CN103012207B - Diaryl propionyl-N-methyl hydroxamic acid type urease inhibitor and synthesis and application thereof - Google Patents

Diaryl propionyl-N-methyl hydroxamic acid type urease inhibitor and synthesis and application thereof Download PDF

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CN103012207B
CN103012207B CN 201210589876 CN201210589876A CN103012207B CN 103012207 B CN103012207 B CN 103012207B CN 201210589876 CN201210589876 CN 201210589876 CN 201210589876 A CN201210589876 A CN 201210589876A CN 103012207 B CN103012207 B CN 103012207B
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肖竹平
王旭东
易利成
胡小军
杨盼
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吉首大学
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一类二芳基丙酰-N-甲基氧肟酸化合物,它们具有如下结构通式:它们对尿素酶有较好的抑制作用,可以用于制备抗胃炎、胃溃疡、尿路结石等药物,本发明公开了其制法。 A class of diaryl propionyloxy -N- methyl hydroxamic acid compounds having the general structural formula: they have good inhibition of urease, may be used to prepare anti-gastritis, gastric ulcer, urolithiasis and other drugs the present invention discloses a preparation method thereof.

Description

二芳基丙酰-N-甲基氧肟酸类尿素酶抑制剂及其合成和用途 Diaryl propionyloxy -N- methyl hydroxamic acid urease inhibitors and their synthesis and use

技术领域 FIELD

[0001] 本发明涉及一类二芳基丙酰-N-甲基氧肟酸类尿素酶抑制剂的制法以及它们在制备抗胃炎、胃溃疡药物中的应用。 [0001] The present invention relates to a class of diaryl propionyloxy -N- methyl hydroxamic acid inhibitors of urease preparation method and applications thereof ulcer medicament in preparation of anti-gastritis. 技术背景 technical background

[0002] 幽门螺旋杆菌(Helicobacterpylari)会引发胃炎、胃溃瘍、十二指肠溃瘍、胃萎缩、肠上皮化生、胃癌、胃淋巴瘤等多种疾病。 [0002] Helicobacter pylori (Helicobacterpylari) cause gastritis, gastric ulcer, duodenal ulcer, gastric atrophy, intestinal metaplasia, gastric cancer, gastric lymphoma, and other diseases. 1994年世界卫生组织和国际癌症研究中心将H.pylori列为第一类致癌因子。 In 1994 the World Health Organization and the International Cancer Research Center will H.pylori as a first class carcinogen. 据统计,世界人口大约有一半感染了H.pylori,在发展中国家中感染率高达80-90%。 According to statistics, about half the world's population infected with H.pylori, infection rates as high as 80-90% in developing countries. 我国的感染率为60%左右。 Our infection rate is about 60%. 胃炎患者的H.pylori检出率为80-90%,消化性溃疡患者更高,达95%以上。 H.pylori gastritis detection rate of 80-90%, more peptic ulcer patients, more than 95%. 超过90%的十二指肠溃疡和80%左右的胃溃疡是H.pylori所致。 More than 90% of duodenal ulcers and 80% of gastric ulcers are caused by H.pylori. 根除H.pylori是治疗上述疾病以及防止复发的前提。 H.pylori eradication is a prerequisite for treatment of these diseases and prevention of recurrence. 目前根除H.pylori 最常用的是三联法:一种质子泵抑制剂(奥美拉唑或兰索拉唑)和两种抗生素(阿莫西林、氧氟沙星或甲硝唑)。 H.pylori eradication currently the most commonly used method is triple: one kind of proton pump inhibitor (lansoprazole or omeprazole) and two antibiotic (amoxicillin, ofloxacin or metronidazole). 但是,奥美拉唑有明显的副作用:除会引起腹痛、呕吐、胀气等副作用外, 还会引起肝重量增大等;还有诱发胃类癌、引起肾衰等危险。 However, there are significant side effects Omeprazole: In addition to cause abdominal pain, vomiting, flatulence and other side effects, it will also lead to increased liver weight, etc.; also induced gastric carcinoid tumors, causing kidney failure and other dangerous. 此外H.pylori对所用的抗生素容易产生耐药性,因此,这一方法的有效率正逐年下降。 In addition to antibiotics used H.pylori prone to drug resistance, and therefore, is declining efficiency of this approach.

[0003] 众所周知,胃内是一个强酸环境,幽门螺旋杆菌能在胃内存活的最主要原因是它的尿素酶活性。 [0003] It is well known, is a strongly acidic environment in the stomach, H. pylori can survive in the stomach and the main reason is its urease activity. 尿素酶水解尿素释放出来的氨能提高pH值,并且最新研究显示,受体结构中尿素分子是幽门螺旋杆菌感知和避免胃酸环境的关键因素。 Hydrolysis of urea urease ammonia can be released to raise the pH, and new research shows the structure of the receptor molecule is a key factor in urea Helicobacter pylori and avoid gastric environment perception. 因此尿素酶的作用为H.pylori营造了一个适宜的微环境。 Therefore, the role of H.pylori urease to create a suitable microenvironment. 其他一些病菌,如普通变形杆菌(Proteusvulgaris)、 奇异变形杆菌(Proteusmirabilis)、解脲脲原体(Ureaplasmaurealyticum)等,当它们感染尿路系统后,因为尿素酶的作用引起尿的pH升高,导致磷酸铵镁等物质的沉淀,进而发展成尿路结石。 Other bacteria, such as Proteus vulgaris (Proteusvulgaris), Proteus mirabilis (Proteusmirabilis), etc. Ureaplasma urealyticum (Ureaplasmaurealyticum), urinary tract infection when they, pH due to urease action because the urine increased, resulting in precipitation of magnesium ammonium phosphate and other substances, and then developed into urolithiasis. 具有尿素酶活性的病原菌要么靠尿素酶水解尿素产生氨为自身的生命活动提供氮源,要么利用氨的碱性为其生存提供一个适宜的微环境。 Pathogens having urease activity against urease to produce ammonia or urea to provide a nitrogen source for the hydrolysis of their life activities, using an alkaline or ammonia to provide a suitable microenvironment for their survival. 故阻断了尿素酶活性,就能有效的杀灭这类病菌。 Therefore, blocking the urease activity, can effectively kill such bacteria. 因此,尿素酶抑制剂必将成为治疗这类疾病的一线药物。 Therefore, urease inhibitors will become the first-line therapy of such diseases. 但现有的尿素酶抑制剂存在一些不足,比如乙酰氧肟酸由于活性低,用量大,导致了一些副作用,而高活性的磷酸二酰胺类尿素酶抑制剂在酸性环境中不稳定,阻碍了其在临床上的应用。 However, the existing urease inhibitor has some disadvantages, such as acetohydroxamic acid due to low activity, the amount of large, resulting in a number of side effects, while the high activity of acid urease inhibitor diamides unstable in an acidic environment, hindering its application in clinical practice. 因此新型高效低毒尿素酶抑制剂的筛选是开发这类药物的关键。 Thus the screening of new low toxicity urease inhibitors are key to the development of such drugs.

[0004] 利用计算机模拟技术,通过骨架改造与迁越,设计并合成了具有I所示结构的新型尿素酶抑制剂。 [0004] The use of computer simulation technology, and transformation of the skeleton by hopping designed and synthesized novel urease inhibitor has the structure I is shown. 试验表明,有些化合物对尿素酶表现出了优良的抑制活性。 Tests showed that some compounds exhibit an excellent urease inhibitory activity.

[0005] [0005]

Figure CN103012207BD00051

发明内容 SUMMARY

[0006] 本发明的目的在于设计并合成一系列二芳基丙酰-N-甲基氧肟酸(I)类尿素酶抑制剂,在深入研究构效关系的基础上,发现了活性更高、毒副作用更低的新型尿素酶抑制齐U,并提供二芳基丙酰-N-甲基氧肟酸化合物的制法。 [0006] The object of the present invention is designed and synthesized a series of diaryl urea class propionyl -N- methyl hydroxamic acid inhibitors (the I), in-depth study on the structure-activity relationship found higher activity , lower toxicity novel urease inhibition homogeneous U, and to provide a diaryl method propionyl -N- methyl hydroxamic acid compound.

[0007] 本发明的技术方案如下: [0007] aspect of the present invention is as follows:

[0008] -类二芳基丙酰-N-甲基氧肟酸化合物,它们具有如下结构通式: [0008] - propionyloxy class diaryl -N- methyl hydroxamic acid compounds having the general structural formula:

Figure CN103012207BD00052

[0010] 式I中R1、R2、R3、R4、R5、R6、R7和R8的定义取自下列各组之任一组: [0010] Formula I, R1, R2, R3, R4, R5, R6, R7 and R8 are taken from the definition of any group of the following groups:

[0011] (1)R2=R3=R4=R5=R6=R7=R8=H,RkF、Cl、Br、N02、OH、OMe、OEt或NH2; [0011] (1) R2 = R3 = R4 = R5 = R6 = R7 = R8 = H, RkF, Cl, Br, N02, OH, OMe, OEt, or NH2;

[0012] (2) #=1?3=1?4=1?5=1?6=1? 7=1?8=11,R2=F、Cl、Br、N02、OH、OMe、OEt或NH2; [0012] (2) # = 1? 3 = 1? 4 = 1? 5 = 1? 6 = 1? 7 = 1? 8 = 11, R2 = F, Cl, Br, N02, OH, OMe, OEt, or NH2;

[0013] (3) #=1?2=1?4=1?5=1?6=1? 7=1?8=11,R3=F、Cl、Br、N02、OH、OMe、OEt或NH2; [0013] (3) # = 1? 2 = 1? 4 = 1? 5 = 1? 6 = 1? 7 = 1? 8 = 11, R3 = F, Cl, Br, N02, OH, OMe, OEt, or NH2;

[0014] (4)R2=R3=R4=R5=R6=R7=H,Ri=R8=F、Cl、Br、N02、OH、OMe、OEt或NH2; [0014] (4) R2 = R3 = R4 = R5 = R6 = R7 = H, Ri = R8 = F, Cl, Br, N02, OH, OMe, OEt, or NH2;

[0015] (5) #=1?3=1?4=1?5=1?6=1? 7=11,R2=R7=F、Cl、Br、N02、OH、OMe、OEt或NH2; [0015] (5) # = 1 3 = 1 4 = 1 5 = 1 6 = 1 7 = 11, R2 = R7 = F, Cl, Br, N02, OH, OMe, OEt, or NH2?????;

[0016] (6)R^R^R^R^R^R^H,R3=R6=CH3^N(CH3) 3; [0016] (6) R ^ R ^ R ^ R ^ R ^ R ^ H, R3 = R6 = CH3 ^ N (CH3) 3;

[0017] (7)R2=R4=R5=R7=R8=H,RkOH,R3=0Me或0 (CH2) 7CH3; [0017] (7) R2 = R4 = R5 = R7 = R8 = H, RkOH, R3 = 0Me or 0 (CH2) 7CH3;

[0018] (8)R^R^R^R^R^R^H,R2=R3=CH3; [0018] (8) R ^ R ^ R ^ R ^ R ^ R ^ H, R2 = R3 = CH3;

[0019] (9)R2=R3=R4=R5=R7=R8=H,R^R^F; [0019] (9) R2 = R3 = R4 = R5 = R7 = R8 = H, R ^ R ^ F;

[0020] (10)R2=R4=R5=R6=R7=R8=H,R^R^F; [0020] (10) R2 = R4 = R5 = R6 = R7 = R8 = H, R ^ R ^ F;

[0021] (lDR^R^R^R^R^R^H,R2=R3=F; [0021] (lDR ^ R ^ R ^ R ^ R ^ R ^ H, R2 = R3 = F;

[0022] (12)R4=R5=R6=R8=H,RkRlOH,R2=R7=0H或H ; [0022] (12) R4 = R5 = R6 = R8 = H, RkRlOH, R2 = R7 = 0H or H;

[0023] (13)R2=R4R5=R6=R7=R8=H,RbCl,R3=N02; [0023] (13) R2 = R4R5 = R6 = R7 = R8 = H, RbCl, R3 = N02;

[0024] (14)R^R^R^R^R^R^R^H,R3=CH3; [0024] (14) R ^ R ^ R ^ R ^ R ^ R ^ R ^ H, R3 = CH3;

[0025] (15)R2=R4=R5=R6=R7=R8=H,Ri=NH2,妒=勵2或Cl ; [0025] (15) R2 = R4 = R5 = R6 = R7 = R8 = H, Ri = NH2, jealous Li = 2 or Cl;

[0026] (16)R2=R3=R4=R5=R6=R7=H,RtOH、NH2、N02、OMe或OEt,R8=F、Cl或; [0026] (16) R2 = R3 = R4 = R5 = R6 = R7 = H, RtOH, NH2, N02, OMe, or OEt, R8 = F, Cl, or;

[0027] (17)R2=R3=R4=R5=R6=R8=H,RbOH、NH2、勵2或OMe,R7=F、Cl或; [0027] (17) R2 = R3 = R4 = R5 = R6 = R8 = H, RbOH, NH2, or Li 2 OMe, R7 = F, Cl, or;

[0028] (18)R2=R3=R4=R5=R6=R8=H,RbOEt,R7=C1 或; [0028] (18) R2 = R3 = R4 = R5 = R6 = R8 = H, RbOEt, R7 = C1 or;

[0029] (19)RbRkRkRkRLRkH,R2=〇H,R7=F、Cl或fc。 [0029] (19) RbRkRkRkRLRkH, R2 = 〇H, R7 = F, Cl, or fc.

[0030] -种制备二芳基丙酰-N-甲基氧肟酸系列化合物的方法,它基本上由下列步骤组成: [0030] - propionyloxy diaryl -N- methyl hydroxamic acid series compounds processes for preparing species, consisting essentially of the following steps:

[0031]步骤1•将1-#-2-1?2-3-1?3-4-1?4取代苯加入到BF3 .Et20 中,升温至40-50°C之间, 待l-Ry-RM-RM-R4取代苯溶解后,加入2-R8-3-R7-4-R6-5-R5取代苯甲酸,物质的量之t匕苯:2-R8-3-R7-4-R6-5-R5取代苯甲酸:BF3*Et20=l: (1~4): (60~100),升温至65-110°C之间反应4~24h,反应完毕,倒入AcONa的水溶液中,搅拌2~10h,抽滤,洗涤,Et0H-H20 重结晶,得到1-1^-2-1?2-3-1?3-4-1?4-2' -R8-3' -R7-4' -R6-5' -R5 取代二苯基甲酮(II); [0031] Step 1 • Pull 1-- # - 2-12-3-13-4-14 added to BF3 .Et20 substituted benzene and heated to between 40-50 ° C, L-be??? after ry-RM-RM-R4-substituted benzene was dissolved, was added 2-R8-3-R7-4-R6-5-R5-substituted benzoic acid, the amount of material t dagger benzene: 2-R8-3-R7-4- R6-5-R5-substituted benzoic acid: BF3 * Et20 = l: (1 ~ 4): (60 ~ 100), the reaction temperature was raised to between 65-110 ° C 4 ~ 24h, the reaction is completed, the solution was poured into AcONa , stirred for 2 ~ 10h, filtration, washing, Et0H-H20 recrystallized 1-1 ^ -2-1? 2-3-1? 3-4-1? 4-2 '-R8-3' -R7 -4 '-R6-5' -R5-substituted benzophenone (II);

Figure CN103012207BD00061

[0033]步骤2•将1-1^-2-1?2-3-1?3-4-1?4-2' -R8-3' -R7-4' -R6-5' -R5取代二苯基甲酮(II)、Zn粉、NH4C1、溴乙酸乙酯一起研磨均匀,物质的量之比d-Rij-fS-lfH4-]' -R8 -3' -R7-4' -R6-5' -R5取代二苯基甲酮(II) :Zn:NH4Cl:溴乙酸乙酯=1:10:9: (1 ~5),室温静置10~24h后,倒入饱和NH4C1溶液,AcOEt萃取,无水MgS04干燥,蒸去溶剂,用硅胶柱纯化,洗脱剂体积比:AcOEt:石油醚=1:12~2:1,得到3-(2-1^-3-1?2-4-1?3-5-1?4取代苯基)-3-(2-R8-3-R7-4-R6-5-R5取代苯基)-3-羟基丙酸乙酯(III); [0033] Step 2 • The 1-1 ^ -2-1? 2-3-1? 3-4-1? 4-2 '-R8-3' -R7-4 '-R6-5' -R5 replaced benzophenone (II), Zn powder, NH4C1, triturated with ethyl bromoacetate uniform than d-Rij-fS-lfH4- amount of a substance] '-R8 -3' -R7-4 '-R6- 5 '-R5-substituted benzophenone (II): Zn: NH4Cl: ethyl bromoacetate = 1: 10: 9: (1-5), 10 ~ 24h after standing at room temperature, poured into saturated NH4C1 solution, AcOEt extraction, drying over anhydrous MgS04, the solvent was evaporated, purified by silica gel column, eluent volume ratio: AcOEt: petroleum ether = 1: 12 to 2: 1, to give 3- (2-1 ^ -3-12-? ?? 4-13-5-14 substituted phenyl) -3- (2-R8-3-R7-4-R6-5-R5-substituted phenyl) -3-hydroxy-propanoate (III);

