CN109096156B - 二磺酰基间芳基二胺类尿素酶抑制剂及其制法和用途 - Google Patents
二磺酰基间芳基二胺类尿素酶抑制剂及其制法和用途 Download PDFInfo
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- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/44—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
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Abstract
一类二磺酰基间芳基二胺类化合物,它们具有如下结构通式:
Description
技术领域
本发明涉及一类二磺酰基间芳基二胺类尿素酶抑制剂的制法以及它们在制备抗胃炎、抗胃溃疡、抗尿路结石药物中的应用。
技术背景
幽门螺旋杆菌(Helicobacter pylari)会引发胃炎、胃溃疡、十二指肠溃疡、胃萎缩、肠上皮化生、胃癌、胃淋巴瘤等多种疾病。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。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%。我国的感染率为60%左右。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。超过90%的十二指肠溃疡和80%左右的胃溃疡是H.pylori所致。根除H.pylori是治疗上述疾病以及防止复发的前提。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)。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。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。
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。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。因此尿素酶的作用为H.pylori营造了一个适宜的微环境。其它一些病菌,如普通变形杆菌(Proteus vulgaris)、奇异变形杆菌(Proteus mirabilis)、解脲脲原体(Ureaplasma urealyticum)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。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。但是氨的释放会造成细胞毒性、引发炎症或溃疡,也会因造成血氨过高引发肝性脑病等等,此外尿素酶本身会通过免疫反应,刺激人中性粒细胞的氧化爆发,产生氯氨,参与细胞损伤和诱发癌变,因此尿素酶是上述致病菌重要的毒力因子。故阻断了尿素酶活性,就能有效的抑制甚至杀灭这类病菌,达到治疗上述疾病的目的。同时,毒力因子并非像DNA、蛋白质等一样,是细菌生存必不可少的,因此与传统抗生素相比,抑制毒力因子细菌不容易发展耐药性。这些优越性表明尿素酶抑制剂将有可能成为治疗上述疾病的一线药物。
现已报道了多种结构类型的尿素酶抑制剂,包括磷酸二酰胺类、酚类、醌类、硫脲类、氧肟酸类等等。磷酸二酰胺类是已报道尿素酶抑制剂中活性最好,氧肟酸类是至今唯一一个有临床应用的尿素酶抑制剂,但磷酸二酰胺类在酸性环境中不稳定,氧肟酸类有致畸风险,这些缺点阻碍了它们进一步的发展。因此急需探索新型的尿素酶抑制剂,本发明基于这种情形,发现出了二磺酰基间芳基二胺类新型尿素酶抑制剂,具有良好的尿素酶抑制活性。
发明内容
利用计算机辅助药物设计技术,根据特异性药物与靶点作用的原理,基于药物分子与靶点之间互补性,设计并合成了具有I所示结构的新型尿素酶抑制剂。
试验表明,所有化合物对尿素酶表现出了优良的抑制活性。
本发明的目的在于设计并合成一系列二磺酰基间芳基二胺类(I)尿素酶抑制剂,发现了活性高、毒副作用低的新型尿素酶抑制剂,并提供二磺酰基间芳基二胺类系列化合物的制法。
本发明的技术方案如下:
一类二磺酰基间芳基二胺类化合物,它们具有如下结构通式:
式I中当X=CH时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(1)R1=R2=R4=R5=H,R3=F、Cl、Br、H、Me、NO2、NH2、CN、OH或OMe;
(2)R2=R3=R4=R5=H,R1=OMe、F、Cl、Br、Me、NO2、NH2、CN或OH;
(3)R1=R3=R4=R5=H,R2=OMe、F、Cl、Me、Br、OH、NH2或NO2;
(4)R1=R3=R5=H,R2=R4=Cl、Br、Me、OMe、OH、NO2、NH2或F;
(5)R3=R4=R5=H,R1=R2=Cl、F、Br、Me、OH、OMe或NO2;
(6)R2=R4=R5=H,R1=R3=Cl、Me、OMe、OH、Br或NO2;
(7)R1=R4=R5=H,R2=R3=F、Cl、Br、OMe、OH、CN、NO2、NH2或Me;
(8)R2=R3=R5=H,R1=R4=Cl、F、Br、Me、OH、CN或NO2;
(9)R2=R3=R4=H,R1=R5=F、Cl、Br、OH、CN、OMe或Me;
式I中当X=N时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(10)R1=R2=R4=R5=H,R3=F、Cl、Br、H、或OMe;
(11)R2=R3=R4=R5=H,R1=OMe、F、NO2、NH2、CN或Br;
(12)R1=R3=R4=R5=H,R2=OMe、Cl、Br、NH2或OH;
(13)R1=R3=R5=H,R2=R4=Me、OH、NH2或Cl;
(14)R3=R4=R5=H,R1=R2=Cl、F、NO2、OMe或OH;
(15)R2=R4=R5=H,R1=R3=Cl、NO2或OH;
(16)R1=R4=R5=H,R2=R3=Cl、Br、CN、Me或NO2;
(17)R2=R3=R5=H,R1=R4=Cl、NO2、OH或Me;
(18)R2=R3=R4=H,R1=R5=Cl、Br、或CN;
一种制备二磺酰基间芳基二胺类系列化合物的方法,它包括下列步骤:
取2-R1-3-R2-4-R3-5-R4-6-R5取代苯磺酰氯(II)溶解到无水甲醇中,搅拌20min,加入间芳基二胺(III)和三乙胺,物质的量之比为:2-R1-3-R2-4-R3-5-R4-6-R5取代苯磺酰氯(II):间芳基二胺(III):三乙胺=1:(1~2):(4~12),控制反应温度在30~70℃之间,反应4~24h,冷却,蒸去甲醇,加水,用乙酸乙酯萃取三次,合并有机相,水洗,无水MgSO4干燥,蒸去溶剂,硅胶柱层析纯化,洗脱剂体积比:AcOEt:石油醚=1:1.5~1:9,得白色固体N,N'-双(2-R1-3-R2-4-R3-5-R4-6-R5苯磺酰基)间芳基二胺(I);其中所述的R1、R2、R3、R4和R5的定义与上述(I)式的定义相同。
