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This invention provides compounds of Formula; wherein: R is a moiety selected from the group: and n is an integer of 1 or 2; R is selected from hydrogen, amino,-NRR, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, alkenyl of 2 to 12 carbon atoms optionally substituted, alkynyl of 2 to 12 carbon atoms optionally substituted, halogen, and a 5 to 10 membered heteroaryl ring optionally substituted, having 1 to 4 heteroatoms independently selected from N, O and S; R is selected from hydrogen, alkyl of 1 to 12 carbon atoms optionally substituted, aryl of 6, 10 or 14 carbon atoms optionally substituted, alkenyl of 2 to 12 carbon atoms optionally substituted, vinyl, alkynyl of 2 to 12 carbon atoms optionally substituted and halogen; R is H, alkyl of 1 to 12 carbon atoms optionally substituted, cycloalkyl of 3 to 8 carbon atoms, bicycloalkyl of 5 to 10 carbon atoms or aralkyl optionally substituted; R is OH or -OH; R and R are each independently H or alkyl of 1 to 12 carbon atoms or when optionally taken together with the nitrogen atom to which each is attached form a 3 to 8 membered saturated heterocyclyl ring; R is alkyl of 1 to 12 carbon atoms optionally substituted; or a tautomer or pharmaceutically acceptable salts thereof.
本发明提供式的化合物;其中:R 1 为选自基团和的部分;n为整数1或2;R 2 选自氢、氨基、-NR 6 R 7 、具有1到12个碳原子的视情况经取代的烷基、具有6个、10个或14个碳原子的视情况经取代的芳基、具有2到12个碳原子的视情况经取代的烯基、具有2到12个碳原子的视情况经取代的炔基、卤素和具有1到4个独立地选自N、O和S的杂原子的视情况经取代的5元到10元杂芳基环;R 3 选自氢、具有1到12个碳原子的视情况经取代的烷基、具有6个、10个或14个碳原子的视情况经取代的芳基、具有2到12个碳原子的视情况经取代的烯基、乙烯基、具有2到12个碳原子的视情况经取代的炔基和卤素;R 4 为H、具有1到12个碳原子的视情况经取代的烷基、具有3到8个碳原子的环烷基、具有5到10个碳原子的双环烷基或视情况经取代的芳烷基;R 5 为OH或-OH 8 ;R 6 和R 7 各自独立地为H或具有1到12个碳原子的烷基,或当视情况与其所连接的氮原子连接在一起时形成3元到8元饱和杂环基环;R 8 为具有1到12个碳原子的视情况经取代的烷基;或其互变异构体或医药学上可接受的盐。
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Experimental results show that the different substituted location and different substituted group on benzene cycle would result in the diversity of reduction properties of substituted aryl nitrobenzene. Substituted nitrobenzenes with withdrawing group will be reduced at more positive potential, while those with repelling group will be reduced at more negative potential. In addition, the reduction potential of nitro group of o-nitrobenzene shifts more negative due to the effect of space resistance.
结果表明,芳族硝基化合物在苯环上的取代基位置不同以及在相同位置上取代基的种类不同均可使各芳族硝基化合物的电还原性能发生较大差异:吸电子取代基在电还原过程中电位较正,推电子取代基的电还原电位较负:邻位取代基在反应过程中由于空间位阻效应,苯环上的硝基在电还原时电位往负方向移动。
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Synthesis of target compounds namely: to vanillic acid as the starting material with methanol under reflux conditions for 4 - hydroxy -3 - p-methyl, then ether, and nitration, reduction, cyclization reaction 6 - methoxy -7 - benzyloxy-quinazoline -4 - one, and then by the chloride in place of aniline, benzyloxy-off, such as etherification reaction of the target compounds; target compounds with the second and third occurrence of substitution reactions of amines by the TM1, that is, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(N, N-diethyl amino) oxy c] quinazoline; with ether occurred Ornidazole reaction of TM2, namely, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(2 - methyl -5 - nitroimidazole) C oxy] quinazoline.
本论文以嘌呤类似物喹唑啉为母核,分别在其4位和7位引入结构多样的取代苯氨基和柔性侧链,设计了一系列4-取代苯胺基-6-甲氧基-7-(2-羟基取代丙氧基)喹唑啉类化合物。目标化合物的合成即:以香草酸为起始原料,与甲醇回流条件下得到4-羟基-3-甲氧基苯甲酸甲酯,然后经过醚化、硝化、还原、环合反应得到6-甲氧基-7-苄氧基喹唑啉-4-酮,然后再经氯化、取代苯胺、脱苄氧基、醚化等反应得到目标化合物;目标化合物与二乙胺发生胺取代反应得到了TM1,即4-苯氨基-6-甲氧基-7-[2-羟基-3-丙氧基]喹唑啉;通过与奥硝唑发生醚化反应得到TM2,即4-苯氨基-6-甲氧基-7-[2-羟基-3-(2-甲基-5-硝基咪唑)丙氧基]喹唑啉。
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The present invention relates to compounds of formula wherein R is hydrogen, lower alkyl, lower alkoxy, halogen or lower alkyl substituted by halogen; R is hydrogen or halogen; or R and R are together with the carbon atom to which they are attached -CH=CH-CH=CH-; R is hydrogen, lower alkyl, phenyl optionally substituted by halogen, or is hetaryl, optionally substituted by lower alkyl; R is hydrogen, lower alkyl, phenyl, benzyl, lower alkenyl, lower alkoxy, phenyloxy, benzyloxy, S-lower alkyl, halogen, CN, lower alkyl substituted by halogen or O-lower alkyl substituted by halogen; R is hydrogen or lower alkyl, aryl is phenyl or naphthyl; n is 1, 2 or 3; m is 1 or 2; and pharmaceutically acceptable acid addition salts and tautomeric forms thereof.