Figure CN103012207BD00062

[0035]步骤3•将3-羟基-3- (2-1^-3-1?2-4-1?3-5-1?4取代苯基)-3- (2-R8-3-R7-4-R6-5-R5 取代苯基)丙酸乙酯(III)溶于无水甲醇,然后加入CH3NH0H•HC1、甲醇钠,物质的量之比为:3_ 羟基取代苯基)-3-(2-R8-3-R7-4-R6-5-R5取代苯基)丙酸乙酯(III):CH3NH0H,HCl:CH30Na=l:4: (2~9),搅拌11~30h,蒸去甲醇,加入去离子水, 用AcOEt萃取,合并有机层,MgS04干燥,蒸去溶剂,用硅胶柱纯化,洗脱剂体积比:AcOEt:石油醚=1:10 ~3:1,得3-羟基-3- (2-1^-3-1?2-4-1?3-5-1?4取代苯基)-3- (2-R8-3-R7-4-R6-5-R5 取代苯基)丙酰-N-甲基氧肟酸(I),其中所述的#、1?2、1?3、1?4、1?5、1?6、矿和1?8的定义与上述的定义相同。 [0035] Step 3 • 3-Hydroxy-3- (2-1 ^ -3-1? 2-4-1? 3-5-1? 4-substituted phenyl) -3- (2-R8-3- R7-4-R6-5-R5-substituted phenyl) propanoate (III) was dissolved in anhydrous methanol, followed by addition of CH3NH0H • HC1, sodium methoxide, the amount of substance ratio: 3_ hydroxy substituted) -3 - (2-R8-3-R7-4-R6-5-R5-substituted phenyl) propanoate (III): CH3NH0H, HCl: CH30Na = l: 4: (2 ~ 9), stirred for 11 ~ 30h, The methanol was evaporated, deionized water was added and extracted with AcOEt, and the organic layers were combined, dried MgSO4, the solvent was evaporated, purified by silica gel column, eluent volume ratio: AcOEt: petroleum ether = 1: 10 ~ 3: 1, to give 3 - hydroxy-3- (2-1 ^ -3-12-4-13-5-1 4 in place of phenyl???) -3- (2-R8-3-R7-4-R6-5- R5-substituted phenyl) propionyl -N- methyl hydroxamic acid (the I), wherein the # 1? 2,1? 3,1? 4,1? 5,1? 6, and a mineral? 8 It defined the same as defined above.

Figure CN103012207BD00071

具体实施方式 detailed description

[0037] 通过以下实施例进一步详细说明本发明,但应注意本发明的范围并不受这些实施例的任何限制。 [0037] The following Examples further illustrate the present invention in detail, it should be noted that the scope of the present invention is in no way restricted to these examples.

[0038] 实施例1 :3-(3-羟基苯基)-3-(2, 3, 4-三羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(50)的制备 Preparation of methyl hydroxamic acid (50) 3- (3-hydroxyphenyl) -3- (2, 3, 4-Trimethyl-hydroxyphenyl) -3-hydroxy-propionyl -N-: [0038] Example 1

[0039] 将2. 52g焦性没食子酸加入到20mlBF3*Et20中,再加入3. 31g间羟基苯甲酸,升温至85°C之间反应15h,反应完毕,倒入AcONa的水溶液中,抽滤,洗漆,Et0H-H20重结晶,得到3-羟基苯基-2, 3, 4-三羟基苯基甲酮3. 78g,产率77% ; [0039] An aqueous solution of 2. 52g gallic acid pyrophosphate to 20mlBF3 * Et20 was added, and then m-hydroxybenzoic acid was added 3. 31g, 15h the reaction was warmed to between 85 ° C, the reaction is complete, pour the AcONa, suction removers, Et0H-H20 was recrystallized to give 3-hydroxy-2, 3, 4-trihydroxyphenyl ketone 3. 78g, 77% yield;

[0040]将3-羟基苯基-2, 3, 4-三羟基苯基甲酮2. 46g和6. 5gZn粉、4. 82gNH4C1、4. 45mL 溴乙酸乙酯一起研磨均匀。 [0040] A mixture of 3-hydroxy-2, 3, 4-trihydroxyphenyl methanone 2. 46g and 6. 5gZn powder, polishing uniformity with 4. 82gNH4C1,4. 45mL ethyl bromoacetate. 室温静置18h后,倒入饱和NH4C1溶液,AcOEt萃取,无水MgS04 干燥,蒸去溶剂,用硅胶柱纯化,洗脱剂体积比:AcOEt:石油醚=1:2,得3-羟基-3- (3-羟基苯基)-3-(2, 3, 4-三羟基苯基)丙酸乙酯,2. 17g,产率65% ; After standing at room temperature for 18 h, poured into saturated NH4C1 solution, AcOEt was extracted, and dried over anhydrous MgS04, the solvent was evaporated, purified by silica gel column, eluent volume ratio: AcOEt: petroleum ether = 1: 2, to give 3-hydroxy-3 - (3-hydroxyphenyl) -3- (2, 3, 4-Trimethyl-hydroxyphenyl) propionate, 2 17g, 65% yield;

[0041] 再将1.67g3-羟基-3- (3-羟基苯基)-3-(2,3,4_三羟基苯基)丙酸乙酯溶于30mL无水甲醇,搅拌下加入CH3NH0H•HC11. 67g、CH30Nal. 35g,室温搅拌29h,蒸去甲醇后加10mL去离子水,AcOEt萃取,合并有机层,无水MgS04干燥,蒸去溶剂,硅胶(200-300目)柱层析纯化,洗脱剂体积比:AcOEt:石油醚=1:1,得白色固体3-羟基-3-苯基-3- (2, 3, 4-三羟基苯基)丙酰-N-甲基氧肟酸(50)0. 96g,产率57%。 [0041] Then 1.67g3--hydroxy-3- (3-hydroxyphenyl) -3- (2,3,4_ three-hydroxyphenyl) propionate was dissolved in 30mL dry methanol was added with stirring CH3NH0H • HC11. 67g, CH30Nal. 35g, 29H stirring at room temperature, methanol was evaporated and 10mL deionized water was added, AcOEt, the organic layers were combined, dried over anhydrous MgS04, the solvent was distilled off, silica gel (200-300 mesh) column chromatography, volume ratio eluent: AcOEt: petroleum ether = 1: 1, to give a white solid of 3-hydroxy-3-phenyl-3- (2, 3, 4-Trimethyl-hydroxyphenyl) propionyl-methyl hydroxamic -N- acid (50) 0. 96g, 57% yield. 熔点:120-122°C;EIMSm/z:335[M+]; IR(KBiOcnTijTeS(0H),3021 (順);屮NMR(DMS0-d6)Sppm:3. 16 (s,2H),3.29 (s,3H), 3.67 (s,lH),5.76 (s,4H),6.85 (d,lH),7.01 (d,lH),7.26 (dd,lH),7.33 (m,3H),8.21 (s,1H),10. 32 (s,1H)。 Melting point: 120-122 ° C; EIMSm / z: 335 [M +]; IR (KBiOcnTijTeS (0H), 3021 (cis); Cao NMR (DMS0-d6) Sppm:. 3 16 (s, 2H), 3.29 (s , 3H), 3.67 (s, lH), 5.76 (s, 4H), 6.85 (d, lH), 7.01 (d, lH), 7.26 (dd, lH), 7.33 (m, 3H), 8.21 (s, 1H), 10. 32 (s, 1H).

[0042] 实施例2: [0042] Example 2:

[0043] 按实施例1相似的方法,用不同的取代形式的苯甲酸和苯为原料,合成了表1所列的二芳基丙酰-N-甲基氧肟酸系列化合物1~86。 [0043] a similar manner as in Example 1 of the embodiment, different forms of substituted benzoic acid and benzene as raw materials listed in Table 1 were synthesized diaryl propionyloxy -N- methyl hydroxamic acid series compounds 1 to 86.

[0044] 表1通式I中二芳基丙酰-N-甲基氧肟酸系列化合物的各R基团 [0044] Table 1 in formula I diaryl propionyl -N- each R group is methyl hydroxamic acid series compound

Figure CN103012207BD00072

Figure CN103012207BD00081

Figure CN103012207BD00091

[0047] [0047]

Figure CN103012207BD00101

Figure CN103012207BD00111

[0048] 注:初始原料均购自于aldrich公司 [0048] Note: The starting materials were purchased from the company aldrich

[0049] 实施例3 :化合物的抑酶活性 [0049] Example 3: The inhibitory activity of compound

[0050] 往96孔板中加入25iiLJackbean(刀豆)尿素酶(4U)和25iiL(ImM)被测化合物的溶液,在37°C下培育2h,然后加入含有100mM尿素和100mM的磷酸缓冲液55iiL,在30°C 下培育15min,加入45iiL酚试剂(含苯酚1%与含硝普钠0. 005%的混合溶液)和70iiL碱试剂(含NaOHO. 5%与0. 1%活性氯的NaOCl的混合溶液),在室温下放置50min后,用酶标仪测定630nm下的0D值,百分抑制率按下式计算: [0050] 96 was added to 25iiLJackbean (ConA) urease (4U) and 25iiL (ImM) solution of the test compound, incubated 2h at 37 ° C, followed by addition of urea and 100mM phosphate buffer containing 100mM of 55iiL , incubated 15min at 30 ° C, was added 45iiL phenol reagent (containing 1% phenol and a mixed solution containing 0.005% of sodium nitroprusside) and 70iiL alkali agent (including NaOHO. 5% and 0.1% active chlorine in NaOCl after the mixed solution), placed at room temperature for 50min, measured 0D value at 630nm using a microplate reader, percent inhibition is calculated as follows:

[0051] [0051]

Figure CN103012207BD00121

[0052] 所有的试验都在pH为8. 2的溶液中进行(0• 01M的K2HP04,ImM的EDTA,0• 01M的LiCl),活性的高低以半抑制率IC5(I来表示,IC5(I越小,此化合物的活性越高,结果见表2。 [0052] All experiments were performed at pH 8.2 in solution (K2HP04 0 • 01M of, the ImM EDTA, 0 • LiCl 01M) and the level of activity inhibitory rate in semi IC5 (I represented, IC5 ( I, the higher the activity of the compound, the results shown in Table 2.

[0053] 结果表明:本发明所述的部分二芳基丙酰-N-甲基氧肟酸系列化合物对尿素酶有较好的抑制活性,一些比阳性对照乙酰氧肟酸的活性更高。 [0053] The results show that: the part of the invention diaryl propionyloxy -N- methyl hydroxamic acid-based compound has good activity against urease inhibition, some of the higher activity acetohydroxamic acid than the positive control.

[0054] 表2二芳基丙酰-N-甲基氧肟酸系列化合物对刀豆尿素酶的抑制作用(IC5(I) [0054] Table 2 diaryl propionyloxy -N- methyl hydroxamic acid series compounds urease inhibition of ConA (IC5 (I)

Figure CN103012207BD00122

Figure CN103012207BD00131

[0057] 结果表明,化合物3、15、23、32、39、43、50、57、65、69、75、80对刀豆尿素酶有显著的抑制作用,且抑制作用较乙酰氧肟酸更高,活性最好的达到乙酰氧肟酸的212倍。 [0057] The results show that the compounds 3,15,23,32,39,43,50,57,65,69,75,80 significantly inhibited Con urease, and the inhibition of more than acetohydroxamic acid high activity reached 212 times the best acetohydroxamic acid.

[0058] 本发明的上述实施例表明:在合成的二芳基丙酰-N-甲基氧肟酸系列化合物中, 一部分的尿素酶抑制作用高于阳性对照物乙酰氧肟酸,对大鼠的急毒实验表明,化合物15、 32、50、69、80的剂量达到5g/kg(此剂量为药典规定的无毒剂量)时,没有发现大鼠有中毒迹象,因此在正常剂量下,它们作为药物应用是安全的。 [0058] The above-described embodiments of the present invention shows that: in the synthesis of diaryl propionyloxy -N- methyl hydroxamic acid compound series, a part of the urease inhibition than was the positive control acetohydroxamic acid, rats the acute toxicity experiments show that the compounds 15, 32,50,69,80 the dose of 5g / kg (this dose is the Pharmacopoeia nontoxic amount), the rats have found no signs of toxicity, and so in normal doses, they as drug use is safe.

[0059] 化合物1~86的熔点、质谱、红外及核磁氢谱数据: [0059] Compounds 1 to 86, melting point, mass spectrum, IR and NMR spectrum data hydrogen:

[0060] 3-苯基-3- (2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(1) [0060] 3-phenyl-3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (1)

[0061]Mpl37-139°C;EIMSm/z:289[M+];IR(KBr)cm_1:2761 (OH),3025 (NH) ;:HNMR (DMS0-d6)8ppm:3. 20 (s,2H),3. 28 (s,3H),3. 60 (s, 1H), 7. 21~7. 28 (m, 1H), 7. 46~7. 53 (m,6H),7. 53~7. 71 (m,2H),8. 21 (s,lH),l〇. 25 (s,lH)〇 [0061] Mpl37-139 ° C; EIMSm / z: 289 [M +]; IR (KBr) cm_1: 2761 (OH), 3025 (NH);: HNMR (DMS0-d6) 8ppm: 3 20 (s, 2H. ), 3. 28 (s, 3H), 3. 60 (s, 1H), 7. 21 ~ 7. 28 (m, 1H), 7. 46 ~ 7. 53 (m, 6H), 7. 53 ~ 7. 71 (m, 2H), 8. 21 (s, lH), l〇. 25 (s, lH) square

[0062] 3-苯基-3-(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(2) [0062] 3-phenyl-3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (2)

[0063]Mpl42-144°C;EIMSm/z:305[M+];IR(KBr)cm_1:2764 (OH),3023 (NH) ;:HNMR (DMS0-d6)8ppm:3. 17 (s,2H),3. 29 (s,3H),3. 57 (s, 1H), 7. 33~7. 40 (m, 1H), 7. 45~7. 53 (m,5H),7. 53~7. 61 (m, 2H), 7. 82~7. 90 (m, 1H),8. 25 (s,lH),l〇. 23 (s,lH)〇 [0063] Mpl42-144 ° C; EIMSm / z: 305 [M +]; IR (KBr) cm_1: 2764 (OH), 3023 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 29 (s, 3H), 3. 57 (s, 1H), 7. 33 ~ 7. 40 (m, 1H), 7. 45 ~ 7. 53 (m, 5H), 7. 53 ~ 7. 61 (m, 2H), 7. 82 ~ 7. 90 (m, 1H), 8. 25 (s, lH), l〇. 23 (s, lH) square

[0064] 3-苯基-3-(2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(3) [0064] 3-phenyl-3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (3)

[0065]Mpl54-156°C;EIMSm/z:335[M+];IR(KBr)cm_1:2765 (OH),3027 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 30 (s,3H),3. 58 (s, 1H), 7. 36~7. 42 (m, 2H), 7. 45~7. 51 (m,4H),7. 55~7. 63 (m, 2H), 7. 63~7. 71 (m, 1H),8. 23 (s,lH),l〇. 24 (s,lH)〇 [0065] Mpl54-156 ° C; EIMSm / z: 335 [M +]; IR (KBr) cm_1: 2765 (OH), 3027 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 30 (s, 3H), 3. 58 (s, 1H), 7. 36 ~ 7. 42 (m, 2H), 7. 45 ~ 7. 51 (m, 4H), 7. 55 ~ 7. 63 (m, 2H), 7. 63 ~ 7. 71 (m, 1H), 8. 23 (s, lH), l〇. 24 (s, lH) square

[0066] 3-苯基-3-(2-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(4) [0066] 3-phenyl-3- (2-nitrophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (4)

[0067]Mpl66-167°C;EIMSm/z316[M+];IR(KBr)cm_1:2768 (OH),3026 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 31 (s,3H),3. 56 (s, 1H), 7. 42~7. 50 (m, 3H), 7. 54~7. 62 (m,2H),7. 71~7. 77 (m, 2H), 7. 82~7.88(m, 1H),8. 30~8. 41 (m,2H),l〇. 20 (s,lH)〇 [0067] Mpl66-167 ° C; EIMSm / z316 [M +]; IR (KBr) cm_1: 2768 (OH), 3026 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 31 (s, 3H), 3. 56 (s, 1H), 7. 42 ~ 7. 50 (m, 3H), 7. 54 ~ 7. 62 (m, 2H), 7. 71 ~ 7. 77 (m, 2H), 7. 82 ~ 7.88 (m, 1H), 8. 30 ~ 8. 41 (m, 2H), l〇. 20 (s, lH) square

[0068] 3-苯基-3-(2-羟基苯)-3-羟基丙酰-N-甲基氧肟酸(5) [0068] 3-phenyl-3- (2-hydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (5)

[0069] Mpl38-140°C;EIMSm/z:287[M+];IR(KBr)cm_1:2765 (OH),3029 (NH) ;:HNMR (DMS0-d6)8ppm:3. 17 (s,2H),3. 30 (s,3H),3. 60 (s,lH),5. 48 (s, 1H), 7. 02~7. 17 (m, 2H),7. 39~7. 47 (m, 2H), 7. 48~7. 53 (m, 3H), 7. 57~7. 61 (m,2H),8. 22 (s,lH),l〇. 20 (s, 1H)。 [0069] Mpl38-140 ° C; EIMSm / z: 287 [M +]; IR (KBr) cm_1: 2765 (OH), 3029 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 30 (s, 3H), 3. 60 (s, lH), 5. 48 (s, 1H), 7. 02 ~ 7. 17 (m, 2H), 7. 39 ~ 7. 47 ( m, 2H), 7. 48 ~ 7. 53 (m, 3H), 7. 57 ~ 7. 61 (m, 2H), 8. 22 (s, lH), l〇. 20 (s, 1H).

