通过原子经济的Mannich反应实现了磺胺嘧啶、1-萘乙酮与芳香醛三组分的连接,直接合成了16个含有磺胺嘧啶结构单元的未见报道的β-氨基酮;所得化合物经1H NMR、13C NMR、HRMS和MS等技术手段确证其结构.生物活性测试结果显示,在17.04～ 19.69 nmol/L浓度范围内,所有目标分子的α-葡萄糖苷酶抑制活性很弱,但部分目标分子的过氧化物酶体增殖物激活受体反应元件(PPRE)激动活性较好,最高达到了52％.
参考文献
| [1] | 刘建朝;嵇汝运.促胰岛素分泌抗糖尿病药物研究进展[J].中国药学杂志,2005(6):408-410. |
| [2] | Chang CH;McNamara LA;Wu MS;Muise ES;Tan Y;Wood HB;Meinke PT;Thompson JR;Doebber TW;Berger JP;McCann ME.A novel selective peroxisome proliferator-activator receptor-gamma modulator-SPPARgammaM5 improves insulin sensitivity with diminished adverse cardiovascular effects.[J].European Journal of Pharmacology: An International Journal,20081(1):192-201. |
| [3] | Kaori Yoshida;Atsuyuki Hishida;Osamu Iida.Flavonol Caffeoylglycosides as α-Glucosidase Inhibitors from Spiraea cantoniensis Flower[J].Journal of Agricultural and Food Chemistry,200812(12):4367-4371. |
| [4] | Park H;Hwang KY;Kim YH;Oh KH;Lee JY;Kim K.Discovery and biological evaluation of novel alpha-glucosidase inhibitors with in vivo antidiabetic effect.[J].Bioorganic and Medicinal Chemistry Letters,200813(13):3711-3715. |
| [5] | Joshi S;Manikpuri AD;Tiwari P.Synthesis and biological study of medicinally important Mannich bases derived from 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a pentahydroxy naphthacene carboxamide.[J].Bioorganic and Medicinal Chemistry Letters,20073(3):645-648. |
| [6] | Das U;Das S;Bandy B;Stables JP;Dimmock JR.N-Aroyl-3,5-bis(benzylidene)-4-piperidones: a novel class of antimycobacterial agents.[J].Bioorganic and medicinal chemistry,20087(7):3602-3607. |
| [7] | Karczmarzyk, Z;Malinka, W.Structural characterization of analgesic isothiazolopyridines of Mannich base type; X-ray analysis of 2-[(4-phenylpiperazin-1-yl)ethyl]- and 2-[(4-methylpiperazin-1-yl)methyl]-4,6-dimethylisothiazolo[5,4-b]pyridin-3 (2H)-ones[J].Journal of Molecular Structure,20081/3(1/3):160-167. |
| [8] | Zhou,C;Wu,G;Feng,Y;Li,Q;Su,H;Mais,DE;Zhu,Y;Li,N;Deng,Y;Yang,D;Wang,MW.Discovery and biological characterization of a novel series of androgen receptor modulators.[J].British Journal of Pharmacology,20082(2):440-450. |
| [9] | 许荩;晏菊芳;范莉;宋小礼;唐雪梅;杨大成.N-（1,5-二芳基-3-戊酮-1-基）-4-氨基苯甲酸的合成与α-葡糖苷酶抑制活性初步研究[J].药学学报,2009(1):48-55. |
| [10] | 宋小礼;晏菊芳;范莉;陈欣;许荩;周祖文;杨大成.4-（1-芳基-3-烃基-3-氧代丙胺基）-N-（5-甲基-3-异噁唑基）苯磺酰胺的合成与抗糖尿病活性的初步研究[J].有机化学,2009(4):606-613. |
| [11] | Seoung Jong Kim;Myung Ho Jung;Kyung Ho Yoo;Jung Hyuck Cho;Chang Hyun Oh.Synthesis and antibacterial activities of novel oxazolidinones having cyclic sulfonamide moieties[J].Bioorganic and Medicinal Chemistry Letters,200821(21):5815-5818. |
| [12] | Seri K;Sanai K;Kurashima K;Imamura Y;Akita H.R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity.[J].European Journal of Pharmacology: An International Journal,20002/3(2/3):253-256. |
| [13] | Temperini C;Cecchi A;Scozzafava A;Supuran CT.Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.[J].Bioorganic and Medicinal Chemistry Letters,20088(8):2567-2573. |
| [14] | 缪有盼;李爱秀;刘涛;吴可柱;马翼.基于"底物包膜"假说筛选新型HIV-1蛋白酶抑制剂[J].化学学报,2009(10):1098-1102. |
| [15] | Hopkins CR;O'neil SV;Laufersweiler MC;Wang Y;Pokross M;Mekel M;Evdokimov A;Walter R;Kontoyianni M;Petrey ME;Sabatakos G;Roesgen JT;Richardson E;Demuth TP Jr.Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis.[J].Bioorganic and Medicinal Chemistry Letters,200621(21):5659-5663. |
| [16] | 杨龙;晏菊芳;范莉;陈欣;上官瑞燕;汪林发;杨大成.含有对氨基苯甲酸和苯磺酰胺结构单元的新型分子及其抗糖尿病活性[J].有机化学,2012(10):1908-1918. |
| [17] | 杨艳;晏菊芳;范莉;陈欣;蒋理;杨大成.含苯磺酰胺结构单元的新型苯乙酸衍生物的合成及其PPAR激动活性[J].药学学报,2012(12):1630-1639. |
| [18] | 唐雪梅;晏菊芳;张映霞;张蔚瑜;苏小燕;陈欣;周祖文;杨大成.4-[3-（4-溴苯基）-3-氧代-1-芳基丙氨基]-N-（嘧啶-2-基）苯磺酰胺的合成及其Cr-葡萄糖苷酶抑制活性初步研究[J].有机化学,2009(11):1790-1798. |
| [19] | TANG GuangXia;YAN JuFang;FAN Li;XU Jin;SONG XiaoLi;JIANG Li;LUO LingFei.Synthesis of novel β-amino ketones containing a p-aminobenzoic acid moiety and evaluation of their antidiabetic activities[J].中国科学:化学（英文版）,2013(4):490-504. |
| [20] | Wang,H.;Yan,J.-F.;Song,X.-L.;Fan,L.;Xu,J.;Zhou,G.-M.;Jiang,L.;Yang,D.-C..Synthesis and antidiabetic performance of β-amino ketone containing nabumetone moiety[J].Bioorganic and medicinal chemistry,20126(6):2119-2130. |
| [21] | 杨大成;章国林;杨宇;钟裕国.对-甲苯乙酮与芳香醛和芳香胺的Mannich反应[J].高等学校化学学报,2000(11):1694-1696. |
| [22] | 冯君;郭彦伸;陆颖;郭宗儒.PPAR激动剂的定向设计、虚拟筛选及合成[J].化学学报,2004(16):1544-1550. |
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