本发明所述的二磺酰基间芳基二胺类系列化合物对尿素酶有较好的抑制活性,比阳性对照乙酰氧肟酸的活性更好。可以用于制备抗胃炎、胃溃疡或抗尿路结石的药物。
具体实施方式
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。
实施例1:N,N'-双(2,6-二氯苯磺酰基)间苯二胺(69)
取245mg 2,6-二氯苯磺酰氯溶解到20mL无水甲醇中,搅拌20min,加入间苯二胺450mg和三乙胺3mL,在70℃下搅拌12h冷却,蒸去甲醇,加水,用乙酸乙酯萃取三次,合并有机相,水洗,无水MgSO4干燥,蒸去溶剂,硅胶柱层析纯化,洗脱剂体积比:AcOEt:石油醚=1:4,得白色固体N,N'-双(2,6-二氯苯磺酰基)间苯二胺515mg,产率98%。熔点:201~202.5℃;EIMS m/z:524[M+];1H NMR(500MHz,DMSO,δ):7.55(dd,2H),7.52–7.46(m,4H),7.09(s,2H),6.94(t,1H),6.76(dd,2H),5.86(t,1H)。
实施例2:
按实施例1相似的方法,用不同的取代形式的苯磺酰氯为原料,合成了表1、表2表3所列的苯磺酰胺系列化合物1~105。
表1通式I中X=CH时二磺酰胺系列化合物的各R基团
表2通式I中X=N时二磺酰胺系列化合物的各R基团
注:初始原料均购自于aldrich公司
实施例3:化合物的抑酶活性
往96孔板中加入25μLJack bean(刀豆)尿素酶(4U)和25μL(1mM)被测化合物的溶液,在37℃下培育2h,然后加入含有100mM尿素和100mM的磷酸缓冲液55μL,在30℃下培育15min,加入45μL酚试剂(含苯酚1%与含硝普钠0.005%的混合溶液)和70μL碱试剂(含NaOH0.5%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OD值,百分抑制率按下式计算:
所有的试验都在pH为8.2的溶液中进行(0.01M的K2HPO4,1mM的EDTA,0.01M的LiCl),活性的高低以半抑制率IC50来表示,IC50越小,此化合物的活性越高,结果见表3。
结果表明:本发明所述的部分二磺酰基间芳基二胺类系列化合物对尿素酶有较好的抑制活性,均比阳性对照乙酰氧肟酸的活性更高。
表3二磺酰基间芳基二胺类系列化合物对刀豆尿素酶的抑制作用(IC50)
结果表明,所有化合物对刀豆尿素酶有显着的抑制作用,是市场药物乙酰氧肟酸的40-1000倍。
本发明的上述实施例表明:本发明找到化合物与尿素酶作用的关键位点,显著提高了抑制尿素酶的活性,并且对大鼠的急毒实验表明,化合物7、16、19、24、29、38、40、45、51、61、64、72、90、91、105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。
化合物1~98的熔点、质谱及氢谱数据:
N,N'-双(3-氟苯磺酰基)间苯二胺(1):
Mp 173~174℃;EIMS m/z:424[M+];1H NMR(400MHz,DMSO,δ):7.68(dt,2H),7.54–7.46(m,4H),7.32(ddt,2H),6.98(t,1H),6.76(dd,2H),6.06(s,2H),5.86(t,1H)。
N,N'-双(3-氯苯磺酰基)间苯二胺(2):
Mp 179~180℃;EIMS m/z:456[M+];1H NMR(400MHz,DMSO,δ):7.83–7.75(m,4H),7.70(dt,2H),7.45(t,2H),6.98(t,1H),6.76(dd,2H),6.04(s,2H),5.86(t,1H)。
N,N'-双(3-溴苯磺酰基)间苯二胺(3):
Mp 189~191℃;EIMS m/z:544[M+];1H NMR(400MHz,DMSO,δ):7.95(t,2H),7.88(dt,2H),7.78(dt,2H),7.41(t,2H),6.99(t,1H),6.76(dd,2H),6.04(s,2H),5.86(t,1H)。
N,N'-双苯磺酰基间苯二胺(4):
Mp 185~187℃;EIMS m/z:197[M+];1H NMR(400MHz,DMSO,δ):7.71–7.59(m,6H),7.62–7.51(m,4H),6.94(t,1H),6.76(dd,2H),6.18(s,2H),5.86(t,1H)。
N,N'-双(3-甲基苯磺酰基)间苯二胺(5):
Mp 207~208℃;EIMS m/z:416[M+];1H NMR(400MHz,DMSO,δ):7.85(dt,2H),7.80(dt,2H),7.64–7.58(m,2H),7.54(t,2H),6.92(t,1H),6.76(dd,2H),6.00(s,2H),5.86(t,1H),2.42(s,4H),2.42(d,2H)。
N,N'-双(3-硝基苯磺酰基)间苯二胺(6):
Mp 198~199℃;EIMS m/z:478[M+];1H NMR(400MHz,DMSO,δ):8.60–8.51(m,4H),8.19(dt,2H),7.74(t,2H),6.97(t,1H),6.76(dd,2H),6.21(s,2H),5.86(t,1H)。
N,N'-双(3-甲氧基苯磺酰基)间苯二胺(7):
Mp 203~204℃;EIMS m/z:448[M+];1H NMR(400MHz,DMSO,δ):7.49(dp,2H),7.43(t,1H),7.17(dt,1H),6.76(dd,1H),5.86(d,2H),3.81(s,3H)。
N,N'-双(3-羟基苯磺酰基)间苯二胺(8):
Mp 203~205℃;EIMS m/z:420[M+];1H NMR(400MHz,DMSO,δ):7.44–7.35(m,4H),7.32(t,2H),7.19(dt,2H),7.01(t,1H),6.76(dd,2H),6.54(s,2H),5.86(t,1H),5.84(s,2H)。
N,N'-双(3-氰基苯磺酰基)间苯二胺(9):
Mp 197~198℃;EIMS m/z:438[M+];1H NMR(400MHz,DMSO,δ):8.33(t,2H),8.24(dt,2H),7.96(dt,2H),7.68(t,2H),6.95(t,1H),6.76(dd,2H),6.12(s,2H),5.86(t,1H)。
N,N'-双(3-胺基苯磺酰基)间苯二胺(10):
Mp 195~196℃;EIMS m/z:418[M+];1H NMR(400MHz,DMSO,δ):7.37–7.29(m,4H),7.24(s,1H),7.24(d,1H),7.04–6.95(m,3H),6.76(dd,2H),5.86(t,1H),5.79(s,2H),4.16(s,4H)。