[0070] 3-苯基-3-(2-甲氧基基苯基)-3-羟基丙酰-N-甲基氧肟酸(6) [0070] 3-phenyl-3- (2-methoxy group) -3-hydroxy-propionyl -N- methyl hydroxamic acid (6)

[0071] Mpl47-149°C;EIMSm/z:301[M+];IR(KBr)cm_1:2766 (OH),3025 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 64 (s,lH),4. 04 (s, 3H), 7. 15~7. 22 (m, 3H),7. 36~7. 40 (m, 1H), 7. 45~7. 50 (m, 3H), 7. 54~7. 63 (m,2H),8. 24 (s,lH),l〇. 22 (s, 1H)。 [0071] Mpl47-149 ° C; EIMSm / z: 301 [M +]; IR (KBr) cm_1: 2766 (OH), 3025 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 29 (s, 3H), 3. 64 (s, lH), 4. 04 (s, 3H), 7. 15 ~ 7. 22 (m, 3H), 7. 36 ~ 7. 40 ( m, 1H), 7. 45 ~ 7. 50 (m, 3H), 7. 54 ~ 7. 63 (m, 2H), 8. 24 (s, lH), l〇. 22 (s, 1H).

[0072] 3-苯基-3-(2-乙氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(7) [0072] 3-phenyl-3- (2-ethoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (7)

[0073] Mpl70-172°C;EIMSm/z:315[M+];IR(KBr)cm_1:2767 (OH),3025 (NH) ;:HNMR (DMS0-d6) 8ppm:1. 18 (t,3H),3. 19 (s,2H),3. 28 (s,3H),3. 39 (m,2H),3. 64 (s,lH), 7. 17-7.23 (m,3H),7. 36~7. 40 (m, 1H), 7. 46~7. 51 (m, 3H), 7. 55~7. 63 (m,2H),8. 22 (s, 1H),10. 23 (s,lH)〇 [0073] Mpl70-172 ° C; EIMSm / z: 315 [M +]; IR (KBr) cm_1: 2767 (OH), 3025 (NH);: HNMR (DMS0-d6) 8ppm: 1 18 (t, 3H. ), 3. 19 (s, 2H), 3. 28 (s, 3H), 3. 39 (m, 2H), 3. 64 (s, lH), 7. 17-7.23 (m, 3H), 7 . 36 ~ 7. 40 (m, 1H), 7. 46 ~ 7. 51 (m, 3H), 7. 55 ~ 7. 63 (m, 2H), 8. 22 (s, 1H), 10. 23 (s, lH) square

[0074] 3-苯基-3-(2-氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(8) [0074] 3-phenyl-3- (2-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (8)

[0075] Mpl31-133°C;EIMSm/z:286[M+];IR(KBr)cm_1:2768 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 27 (s,3H),3. 62 (s,lH),6. 53 (s, 2H),6. 91~6. 97 (m, 2H),7. 24~7. 30 (m, 2H), 7. 47~7. 53 (m, 3H), 7. 57~7. 63 (m,2H),8. 22 (s,lH),l〇. 24 (s, 1H)。 [0075] Mpl31-133 ° C; EIMSm / z: 286 [M +]; IR (KBr) cm_1: 2768 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 27 (s, 3H), 3. 62 (s, lH), 6. 53 (s, 2H), 6. 91 ~ 6. 97 (m, 2H), 7. 24 ~ 7. 30 ( m, 2H), 7. 47 ~ 7. 53 (m, 3H), 7. 57 ~ 7. 63 (m, 2H), 8. 22 (s, lH), l〇. 24 (s, 1H).

[0076] 3-苯基-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(9) [0076] 3-phenyl-3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl-hydroxamic acid (9)

[0077] Mpl39-141°C;EIMSm/z289[M+];IR(KBr)cm_1:2765 (OH),3029 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 31 (s,3H),3. 63 (s,lH),7. 09 (t, 1H), 7. 32~7. 40 (m, 2H),7. 48~7. 55 (m, 4H), 7. 55~7. 62 (m,2H),8. 21 (s,lH),l〇. 23 (s,lH)〇 [0077] Mpl39-141 ° C; EIMSm / z289 [M +]; IR (KBr) cm_1: 2765 (OH), 3029 (NH);:. HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H), 3. 31 (s, 3H), 3. 63 (s, lH), 7. 09 (t, 1H), 7. 32 ~ 7. 40 (m, 2H), 7. 48 ~ 7. 55 (m, 4H), 7. 55 ~ 7. 62 (m, 2H), 8. 21 (s, lH), l〇. 23 (s, lH) square

[0078] 3-苯基-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(10) [0078] 3-phenyl-3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (10)

[0079] Mpl62-164°C;EIMSm/z:305[M+];IR(KBr)cm_1:2762 (OH),3029 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 19 (s,2H),3. 29 (s,3H),3. 63 (s, 1H), 7. 47~7. 55 (m, 5H), 7. 58~7. 63 (m,3H),7. 74 (t,lH),8. 24 (s,lH),l〇. 20 (s,lH)〇 [0079] Mpl62-164 ° C; EIMSm / z: 305 [M +]; IR (KBr) cm_1: 2762 (OH), 3029 (NH);: HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H. ), 3. 29 (s, 3H), 3. 63 (s, 1H), 7. 47 ~ 7. 55 (m, 5H), 7. 58 ~ 7. 63 (m, 3H), 7. 74 ( t, lH), 8. 24 (s, lH), l〇. 20 (s, lH) square

[0080] 3-苯基-3- (3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(11) [0080] 3-phenyl-3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (11)

[0081] Mpl75-177°C;EIMSm/z349[M+];IR(KBr)cm_1:2763 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 29 (s,3H),3. 68 (s, 1H), 7. 33~7. 40 (m, 1H), 7. 45~7. 52 (m,4H),7. 54~7. 60 (m, 2H), 7. 62~7. 70 (m,2H),8. 21 (s,lH),l〇. 22 (s,lH)〇 [0081] Mpl75-177 ° C; EIMSm / z349 [M +]; IR (KBr) cm_1: 2763 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H),. 3. 29 (s, 3H), 3. 68 (s, 1H), 7. 33 ~ 7. 40 (m, 1H), 7. 45 ~ 7. 52 (m, 4H), 7. 54 ~ 7. 60 (m, 2H), 7. 62 ~ 7. 70 (m, 2H), 8. 21 (s, lH), l〇. 22 (s, lH) square

[0082] 3-苯基-3-(3-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(12) [0082] 3-phenyl-3- (3-nitrophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (12)

[0083] Mpl69-170°C;EIMSm/z316[M+];IR(KBr)cm_1:2761 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 31 (s,3H),3. 67 (s, 1H), 7. 42~7. 50 (m, 3H), 7. 53~7. 61 (m,3H),7. 81~7. 87 (m, 1H),7. 92~7. 96 (m, 1H),8. 20 (s, 1H),8. 41~8. 46 (m, 1H), 10. 21 (s, 1H)。 [0083] Mpl69-170 ° C; EIMSm / z316 [M +]; IR (KBr) cm_1: 2761 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H),. 3. 31 (s, 3H), 3. 67 (s, 1H), 7. 42 ~ 7. 50 (m, 3H), 7. 53 ~ 7. 61 (m, 3H), 7. 81 ~ 7. 87 (m, 1H), 7. 92 ~ 7. 96 (m, 1H), 8. 20 (s, 1H), 8. 41 ~ 8. 46 (m, 1H), 10. 21 (s, 1H) .

[0084]3-苯基-3-(3-羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(13) [0084] 3-phenyl-3- (3-hydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (13)

[0085] Mpl49-151°C;EIMSm/z287[M+];IR(KBr)cm_1:2765 (OH),3029 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 29 (s,3H),3. 68 (s, 1H),5. 47 (s, 1H),6. 97-7. 05 (m, 1H), 7.11-7. 18 (m, 1H),7. 26~7. 33 (m, 1H), 7. 35~7. 43 (m, 1H), 7. 44~7. 50 (m, 3H), 7. 58~7. 65 (m,2H),8.21 (s,lH),10.21 (s,lH)。 [0085] Mpl49-151 ° C; EIMSm / z287 [M +]; IR (KBr) cm_1: 2765 (OH), 3029 (NH);:. HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H), 3. 29 (s, 3H), 3. 68 (s, 1H), 5. 47 (s, 1H), 6. 97-7. 05 (m, 1H), 7.11-7. 18 (m, 1H) , 7. 26 ~ 7. 33 (m, 1H), 7. 35 ~ 7. 43 (m, 1H), 7. 44 ~ 7. 50 (m, 3H), 7. 58 ~ 7. 65 (m, 2H), 8.21 (s, lH), 10.21 (s, lH).

[0086] 3-苯基-3-(3-甲氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(14) [0086] 3-phenyl-3- (3-methoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (14)

[0087] Mpl60-162 °C ;EIMS m/z301[M+] ;IR (KBr) cm_1:2760 (OH),3024 (NH);:H NMR (DMS0-d6) 8 ppm:3. 17 (s,2H),3. 31 (s,3H),3. 64 (s,lH),4. 13 (s, 3H), 7. 12~7. 19 (m, 2H),7. 25~7. 32 (m, 1H), 7. 35~7. 41 (m, 1H), 7. 47~7. 53 (m, 3H), 7. 57~7. 62 (m,2H),8. 22 (s, 1H)10.24 (s,lH)〇 [0087] Mpl60-162 ° C; EIMS m / z301 [M +]; IR (KBr) cm_1:. 2760 (OH), 3024 (NH) ;: H NMR (DMS0-d6) 8 ppm: 3 17 (s, 2H), 3. 31 (s, 3H), 3. 64 (s, lH), 4. 13 (s, 3H), 7. 12 ~ 7. 19 (m, 2H), 7. 25 ~ 7. 32 (m, 1H), 7. 35 ~ 7. 41 (m, 1H), 7. 47 ~ 7. 53 (m, 3H), 7. 57 ~ 7. 62 (m, 2H), 8. 22 (s , 1H) 10.24 (s, lH) square

[0088] 3-苯基-3-(3-乙氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(15) [0088] 3-phenyl-3- (3-ethoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (15)

[0089] Mpl82-184 °C ;EIMS m/z315[M+] ;IR (KBr) cm_1:2764 (OH),3022 (NH);:H NMR (DMS0-d6) 8ppm:l. 16 (t,3H),3. 17 (s,2H),3. 31 (s, 3H), 3. 41-3. 54 (m,2H),3. 68 (s, 1H),7. 07~7. 13 (m,2H),7. 29 (s, 1H),7. 47~7. 54 (m,4H),7. 57~7. 64 (m,2H),8. 23 (s, 1H) 10.25 (s,lH)〇 [0089] Mpl82-184 ° C; EIMS m / z315 [M +]; IR (KBr) cm_1: 2764 (OH), 3022 (NH) ;: H NMR (DMS0-d6) 8ppm: l 16 (t, 3H. ), 3. 17 (s, 2H), 3. 31 (s, 3H), 3. 41-3. 54 (m, 2H), 3. 68 (s, 1H), 7. 07 ~ 7. 13 ( m, 2H), 7. 29 (s, 1H), 7. 47 ~ 7. 54 (m, 4H), 7. 57 ~ 7. 64 (m, 2H), 8. 23 (s, 1H) 10.25 ( s, lH) square

[0090] 3-苯基-3-(3-氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(16) [0090] 3-phenyl-3- (3-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (16)

[0091] Mpl44-146 °C ;EIMS m/z:286[M+] ;IR (KBr) cm_1:2766 (OH),3025 (NH);:H NMR (DMS0-d6) 8 ppm:3. 15 (s,2H),3. 29 (s,3H),3. 67 (s,lH),6. 81 (s, 2H), 7. 13~7. 20 (m, 3H),7. 29~7. 31 (m, 1H), 7. 47~7. 55 (m, 3H), 7. 57~7. 64 (m,2H),8. 21 (s,lH) 10.23 (s, 1H)。 [0091] Mpl44-146 ° C; EIMS m / z: 286 [M +]; IR (KBr) cm_1:. 2766 (OH), 3025 (NH) ;: H NMR (DMS0-d6) 8 ppm: 3 15 ( s, 2H), 3. 29 (s, 3H), 3. 67 (s, lH), 6. 81 (s, 2H), 7. 13 ~ 7. 20 (m, 3H), 7. 29 ~ 7 . 31 (m, 1H), 7. 47 ~ 7. 55 (m, 3H), 7. 57 ~ 7. 64 (m, 2H), 8. 21 (s, lH) 10.23 (s, 1H).

[0092] 3-苯基-3-(4-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(17) [0092] 3-phenyl-3- (4-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (17)

[0093] Mpl37-139°C;EIMSm/z:289[M+];IR(KBr)cm_1:2764 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 12 (s,2H),3. 29 (s,3H),3. 66 (s,lH),7. 32 (t, 2H), 7. 45~7. 53 (m, 5H),7. 57~7. 63 (m,2H),8. 22 (s,lH),l〇. 22 (s,lH)〇 [0093] Mpl37-139 ° C; EIMSm / z: 289 [M +]; IR (KBr) cm_1: 2764 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 12 (s, 2H. ), 3. 29 (s, 3H), 3. 66 (s, lH), 7. 32 (t, 2H), 7. 45 ~ 7. 53 (m, 5H), 7. 57 ~ 7. 63 ( m, 2H), 8. 22 (s, lH), l〇. 22 (s, lH) square

[0094] 3-苯基-3-(4-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(18) [0094] 3-phenyl-3- (4-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (18)

[0095] Mpl44-145°C;EIMSm/z:305[M+];IR(KBr)cm_1:2764 (OH),3022 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 10 (s,2H),3. 30 (s,3H),3. 69 (s,lH),7. 34 (t, 2H), 7. 45~7. 52 (m, 3H),7. 62 (t,2H),7. 57~7. 66 (m,2H),8. 26 (s,lH),l〇. 23 (s,lH)〇 [0095] Mpl44-145 ° C; EIMSm / z: 305 [M +]; IR (KBr) cm_1: 2764 (OH), 3022 (NH);: HNMR (DMS0-d6) 8ppm: 3 10 (s, 2H. ), 3. 30 (s, 3H), 3. 69 (s, lH), 7. 34 (t, 2H), 7. 45 ~ 7. 52 (m, 3H), 7. 62 (t, 2H) , 7. 57 ~ 7. 66 (m, 2H), 8. 26 (s, lH), l〇. 23 (s, lH) square

[0096] 3-苯基-3-(4-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(19) [0096] 3-phenyl-3- (4-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (19)

[0097] Mpl86-188°C;EIMSm/z:349[M+];IR(KBr)cm_1:2768 (OH),3022 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 12 (s,2H),3. 26 (s,3H),3. 69 (s,lH),7. 33 (t, 2H), 7. 45~7. 53 (m, 3H),7. 59~7. 68 (m,2H),8. 12 (t,2H),8. 24 (s,lH),l〇. 24 (s,lH)〇 [0097] Mpl86-188 ° C; EIMSm / z: 349 [M +]; IR (KBr) cm_1: 2768 (OH), 3022 (NH);: HNMR (DMS0-d6) 8ppm: 3 12 (s, 2H. ), 3. 26 (s, 3H), 3. 69 (s, lH), 7. 33 (t, 2H), 7. 45 ~ 7. 53 (m, 3H), 7. 59 ~ 7. 68 ( m, 2H), 8. 12 (t, 2H), 8. 24 (s, lH), l〇. 24 (s, lH) square

