activation of NOS, was used to determine whether or not Ca(II)(3)(3,5-DIPS)(6) could be used as a substitute for the addition of Ca. The decrease in absorbance at 340 nm, lambda maximum for NADPH, was measured to determine NOS activity following the addition of NOS to the complete reaction mixture containing either CaCl(2), Ca(II)(3)(3,5-DIPS)(6), or neither Ca compound. Increasing the concentration of Ca(II)(3)(3,5-DIPS)(6) caused a concentration related decrease in activated platelet aggregation. The addition of L-NMMA to activated platelets, in the absence of Ca(II)(3)(3,5-DIPS)(6), caused a 129% increase in initial rate of platelet aggregation. The initial rate of platelet aggregation decreased 74% with the addition of 250 muM Ca(II)(3)(3,5-DIPS)(6) and the addition of L-NMMA plus 250 muM Ca(II)(3)(3,5-DIPS)(6) caused a 197% decrease in initial rate of aggregation compared to the initial rate observed width the presence of 1 mM L-NMMA alone. There was only a small, 27%, increase in initial rate of 0.4 mM NADPH oxidation when 0.9 mM CaCl(2) was added to the NOS reaction mixture in comparison to the initial rate of NADPH oxidation with no addition of CaCI(2). Addition of an equivalent amount of Ca in the form of Ca(II)(3)(3,5-DIPS)(6), 333 muM, caused a 37% increase in initial rate of NADPH oxidation compared to the addition of 0.9 mM CaCl(2). Addition of increasing concentrations of L-NMMA plus 0.9 mM CaCl(2) or 333 muM Ca(II)(3)(3,5-DIPS)(6) to the NOS reaction mixture caused a concentration related increase in initial rate of NADPH oxidation. Addition of L-NMMA while expected to decrease NADPH oxidation actually increased the rate of NADPH oxidation. Additions of 133 muM or 267 muM Ca(II)(3)(3,5- DIPS)(6) also caused concentration related increases in initial rate of NADPH oxidation in the presence of 113 muM L-NMMA. However, the addition of 533 muM Ca(II)(3)(3,5-DIPS)(6) caused a dramatic decrease in initial rate of NADPH oxidation by NOS. It is concluded that: 1) Ca(II)(3)(3,5- DIPS)(6) activates platelet NOS in preventing platelet aggregation, 2) in vitro NOS activity can be observed spectrophotometrically by following the consumption of NADPH as a decrease in absorbance at 340 nm, 3) Ca(II)(3)(3,5-DIPS)(6) plays a role in enhancing Bovine Brain NOS activity resulting in an increased rate of NADPH oxidation by NOS, 4) Ca(II)(3)(3,5-DIPS)(6) is a useful form of Ca in activating NOS and superior to CaCl(2) with regard to the facilitation of a NADPH oxidation, and 5) L-NMMA stimulates Bovine Brain NOS activity rather than causing an inhibition of this enzyme and must serve as a reducible substrate for Bovine Brain NOS.     

β-(3,5-二叔丁基-4-羟基苯基)丙酰氯的合成研究

以β-(3,5-二叔丁基-4-羟基苯基)丙酸甲酯为原料,通过水解反应和酰氯合成反应合成了抗氧剂中间体β-(3,5-二叔丁基-4-羟基苯基)丙酰氯。对酰氯合成条件进行了研究,得出优惠反应条件为:以氯仿作溶剂、β-(3,5-二叔丁基-4-羟基苯基)丙酸0.02mol、二氯亚砜0.054mol、反应温度50℃、反应时间5h,优惠条件下产品的收率为98.9%。