N,N'-双(2-甲氧基苯磺酰基)间苯二胺(11):
Mp 196~198℃;EIMS m/z:448[M+];1H NMR(400MHz,DMSO,δ):7.95(dd,2H),7.55(td,2H),7.17(td,2H),7.03(dd,2H),6.94(t,1H),6.76(dd,2H),6.71(s,2H),5.86(t,1H),3.95(s,6H)。
N,N'-双(2-氟苯磺酰基)间苯二胺(12):
Mp 223~224℃;EIMS m/z:424[M+];1H NMR(400MHz,DMSO,δ):7.95(ddd,2H),7.68(tdd,2H),7.26(ddt,4H),7.07(t,1H),6.76(dd,2H),5.86(t,1H),5.80(s,2H)。
N,N'-双(2-氯苯磺酰基)间苯二胺(13):
Mp 203~204℃;EIMS m/z:456[M+];1H NMR(400MHz,DMSO,δ):8.00(dd,2H),7.68(dd,2H),7.57(td,2H),7.38(td,2H),7.05(t,1H),6.76(dd,2H),5.86(t,1H),5.85(s,2H)。
N,N'-双(2-溴苯磺酰基)间苯二胺(14):
Mp 192~193℃;EIMS m/z:544[M+];1H NMR(400MHz,DMSO,δ):1H NMR(500MHz,Chloroform-d)δ8.27(dd,2H),7.67(dd,2H),7.50(td,2H),7.42(td,2H),7.07(t,1H),6.76(dd,2H),6.34(s,2H),5.86(t,1H)。
N,N'-双(2-羟基苯磺酰基)间苯二胺(15):
Mp 167~168℃;EIMS m/z:420[M+];1H NMR(400MHz,DMSO,δ):7.59(dd,2H),7.49(td,2H),7.14–7.03(m,4H),6.97(t,1H),6.76(dd,2H),6.24(s,2H),5.93(s,2H),5.86(t,1H)。
N,N'-双(2-甲基苯磺酰基)间苯二胺(16):
Mp 236~237℃;EIMS m/z:416[M+];H NMR(400MHz,DMSO,δ):7.87(dd,2H),7.54(td,2H),7.39(dd,4H),7.04(t,1H),6.76(dd,2H),5.86(t,1H),5.74(s,2H),2.60(s,6H)。
N,N'-双(2-硝基苯磺酰基)间苯二胺(17):
Mp 203~205℃;EIMS m/z:478[M+];1H NMR(400MHz,DMSO,δ):8.91(s,2H),8.11(ddd,4H),7.82(td,2H),7.75(td,2H),7.06(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2-胺基苯磺酰基)间苯二胺(18):
Mp 192~194℃;EIMS m/z:418[M+];1H NMR(400MHz,DMSO,δ):7.59(dd,2H),7.28(td,2H),7.06(t,1H),6.87–6.73(m,6H),5.91–5.84(m,3H),4.35(s,4H)。
N,N'-双(2-氰基苯磺酰基)间苯二胺(19):
Mp 198~199℃;EIMS m/z:438[M+];1H NMR(400MHz,DMSO,δ):8.18(dd,2H),7.89(dd,2H),7.77(td,2H),7.70(td,2H),7.05(s,2H),6.97(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(3-甲氧基苯磺酰基)间苯二胺(20):
Mp 198~199℃;EIMS m/z:448[M+];1H NMR(400MHz,DMSO,δ):7.49(dp,2H),7.42(t,1H),7.17(dt,1H),6.76(dd,1H),5.86(d,2H),3.81(s,3H)。
N,N'-双(3-羟基苯磺酰基)间苯二胺(21):
Mp 189~191℃;EIMS m/z:420[M+];1H NMR(400MHz,DMSO,δ):7.44–7.35(m,4H),7.32(t,2H),7.19(dt,2H),7.01(t,1H),6.76(dd,2H),6.54(s,2H),5.86(t,1H),5.84(s,2H)。
N,N'-双(3-胺基苯磺酰基)间苯二胺(22):
Mp 169~171℃;EIMS m/z:418[M+];1H NMR(400MHz,DMSO,δ):7.37–7.29(m,4H),7.24(s,1H),7.24(d,1H),7.04–6.95(m,3H),6.76(dd,2H),5.86(t,1H),5.79(s,2H),4.16(s,4H)。
N,N'-双(3-氟苯磺酰基)间苯二胺(23):
Mp 186~188℃;EIMS m/z:424[M+];1H NMR(400MHz,DMSO,δ):7.68(dt,2H),7.54–7.46(m,4H),7.32(ddt,2H),6.98(t,1H),6.76(dd,2H),6.06(s,2H),5.86(t,1H)。
N,N'-双(3-硝基苯磺酰基)间苯二胺(24):
Mp 196~198℃;EIMS m/z:478[M+];1H NMR(400MHz,DMSO,δ):8.59–8.51(m,4H),8.22(dt,2H),7.79(t,2H),6.97(t,1H),6.76(dd,2H),6.39(s,2H),5.86(t,1H)。
N,N'-双(3-甲基苯磺酰基)间苯二胺(25):
Mp 177~178℃;EIMS m/z:416[M+];1H NMR(400MHz,DMSO,δ):7.85(dt,2H),7.80(dt,2H),7.64–7.58(m,2H),7.54(t,2H),6.92(t,1H),6.76(dd,2H),6.00(s,2H),5.86(t,1H),2.42(s,4H),2.42(d,2H)。
N,N'-双(3-氯苯磺酰基)间苯二胺(26):
Mp 221~222℃;EIMS m/z:456[M+];1H NMR(400MHz,DMSO,δ):7.75(m,4H),7.70(dt,2H),7.45(t,2H),6.98(t,1H),6.76(dd,2H),6.04(s,2H),5.86(t,1H)。N,N'-双(3-溴苯磺酰基)间苯二胺(27):
Mp 198~199℃;EIMS m/z:544[M+];1H NMR(400MHz,DMSO,δ):7.95(t,2H),7.88(dt,2H),7.78(dt,2H),7.41(t,2H),6.99(t,1H),6.76(dd,2H),6.04(s,2H),5.86(t,1H)。
N,N'-双(3,5-二甲基苯磺酰基)间苯二胺(28):