[0098] 3-苯基-3-(4-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(20) [0098] 3-phenyl-3- (4-nitrophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (20)

[0099] Mpl65-167°C;EIMSm/z:316[M+];IR(KBr)cm_1:2768 (OH),3023 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 19 (s,2H),3. 29 (s,3H),3. 66 (s, 1H), 7. 45~7. 52 (m, 3H), 7. 57~7. 63 (m,2H),7. 92 (t,2H),8. 22 (s,lH),8. 32 (t,2H),l〇. 25 (s,lH)〇 [0099] Mpl65-167 ° C; EIMSm / z: 316 [M +]; IR (KBr) cm_1: 2768 (OH), 3023 (NH);: HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H. ), 3. 29 (s, 3H), 3. 66 (s, 1H), 7. 45 ~ 7. 52 (m, 3H), 7. 57 ~ 7. 63 (m, 2H), 7. 92 ( t, 2H), 8. 22 (s, lH), 8. 32 (t, 2H), l〇. 25 (s, lH) square

[0100] 3-苯基-3-(4-羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(21) [0100] 3-phenyl-3- (4-hydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (21)

[0101] Mpl31-133°C;EIMSm/z:287[M+];IR(KBr)cm_1:2765 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 19 (s,2H),3. 26 (s,3H),3. 68 (s, 1H),5. 75 (s, 1H),6. 92 (t,2H),7. 36 (t,2H),7. 46~7. 53 (m, 3H), 7. 57~7. 63 (m,2H),8. 22 (s,lH),l〇. 21 (s,lH)〇 [0101] Mpl31-133 ° C; EIMSm / z: 287 [M +]; IR (KBr) cm_1: 2765 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H. ), 3. 26 (s, 3H), 3. 68 (s, 1H), 5. 75 (s, 1H), 6. 92 (t, 2H), 7. 36 (t, 2H), 7. 46 ~ 7. 53 (m, 3H), 7. 57 ~ 7. 63 (m, 2H), 8. 22 (s, lH), l〇. 21 (s, lH) square

[0102] 3-苯基-3-(4-甲氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(22) [0102] 3-phenyl-3- (4-methoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (22)

[0103] Mpl38-139 °C ;EIMS m/z:301[M+] ;IR (KBr) cm_1:2764 (OH),3027 (NH);:H NMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 69 (s, 1H),4. 19 (s,3H),7. 13 (t,2H),7. 39 (t,2H),7. 44~7. 50 (m, 3H), 7. 57~7. 64 (m,2H),8. 22 (s,lH),l〇. 23 (s,lH)〇 [0103] Mpl38-139 ° C; EIMS m / z: 301 [M +]; IR (KBr) cm_1: 2764 (OH), 3027 (NH) ;: H NMR (DMS0-d6) 8ppm: 3 18 (s. , 2H), 3. 29 (s, 3H), 3. 69 (s, 1H), 4. 19 (s, 3H), 7. 13 (t, 2H), 7. 39 (t, 2H), 7 . 44 ~ 7. 50 (m, 3H), 7. 57 ~ 7. 64 (m, 2H), 8. 22 (s, lH), l〇. 23 (s, lH) square

[0104] 3-苯基-3-(4-乙氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(23) [0104] 3-phenyl-3- (4-ethoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (23)

[0105] Mpl40-142°C;EIMSm/z:315[M+];IR(KBr)cm_1:2762 (OH),3027 (NH) ;:HNMR (DMS0-d6) 8ppm:1. 19 (t,3H),3. 17 (s,2H),3. 31 (s, 3H), 3. 42~3. 50 (m,2H),3. 68 (s, 1H),7. 13 (t,2H),7. 37 (t,2H),7. 46~7. 54 (m,3H),7. 57~7. 63 (m,2H),8. 24 (s, 1H), 10. 21 (s,lH)。 [0105] Mpl40-142 ° C; EIMSm / z: 315 [M +]; IR (KBr) cm_1: 2762 (OH), 3027 (NH);: HNMR (DMS0-d6) 8ppm: 1 19 (t, 3H. ), 3. 17 (s, 2H), 3. 31 (s, 3H), 3. 42 ~ 3. 50 (m, 2H), 3. 68 (s, 1H), 7. 13 (t, 2H) , 7. 37 (t, 2H), 7. 46 ~ 7. 54 (m, 3H), 7. 57 ~ 7. 63 (m, 2H), 8. 24 (s, 1H), 10. 21 (s , lH).

[0106] 3-苯基-3-(4-氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(24) [0106] 3-phenyl-3- (4-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (24)

[0107] Mpl32-134〇C;EIMSm/z:286[M+];IR(KBr)cm^l:2767 (OH), 3029 (NH)NMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 31 (s,3H),3. 68 (s,lH),6. 57 (s,2H),7. 29 (t,2H), 7.44-7.54 (m,3H),7. 58~7. 62 (m,2H),7. 88 (t,2H),8. 22 (s,lH),l〇. 24 (s,lH)〇 [0107] Mpl32-134〇C; EIMSm / z: 286 [M +]; IR (KBr) cm ^ l: 2767 (OH), 3029 (NH) NMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 31 (s, 3H), 3. 68 (s, lH), 6. 57 (s, 2H), 7. 29 (t, 2H), 7.44-7.54 (m, 3H), 7. 58 ~ 7. 62 (m, 2H), 7. 88 (t, 2H), 8. 22 (s, lH), l〇. 24 (s, lH) square

[0108] 3, 3-二(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(25) [0108] 3, 3-di (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (25)

[0109] Mpl95-197°C;EIMSm/z:307[M+];IR(KBr)cm_1:2765 (OH),3027 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 29 (s,3H),3. 66 (s, 1H), 7. 29~7. 35 (m, 2H), 7. 45~7. 52 (m,2H),7. 76~7. 82 (m, 2H), 7. 89~7. 93 (m,2H),8. 24 (s,lH),l〇. 23 (s,lH)〇 [0109] Mpl95-197 ° C; EIMSm / z: 307 [M +]; IR (KBr) cm_1: 2765 (OH), 3027 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 29 (s, 3H), 3. 66 (s, 1H), 7. 29 ~ 7. 35 (m, 2H), 7. 45 ~ 7. 52 (m, 2H), 7. 76 ~ 7. 82 (m, 2H), 7. 89 ~ 7. 93 (m, 2H), 8. 24 (s, lH), l〇. 23 (s, lH) square

[0110] 3, 3-二(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(26) [0110] 3, 3-di (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (26)

[0111] Mp203-205 °C;EIMSm/z:339[M+];IR(KBr)cm_1:2760 (OH),3028 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 31 (s,3H),3. 68 (s, 1H), 7. 34~7. 42 (m, 2H), 7. 48~7. 51 (m,4H),7. 86~7. 93 (m,2H),8. 21 (s,lH),l〇. 24 (s,lH)〇 [0111] Mp203-205 ° C; EIMSm / z: 339 [M +]; IR (KBr) cm_1: 2760 (OH), 3028 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 31 (s, 3H), 3. 68 (s, 1H), 7. 34 ~ 7. 42 (m, 2H), 7. 48 ~ 7. 51 (m, 4H), 7. 86 ~ 7. 93 (m, 2H), 8. 21 (s, lH), l〇. 24 (s, lH) square

[0112] 3, 3-二(2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(27) [0112] 3, 3-di (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (27)

[0113] Mp218-219 °C;EIMSm/z:426[M+];IR(KBr)cm_1:2768 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 30 (s,3H),3. 68 (s, 1H), 7. 34~7. 40 (m, 4H), 7. 48~7. 53 (m,2H),7. 75~7. 83 (m,2H),8. 21 (s,lH),l〇. 21 (s,lH)〇 [0113] Mp218-219 ° C; EIMSm / z: 426 [M +]; IR (KBr) cm_1: 2768 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 30 (s, 3H), 3. 68 (s, 1H), 7. 34 ~ 7. 40 (m, 4H), 7. 48 ~ 7. 53 (m, 2H), 7. 75 ~ 7. 83 (m, 2H), 8. 21 (s, lH), l〇. 21 (s, lH) square

[0114] 3, 3-二(2-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(28) [0114] 3, 3-di (2-nitrophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (28)

[0115] Mp212-214°C;EIMSm/z:361[M+];IR(KBr)cm_1:2762 (OH),3023 (NH) ;:HNMR (DMS0-d6)Sppm:3.17 (s,2H),3.29 (s,3H),3.69 (s,lH),7.81 ~7.88 (m,4H),795~804 (m,2H),831~839 (m,3H),1023 (s,lH)。 [0115] Mp212-214 ° C; EIMSm / z: 361 [M +]; IR (KBr) cm_1: 2762 (OH), 3023 (NH);: HNMR (DMS0-d6) Sppm: 3.17 (s, 2H), 3.29 (s, 3H), 3.69 (s, lH), 7.81 ~ 7.88 (m, 4H), 795 ~ 804 (m, 2H), 831 ~ 839 (m, 3H), 1023 (s, lH).

[0116] 3, 3-二(2-羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(29) [0116] 3,3-bis (2-hydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (29)

[0117] Mpl79-181°C;EIMSm/z303[M+];IR(KBr)cm_1:2763 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 19 (s,2H),3.29 (s,3H),3.69 (s,lH),5.78 (s,2H),7. 19 (t,4H), 7.35-7.42 (m,4H),8. 26 (s,lH),l〇. 23 (s,lH)〇 [0117] Mpl79-181 ° C; EIMSm / z303 [M +]; IR (KBr) cm_1: 2763 (OH), 3026 (NH);:. HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H), 3.29 (s, 3H), 3.69 (s, lH), 5.78 (s, 2H), 7. 19 (t, 4H), 7.35-7.42 (m, 4H), 8. 26 (s, lH), l〇 . 23 (s, lH) square

[0118] 3, 3-二(2-甲氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(30) [0118] 3, 3-di (2-methoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (30)

[0119] Mp213-215°C;EIMSm/z:331[M+];IR(KBr)cm_1:2764 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 27 (s,3H),3. 68 (s,lH),4. 14 (s, 6H), 7. 11~7. 20 (m, 6H),7. 35~7. 40 (m,2H),8. 26 (s,lH),l〇. 22 (s,lH)〇 [0119] Mp213-215 ° C; EIMSm / z: 331 [M +]; IR (KBr) cm_1: 2764 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H. ), 3. 27 (s, 3H), 3. 68 (s, lH), 4. 14 (s, 6H), 7. 11 ~ 7. 20 (m, 6H), 7. 35 ~ 7. 40 ( m, 2H), 8. 26 (s, lH), l〇. 22 (s, lH) square

[0120] 3, 3-二(2-乙氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(31) [0120] 3, 3-di (2-ethoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (31)

[0121] Mp217-219°C;EIMSm/z:359[M+];IR(KBr)cm_1:2766 (OH),3029 (NH) ;:HNMR (DMS0-d6) 8ppm:1. 21 (t,6H),3. 17 (s,2H),3. 27 (s, 3H), 3. 42~3. 47 (m,4H),3. 69 (s, 1H),7. 11~7. 20 (m,6H),7. 35~7. 43 (m,2H),8. 26 (s,lH),l〇. 23 (s,lH)〇 [0121] Mp217-219 ° C; EIMSm / z: 359 [M +]; IR (KBr) cm_1: 2766 (OH), 3029 (NH);: HNMR (DMS0-d6) 8ppm: 1 21 (t, 6H. ), 3. 17 (s, 2H), 3. 27 (s, 3H), 3. 42 ~ 3. 47 (m, 4H), 3. 69 (s, 1H), 7. 11 ~ 7. 20 ( m, 6H), 7. 35 ~ 7. 43 (m, 2H), 8. 26 (s, lH), l〇. 23 (s, lH) square

[0122] 3, 3-二(2-氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(32) [0122] 3, 3-di (2-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (32)

[0123] Mpl384-186°C;EIMSm/z301[M+];IR(KBr)cm_1:2763 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 27 (s,3H),3. 69 (s,lH),6. 63 (s, 4H),6. 92~7. 01 (m, 4H),7. 38~7. 44 (m,4H),8. 26 (s,lH),l〇. 25 (s,lH)〇 [0123] Mpl384-186 ° C; EIMSm / z301 [M +]; IR (KBr) cm_1: 2763 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 27 (s, 3H), 3. 69 (s, lH), 6. 63 (s, 4H), 6. 92 ~ 7. 01 (m, 4H), 7. 38 ~ 7. 44 (m, 4H), 8. 26 (s, lH), l〇. 25 (s, lH) square

[0124] 3, 3-二(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(33) [0124] 3, 3-di (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (33)

[0125] Mpl90-192°C;EIMSm/z307[M+];IR(KBr)cm_1:2768 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 29 (s,3H),3. 72 (s,lH),7. 21 (t, 2H), 7. 33~7. 39 (m, 2H),7. 40~7. 47 (m, 2H), 7. 48~7. 54 (m,2H),8. 28 (s,lH),l〇. 22 (s,lH)〇 [0125] Mpl90-192 ° C; EIMSm / z307 [M +]; IR (KBr) cm_1: 2768 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H), 3. 29 (s, 3H), 3. 72 (s, lH), 7. 21 (t, 2H), 7. 33 ~ 7. 39 (m, 2H), 7. 40 ~ 7. 47 (m, 2H), 7. 48 ~ 7. 54 (m, 2H), 8. 28 (s, lH), l〇. 22 (s, lH) square

[0126] 3, 3-二(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(34) [0126] 3, 3-di (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (34)

[0127] Mp204-206°C;EIMSm/z339[M+];IR(KBr)cm_1:2764 (OH),3021 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 29 (s,3H),3. 65 (s,lH),7. 21 (t, 2H), 7. 31~7. 36 (m, 2H),7. 40~7. 47 (m, 2H), 7. 48~7. 54 (m,2H),8. 26 (s,lH),l〇. 20 (s,lH)〇 [0127] Mp204-206 ° C; EIMSm / z339 [M +]; IR (KBr) cm_1: 2764 (OH), 3021 (NH);:. HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H), 3. 29 (s, 3H), 3. 65 (s, lH), 7. 21 (t, 2H), 7. 31 ~ 7. 36 (m, 2H), 7. 40 ~ 7. 47 (m, 2H), 7. 48 ~ 7. 54 (m, 2H), 8. 26 (s, lH), l〇. 20 (s, lH) square

[0128] 3, 3-二(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(35) [0128] 3, 3-di (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (35)

[0129] Mp220-222°C;EIMSm/z:428[M+];IR(KBr)cm_1:2765 (OH),3020 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 29 (s,3H),3. 65 (s, 1H), 7. 33~7. 42 (m, 2H), 7. 58~7. 63 (m,2H),7. 72~7. 78 (m,4H),8. 26 (s,lH),l〇. 23 (s,lH)〇 [0129] Mp220-222 ° C; EIMSm / z: 428 [M +]; IR (KBr) cm_1: 2765 (OH), 3020 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 29 (s, 3H), 3. 65 (s, 1H), 7. 33 ~ 7. 42 (m, 2H), 7. 58 ~ 7. 63 (m, 2H), 7. 72 ~ 7. 78 (m, 4H), 8. 26 (s, lH), l〇. 23 (s, lH) square

[0130] 3, 3-二(3-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(36) [0130] 3, 3-di (3-nitrophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (36)

[0131] Mpl67-169°C;EIMSm/z361[M+];IR(KBr)cm_1:2764 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 32 (s,3H),3. 69 (s, 1H), 7. 85~7. 93 (m,4H),8. 17 (d, 2H),8. 28 (s,lH),8. 34 (dd, 2H), 10. 24 (s,lH)〇 [0131] Mpl67-169 ° C; EIMSm / z361 [M +]; IR (KBr) cm_1: 2764 (OH), 3027 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 32 (s, 3H), 3. 69 (s, 1H), 7. 85 ~ 7. 93 (m, 4H), 8. 17 (d, 2H), 8. 28 (s, lH), 8 . 34 (dd, 2H), 10. 24 (s, lH) square

[0132] 3, 3-二(3-羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(37) [0132] 3,3-bis (3-hydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (37)

[0133] Mpl66-168°C;EIMSm/z:303[M+];IR(KBr)cm_1:2763 (OH),3025 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 19 (s,2H),3. 29 (s,3H),3. 69 (s,lH),5. 79 (s, 2H), 7. 02~7. 11 (m, 2H),7. 17~7. 25 (m, 4H), 7. 46~7. 53 (m,2H),8. 28 (s,lH),l〇. 23 (s,lH)〇 [0133] Mpl66-168 ° C; EIMSm / z: 303 [M +]; IR (KBr) cm_1: 2763 (OH), 3025 (NH);: HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, lH), 5. 79 (s, 2H), 7. 02 ~ 7. 11 (m, 2H), 7. 17 ~ 7. 25 ( m, 4H), 7. 46 ~ 7. 53 (m, 2H), 8. 28 (s, lH), l〇. 23 (s, lH) square

[0134] 3, 3-二(3-甲氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(38) [0134] 3, 3-di (3-methoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (38)

[0135] Mpl81-183°C;EIMSm/z331[M+];IR(KBr)cm_1:2768 (OH),3023 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 33 (s,3H),3. 67 (s,lH),4. 19 (s, 6H), 7. 02~7. 11 (m, 4H),7. 28~7. 36 (m, 2H), 7. 46~7. 52 (m,2H),8. 29 (s,lH),l〇. 27 (s,lH)〇 [0135] Mpl81-183 ° C; EIMSm / z331 [M +]; IR (KBr) cm_1: 2768 (OH), 3023 (NH);:. HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H), 3. 33 (s, 3H), 3. 67 (s, lH), 4. 19 (s, 6H), 7. 02 ~ 7. 11 (m, 4H), 7. 28 ~ 7. 36 (m, 2H), 7. 46 ~ 7. 52 (m, 2H), 8. 29 (s, lH), l〇. 27 (s, lH) square

[0136] 3, 3-二(3-乙氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(39) [0136] 3, 3-di (3-ethoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (39)

[0137] Mpl76-178°C;EIMSm/z359[M+];IR(KBr)cm_1:2763 (OH),3021 (NH) ;:HNMR (DMS0-d6) 8ppm:1. 24 (t,6H),3. 16 (s,2H),3. 26 (s,3H),3. 67 (s, 1H),4. 45~4. 53 (m, 4H), 7.02-7. 13 (m,4H),7. 28~7. 36 (m, 2H), 7. 46~7. 52 (m,2H),8. 23 (s,lH),l〇. 24 (s, 1H)。 [0137] Mpl76-178 ° C; EIMSm / z359 [M +]; IR (KBr) cm_1: 2763 (OH), 3021 (NH);:. HNMR (DMS0-d6) 8ppm: 1 24 (t, 6H), 3. 16 (s, 2H), 3. 26 (s, 3H), 3. 67 (s, 1H), 4. 45 ~ 4. 53 (m, 4H), 7.02-7. 13 (m, 4H) , 7. 28 ~ 7. 36 (m, 2H), 7. 46 ~ 7. 52 (m, 2H), 8. 23 (s, lH), l〇. 24 (s, 1H).