本发明涉及式化合物及其可药用的酸加成盐和互变异构形式,其中R 1 是氢、低级烷基、低级烷氧基、卤素或被卤素取代的低级烷基;R是氢或卤素;或R 1 和R与它们连接的碳原子一起是-CH=CH-CH=CH-;R 2 是氢、低级烷基、任选被卤素取代的苯基或者是任选被低级烷基取代的杂芳基;R 3 是氢、低级烷基、苯基、苄基、低级链烯基、低级烷氧基、苯氧基、苄氧基、S-低级烷基、卤素、CN、被卤素取代的低级烷基或被卤素取代的O-低级烷基;R 4 是氢或低级烷基,芳基是苯基或萘基;n是1、2或3;m是1或2。
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The bay area has no substituent and has electron-withdrawing groups,such as bromine atom,cyano-group and 4-formyl phenoxy group compounds have strong absorption in 525 nm,when excitated them,they have strong yellow and salmon pink luminescence bettwen 538 and 566 nm.When introduce electron-donating substituents,such as phenoxy group,morpholinyl,piperidinyl and n-butylamino group,the absorption bathochromic shift while the electron-donating ability is improved,bettwen 536 and 692 nm have strong absorption,reach to the near-infrared region. When excitated them,only the phenoxy group compound has strong salmon pink luminescence in 572 nm,the others have no fluorescence.
其中,港湾位无取代的以及含吸电基团(—Br、—CN、对甲酰基苯氧基)化合物在525 nm左右处均有很强的吸收ε>10~4M~(-1cm~(-1),当光激发时,港湾位无取代、溴代和氰基取代物发出538~547 nm的强烈黄色荧光,对甲酰基苯氧基取代物则发出566 nm的强烈橙红色荧光;含供电基团(苯氧基、吗啉基、哌啶基、正丁氨基)化合物随着供电子能力的增强,吸收发生红移,在536~692 nm处均有很强的吸收ε>10~4M~(-1cm~(-1),达到了近红外区,当光激发时,只有苯氧基取代物发出572 nm的强烈橙红色荧光,而含氮供电基取代物均发生了荧光淬灭。
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The results of bioassay suggest that 2-methylthio-6-methyl-4-substituted pyrimidine and 4, 6-dimethoxy-2-substituted pyrimidine derivatives show herbicidal activity. In these target compounds, 4, 6-dimethoxy-2-substituted pyrimidine benzylamine and 4, 6-dimethoxy-2-Substituted pyrimidine benzylidene amine exhibit good herbicidal activity, and the herbicidal will be affected by the substituents in the benzene ring.
对分子库中的目标分子进行了生物活性筛选研究,发现其中的2-甲硫基-6-甲基-4-取代嘧啶衍生物和4,6-二甲氧基-2-取代嘧啶类化合物显示出除草活性,其中4,6-二甲氧基-2-取代嘧啶苄胺类化合物和4,6-二甲氧基-2-取代嘧啶亚苄胺类化合物具有较好的除草活性,而且其活性和苯环上的取代基有关。
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The results showed that the degree of butyryl substitution of CAB increased and the degree of acetyl substitution of CAB decreased as the activation time increased. The degree of substitution of CAB changed slightly after the esterification went along about 2h.
随着活化时间的增加,CAB的丁酯取代度会逐渐增大,乙酯取代度会逐渐减小;酯化反应2h后,CAB取代度变化不大;CAB的丁酯取代度随着反应体系中丁酰基摩尔分数的增加而增大,而乙酯取代度则随着丁酰基摩尔分数的增加而减小。
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By means of GPC,IR,GC-MS,~(13)CNMR,~1HNMR,Methylation analysisetc,structural properties of PST-1 were identified as follows:The Mwof PST-1 was 3.44×10~6 Da and its optical rotation was _D~(20)=+0.110°(c0.1, H_2O); PST-1 constituted 8 simple sugars and the molar ratio was 2,4-Dimethoxy-Mannose:Rhamnose:Ara-binose:Xylose:Galactose:D-Galacturonic acid:Mannose:D-glucuronic acid=2%:5%:24%:9%:3%:1%:46%:10%;The chief bone of PST-1 was 1,3,6-linked-β-D-Man residue and the side chains contained Furanoid and Pyranoid residues.