Mp 223~224℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.54(d,4H),7.52–7.47(m,2H),6.94(t,1H),6.76(dd,2H),6.01(s,2H),5.86(t,1H),2.31(s,11H)。
N,N'-双(3,5-二氟苯磺酰基)间苯二胺(29):
Mp 198~200℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.47–7.40(m,4H),7.13(tt,2H),7.02(t,1H),6.76(dd,2H),6.01(s,2H),5.86(t,1H).。
N,N'-双(3,5-二甲氧基苯磺酰基)间苯二胺(30):
Mp 192~194℃;EIMS m/z:508[M+];1H NMR(400MHz,DMSO,δ):7.17(d,2H),6.76(dd,1H),6.69(t,1H),5.87(d,2H),3.81(s,6H)。
N,N'-双(3,5-二氯苯磺酰基)间苯二胺(31):
Mp 179~180℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):7.85(d,4H),7.76(t,2H),7.02(t,1H),6.76(dd,2H),5.96(s,2H),5.86(t,1H)。
N,N'-双(3,5-二溴苯磺酰基)间苯二胺(32):
Mp 223~224℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):8.08(d,4H),7.95(t,2H),6.91(t,1H),6.76(dd,2H),6.01(s,2H),5.86(t,1H)。
N,N'-双(3,5-二硝基苯磺酰基)间苯二胺(33):
Mp 198~199℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):9.13(t,1H),9.02(t,1H),8.97(d,2H),8.91(dt,2H),7.04(t,1H),6.76(dd,2H),6.61(s,1H),6.04(s,1H),5.86(t,1H)。
N,N'-双(3,5-二胺基苯磺酰基)间苯二胺(34):
Mp 193~195℃;EIMS m/z:448[M+];1H NMR(400MHz,DMSO,δ):6.95(t,1H),6.76(dd,2H),6.64(d,4H),6.18(s,2H),6.09(t,2H),5.86(t,1H),4.31(s,8H)。N,N'-双(3,5-二羟基苯磺酰基)间苯二胺(35):
Mp 235~237℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):7.09(s,4H),7.01(d,4H),6.95(t,1H),6.76(dd,2H),6.63(t,2H),6.17(s,2H),5.86(t,1H)。N,N'-双(3,5-二氟苯磺酰基)间苯二胺(36):
Mp 245~246℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.47–7.40(m,4H),7.13(tt,2H),7.02(t,1H),6.76(dd,2H),6.01(s,2H),5.86(t,1H)。
N,N'-双(2,3-二氯苯磺酰基)间苯二胺(37):
Mp 201~203℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):7.91(dd,2H),7.80(dd,2H),7.32(t,2H),7.03–6.95(m,3H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,3-二甲基苯磺酰基)间苯二胺(38):
Mp 212~213℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.79(dd,2H),7.43–7.32(m,4H),7.03(t,1H),6.76(dd,2H),5.91(s,2H),5.86(t,1H),2.71(s,6H),2.32(d,6H)。
N,N'-双(2,3-二甲氧基苯磺酰基)间苯二胺(39):
Mp 231~232℃;EIMS m/z:508[M+];1H NMR(400MHz,DMSO,δ):7.69(t,2H),7.30(d,4H),6.99(t,1H),6.77(s,3H),6.75(d,1H),5.86(t,1H),3.90(d,12H)。N,N'-双(2,3-二羟基苯磺酰基)间苯二胺(40):
Mp 225~226℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):7.40(dd,2H),7.04–6.94(m,4H),6.85(dd,1H),6.76(dd,2H),6.13(s,2H),5.86(d,3H),5.46(s,2H)。
N,N'-双(2,3-二硝基苯磺酰基)间苯二胺(41):
Mp 202~204℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):8.52(dd,1H),8.42–8.32(m,3H),8.03(t,1H),8.01–7.94(m,2H),7.08(s,1H),6.92(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,3-二溴苯磺酰基)间苯二胺(42):
Mp 236~237℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):8.14(dd,2H),7.84(dd,2H),7.35(t,2H),6.99(t,1H),6.91(s,2H),6.76(dd,2H),5.86(t,1H)。N,N'-双(2,3-二氟苯磺酰基)间苯二胺(43):
Mp 234~236℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.73(ddd,2H),7.36–7.22(m,4H),6.97(t,1H),6.76(dd,2H),6.12(s,2H),5.86(t,1H)。
N,N'-双(2,4-二氯苯磺酰基)间苯二胺(44):
Mp 206~208℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):7.93(d,2H),7.82(d,2H),7.53(dd,2H),7.04(t,1H),6.76(dd,2H),6.08(s,2H),5.86(t,1H)。
N,N'-双(2,4-二羟基苯磺酰基)间苯二胺(45):
Mp 195~196℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):8.30(s,2H),7.65(d,2H),6.76(dd,2H),6.72(s,2H),6.63(d,2H),6.56(dd,2H),5.93(s,2H),5.86(t,1H)。