[0138] 3, 3-二(3-氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(40) [0138] 3, 3-di (3-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (40)

[0139] Mpl81-183°C;EIMSm/z301[M+];IR(KBr)cm_1:2766 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 31 (s,3H),3. 67 (s, 1H),4. 45~4. 54 (m,4H), 7. 02~7. 11 (m,4H),7. 28~7. 36 (m, 2H), 7. 46~7. 52 (m,2H),8. 22 (s,lH),l〇. 21 (s,lH)〇 [0139] Mpl81-183 ° C; EIMSm / z301 [M +]; IR (KBr) cm_1: 2766 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H), 3. 31 (s, 3H), 3. 67 (s, 1H), 4. 45 ~ 4. 54 (m, 4H), 7. 02 ~ 7. 11 (m, 4H), 7. 28 ~ 7. 36 (m, 2H), 7. 46 ~ 7. 52 (m, 2H), 8. 22 (s, lH), l〇. 21 (s, lH) square

[0140] 3, 3-二(4-甲基苯基)-3-羟基丙酰-N-甲基氧肟酸(41) [0140] 3, 3-di (4-methylphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (41)

[0141] Mpl65-167°C;EIMSm/z299[M+];IR(KBr)cm_1:2764 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:2. 47 (s,6H),3. 18 (s,2H),3. 29 (s,3H),3. 69 (s,lH),6. 92 (dd,4H), 7.39 (dd,4H),8.26 (s,lH),10.23 (s,lH)。 [0141] Mpl65-167 ° C; EIMSm / z299 [M +]; IR (KBr) cm_1: 2764 (OH), 3027 (NH);:. HNMR (DMS0-d6) 8ppm: 2 47 (s, 6H), 3. 18 (s, 2H), 3. 29 (s, 3H), 3. 69 (s, lH), 6. 92 (dd, 4H), 7.39 (dd, 4H), 8.26 (s, lH), 10.23 (s, lH).

[0142] 3, 3-二(3-甲氨基苯基)-3-羟基丙酰-N-甲基氧肟酸(42) [0142] 3,3-bis (3-aminophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (42)

[0143]Mpl86-188°C;EIMSm/z:357[M+];IR(KBr)cm_1:2761 (OH),3026 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 26 (s,3H),3. 37 (s,12H),3. 65 (s,lH),6. 87 (dd,4H), 7.27 (dd,4H),8.24 (s,lH),10.23 (s,lH)。 [0143] Mpl86-188 ° C; EIMSm / z: 357 [M +]; IR (KBr) cm_1: 2761 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3. 26 (s, 3H), 3. 37 (s, 12H), 3. 65 (s, lH), 6. 87 (dd, 4H), 7.27 (dd, 4H), 8.24 (s, lH ), 10.23 (s, lH).

[0144] 3-苯基-3-(2-羟基-3-辛氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(43) [0144] 3-phenyl-3- (2-hydroxy-3-octyloxy-phenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (43)

[0145]Mpl60-162°C;EIMSm/z:415[M+];IR(KBr)cm_1:2767 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:1. 35~1. 44 (m, 15H),3. 16 (s,2H),3. 31 (s,3H),3. 67 (s,lH),4. 12 (t, 2H),5. 79 (s, 1H),6. 73 (dd,2H),7. 18 (d, 1H),7. 46~7. 50 (m,3H),7. 52~7. 58 (m,2H),8. 24 (s,1H),10. 23 (s,lH)〇 [0145] Mpl60-162 ° C; EIMSm / z: 415 [M +]; IR (KBr) cm_1: 2767 (OH), 3024 (NH);:.. HNMR (DMS0-d6) 8ppm: 1 35 ~ 1 44 (m, 15H), 3. 16 (s, 2H), 3. 31 (s, 3H), 3. 67 (s, lH), 4. 12 (t, 2H), 5. 79 (s, 1H) , 6. 73 (dd, 2H), 7. 18 (d, 1H), 7. 46 ~ 7. 50 (m, 3H), 7. 52 ~ 7. 58 (m, 2H), 8. 24 (s , 1H), 10. 23 (s, lH) square

[0146] 3-苯基-3-(3, 4-二甲基苯基)-3-羟基丙酰-N-甲基氧肟酸(44) [0146] 3-phenyl-3- (3,4-dimethylphenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (44)

[0147]Mpl47-149°C;EIMSm/z:299[M+];IR(KBr)cm_1:2762 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:2. 75 (s,6H),3. 19 (s,2H),3. 29 (s,3H),3. 64 (s, 1H),7. 13 (d,2H),7. 29 (d, 1H),7. 46~7. 51 (m, 3H), 7. 54~7. 63 (m,2H),8. 24 (s,lH),l〇. 21 (s,lH)〇 [0147] Mpl47-149 ° C; EIMSm / z: 299 [M +]; IR (KBr) cm_1: 2762 (OH), 3027 (NH);:. HNMR (DMS0-d6) 8ppm: 2 75 (s, 6H ), 3. 19 (s, 2H), 3. 29 (s, 3H), 3. 64 (s, 1H), 7. 13 (d, 2H), 7. 29 (d, 1H), 7. 46 ~ 7. 51 (m, 3H), 7. 54 ~ 7. 63 (m, 2H), 8. 24 (s, lH), l〇. 21 (s, lH) square

[0148] 3-苯基-3-(2-羟基-4-甲氧基苯基)-3-羟基丙酰-N-甲基氧肟酸(45) [0148] 3-phenyl-3- (2-hydroxy-4-methoxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (45)

[0149]Mpl27-129°C;EIMSm/z:317[M+];IR(KBr)cm_1:2762 (OH),3022 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 69 (s, 1H),4. 13 (s,3H),5. 74 (s, 1H),6. 77 (d,2H),7. 18 (d, 1H),7. 46~7. 52 (m,3H),7. 57-7.64 (m,2H),8. 24 (s,lH),l〇. 23 (s,lH)〇 [0149] Mpl27-129 ° C; EIMSm / z: 317 [M +]; IR (KBr) cm_1: 2762 (OH), 3022 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, 1H), 4. 13 (s, 3H), 5. 74 (s, 1H), 6. 77 (d, 2H), 7. 18 (d, 1H), 7. 46 ~ 7. 52 (m, 3H), 7. 57-7.64 (m, 2H), 8. 24 (s, lH), l〇. 23 (s, lH) square

[0150] 3-(2-氟苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(46) [0150] 3- (2-fluorophenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (46)

[0151]Mpl34-136°C;EIMSm/z:307[M+];IR(KBr)cm_1:2762 (OH),3023 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3.31 (s,3H),3.67 (s,lH),7.09 (d,lH),7.24 (m,2H), 7.34-7.43 (m, 1H),7. 46~7. 50 (m,2H),7. 76 (dd, 1H), 7. 81~7. 89 (m, 1H),8. 21 (s,lH), 10.20 (s,lH)〇 [0151] Mpl34-136 ° C; EIMSm / z: 307 [M +]; IR (KBr) cm_1: 2762 (OH), 3023 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3.31 (s, 3H), 3.67 (s, lH), 7.09 (d, lH), 7.24 (m, 2H), 7.34-7.43 (m, 1H), 7. 46 ~ 7. 50 (m, 2H ), 7. 76 (dd, 1H), 7. 81 ~ 7. 89 (m, 1H), 8. 21 (s, lH), 10.20 (s, lH) square

[0152] 3-苯基-3-(2, 4-二氟苯基)-3-羟基丙酰-N-甲基氧肟酸(47) [0152] 3-phenyl-3- (2,4-difluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (47)

[0153] Mpl49-151°C;EIMSm/z:307[M+];IR(KBr)cm_1:2761 (OH),3025 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 32 (s,3H),3. 67 (s,lH),6. 91 (d,lH),7. 14 (dd,lH), 7.45 (dd, 1H),7. 46~7. 53 (m, 3H), 7. 56~7. 65 (m,2H),8. 24 (s,lH),l〇. 25 (s,lH)〇 [0153] Mpl49-151 ° C; EIMSm / z: 307 [M +]; IR (KBr) cm_1: 2761 (OH), 3025 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3. 32 (s, 3H), 3. 67 (s, lH), 6. 91 (d, lH), 7. 14 (dd, lH), 7.45 (dd, 1H), 7. 46 ~ 7 . 53 (m, 3H), 7. 56 ~ 7. 65 (m, 2H), 8. 24 (s, lH), l〇. 25 (s, lH) square

[0154] 3-苯基-3-(3, 4-二氟苯基)-3-羟基丙酰-N-甲基氧肟酸(48) [0154] 3-phenyl-3- (3,4-difluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (48)

[0155]Mpl34-136°C;EIMSm/z:307[M+];IR(KBr)cm_1:2762 (OH),3023 (NH) ;:HNMR (DMS0-d6)8ppm:3. 16 (s,2H),3. 26 (s,3H),3. 67 (s,lH),7. 13 (d,lH),7. 21 (dd,lH), 7.27 (d, 1H),7. 46~7. 53 (m, 3H), 7. 56~7. 65 (m,2H),8. 24 (s,lH),l〇. 20 (s,lH)〇 [0155] Mpl34-136 ° C; EIMSm / z: 307 [M +]; IR (KBr) cm_1: 2762 (OH), 3023 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3. 26 (s, 3H), 3. 67 (s, lH), 7. 13 (d, lH), 7. 21 (dd, lH), 7.27 (d, 1H), 7. 46 ~ 7 . 53 (m, 3H), 7. 56 ~ 7. 65 (m, 2H), 8. 24 (s, lH), l〇. 20 (s, lH) square

[0156] 3-(3-羟基苯基)-3-(2, 3, 4-三羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(49) [0156] 3- (3-hydroxyphenyl) -3- (2, 3, 4-trihydroxyphenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (49)

[0157]Mpl70-172°C;EIMSm/z335[M+];IR(KBr)cm_1:2764 (OH),3020 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 69 (s, 1H),5. 78 (s,4H),6. 84 (d, 1H),7. 01 (d, 1H),7. 25 (dd, 1H),7. 33~7. 41 (m,3H),8. 26 (s,lH),l〇. 31 (s,lH)〇 [0157] Mpl70-172 ° C; EIMSm / z335 [M +]; IR (KBr) cm_1: 2764 (OH), 3020 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 29 (s, 3H), 3. 69 (s, 1H), 5. 78 (s, 4H), 6. 84 (d, 1H), 7. 01 (d, 1H), 7. 25 (dd , 1H), 7. 33 ~ 7. 41 (m, 3H), 8. 26 (s, lH), l〇. 31 (s, lH) square

[0158] 3-苯基-3-(2, 4-二羟基苯基)-3-羟基丙酰-N-甲基氧肟酸(50) [0158] 3-phenyl-3- (2,4-dihydroxyphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (50)

[0159]Mpl70-172°C;EIMSm/z:335[M+];IR(KBr)cm_1:2768 (OH),3021 (NH) ;:HNMR (DMS0-d6)8ppm:3. 16 (s,2H),3. 29 (s,3H),3. 29 (s,3H),3. 67 (s, 1H),5. 76 (s,4H),6. 85 (d,lH),7.01 (d,lH),7.26 (dd,lH),7.33 (m,3H),8.21 (s,lH),10.32 (s,lH)。 [0159] Mpl70-172 ° C; EIMSm / z: 335 [M +]; IR (KBr) cm_1: 2768 (OH), 3021 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3. 29 (s, 3H), 3. 29 (s, 3H), 3. 67 (s, 1H), 5. 76 (s, 4H), 6. 85 (d, lH), 7.01 (d , lH), 7.26 (dd, lH), 7.33 (m, 3H), 8.21 (s, lH), 10.32 (s, lH).

[0160] 3-苯基-3-(2-氯-4-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(51) [0160] 3-phenyl-3- (2-chloro-4-nitrophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (51)

[0161]Mpl93-194°C;EIMSm/z350[M+];IR(KBr)cm_1:2762 (OH),3025 (NH) ;:HNMR (DMS0-d6)8ppm:3. 17 (s,2H),3. 33 (s,3H),3. 67 (s,lH),5. 79 (s, 2H), 7. 46~7. 52 (m, 3H),7. 76 (d, 1H),8. 12 (dd, 1H),8. 24 (s,lH),8. 31 (d, 1H),10. 19 (s,lH)〇 [0161] Mpl93-194 ° C; EIMSm / z350 [M +]; IR (KBr) cm_1: 2762 (OH), 3025 (NH);:. HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H), 3. 33 (s, 3H), 3. 67 (s, lH), 5. 79 (s, 2H), 7. 46 ~ 7. 52 (m, 3H), 7. 76 (d, 1H), 8 . 12 (dd, 1H), 8. 24 (s, lH), 8. 31 (d, 1H), 10. 19 (s, lH) square

[0162] 3-苯基-3-(4-甲基苯基)-3-羟基丙酰-N-甲基氧肟酸(52) [0162] 3-phenyl-3- (4-methylphenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (52)

[0163]Mpl48-149°C;EIMSm/z285[M+];IR(KBr)cm_1:2763 (OH),3021 (NH) ;:HNMR (DMS0-d6)8ppm:2. 37 (s,3H),3. 17 (s,2H),3. 26 (s,3H),3. 67 (s, 1H),5. 72 (s,2H),6. 92 (dd, 1H),7. 30 (dd,2H),7. 46~7. 56 (m,3H),7. 70 (d, 1H),8. 20 (s,lH),l〇. 18 (s,lH)〇 [0163] Mpl48-149 ° C; EIMSm / z285 [M +]; IR (KBr) cm_1: 2763 (OH), 3021 (NH);:. HNMR (DMS0-d6) 8ppm: 2 37 (s, 3H), 3. 17 (s, 2H), 3. 26 (s, 3H), 3. 67 (s, 1H), 5. 72 (s, 2H), 6. 92 (dd, 1H), 7. 30 (dd , 2H), 7. 46 ~ 7. 56 (m, 3H), 7. 70 (d, 1H), 8. 20 (s, lH), l〇. 18 (s, lH) square

[0164] 3-苯基-3-(2-氨基-4-硝基苯基)-3-羟基丙酰-N-甲基氧肟酸(53) [0164] 3-phenyl-3- (2-amino-4-nitrophenyl) -N- methyl-3-hydroxy-propionyl hydroxamic acid (53)