结合GPC、旋光度测定、IR、GC-MS、~(13)CNMR、~1HNMR、高碘酸氧化法、Smith降解以及甲基化方法等分析测试方法,得到PST-1的单糖组成及结构表征,实验结果如下:红豆杉多糖PST-1是重均分子量为3.44×10~6 Da的支链多糖,旋光度为20D=+0.110~0(c0.1,H_2O);PST-1单糖组成为:2,4-Dimethoxy-Mannose:Rhamnose:Arabinose:Xylose:Galactose:D-Galacturonic acid:Mannose:D-glucuronic acid=2%:5%:24%:9%:3%:1%:46%:10%;PST-1的骨架结构为:具有1,3,6-连接的β-D-甘露糖残基骨架,侧链分枝包括非还原末端的呋喃型α-L-阿拉伯糖残基、吡喃型α-L-阿拉伯糖残基、β-D-木糖残基、β-D-甘露糖残基、2,4-二氧甲基-β-D-甘露糖残基和α-D-葡萄糖醛酸残基;侧链的糖残基也可能存在2,5-二氧-取代呋喃型α-L-阿拉伯糖基、3-氧-取代的β-D-木糖残基、6-氧-取代的α-D-半乳糖醛酸残基、6-氧-取代的α-D-半乳糖残基、4-氧-取代的α-D-葡萄糖醛酸残基和2-氧-取代的α-L-鼠李糖残基,同时后者也可能穿插在主链上。
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The results of calculation will be fundmentally consistent with the experimental values.In addition, we calculated dibenzene chromium and its derivatives, ferroceneand its derivatives. The former had higher symmetry. We studied the substituenteffects by calculating their NMR spectra. The results show that: when we add asubstitute group on one ring of dibenzene chromium, the substitute group will affecttwo benzene rings. The effect is similar to the effect of branched alkanes, namely:the effect on neighbouring groups has transmissibility. Furthermore, the nearer theneighbouring group is, the stronger the effect is. This effect is observed not only onthe substituted ring, but also on the unsubstituted ring.
此外,我们重点计算了二苯铬及其衍生物和二茂铁及其衍生物的核磁共振谱,其中二苯铬及其衍生物选择的是对称性较好的体系,通过计算其核磁共振四川师范大学硕士学位论文谱,探讨其取代基效应,结果表明:在二苯铬的一个环上引入取代基后,取代基对两个苯环的影响,类似于支链院烃引入取代基后的影响:即对邻近基团的影响有传递性,并且对离得近的作用强,对离得远的作用弱,这种作用不仅体现在连有取代基的环上,也体现在没有带取代基的环上。
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The reaction result showed that the reactivity of Grignard reagent was different in THF and diethyl ether when subjected to substitution reaction, which gave three products with different substitution degree.
研究表明,生成的Grignard试剂在THF和乙醚中的反应性不同,与甲基三硅烷或四乙氧基硅烷发生取代反应时生成不同取代度的产物,控制反应条件可得到以单取代、双取代或三取代硅烷为主的产物。
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Replace Temp with Query:(以查询取代暂时变数)
Replace Subclass with Fields(以栏位取代子类别) 232 | Replace Temp With Query(以查询取代暂时变数) 120 | Replace Type Code with Class(以类别取代型别代码) 218
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Replace Subclass with Fields:(以栏位取代子类别)
Replace Record with Data Class(以资料类别取代记录) 217 | Replace Subclass with Fields(以栏位取代子类别) 232 | Replace Temp With Query(以查询取代暂时变数) 120
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Replace Color:(取代顏色):取代某特定的顏色
Bitmap (點陣圖):影像以黑白兩種色彩顯示 | Replace Color (取代顏色):取代某特定的顏色 | Selective Color (選取顏色):可以加上或減少某特定的顏色
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Replace All:全部取代
replace 取代 | replace all 全部取代 | replace in files 多重档案取代
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replaceable character:可取代的字元
replaceable parameter data 可取代的参数资料 | replaceable character 可取代的字元 | replaceable text 可取代的文字
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replaceable character:可取代的字符
replace in projects 专案中取代 | replaceable character 可取代的字符 | replaceable character data 可取代的字符数据
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substituent:取代者;取代基
substation 分站;变电所;分台;用户话机 | substituent 取代者;取代基 | substitutability analysis 置换分析
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substituent effect:取代基效應 取代基效应
substituent 取代基 取代基 | substituent effect 取代基效應 取代基效应 | substitute 替代藥 替代药
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substituting agent:取代剂
substituted 取代的;代替的 | substituting agent 取代剂 | substituting group 取代基
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Replaces:取代
这种矛盾性关系是冲突(Conflicts)与取代(Replaces),取代的主要用途是新版用於取代旧版,绝大部分的函式库可以新旧并存,但是部份软体不可行,有时候是套件名称更改,因此新名称取代旧名称软体,冲突则是两种不同的软体或软体的版本水火不容,