N,N'-双(2,4-二硝基苯磺酰基)间苯二胺(46):
Mp 223~224℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):8.68(dd,1H),8.64–8.57(m,2H),8.50(d,1H),8.43(d,1H),8.32(d,1H),7.09(t,1H),6.76(dd,2H),6.46(s,1H),5.97(s,1H),5.86(t,1H)。
N,N'-双(2,4-二甲基苯磺酰基)间苯二胺(47):
Mp 235~237℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.91(d,2H),7.20–7.12(m,4H),7.03(t,1H),6.76(dd,2H),5.92–5.84(m,3H),2.66(d,6H),2.36(d,6H)。
N,N'-双(2,4-二溴苯磺酰基)间苯二胺(48):
Mp 256~257℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):7.94–7.84(m,4H),7.67(dd,2H),7.04(t,1H),6.76(dd,2H),6.00(s,2H),5.86(t,1H)。
N,N'-双(2,4-二甲氧基苯磺酰基)间苯二胺(49):
Mp 198~200℃;EIMS m/z:508[M+];1H NMR(400MHz,DMSO,δ):7.85(d,2H),6.97(t,1H),6.89(s,2H),6.81(s,3H),6.83–6.73(m,3H),5.86(t,1H),3.78(s,6H),3.44(s,6H)。
N,N'-双(3,4-二氯苯磺酰基)间苯二胺(50):
Mp 190~192℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):8.00(d,2H),7.78(dd,2H),7.72(d,2H),6.98(t,1H),6.76(dd,2H),6.00(s,2H),5.86(t,1H).。
N,N'-双(3,4-二溴苯磺酰基)间苯二胺(51):
Mp 212~214℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):8.05(d,2H),7.81(dd2H),7.67(d,2H),6.98(t,1H),6.76(dd,2H),5.98(s,2H),5.86(t,1H)。N,N'-双(3,4-二硝基苯磺酰基)间苯二胺(52):
Mp 198~199℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):8.79(dd,2H),8.63(dd,1H),8.53(dd,1H),8.41(d,1H),8.25(d,1H),6.95(t,1H),6.76(dd,2H),6.27(s,1H),6.17(s,1H),5.86(t,1H)。
N,N'-双(3,4-二甲基苯磺酰基)间苯二胺(53):
Mp 198~200℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.74(dd,2H),7.59–7.54(m,2H),7.26(dd,2H),6.94(t,1H),6.76(dd,2H),6.02(s,2H),5.86(t,1H),2.34(d,6H),2.28(d,6H)。
N,N'-双(3,4-二氟苯磺酰基)间苯二胺(54):
Mp 231~233℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.79(ddd,2H),7.68(ddd,2H),7.50(ddd,2H),6.97(t,1H),6.76(dd,2H),6.03(s,2H),5.86(t,1H)。
N,N'-双(3,4-二羟基苯磺酰基)间苯二胺(55):
Mp 198~199℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):7.37(d,2H),7.28(dd,2H),7.02(t,1H),6.92(d,2H),6.76(dd,2H),6.39(s,2H),5.93(s,2H),5.86(t,1H),5.56(s,2H)。
N,N'-双(3,4-二甲氧基苯磺酰基)间苯二胺(56):
Mp 203~204℃;EIMS m/z:508[M+];1H NMR(400MHz,DMSO,δ):7.77(d,2H),7.51(dd,2H),7.25(d,2H),6.76(dd,2H),5.91(s,2H),5.86(t,1H),3.89(d,12H).。
N,N'-双(3,4-二胺基苯磺酰基)间苯二胺(57):
Mp 212~214℃;EIMS m/z:448[M+];1H NMR(400MHz,DMSO,δ):7.07(dd,2H),6.84(d,2H),6.76(dd,2H),6.62(d,2H),6.10(s,2H),5.86(t,1H),4.35(s,8H)。N,N'-双(3,4-二氰基苯磺酰基)间苯二胺(58):
Mp 190~192℃;EIMS m/z:488[M+];1H NMR(400MHz,DMSO,δ):8.47–8.38(m,4H),8.11(d,2H),7.00(t,1H),6.76(dd,2H),5.99(s,2H),5.86(t,1H)。
N,N'-双(2,5-二氟苯磺酰基)间苯二胺(59):
Mp 206~207℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.71(ddd,2H),7.38(dddd,2H),7.23(ddd,2H),6.96(t,1H),6.76(dd,2H),6.10(s,2H),5.86(t,1H)。
N,N'-双(2,5-二氯苯磺酰基)间苯二胺(60):
Mp 236~237℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):7.97(d,2H),7.74–7.65(m,4H),6.96(t,1H),6.76(dd,2H),5.99(s,2H),5.86(t,1H)。
N,N'-双(2,5-二溴苯磺酰基)间苯二胺(61):
Mp 217~219℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):8.21(d,2H),7.67(dd,2H),7.58(d,2H),6.96(t,1H),6.76(dd,2H),6.05(s,2H),5.86(t,1H)。
N,N'-双(2,5-二甲基苯磺酰基)间苯二胺(62):
Mp 236~237℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.81–7.76(m,2H),7.44–7.38(m,2H),7.32(dd,2H),7.03(t,1H),6.76(dd,2H),5.91–5.84(m,3H),2.64(d,6H),2.33(d,6H).。