[0165]Mpl22-124°C;EIMSm/z331[M+];IR(KBr)cm_1:2767 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:3. 17 (s,2H),3. 32 (s,3H),3. 67 (s,lH),6. 59 (s, 2H), 7. 40~7. 47 (m, 3H),7. 49~7. 56 (dd, 1H), 7. 56~7. 61 (m, 2H), 7. 63~7. 74 (d, 1H),7. 73 (d, 1H),8. 24 (s, 1H),10. 14 (s,lH)〇 [0165] Mpl22-124 ° C; EIMSm / z331 [M +]; IR (KBr) cm_1: 2767 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H), 3. 32 (s, 3H), 3. 67 (s, lH), 6. 59 (s, 2H), 7. 40 ~ 7. 47 (m, 3H), 7. 49 ~ 7. 56 (dd, 1H), 7. 56 ~ 7. 61 (m, 2H), 7. 63 ~ 7. 74 (d, 1H), 7. 73 (d, 1H), 8. 24 (s, 1H), 10. 14 (s, lH) square

[0166] 3-苯基-3-(2-氨基-4-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(54) [0166] 3-phenyl-3- (2-amino-4-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (54)

[0167]Mpl47-149°C;EIMSm/z320[M+];IR(KBr)cm_1:2765 (OH),3020 (NH) ;:HNMR (DMS0-d6)8ppm:3. 19 (s,2H),3. 29 (s,3H),3. 65 (s, 1H),6. 58 (s,2H),6. 83 (d, 1H),7. 14 (d, 1H),7. 38~7. 46 (m,3H),7. 51~7. 62 (m,2H),7. 94 (dd, 1H),8. 20 (s, 1H), 10. 19 (s,lH)〇 [0167] Mpl47-149 ° C; EIMSm / z320 [M +]; IR (KBr) cm_1: 2765 (OH), 3020 (NH);:. HNMR (DMS0-d6) 8ppm: 3 19 (s, 2H), 3. 29 (s, 3H), 3. 65 (s, 1H), 6. 58 (s, 2H), 6. 83 (d, 1H), 7. 14 (d, 1H), 7. 38 ~ 7 . 46 (m, 3H), 7. 51 ~ 7. 62 (m, 2H), 7. 94 (dd, 1H), 8. 20 (s, 1H), 10. 19 (s, lH) square

[0168] 3-(2-羟基苯基)-3-(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(55) [0168] 3- (2-hydroxyphenyl) -3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (55)

[0169] Mpl86-188°C;EIMSm/z305[M+];IR(KBr)cm_1:2766 (OH),3023 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 17 (s,2H),3. 27 (s,3H),3. 67 (s,lH),5. 76 (s,lH),7. 14 (dd,lH), 7.27 (dd, 1H),7. 43~7. 56 (m,4H),7. 73 (d, 1H), 7. 90~7. 97 (m, 1H),8. 22 (s,lH),l〇. 21 (s,lH)。 [0169] Mpl86-188 ° C; EIMSm / z305 [M +]; IR (KBr) cm_1: 2766 (OH), 3023 (NH);:. HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H), 3. 27 (s, 3H), 3. 67 (s, lH), 5. 76 (s, lH), 7. 14 (dd, lH), 7.27 (dd, 1H), 7. 43 ~ 7. 56 (m, 4H), 7. 73 (d, 1H), 7. 90 ~ 7. 97 (m, 1H), 8. 22 (s, lH), l〇. 21 (s, lH).

[0170] 3-(2-羟基苯基)-3-(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(56) [0170] 3- (2-hydroxyphenyl) -3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (56)

[0171]Mp204-206°C;EIMSm/z:321[M+];IR(KBr)cm_1:2763 (OH),3021 (NH) ;:HNMR (DMS0-d6)8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 64 (s,lH),5. 78 (s, 1H), 7. 03-7. 13 (m, 1H),7. 14 (dd, 1H),7. 24~7. 33 (m, 1H), 7. 37~7. 42 (m, 2H), 7. 47~7. 55 (m,2H),7. 87 (dd, 1H),8. 24 (s, 1H), 10. 16 (s,lH)〇 [0171] Mp204-206 ° C; EIMSm / z: 321 [M +]; IR (KBr) cm_1: 2763 (OH), 3021 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 29 (s, 3H), 3. 64 (s, lH), 5. 78 (s, 1H), 7. 03-7. 13 (m, 1H), 7. 14 (dd, 1H) , 7. 24 ~ 7. 33 (m, 1H), 7. 37 ~ 7. 42 (m, 2H), 7. 47 ~ 7. 55 (m, 2H), 7. 87 (dd, 1H), 8 . 24 (s, 1H), 10. 16 (s, lH) square

[0172] 3-(2-羟基苯基)-3-(2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(57) [0172] 3- (2-hydroxyphenyl) -3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (57)

[0173]Mp217-219°C;EIMSm/z365[M+];IR(KBr)cm_1:2765 (OH),3021 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 64 (s,lH),5. 78 (s, 1H), 7. 03-7. 13 (m, 1H),7. 14 (dd, 1H),7. 24~7. 32 (m, 1H), 7. 35~7. 42 (m, 2H), 7. 49~7. 53 (m,2H),7. 91 (dd, 1H),8. 27 (s, 1H), 10. 18 (s,lH)〇 [0173] Mp217-219 ° C; EIMSm / z365 [M +]; IR (KBr) cm_1: 2765 (OH), 3021 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 29 (s, 3H), 3. 64 (s, lH), 5. 78 (s, 1H), 7. 03-7. 13 (m, 1H), 7. 14 (dd, 1H), 7 . 24 ~ 7. 32 (m, 1H), 7. 35 ~ 7. 42 (m, 2H), 7. 49 ~ 7. 53 (m, 2H), 7. 91 (dd, 1H), 8. 27 (s, 1H), 10. 18 (s, lH) square

[0174] 3-(2-氨基苯基)-3-(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(58) [0174] 3- (2-aminophenyl) -3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (58)

[0175]Mpl94-196°C;EIMSm/z304[M+];IR(KBr)cm_1:2760 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:3. 15 (s,2H),3. 27 (s,3H),3. 67 (s,lH),6. 58 (s, 2H), 7. 15~7. 20 (m, 2H),7. 24~7. 33 (m,3H),7. 47 (dd, 1H),7.66(dd, 1H), 7. 89~7. 92 (m, 1H),8. 22 (s,lH), 10.17 (s,lH)〇 [0175] Mpl94-196 ° C; EIMSm / z304 [M +]; IR (KBr) cm_1: 2760 (OH), 3027 (NH);:. HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H), 3. 27 (s, 3H), 3. 67 (s, lH), 6. 58 (s, 2H), 7. 15 ~ 7. 20 (m, 2H), 7. 24 ~ 7. 33 (m, 3H), 7. 47 (dd, 1H), 7.66 (dd, 1H), 7. 89 ~ 7. 92 (m, 1H), 8. 22 (s, lH), 10.17 (s, lH) square

[0176] 3-(2-氨基苯基)-3-(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(59) [0176] 3- (2-aminophenyl) -3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (59)

[0177] Mpl80-182°C;EIMSm/z320[M+];IR(KBr)cm_1:2764 (OH),3023 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 32 (s,3H),3. 67 (s,lH),6. 59 (s, 2H), 7. 15~7. 23 (m, 2H),7. 24~7. 33 (m, 2H), 7. 35~7. 41 (m,2H),7. 46 (dd, 1H),7. 82 (dd,lH),8. 22 (s,lH), 10.18 (s,lH)〇 [0177] Mpl80-182 ° C; EIMSm / z320 [M +]; IR (KBr) cm_1: 2764 (OH), 3023 (NH);:. HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H), 3. 32 (s, 3H), 3. 67 (s, lH), 6. 59 (s, 2H), 7. 15 ~ 7. 23 (m, 2H), 7. 24 ~ 7. 33 (m, 2H), 7. 35 ~ 7. 41 (m, 2H), 7. 46 (dd, 1H), 7. 82 (dd, lH), 8. 22 (s, lH), 10.18 (s, lH) square

[0178] 3- (2-氨基苯基)-3- (2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(60 ) [0178] 3- (2-aminophenyl) -3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (60)

[0179] Mp217-219°C;EIMSm/z364[M+];IR(KBr)cm_1:2765 (OH),3021 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 69 (s,lH),6. 56 (s, 2H), 7. 15~7. 23 (m, 2H),7. 24~7. 31 (m, 2H), 7. 38~7. 40 (m, 2H), 7. 51~7. 57 (m, 1H),7. 76 (dd, 1H),8. 20 (s, 1H),10. 19 (s,lH)〇 [0179] Mp217-219 ° C; EIMSm / z364 [M +]; IR (KBr) cm_1: 2765 (OH), 3021 (NH);:. HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H), 3. 29 (s, 3H), 3. 69 (s, lH), 6. 56 (s, 2H), 7. 15 ~ 7. 23 (m, 2H), 7. 24 ~ 7. 31 (m, 2H), 7. 38 ~ 7. 40 (m, 2H), 7. 51 ~ 7. 57 (m, 1H), 7. 76 (dd, 1H), 8. 20 (s, 1H), 10. 19 (s, lH) square

[0180] 3-(2-硝基苯基)-3-(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(61) [0180] 3- (2-nitrophenyl) -3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (61)

[0181] Mpl98-200 °C;EIMSm/z:334[M+];IR(KBr)cm_1:2762 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 33 (s,3H),3. 67 (s, 1H), 7. 27~7. 35 (m, 1H),7. 46 (dd, 1H),7. 77 (dd,2H),7. 86~7. 92 (m, 2H), 7. 95~8. 02 (m, 1H),8. 11 (dd,lH),8. 24 (s,lH), 10.18 (s,lH)〇 [0181] Mpl98-200 ° C; EIMSm / z: 334 [M +]; IR (KBr) cm_1: 2762 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 33 (s, 3H), 3. 67 (s, 1H), 7. 27 ~ 7. 35 (m, 1H), 7. 46 (dd, 1H), 7. 77 (dd, 2H) , 7. 86 ~ 7. 92 (m, 2H), 7. 95 ~ 8. 02 (m, 1H), 8. 11 (dd, lH), 8. 24 (s, lH), 10.18 (s, lH ) 〇

[0182] 3- (2-硝基苯基)-3- (2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(62) [0182] 3- (2-nitrophenyl) -3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (62)

[0183] Mp209-211 °C;EIMSm/z:350[M+];IR(KBr)cm_1:2764 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 18 (s,2H),3. 29 (s,3H),3. 69 (s, 1H), 7. 31~7. 39 (m,2H),7. 44 (dd, 1H),7. 72 (dd,2H),7. 86~7. 94 (m, 1H), 7. 95~7. 99 (m, 1H),8. 15 (dd,lH),8. 20 (s,lH), 10.22 (s,lH)〇 [0183] Mp209-211 ° C; EIMSm / z: 350 [M +]; IR (KBr) cm_1: 2764 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 18 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, 1H), 7. 31 ~ 7. 39 (m, 2H), 7. 44 (dd, 1H), 7. 72 (dd, 2H) , 7. 86 ~ 7. 94 (m, 1H), 7. 95 ~ 7. 99 (m, 1H), 8. 15 (dd, lH), 8. 20 (s, lH), 10.22 (s, lH ) 〇

[0184] 3- (2-硝基苯基)-3- (2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(63) [0184] 3- (2-nitrophenyl) -3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (63)

[0185] Mp219-221 °C;EIMSm/z:394[M+];IR(KBr)cm_1:2767 (OH),3022 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 29 (s,3H),3. 69 (s, 1H), 7. 37~7. 41 (m, 2H), 7. 48~7. 56 (m, 1H),7. 65 (dd, 1H),7. 70~7. 79 (m, 1H), 7. 86~7. 92 (m, 1H), 7. 95~8. 05 (m, 1H),8. 11 (dd,lH),8.23 (s,lH),10.16 (s,lH)。 [0185] Mp219-221 ° C; EIMSm / z: 394 [M +]; IR (KBr) cm_1: 2767 (OH), 3022 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, 1H), 7. 37 ~ 7. 41 (m, 2H), 7. 48 ~ 7. 56 (m, 1H), 7. 65 ( dd, 1H), 7. 70 ~ 7. 79 (m, 1H), 7. 86 ~ 7. 92 (m, 1H), 7. 95 ~ 8. 05 (m, 1H), 8. 11 (dd, lH), 8.23 ​​(s, lH), 10.16 (s, lH).

[0186] 3-(2-甲氧基苯基)-3-(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(64) [0186] 3- (2-methoxyphenyl) -3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (64)

[0187] Mp208-209〇C;EIMSm/z:319[M+];IR(KBr)cm-1 :2762 (OH),3025 (NH);1HNMR (DMS0-d6) 8ppm:3. 12 (s,2H),3. 33 (s,3H),3. 67 (s,lH),4. 24 (s,3H),7. 17-7.21 (m, 3H),7. 29~7. 38 (m, 1H),7. 37 (dd, 1H), 7. 46~7. 56 (dd, 1H),7. 70 (dd, 1H), 7. 83~7. 94 (m, 1H),8. 20 (s, 1H), 10. 18 (s,lH)〇 [0187] Mp208-209〇C; EIMSm / z: 319 [M +]; IR (KBr) cm-1: 2762 (OH), 3025 (NH); 1HNMR (DMS0-d6) 8ppm:. 3 12 (s, 2H), 3. 33 (s, 3H), 3. 67 (s, lH), 4. 24 (s, 3H), 7. 17-7.21 (m, 3H), 7. 29 ~ 7. 38 (m , 1H), 7. 37 (dd, 1H), 7. 46 ~ 7. 56 (dd, 1H), 7. 70 (dd, 1H), 7. 83 ~ 7. 94 (m, 1H), 8. 20 (s, 1H), 10. 18 (s, lH) square

[0188] 3-(2-甲氧基苯基)-3-(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(65) [0188] 3- (2-methoxyphenyl) -3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (65)

[0189] Mp202-204°C;EIMSm/z:335[M+];IR(KBr)cm-1:2762 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:3. 12 (s,2H),3. 28 (s,3H),3. 67 (s,lH),4. 29 (s, 3H), 7. 17~7. 22 (m, 3H),7. 41~7. 46 (m,4H),7. 87 (dd, 1H),8. 20 (s,lH),l〇. 20 (s,lH)〇 [0189] Mp202-204 ° C; EIMSm / z: 335 [M +]; IR (KBr) cm-1: 2762 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 12 (s , 2H), 3. 28 (s, 3H), 3. 67 (s, lH), 4. 29 (s, 3H), 7. 17 ~ 7. 22 (m, 3H), 7. 41 ~ 7. 46 (m, 4H), 7. 87 (dd, 1H), 8. 20 (s, lH), l〇. 20 (s, lH) square

[0190] 3-(2-甲氧基苯基)-3-(2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(66) [0190] 3- (2-methoxyphenyl) -3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (66)

[0191] Mp231-233°C;EIMSm/z:379[M+];IR(KBr)cm-1:2762 (OH),3020 (NH) ;:HNMR (DMS0-d6)8ppm:3. 14 (s,2H),3. 29 (s,3H),3. 67 (s,lH),4. 29 (s, 3H), 7. 17~7. 22 (m, 3H),7. 38 (dd,2H),7. 51~7. 64 (m,2H),7. 67 (dd, 1H),8. 20 (s,lH),l〇. 21 (s,lH)〇 [0191] Mp231-233 ° C; EIMSm / z: 379 [M +]; IR (KBr) cm-1: 2762 (OH), 3020 (NH);:. HNMR (DMS0-d6) 8ppm: 3 14 (s , 2H), 3. 29 (s, 3H), 3. 67 (s, lH), 4. 29 (s, 3H), 7. 17 ~ 7. 22 (m, 3H), 7. 38 (dd, 2H), 7. 51 ~ 7. 64 (m, 2H), 7. 67 (dd, 1H), 8. 20 (s, lH), l〇. 21 (s, lH) square

[0192] 3-(2-乙氧基苯基)-3-(2-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(67) [0192] 3- (2-ethoxyphenyl) -3- (2-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (67)

[0193] Mp218-219°C;EIMSm/z:333[M+];IR(KBr)cm-1:2765 (OH),3026 (NH) ;:HNMR (DMS0-d6)8ppm:2. 35 (t,3H),3. 10 (s,2H),3. 29 (s,3H),3. 69 (s, 1H),4. 27~4. 31 (m, 2H),7. 17-7.24 (m, 3H), 7. 27~7. 35 (m, 1H),7. 38 (dd, 1H),7. 46 (dd, 1H)7. 69 (dd, 1H), 7.82-7.87 (m, 1H),8. 23 (s,lH),l〇. 14 (s,lH)〇 [0193] Mp218-219 ° C; EIMSm / z: 333 [M +]; IR (KBr) cm-1: 2765 (OH), 3026 (NH);:. HNMR (DMS0-d6) 8ppm: 2 35 (t , 3H), 3. 10 (s, 2H), 3. 29 (s, 3H), 3. 69 (s, 1H), 4. 27 ~ 4. 31 (m, 2H), 7. 17-7.24 ( m, 3H), 7. 27 ~ 7. 35 (m, 1H), 7. 38 (dd, 1H), 7. 46 (dd, 1H) 7. 69 (dd, 1H), 7.82-7.87 (m, 1H), 8. 23 (s, lH), l〇. 14 (s, lH) square