N,N'-双(2,5-二氰基苯磺酰基)间苯二胺(63):
Mp 231~2372℃;EIMS m/z:488[M+];1H NMR(400MHz,DMSO,δ):8.43(d,2H),8.16(d,2H),8.07(dd,2H),7.15(s,2H),6.99(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,5-二硝基苯磺酰基)间苯二胺(64):
Mp 212~213℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):9.08(d,1H),8.91(d,1H),8.58(ddd,2H),8.30(d,1H),8.20(d,1H),7.40(s,1H),7.11(t,1H),6.76(dd,2H),5.95(s,1H),5.86(t,1H)。
N,N'-双(2,5-二羟基苯磺酰基)间苯二胺(65):
Mp 203~204℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):7.33(d,2H),7.15(dd,2H),6.97(t,1H),6.85(d,2H),6.76(dd,2H),6.41(s,2H),5.92(d,4H),5.86(t,1H).。
N,N'-双(2,6-二氟苯磺酰基)间苯二胺(66):
Mp 242~244℃;EIMS m/z:460[M+];1H NMR(400MHz,DMSO,δ):7.70(tt,2H),7.11–7.03(m,4H),6.95(t,1H),6.76(dd,2H),6.15(s,2H),5.86(t,1H)。
N,N'-双(2,6-二硝基苯磺酰基)间苯二胺(67):
Mp 256~257℃;EIMS m/z:568[M+];1H NMR(400MHz,DMSO,δ):8.45–8.35(m,3H),8.34(dd,1H),8.28(s,1H),7.91(td,2H),7.51(s,1H),6.98(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,6-二溴苯磺酰基)间苯二胺(68):
Mp 263~264℃;EIMS m/z:700[M+];1H NMR(400MHz,DMSO,δ):7.65(d,4H),7.35(t,2H),6.99(t,1H),6.81(s,2H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,6-二氯苯磺酰基)间苯二胺(69):
Mp 206~207℃;EIMS m/z:524[M+];1H NMR(400MHz,DMSO,δ):7.59(dd,2H),7.55–7.50(m,4H),6.94(t,1H),6.76(dd,2H),6.69(s,2H),5.86(t,1H)。
N,N'-双(2,6-二羟基苯磺酰基)间苯二胺(70):
Mp 231~232℃;EIMS m/z:452[M+];1H NMR(400MHz,DMSO,δ):7.35(t,2H),6.95(t,1H),6.76(s,2H),6.76(dd,2H),6.61(d,4H),5.93(s,4H),5.86(t,1H)。N,N'-双(2,6-二氰基苯磺酰基)间苯二胺(71):
Mp 207~208℃;EIMS m/z:488[M+];1H NMR(400MHz,DMSO,δ):8.08(d,4H),7.90(t,2H),7.14(s,2H),7.04(t,1H),6.76(dd,2H),5.86(t,1H)。
N,N'-双(2,6-二甲氧基苯磺酰基)间苯二胺(72):
Mp 203~205℃;EIMS m/z:508[M+];1H NMR(400MHz,DMSO,δ):7.62(t,2H),7.04(d,4H),6.76(dd,2H),6.72(s,2H),5.86(t,1H),3.44(s,12H)。
N,N'-双(2,6-二甲基苯磺酰基)间苯二胺(73):
Mp 206~208℃;EIMS m/z:444[M+];1H NMR(400MHz,DMSO,δ):7.53(t,2H),7.30(d,4H),7.03(t,1H),6.76(dd,2H),5.86(t,1H),5.79(s,2H),2.56(s,12H)。
N,N'-双(3-氟苯磺酰基)--2,6-吡啶二胺(74):
Mp 225~226℃;EIMS m/z:425[M+];1H NMR(400MHz,DMSO,δ):7.64(dt,1H),7.53–7.39(m,2H),7.33(ddt,1H),6.51(d,1H),5.74(s,1H)。
N,N'-双(3-氯苯磺酰基)--2,6-吡啶二胺(75):
Mp 236~237℃;EIMS m/z:457[M+];1H NMR(400MHz,DMSO,δ):7.79–7.72(m,2H),7.70(dt,1H),7.44(td,2H),6.51(d,1H),5.71(s,1H)。
N,N'-双(3-溴苯磺酰基)-2,6-吡啶二胺(76):
Mp 264~266℃;EIMS m/z:545[M+];1H NMR(400MHz,DMSO,δ):7.92(t,1H),7.81(ddt,2H),7.42(dt,2H),6.51(d,1H),5.68(s,1H)。
N,N'-双苯磺酰基-2,6-吡啶二胺(77):
Mp 227~228℃;EIMS m/z:389[M+];1H NMR(400MHz,DMSO,δ):7.73–7.67(m,4H),7.62(ddt,2H),7.55(t,4H),7.41(t,1H),6.51(d,2H),5.74(s,2H)。
N,N'-双(3-甲氧基苯磺酰基)-2,6-吡啶二胺(78):
Mp 206~207℃;EIMS m/z:449[M+];1H NMR(400MHz,DMSO,δ):7.53(dt,1H),7.51–7.44(m,2H),7.21(dt,1H),6.51(d,1H),6.02(s,1H),3.81(s,3H)。
N,N'-双(2-甲氧基苯磺酰基)-2,6-吡啶二胺(79):
Mp 212~213℃;EIMS m/z:449[M+];1H NMR(400MHz,DMSO,δ):7.89(dd,1H),7.59(td,1H),7.24(td,1H),7.18(dd,1H),6.51(d,1H),6.21(s,1H),3.95(s,3H)。
N,N'-双(2-氟苯磺酰基)-2,6-吡啶二胺(80):
Mp 217~219℃;EIMS m/z:425[M+];1H NMR(400MHz,DMSO,δ):7.95(ddd,1H),7.67(tdd,1H),7.40–7.22(m,3H),6.51(d,1H),6.04(s,1H)。
N,N'-双(2-氰基苯磺酰基)-2,6-吡啶二胺(81):