[0194] 3-(2-乙氧基苯基)-3-(2-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(68) [0194] 3- (2-ethoxyphenyl) -3- (2-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (68)

[0195]Mp206-208°C;EIMSm/z:349[M+];IR(KBr)cm_1:2761 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:2. 38 (t,3H),3. 14 (s,2H),3. 29 (s,3H),3. 67 (s, 1H),4. 27~4. 31 (m, 2H),7. 17~7. 25 (m, 3H), 7. 27~7. 30 (m, 1H), 7. 51~7. 59 (m,3H)7. 87 (dd, 1H),8. 20 (s, 1H),10. 22 (s,lH)〇 [0195] Mp206-208 ° C; EIMSm / z: 349 [M +]; IR (KBr) cm_1: 2761 (OH), 3027 (NH);:. HNMR (DMS0-d6) 8ppm: 2 38 (t, 3H ), 3. 14 (s, 2H), 3. 29 (s, 3H), 3. 67 (s, 1H), 4. 27 ~ 4. 31 (m, 2H), 7. 17 ~ 7. 25 ( m, 3H), 7. 27 ~ 7. 30 (m, 1H), 7. 51 ~ 7. 59 (m, 3H) 7. 87 (dd, 1H), 8. 20 (s, 1H), 10. 22 (s, lH) square

[0196] 3-(2-乙氧基苯基)-3-(2-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(69) [0196] 3- (2-ethoxyphenyl) -3- (2-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (69)

[0197]Mp227-229°C;EIMSm/z:393[M+];IR(KBr)cm_1:2763 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:2. 38 (t,3H),3. 10 (s,2H),3. 26 (s,3H),3. 67 (s, 1H),4. 27~4. 31 (m, 2H),7. 17~7. 27 (m, 3H), 7. 27~7. 32 (m, 1H), 7. 49~7. 53 (m,3H)7. 63 (dd, 1H),8. 20 (s, 1H),10. 19 (s,lH)〇 [0197] Mp227-229 ° C; EIMSm / z: 393 [M +]; IR (KBr) cm_1: 2763 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 2 38 (t, 3H ), 3. 10 (s, 2H), 3. 26 (s, 3H), 3. 67 (s, 1H), 4. 27 ~ 4. 31 (m, 2H), 7. 17 ~ 7. 27 ( m, 3H), 7. 27 ~ 7. 32 (m, 1H), 7. 49 ~ 7. 53 (m, 3H) 7. 63 (dd, 1H), 8. 20 (s, 1H), 10. 19 (s, lH) square

[0198] 3-(2-羟基苯基)-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(70) [0198] 3- (2-hydroxyphenyl) -3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (70)

[0199]Mp212-214°C;EIMSm/z:321[M+];IR(KBr)cm_1:2764 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:3. 10 (s,2H),3. 28 (s,3H),3. 67 (s,lH),5. 69(s, 1H),6. 92~7. 04 (m, 2H),7. 33~7. 39 (m, 2H), 7. 47~7. 55 (m, 2H), 7. 58~7. 64 (m, 1H),7. 79 (dd, 1H),8. 22 (s, 1H),10. 16 (s,lH)〇 [0199] Mp212-214 ° C; EIMSm / z: 321 [M +]; IR (KBr) cm_1: 2764 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 10 (s, 2H. ), 3. 28 (s, 3H), 3. 67 (s, lH), 5. 69 (s, 1H), 6. 92 ~ 7. 04 (m, 2H), 7. 33 ~ 7. 39 ( m, 2H), 7. 47 ~ 7. 55 (m, 2H), 7. 58 ~ 7. 64 (m, 1H), 7. 79 (dd, 1H), 8. 22 (s, 1H), 10 . 16 (s, lH) square

[0200] 3-(2-羟基苯基)-3-(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(71) [0200] 3- (2-hydroxyphenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (71)

[0201]Mpl75-177°C;EIMSm/z:365[M+];IR(KBr)cm_1:2768 (OH),3026 (NH) ;:HNMR (DMS0-d6)8ppm:3. 10 (s,2H),3. 29 (s,3H),3. 69 (s,lH),5. 69 (s, 1H),6. 92~7. 02 (m, 2H),7. 37~7. 45 (m, 3H), 7. 49~7. 55 (m, 1H),7. 69 (dd,2H),8. 20 (s,lH),l〇. 23 (s,lH)〇 [0201] Mpl75-177 ° C; EIMSm / z: 365 [M +]; IR (KBr) cm_1: 2768 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 10 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, lH), 5. 69 (s, 1H), 6. 92 ~ 7. 02 (m, 2H), 7. 37 ~ 7. 45 ( m, 3H), 7. 49 ~ 7. 55 (m, 1H), 7. 69 (dd, 2H), 8. 20 (s, lH), l〇. 23 (s, lH) square

[0202] 3-(2-羟基苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(72) [0202] 3- (2-hydroxyphenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (72)

[0203]Mp205-207°C;EIMSm/z:305[M+];IR(KBr)cm_1:2765 (OH),3027 (NH) ;:HNMR (DMS0-d6)8ppm:3. 10 (s,2H),3. 29 (s,3H),3. 69 (s,lH),5. 69 (s, 1H),6. 92~7. 04 (m, 31〇,7.37~7.41(111,41〇,7.50~7.58(111,11〇,8.20(8,11〇,10.19(8,11〇。3-(2-氨基苯基)-3_ (3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(73 ) [0203] Mp205-207 ° C; EIMSm / z: 305 [M +]; IR (KBr) cm_1: 2765 (OH), 3027 (NH);: HNMR (DMS0-d6) 8ppm: 3 10 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, lH), 5. 69 (s, 1H), 6. 92 ~ 7. 04 (m, 31〇, 7.37 ~ 7.41 (111,41〇 , 7.50 ~ 7.58 (111,11〇, 8.20 (8,11〇, 10.19 (8,11〇.3- (2-aminophenyl) -3_ (3-chlorophenyl) -3-hydroxy-propionyl -N - methyl hydroxamic acid (73)

[0204]Mpl69-171°C;EIMSm/z:320[M+];IR(KBr)cm_1:2764 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:3. 17 (s,2H),3. 29 (s,3H),3. 67 (s,lH),6. 57 (s, 2H),6. 97~7. 05 (m, 2H),7. 28~7. 32 (m, 2H), 7. 48~7. 56 (m, 2H), 7. 55~7. 60 (m,2H),8. 22 (s,lH),l〇. 18 (s, 1H)。 [0204] Mpl69-171 ° C; EIMSm / z: 320 [M +]; IR (KBr) cm_1: 2764 (OH), 3024 (NH);:. HNMR (DMS0-d6) 8ppm: 3 17 (s, 2H ), 3. 29 (s, 3H), 3. 67 (s, lH), 6. 57 (s, 2H), 6. 97 ~ 7. 05 (m, 2H), 7. 28 ~ 7. 32 ( m, 2H), 7. 48 ~ 7. 56 (m, 2H), 7. 55 ~ 7. 60 (m, 2H), 8. 22 (s, lH), l〇. 18 (s, 1H).

[0205]3- (2-氨基苯基)-3- (3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(74) [0205] 3- (2-aminophenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (74)

[0206]Mp215-217°C;EIMSm/z:365[M+];IR(KBr)cm_1:2760 (OH),3026 (NH) ;:HNMR (DMS0-d6)8ppm:3. 11 (s,2H),3. 29 (s,3H),3. 69 (s,lH),6. 55 (s, 2H),6. 98~7. 05 (m, 2H),7. 28~7. 35 (m, 2H), 7. 39~7. 43 (m, 1H), 7. 51~7. 57 (m, 1H), 7. 69~7. 74 (m,2H),8. 20 (s,1H),10. 19 (s,lH)〇 [0206] Mp215-217 ° C; EIMSm / z: 365 [M +]; IR (KBr) cm_1: 2760 (OH), 3026 (NH);: HNMR (DMS0-d6) 8ppm: 3 11 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, lH), 6. 55 (s, 2H), 6. 98 ~ 7. 05 (m, 2H), 7. 28 ~ 7. 35 ( m, 2H), 7. 39 ~ 7. 43 (m, 1H), 7. 51 ~ 7. 57 (m, 1H), 7. 69 ~ 7. 74 (m, 2H), 8. 20 (s, 1H), 10. 19 (s, lH) square

[0207] 3-(2-氨基苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(75) [0207] 3- (2-aminophenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (75)

[0208]Mpl61-163 °C;EIMSm/z:304[M+];IR(KBr)cm_1:2766 (OH),3023 (NH) ; :HNMR (DMS0-d6)8ppm:3. 12 (s,2H),3. 31 (s,3H),3.66(s,lH),6. 54 (s, 2H),6. 95~7. 02 (m, 3H),7. 29~7. 37(m,3H), 7. 35~7. 40(m,1H), 7. 43~7. 54(m,1H),8. 22 (s,lH),l〇. 22 (s, 1H)。 [0208] Mpl61-163 ° C; EIMSm / z: 304 [M +]; IR (KBr) cm_1: 2766 (OH), 3023 (NH);: HNMR (DMS0-d6) 8ppm: 3 12 (s, 2H. ), 3. 31 (s, 3H), 3.66 (s, lH), 6. 54 (s, 2H), 6. 95 ~ 7. 02 (m, 3H), 7. 29 ~ 7. 37 (m, 3H), 7. 35 ~ 7. 40 (m, 1H), 7. 43 ~ 7. 54 (m, 1H), 8. 22 (s, lH), l〇. 22 (s, 1H).

[0209] 3-(2-硝基苯基)-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(76) [0209] 3- (2-nitrophenyl) -3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (76)

[0210] Mp206-208 °C;EIMSm/z:350[M+];IR(KBr)cm_1:2760 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 16 (s,2H),3. 29 (s,3H),3.66(s, 1H), 7. 45~7. 53 (m, 2H), 7. 58~7. 63 (m,2H),7. 86~7. 94 (m, 3H), 7. 97~8. 06 (dd, 1H),8. 22 (s,lH),l〇. 15 (s,lH)〇 [0210] Mp206-208 ° C; EIMSm / z: 350 [M +]; IR (KBr) cm_1: 2760 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 16 (s, 2H. ), 3. 29 (s, 3H), 3.66 (s, 1H), 7. 45 ~ 7. 53 (m, 2H), 7. 58 ~ 7. 63 (m, 2H), 7. 86 ~ 7. 94 (m, 3H), 7. 97 ~ 8. 06 (dd, 1H), 8. 22 (s, lH), l〇. 15 (s, lH) square

[0211] 3-(2-硝基苯基)-3-(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(77) [0211] 3- (2-nitrophenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (77)

[0212]Mp219-221 °C;EIMSm/z:394[M+];IR(KBr)cm_1:2762 (OH),3020 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 29 (s,3H),3. 69 (s,lH),7. 37 (dd, 1H),7. 46 (dd, 1H), 7.53 (m,2H), 7. 86-796 (m,3H),7. 97 (dd, 1H),8. 23 (s,lH),l〇. 18 (s,lH)〇 [0212] Mp219-221 ° C; EIMSm / z: 394 [M +]; IR (KBr) cm_1: 2762 (OH), 3020 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 29 (s, 3H), 3. 69 (s, lH), 7. 37 (dd, 1H), 7. 46 (dd, 1H), 7.53 (m, 2H), 7. 86-796 (m, 3H), 7. 97 (dd, 1H), 8. 23 (s, lH), l〇. 18 (s, lH) square

[0213] 3-(2-硝基苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(78) [0213] 3- (2-nitrophenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (78)

[0214]Mpl66-168 °C;EIMSm/z:334[M+];IR(KBr)cm_1:2762 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 15 (s,2H),3. 30 (s,3H),3. 62 (s,lH),7. 13 (dd, 1H), 7. 22~7. 33 (m, 1H),7. 33~7. 40 (m, 1H),7. 43~7. 49 (m, 1H), 7. 86~7. 91 (m,3H),7. 97 (dd, 1H),8. 23 (s, 1H),10. 19 (s,lH)〇 [0214] Mpl66-168 ° C; EIMSm / z: 334 [M +]; IR (KBr) cm_1: 2762 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 15 (s, 2H. ), 3. 30 (s, 3H), 3. 62 (s, lH), 7. 13 (dd, 1H), 7. 22 ~ 7. 33 (m, 1H), 7. 33 ~ 7. 40 ( m, 1H), 7. 43 ~ 7. 49 (m, 1H), 7. 86 ~ 7. 91 (m, 3H), 7. 97 (dd, 1H), 8. 23 (s, 1H), 10 . 19 (s, lH) square

[0215] 3-(2-甲氧基苯基)-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(79) [0215] 3- (2-methoxyphenyl) -3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (79)

[0216]Mpl48-149°C;EIMSm/z:335[M+];IR(KBr)cm_1:2763 (OH),3026 (NH) ;:HNMR (DMS0-d6)8ppm:3. 14~3. 26 (m,5H),3. 29 (s,3H),3.68 (s, 1H),6. 99~7. 05 (m,3H), 7.37-7.42 (m, 1H),7. 43~7. 49 (m,2H),7. 55 (dd,2H),8. 23 (s,lH),l〇. 15 (s,lH)〇 [0216] Mpl48-149 ° C; EIMSm / z: 335 [M +]; IR (KBr) cm_1: 2763 (OH), 3026 (NH);:.. HNMR (DMS0-d6) 8ppm: 3 14 ~ 3 26 (m, 5H), 3. 29 (s, 3H), 3.68 (s, 1H), 6. 99 ~ 7. 05 (m, 3H), 7.37-7.42 (m, 1H), 7. 43 ~ 7. 49 (m, 2H), 7. 55 (dd, 2H), 8. 23 (s, lH), l〇. 15 (s, lH) square

[0217] 3-(2-甲氧基苯基)-3-(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(80) [0217] 3- (2-methoxyphenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (80)

[0218] Mpl54-156 °C;EIMSm/z:379[M+];IR(KBr)cm_1:2764 (OH),3022 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 13 (m,5H),3. 32 (s,3H),3. 65 (s, 1H),6. 97-7. 06 (m, 3H), 7. 39~7. 44 (m,2H),7. 53~7. 62 (m, 1H), 7. 64~7. 71 (m,2H),8. 23 (s,lH),l〇. 23 (s,lH)〇 [0218] Mpl54-156 ° C; EIMSm / z: 379 [M +]; IR (KBr) cm_1: 2764 (OH), 3022 (NH);: HNMR (DMS0-d6) 8ppm: 3 13 (m, 5H. ), 3. 32 (s, 3H), 3. 65 (s, 1H), 6. 97-7. 06 (m, 3H), 7. 39 ~ 7. 44 (m, 2H), 7. 53 ~ 7. 62 (m, 1H), 7. 64 ~ 7. 71 (m, 2H), 8. 23 (s, lH), l〇. 23 (s, lH) square

[0219] 3-(2-甲氧基苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(81) [0219] 3- (2-methoxyphenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (81)

[0220] Mpl34-136°C;EIMSm/z:319[M+];IR(KBr)cm_1:2763 (OH),3024 (NH) ;:HNMR (DMS0-d6) 8ppm:3. 14-3.20 (m,5H),3. 27 (s,3H),3. 62 (s, 1H), 7. 05~7. 15 (m,4H),7. 25 (dd, 1H),7. 37~7. 46 (m, 2H), 7. 47~7. 53 (m, 1H),8. 22 (s,lH),l〇. 21 (s,lH)〇 [0220] Mpl34-136 ° C; EIMSm / z: 319 [M +]; IR (KBr) cm_1: 2763 (OH), 3024 (NH);: HNMR (DMS0-d6) 8ppm: 3 14-3.20 (m. , 5H), 3. 27 (s, 3H), 3. 62 (s, 1H), 7. 05 ~ 7. 15 (m, 4H), 7. 25 (dd, 1H), 7. 37 ~ 7. 46 (m, 2H), 7. 47 ~ 7. 53 (m, 1H), 8. 22 (s, lH), l〇. 21 (s, lH) square

[0221] 3-(2-乙氧基苯基)-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(82) [0221] 3- (2-ethoxyphenyl) -3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (82)