Mp 209~210℃;EIMS m/z:439[M+];1H NMR(400MHz,DMSO,δ):8.17(dd,2H),7.88(dd,2H),7.76(dtd,4H),7.33(t,1H),6.92(s,2H),6.51(d,2H)。
N,N'-双(2-溴苯磺酰基)-2,6-吡啶二胺(82):
Mp 216~217℃;EIMS m/z:545[M+];1H NMR(400MHz,DMSO,δ):8.18(dd,2H),7.67(dd,2H),7.50(td,2H),7.42(td,2H),7.31(t,1H),7.00(s,2H),6.51(d,2H)。
N,N'-双(3-甲氧基苯磺酰基)-2,6-吡啶二胺(83):
Mp 206~207℃;EIMS m/z:449[M+];1H NMR(400MHz,DMSO,δ):7.55–7.44(m,2H),7.47(s,1H),7.21(dt,1H),6.51(d,1H),6.04(s,1H),3.81(s,3H)。
N,N'-双(3-羟基苯磺酰基)-2,6-吡啶二胺(84):
Mp 217~218℃;EIMS m/z:421[M+];1H NMR(400MHz,DMSO,δ):7.83(s,1H),7.56(dt,1H),7.43–7.33(m,3H),7.25(dt,1H),6.51(d,1H),6.00(s,1H)。
N,N'-双(3-氯苯磺酰基)-2,6-吡啶二胺(85):
Mp 209~211℃;EIMS m/z:457[M+];1H NMR(400MHz,DMSO,δ):7.79–7.73(m,2H),7.71(dt,1H),7.44(td,2H),6.51(d,1H),5.71(s,1H)。
N,N'-双(3-溴苯磺酰基)-2,6-吡啶二胺(86):
Mp 231~232℃;EIMS m/z:545[M+];1H NMR(400MHz,DMSO,δ):7.92(t,1H),7.81(ddt,2H),7.42(dt,2H),6.51(d,1H),5.68(s,1H)。
N,N'-双(3-胺基苯磺酰基)-2,6-吡啶二胺(87):
Mp 236~237℃;EIMS m/z:419[M+];1H NMR(400MHz,DMSO,δ):7.34–7.22(m,4H),6.96(dt,1H),6.65(s,1H),6.51(d,1H),4.15(s,2H)。
N,N'-双(3,5-二氯苯磺酰基)-2,6-吡啶二胺(88):
Mp 263~264℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.82(d,4H),7.64(t,2H),7.39(t,1H),6.51(d,2H),6.03(s,2H)。
N,N'-双(3,5-二胺基苯磺酰基)-2,6-吡啶二胺(89):
Mp 269~271℃;EIMS m/z:449[M+];1H NMR(400MHz,DMSO,δ):6.65(d,2H),6.51(d,1H),6.29(s,1H),6.11(t,1H),4.33(s,4H)。
N,N'-双(2,3-二氯苯磺酰基)-2,6-吡啶二胺(90):
Mp 234~235℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.89(ddd,4H),7.37(t,1H),7.32(t,2H),6.51(d,2H),6.12(s,2H)。
N,N'-双(2,3-二氟苯磺酰基)-2,6-吡啶二胺(91):
Mp 223~224℃;EIMS m/z:461[M+];1H NMR(400MHz,DMSO,δ):7.71(ddd,1H),7.41–7.23(m,3H),6.51(d,1H),6.05(s,1H)。
N,N'-双(2,3-二硝基苯磺酰基)-2,6-吡啶二胺(92):
Mp 232~233℃;EIMS m/z:569[M+];1H NMR(400MHz,DMSO,δ):8.63(s,1H),8.52(dd,1H),8.39(dtd,3H),7.99(t,1H),7.93(t,1H),7.40(t,1H),6.51(d,2H),6.13(s,1H)。
N,N'-双(2,3-二甲氧基苯磺酰基)-2,6-吡啶二胺(93):
Mp 221~222℃;EIMS m/z:509[M+];1H NMR(400MHz,DMSO,δ):7.65(dd,1H),7.33(dt,2H),7.22(dd1H),6.56(s,1H),6.51(d,1H),3.89(d,6H)。
N,N'-双(2,3-二羟基苯磺酰基)-2,6-吡啶二胺(94):
Mp 203~205℃;EIMS m/z:453[M+];1H NMR(400MHz,DMSO,δ):7.41–7.32(m,3H),7.00–6.91(m,2H),6.51(d,1H),5.87(s,1H),5.31(s,1H)。
N,N'-双(2,4-二氯苯磺酰基)-2,6-吡啶二胺(95):
Mp 213~214℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.92(d,2H),7.82(d,2H),7.53(dd,2H),7.37(t,1H),6.51(d,2H),6.12(s,2H)。
N,N'-双(3,4-二氯苯磺酰基)-2,6-吡啶二胺(96):
Mp 215~216℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.99(d,2H),7.80–7.72(m,4H),7.40(t,1H),6.51(d,2H),5.93(s,2H)。
N,N'-双(3,4-二溴苯磺酰基)-2,6-吡啶二胺(97):
Mp 204~205℃;EIMS m/z:701[M+];1H NMR(400MHz,DMSO,δ):7.88(d,2H),7.82(dd,2H),7.71(d,2H),7.43(t,1H),6.51(d,2H),5.91(s,2H)。
N,N'-双(3,4-二硝基苯磺酰基)-2,6-吡啶二胺(98):
Mp 219~221℃;EIMS m/z:569[M+];1H NMR(400MHz,DMSO,δ):8.79(d,1H),8.71(d,1H),8.44(dd,1H),8.38–8.29(m,3H),7.47(t,1H),6.51(d,2H),6.08(s,1H),5.77(s,1H)。
N,N'-双(3,4-二甲基苯磺酰基)-2,6-吡啶二胺(99):
Mp 217~218℃;EIMS m/z:445[M+];1H NMR(400MHz,DMSO,δ):7.71(dd,1H),7.56–7.52(m,1H),7.27(dd,1H),6.51(d,1H),6.11(s,1H),2.34(d,3H),2.27(d,3H)。
N,N'-双(3,4-二氰基苯磺酰基)-2,6-吡啶二胺(100):
Mp 226~227℃;EIMS m/z:489[M+];1H NMR(400MHz,DMSO,δ):8.44(d,2H),8.34(dd,2H),8.07(d,2H),7.43(t,1H),6.51(d,2H),5.93(s,2H)。