[0222] Mpl95-197°C;EIMSm/z:349[M+];IR(KBr)cm_1:2763 (OH),3021 (NH) ;:HNMR (DMS0-d6)8ppm:2. 03~2. 12 (m,3H),3. 14-3.21 (m,4H),3. 27 (s,3H),3.61 (s,lH), 7.00- 7. 16 (m,3H),7. 37 (dd, 1H), 7. 46~7. 53 (m, 2H), 7. 54~7. 60 (m, 1H), 7. 63~7. 69 (m, 1H),8. 20 (s, 1H), 10. 22 (s,lH)〇 [0222] Mpl95-197 ° C; EIMSm / z: 349 [M +]; IR (KBr) cm_1: 2763 (OH), 3021 (NH);: HNMR (DMS0-d6) 8ppm: 2 03 ~ 2 12.. (m, 3H), 3. 14-3.21 (m, 4H), 3. 27 (s, 3H), 3.61 (s, lH), 7.00- 7. 16 (m, 3H), 7. 37 (dd, 1H), 7. 46 ~ 7. 53 (m, 2H), 7. 54 ~ 7. 60 (m, 1H), 7. 63 ~ 7. 69 (m, 1H), 8. 20 (s, 1H) , 10. 22 (s, lH) square

[0223] 3-(2-乙氧基苯基)-3-(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(83) [0223] 3- (2-ethoxyphenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (83)

[0224]Mpl97-199°C;EIMSm/z:393[M+];IR(KBr)cm_1:2761 (OH),3025 (NH) ;:HNMR (DMS0-d6)8ppm:2. 04~2. 10 (m, 3H), 3. 17~3. 25 (m,4H),3. 29 (s,3H),3.61 (s,lH), 7.00- 7. 10 (m,3H),7. 38~7. 42 (m, 2H), 7. 47~7. 56 (m, 1H), 7. 67~7. 72 (m,2H),8. 20 (s, 1H),10. 24 (s,lH)〇 [0224] Mpl97-199 ° C; EIMSm / z: 393 [M +]; IR (KBr) cm_1: 2761 (OH), 3025 (NH);:.. HNMR (DMS0-d6) 8ppm: 2 04 ~ 2 10 (m, 3H), 3. 17 ~ 3. 25 (m, 4H), 3. 29 (s, 3H), 3.61 (s, lH), 7.00- 7. 10 (m, 3H), 7. 38 ~ 7. 42 (m, 2H), 7. 47 ~ 7. 56 (m, 1H), 7. 67 ~ 7. 72 (m, 2H), 8. 20 (s, 1H), 10. 24 (s, lH) billion

[0225] 3-(3-乙氧基苯基)-3-(3-氟苯基)-3-羟基丙酰-N-甲基氧肟酸(84) [0225] 3- (3-ethoxyphenyl) -3- (3-fluorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (84)

[0226]Mpl79-17981°C;EIMSm/z:333[M+];IR(KBr)cm_1:2761 (OH),3027 (NH) ;:H NMR(DMS0-d6)Sppm:2.03~2.12 (m,3H),3.12~3.25 (m,4H),3.27 (s,3H),3.61 (s,lH), 6.93- 7.08 (m,3H),7. 22~7. 33 (m, 2H), 7. 39~7. 43 (m, 2H), 7. 49~7. 55 (m, 1H),8. 20 (s, 1H),10. 19 (s,lH)〇 [0226] Mpl79-17981 ° C; EIMSm / z: 333 [M +]; IR (KBr) cm_1: 2761 (OH), 3027 (NH);: H NMR (DMS0-d6) Sppm: 2.03 ~ 2.12 (m, 3H), 3.12 ~ 3.25 (m, 4H), 3.27 (s, 3H), 3.61 (s, lH), 6.93- 7.08 (m, 3H), 7. 22 ~ 7. 33 (m, 2H), 7. 39 ~ 7. 43 (m, 2H), 7. 49 ~ 7. 55 (m, 1H), 8. 20 (s, 1H), 10. 19 (s, lH) square

[0227] 3-(3-乙氧基苯基)-3-(3-氯苯基)-3-羟基丙酰-N-甲基氧肟酸(85) [0227] 3- (3-ethoxyphenyl) -3- (3-chlorophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (85)

[0228]Mpl86-188°C;EIMSm/z:349[M+];IR(KBr)cm_1:2760 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:2. 13-2. 22 (m, 3H), 3. 17~3. 22 (m,4H),3. 29 (s,3H),3. 65 (s,lH), 6.93- 7.05 (m,2H),7. 20~7. 25 (m, 1H), 7. 38~7. 47 (m, 2H), 7. 49~7. 53 (m, 1H), 7. 57~7. 63 (m,2H),8.23 (s,lH),10.22 (s,lH)。 [0228] Mpl86-188 ° C; EIMSm / z: 349 [M +]; IR (KBr) cm_1: 2760 (OH), 3024 (NH);:.. HNMR (DMS0-d6) 8ppm: 2 13-2 22 (m, 3H), 3. 17 ~ 3. 22 (m, 4H), 3. 29 (s, 3H), 3. 65 (s, lH), 6.93- 7.05 (m, 2H), 7. 20 ~ 7. 25 (m, 1H), 7. 38 ~ 7. 47 (m, 2H), 7. 49 ~ 7. 53 (m, 1H), 7. 57 ~ 7. 63 (m, 2H), 8.23 ​​( s, lH), 10.22 (s, lH).

[0229] 3-(3-乙氧基苯基)-3-(3-溴苯基)-3-羟基丙酰-N-甲基氧肟酸(86) [0229] 3- (3-ethoxyphenyl) -3- (3-bromophenyl) -3-hydroxy-propionyl -N- methyl hydroxamic acid (86)

[0230]Mp219-221°C;EIMSm/z:393[M+];IR(KBr)cm_1:2763 (OH),3024 (NH) ;:HNMR (DMS0-d6)8ppm:2. 12~2. 22 (m, 3H), 3. 17~3. 24 (m,4H),3. 31 (s,3H),3.63 (s,lH), 6.97-7.08 (m,2H),7. 20~7. 32 (m, 1H), 7. 35~7. 39 (m, 2H), 7. 45~7. 54 (m, 1H), 7. 66~7. 72 (m,2H),8.26 (s,lH),10.23 (s,lH)。 [0230] Mp219-221 ° C; EIMSm / z: 393 [M +]; IR (KBr) cm_1: 2763 (OH), 3024 (NH);:.. HNMR (DMS0-d6) 8ppm: 2 12 ~ 2 22 (m, 3H), 3. 17 ~ 3. 24 (m, 4H), 3. 31 (s, 3H), 3.63 (s, lH), 6.97-7.08 (m, 2H), 7. 20 ~ 7. 32 (m, 1H), 7. 35 ~ 7. 39 (m, 2H), 7. 45 ~ 7. 54 (m, 1H), 7. 66 ~ 7. 72 (m, 2H), 8.26 (s, lH), 10.23 (s, lH).

Claims (3)

  1. 1. 一类二芳基丙酰-N-甲基氧肟酸化合物,其特征是它们具有如下结构通式: I 1. A class of diaryl propionyloxy -N- methyl hydroxamic acid compounds, characterized in that they have the general structural formula: I
    Figure CN103012207BC00021
    式I中R1、R2、R3、R4、R5、R 6、R7和R8的定义取自下列各组之任一组: (1) R2= R3= R4= R5= R6= R7= R8= H, R1= Br ; (2) R1= R3= R4= R5= R6= R7= R8= H, R2= OEt ; (S)R1= R2= R4= R5= R6= R7= R8= H, R3= OEt ; (4) R2= R3= R4= R5= R6= R7= H, R1= R8= NH2; (5) R1= R3= R4= R5= R6= R8= H, R2= R7= OEt ; (6) R2= R4= R5= R7= R8= H, R1= OH, R3= OH^O(CH2)7CH3; (7) R2= R3= R4= R5= R6= R7= H, R8= Br, R1= OH 或OEt ; (8) R2= R3= R4= R5= R6= R7= H, R8= Cl, R1= OMe ; (9) R2= R3= R4= R5= R6= R8= H, R1= NH2, R7= F ; (10) R2= R3= R4= R5= R6= R8= Η, R1= OMe, R7= Br〇 Formula I, R1, R2, R3, R4, R5, R 6, R7 and R8 are taken from the definition of a set of any of the following groups: (1) R2 = R3 = R4 = R5 = R6 = R7 = R8 = H, R1 = Br; (2) R1 = R3 = R4 = R5 = R6 = R7 = R8 = H, R2 = OEt; R1 = R2 = R4 = R5 = R6 = R7 = R8 (S) = H, R3 = OEt; (4) R2 = R3 = R4 = R5 = R6 = R7 = H, R1 = R8 = NH2; (5) R1 = R3 = R4 = R5 = R6 = R8 = H, R2 = R7 = OEt; (6) R2 = R4 = R5 = R7 = R8 = H, R1 = OH, R3 = OH ^ O (CH2) 7CH3; (7) R2 = R3 = R4 = R5 = R6 = R7 = H, R8 = Br, R1 = OH or OEt; (8) R2 = R3 = R4 = R5 = R6 = R7 = H, R8 = Cl, R1 = OMe; (9) R2 = R3 = R4 = R5 = R6 = R8 = H, R1 = NH2, R7 = F; (10) R2 = R3 = R4 = R5 = R6 = R8 = Η, R1 = OMe, R7 = Br〇
  2. 2. -种制备权利要求1所述的二芳基丙酰-N-甲基氧肟酸化合物的方法,其特征是它包括下列步骤: 步骤1.将I-R1H2-S-R3H4取代苯加入到BF 3 · Et2O中,升温至40-50°C之间, 待I-RiH2I-RM-R4取代苯溶解后,加入2-R 8-3-R7-4-R6-5-R5取代苯甲酸,物质的量之t匕取代苯:2-R8-3-R7-4-R6-5-R5取代苯甲酸:BF 3 · Et2O = I: (1 ~ 4) : (60~100),升温至65-1KTC之间反应4~24h,反应完毕,倒入AcONa的水溶液中,搅拌2 ~10h,抽滤,洗涤,EtOH-H2O 重结晶,得到1-1^-2-1?2-3-1?3-4-1?4-2'-1?8-3'-1? 7-4'-1?6-5' -R5取代二苯基甲酮II; 步骤2.将1-1^-2-1?2-3-1?3-4-1?4-2' -R8-3' -R7-4' -R6-5' -R5取代二苯基甲酮II、 Zn粉、NH4CU溴乙酸乙酯一起研磨均匀,物质的量之比d-R1-〗-!?2^ 3^4-〗' -R8-3' -R7-4' -R6-5' -R5取代二苯基甲酮II:Zn:NH4Cl:溴乙酸乙酯=1:10:9: (1~5),室温静置10~24h后,倒入饱和NH4Cl溶液,AcOEt萃取,无水MgSO4干燥,蒸去溶剂,用硅胶柱纯 2. - Method propionic acid diaryl -N- methyl hydroxamic acid compound prepared as claimed in claim 1 species, characterized in that it comprises the following steps: Step 1. The substituted I-R1H2-S-R3H4 benzene was added after the BF 3 · Et2O, the temperature was raised to between 40-50 ° C, to be I-RiH2I-RM-R4-substituted benzene was dissolved, was added 2-R 8-3-R7-4-R6-5-R5-substituted benzoic acid the amount of material t dagger substituted phenyl: 2-R8-3-R7-4-R6-5-R5-substituted benzoic acid: BF 3 · Et2O = I: (1 ~ 4): (60 ~ 100), warmed to the reaction between the aqueous 65-1KTC 4 ~ 24h, the reaction is complete, pour AcONa and stirred for 2 ~ 10h, filtration, washing, EtOH-H2O recrystallized 1-1 ^ -2-1? 2-3- ????? 1 3-4-1 4-2'-1 8-3'-1 7-4'-1 6-5 '-R5-substituted benzophenone II; step 2. 1-1 ^ -2-1? 2-3-1? 3-4-1? 4-2 '-R8-3' -R7-4 '-R6-5' -R5-substituted benzophenone II, Zn powder, NH4CU triturated with ethyl bromoacetate uniform, the amount of substance ratio of d-R1 -〗 - !? 2 ^ 3 ^ 4-〗 '-R8-3' -R7-4 '-R6-5' -R5 substituted diphenyl yl methanone II: Zn: NH4Cl: ethyl bromoacetate = 1: 10: 9: (1-5), 10 ~ 24h after standing at room temperature, poured into saturated NH4Cl solution, AcOEt was extracted, dried over anhydrous MgSO4, was evaporated The solvent was purified by silica gel column pure ,洗脱剂体积比:AcOEt:石油醚=1:12~2:1,得到SOR 1-S-R2H3-S-R4取代苯基)-3-(2-1? 8-3-1?7-4-1?6-5-1?5取代苯基)-3-羟基丙酸乙酯111 ; 步骤3.将3-羟基-3- (2-1^-3-1?2-4-1?3-5-1?4取代苯基)-3- (2-R 8-3-R7-4-R6-5-R5取代苯基)丙酸乙酯III溶于无水甲醇,然后加入CH3NHOH* HC1、甲醇钠,物质的量之比为: 3-羟基-3-(2-1^-3-1^-4-1^-5-1?4取代苯基)-3-(2-R 8-3-R7-4-R6-5-R5取代苯基)丙酸乙酯IIi = CH3NHOH · HCl = CH3ONa = 1:4: (2~9),搅拌11~30h,蒸去甲醇,加入去离子水,用AcOEt萃取,合并有机层,MgSO4干燥,蒸去溶剂,用硅胶柱纯化,洗脱剂体积比:AcOEt:石油醚=1:10 ~3:1,得3-羟基-3-(2-1^-3-1^-4-1^-5-1?4取代苯基)-3-(2-R8-3-R 7-4-R6-5-R5 取代苯基)丙酰-N-甲基氧肟酸I ; 其中所述的R1、R2、R3、R4、R5、R 6、R7和R8的定义与权利要求1所述的定义相同。 , Volume ratio eluent: AcOEt: petroleum ether = 1: 12 to 2: 1, to give SOR 1-S-R2H3-S-R4-substituted phenyl) -3- (2-18-3-17?? ?? -4-16-5-15 substituted phenyl) -3-hydroxy-propanoate 111; step 3. 3-hydroxy-3- (2-1 ^ -3-12-4-? 1? 3-5-1? 4-substituted phenyl) -3- (2-R 8-3-R7-4-R6-5-R5-substituted phenyl) propionate III dissolved in anhydrous methanol, followed by addition of CH3NHOH * HC1, sodium methoxide, ratio of amount of substance is: 3-hydroxy-3- (2-1 ^ -3-1 -4-1 ^ ^ substituted phenyl -5-14?) -3- (2 -R 8-3-R7-4-R6-5-R5-substituted phenyl) propionate IIi = CH3NHOH · HCl = CH3ONa = 1: 4: (2 ~ 9), stirred for 11 ~ 30h, the methanol was distilled off, deionized water was added and extracted with AcOEt, and the organic layers were combined, MgSO4 dried, the solvent was evaporated, purified by silica gel column, eluent volume ratio: AcOEt: petroleum ether = 1: 10 ~ 3: 1, to give 3-hydroxy-3 - (? ^ 2-1 ^ -3-1 -4-1 ^ -5-14 substituted phenyl) -3- (2-R8-3-R 7-4-R6-5-R5-substituted phenyl) propionyl -N- methyl hydroxamic acid I; wherein R1, R2, R3, R4, R5, R 6, R7 and R8 are as defined in claim 1 the same as defined in the claims.
  3. 3.权利要求1所述的二芳基丙酰-N-甲基氧肟酸系列化合物在制备抗胃炎、胃溃疡或抗尿路结石药物中的应用。 Diaryl propionyl claimed in claim 1 -N- methyl hydroxamic acid compound of urinary tract stones series drugs against gastritis, gastric ulcer or in the preparation of anti.
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US5366989A (en) * 1991-12-09 1994-11-22 Toyama Chemical Co., Ltd. Triazole derivatives and salts thereof and antifungal agent containing the same
CN1214041A (en) * 1996-01-23 1999-04-14 盐野义制药株式会社 Sulfonated amino acid derivatives and metalloproteinase inhibitors contg. same
CN1777577A (en) * 2003-01-08 2006-05-24 希龙公司 Antibacterial agents

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US9738604B2 (en) * 2010-09-03 2017-08-22 Duke University Ethynylbenzene derivatives

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Publication number Priority date Publication date Assignee Title
US5366989A (en) * 1991-12-09 1994-11-22 Toyama Chemical Co., Ltd. Triazole derivatives and salts thereof and antifungal agent containing the same
CN1214041A (en) * 1996-01-23 1999-04-14 盐野义制药株式会社 Sulfonated amino acid derivatives and metalloproteinase inhibitors contg. same
CN1777577A (en) * 2003-01-08 2006-05-24 希龙公司 Antibacterial agents

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