N,N'-双(2,5-二氯苯磺酰基)-2,6-吡啶二胺(101):
Mp 231~232℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.99(d,2H),7.74–7.65(m,4H),7.32(t,1H),6.69(s,2H),6.51(d,2H)。
N,N'-双(2,5-二硝基苯磺酰基)-2,6-吡啶二胺(102):
Mp 233~235℃;EIMS m/z:569[M+];1H NMR(400MHz,DMSO,δ):9.41(s,1H),9.17(t,2H),8.60(ddd,2H),8.29(d,1H),8.23(d,1H),7.37(t,1H),6.83(s,1H),6.51(d,2H)。
N,N'-双(2,6-二氯苯磺酰基)-2,6-吡啶二胺(103):
Mp 203~205℃;EIMS m/z:525[M+];1H NMR(400MHz,DMSO,δ):7.99(d,2H),7.74–7.65(m,4H),7.32(t,1H),6.69(s,2H),6.51(d,2H)。
N,N'-双(2,6-二氰基苯磺酰基)-2,6-吡啶二胺(104):
Mp 214~216℃;EIMS m/z:489[M+];1H NMR(400MHz,DMSO,δ):8.44(d,2H),8.17–8.08(m,4H),7.37(t,1H),6.97(s,2H),6.51(d,2H).。
N,N'-双(2,6-二硝基苯磺酰基)-2,6-吡啶二胺(105):
Mp 218~220℃;EIMS m/z:569[M+];1H NMR(400MHz,DMSO,δ):9.09(d,1H),9.05(d,1H),8.59(dd,1H),8.49(dd,1H),8.28(s,1H),8.22(dd,2H),7.33(t,1H),6.91(s,1H),6.51(d,2H).。
Claims (3)
1.一类二磺酰基间芳基二胺类化合物,其特征在于具有如下结构通式:
式I中当X=CH时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(1)R1=R2=R4=R5=H,R3=CN或OH;
(2)R2=R3=R4=R5=H,R1=OMe、F、Cl、Br、NH2、CN或OH;
(3)R1=R3=R4=R5=H,R2=OMe、F、Cl、Me、Br或OH;
(4)R1=R3=R5=H,R2=R4=Cl、Br、Me、OMe、OH、NO2、NH2或F;
(5)R3=R4=R5=H,R1=R2=Cl、F、Br、Me、OH、OMe或NO2;
(6)R2=R4=R5=H,R1=R3=Cl、Me、OMe、OH、Br或NO2;
(7)R1=R4=R5=H,R2=R3=F、Cl、Br、OMe、OH、CN、NO2、NH2或Me;
(8)R2=R3=R5=H,R1=R4=F、Br、Me、OH、CN或NO2;
(9)R2=R3=R4=H,R1=R5=F、Cl、Br、OH、CN、OMe或Me;
式I中当X=N时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(11)R2=R3=R4=R5=H,R1=OMe、F、NH2、CN或Br;
(12)R1=R3=R4=R5=H,R2=OMe、Cl、NH2或OH;
(13)R1=R3=R5=H,R2=R4=Me、OH、NH2或Cl;
(14)R3=R4=R5=H,R1=R2=Cl、F、NO2、OMe或OH;
(15)R2=R4=R5=H,R1=R3=Cl、NO2或OH;
(16)R1=R4=R5=H,R2=R3=Cl、Br、CN或NO2;
(17)R2=R3=R5=H,R1=R4=NO2、OH或Me;
(18)R2=R3=R4=H,R1=R5=Cl、Br、或CN。
2.一种制备权利要求1所述的二磺酰基间芳基二胺类化合物的方法,其特征是:由下列步骤组成:
取2-R1-3-R2-4-R3-5-R4-6-R5取代苯磺酰氯(II)溶解到无水甲醇中,搅拌20min,加入间芳基二胺(III)和三乙胺,物质的量之比为:2-R1-3-R2-4-R3-5-R4-6-R5取代苯磺酰氯(II):间芳基二胺(III):三乙胺=1:(1~2):(4~12),控制反应温度在30~70℃之间,反应4~24h,冷却,蒸去甲醇,加水,用乙酸乙酯萃取三次,合并有机相,水洗,无水MgSO4干燥,蒸去溶剂,硅胶柱层析纯化,洗脱剂体积比:AcOEt:石油醚=1:1.5~1:9,得白色固体N,N'-二(2-R1-3-R2-4-R3-5-R4-6-R5苯磺酰基)间芳基二胺(I);其中所述的R1、R2、R3、R4和R5的定义与权利要求1所述(I)式的定义相同。
3.一类二磺酰基间芳基二胺类化合物在制备抗胃炎、胃溃疡或抗尿路结石药物中的应用,其特征在于具有如下结构通式:
式I中当X=CH时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(1)R1=R2=R4=R5=H,R3=F、Cl、Br、H、Me、NO2、NH2、CN、OH或OMe;
(2)R2=R3=R4=R5=H,R1=OMe、F、Cl、Br、Me、NO2、NH2、CN或OH;
(3)R1=R3=R4=R5=H,R2=OMe、F、Cl、Me、Br、OH、NH2或NO2;
(4)R1=R3=R5=H,R2=R4=Cl、Br、Me、OMe、OH、NO2、NH2或F;
(5)R3=R4=R5=H,R1=R2=Cl、F、Br、Me、OH、OMe或NO2;
(6)R2=R4=R5=H,R1=R3=Cl、Me、OMe、OH、Br或NO2;
(7)R1=R4=R5=H,R2=R3=F、Cl、Br、OMe、OH、CN、NO2、NH2或Me;
(8)R2=R3=R5=H,R1=R4=Cl、F、Br、Me、OH、CN或NO2;
(9)R2=R3=R4=H,R1=R5=F、Cl、Br、OH、CN、OMe或Me;
式I中当X=N时,R1、R2、R3、R4、和R5的定义取自下列各组之任一组:
(10)R1=R2=R4=R5=H,R3=F、Cl、Br、H、或OMe;
(11)R2=R3=R4=R5=H,R1=OMe、F、NO2、NH2、CN或Br;
(12)R1=R3=R4=R5=H,R2=OMe、Cl、Br、NH2或OH;
(13)R1=R3=R5=H,R2=R4=Me、OH、NH2或Cl;
(14)R3=R4=R5=H,R1=R2=Cl、F、NO2、OMe或OH;
(15)R2=R4=R5=H,R1=R3=Cl、NO2或OH;
(16)R1=R4=R5=H,R2=R3=Cl、Br、CN、Me或NO2;
(17)R2=R3=R5=H,R1=R4=Cl、NO2、OH或Me;
(18)R2=R3=R4=H,R1=R5=Cl、Br、或CN。
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