Tổng hợp một số dẫn chất của 5-cloroisatin và thăm dò tác dụng sinh học

Nghien CLPU - Ky thuat<br /> 4. Dinh Thj Thanh Hai, Tong hgp mot so dan chat benzylidene] thiazolidine-2,4-dione derivatives and<br /> cua 5-nitrofurfural va tham do tac dyng sinh hpc, related compounds for reducing glucose,<br /> Luan an tien sy Dugc hpc, Tnrang Dai hpc Duvc Ha cholesterol, and triglyceride levels in plasma, WO,<br /> Noi, (2003). 2006/08925 Al.<br /> 5. Akerblom E.B, J.Med.Chem, (1994), 17(6), 7. Pafahl M.C, J. Of Applied Chem, (2003), 11(3),<br /> pp.759-762. pp.65-68.<br /> 6. Bishwajit, Abhijeet, Debendranath, Shiv Kumar 8. Vlietlinck A.J, Vanden Berger D.A, Methods in<br /> A.,5-[4-(4-(2-amino-2-methoxycarbonylethyl)phenoxy) plants biochemistry, (1991), 6, 47-68.<br /> <br /> <br /> «7 r m r<br /> <br /> <br /> Tong hop mot so dan chat cua S-cloroisatin<br /> va tham do tac dung sinh hoc<br /> Tran Viet Hung, Dinh Thi Thanh Hai<br /> Hoang Le Hieu Hanh, Nguyen Minh Due<br /> Bp mon Hod Huu ca - Truang dai hoc Duac Ha Noi<br /> <br /> Dat van de - BUO'C 2: Dong vong p-eloroisonitro<br /> Cac d i n chit isatin la mot day chit hu'u eg soaeetanilid duo'i tac dung cua H2SO4 dae a<br /> da dugc quan tam nghien CCPU v i hoa hpc va 80°C thu duge 5-eloroisatin v6'i hi$u suit<br /> 80,3%.<br /> tac dung sinh hpc. Nhiiu e6ng trinh nghien CCPU<br /> Ngung tu 5-eloroisatin v6'i 2-thioxo-4-<br /> da e6ng b i cho thiy cac d i n chit eua isatin co<br /> thiazolidinon va imidazolidin-2,4-dion trong dung<br /> hoat tinh sinh hpc phong phu da dang nhu cac<br /> m6i acid acetic b§ng v& xCie t^c natri acetat<br /> tac dung: khang virus, khang lao, khang khuan,<br /> khan, thu dugc c h i t (2) vS (3). Thuc hien phan<br /> khang n i m , ching ung thu, CPC e h i monoamine<br /> Cpng Mannich d i i vo'i chat (2) va (3) da thu dugc<br /> oxydase'^-^•^"^°>.<br /> 9 d i n c h i t base monoMannieh (4 - 12). Cac<br /> Trong eae thong bao truo'c day ''^" ^°', chung phan Cpng Mannich dugc thuc hien trong dung<br /> t6i da trinh bay k i t qua nghien CCPU t i n g hgp va moi ethanol, a nhiet dp thfch hgp (nhiet dp 40 -<br /> thLP hoat tinh sinh hpc eua mot s i d i n c h i t 70°C). Qua trinh phan Cpng duge theo doi bing<br /> isatin. sac ky lo'p mong de xac djnh tho'i gian phan Cpng<br /> De tiip tue va phat triin huang nghien CCPU thich hgp. K i t qua t i n g hgp 12 chit (1 -12) vo'i<br /> v i day chit nay, trong bai bao nay, chung t6i eae s i lieu ghi 6" bang 1.<br /> trinh bay k i t qua tong hgp va thCr hoat tinh sinh Dp tinh khiit eua eae c h i t t i n g hgp dugc da<br /> hpc eua 5-cloroisatin va d i n chit. dugc kiem tra bing s i c ky lap mong va do nhiet<br /> K i t q u a va b a n l u a n dp nong chay.<br /> Cau true eua ea 11 c h i t ( 2 - 1 2 ) dugc xac<br /> T i n g hgp hoa hoc<br /> nhan qua phan tfeh p h i IR, MS, H^-NMR, " C -<br /> Cac dan chat 5-cloroisatin dwac tong hap<br /> NMR. K i t qua phan tfeh p h i duge ghi a cac<br /> theo sa do 1. bang 2, 3 va 4.<br /> T i n g hgp 5-eloroisatin (1) bing phan Cpng P h i IR eua ca 11 chat d i u co dai h i p thu<br /> Sandmeyer (nam 1919) g i m 2 buo'c: eua lien k i t >C=0 (1703-1696 cm"'' va 1692-<br /> - Buo'c 1: cho p-cloroanilin phan Cpng vo'i 1603 cm"^) vS dai h i p thu cua lien k i t C=C eua<br /> eloral hydrat va hydroxylamin hydroclorid trong nhan benzen trong c^c vung h i p thu (1685-<br /> m6i tru6'ng acid thu dugc p-cloroisonitro 1602 em"\ 1524-1513 cm"''), dai h i p thu cua li§n<br /> soaeetanilid vo'i hieu s u i t 64,6%. k i t Carom-CI (768-676 em"'). ^ ., , ,,:.,<br /> <br /> <br /> 30 TAP CHI DlfQC HQC - 11/2010 (SO 415 NAM 50)<br />  Nghien CLPU - Ky thuat<br /> <br /> CI<br /> i'&:.s'^- • Cl3C-CH(OH)2 + H2N-OH.HCI<br /> NH,<br /> <br /> 1,HCI<br /> 80°C<br /> 2,H2S04<br /> <br /> <br /> <br /> <br /> + HCHO + HNR1R2<br /> <br /> <br /> <br /> <br /> (4) -NRiR2= -N, // \ (11) -NRiR2= -N 0<br /> (8) -NRiR2= H N ^ / VCI<br /> <br /> (5) -NRiR2= HN—(f<br /> <br /> <br /> (6) -NRiR= HN-/j><br /> VCH3<br /> (9) -NRiR=<br /> <br /> <br /> (10) -NRiR=<br /> —N<br /> <br /> <br /> —N<br /> CH,<br /> <br /> CH3<br /> <br /> 0<br /> (12)-NRiR2=<br /> -o<br /> (7)-NRiR2= H N - ^ ^ F<br /> <br /> <br /> S a do 1: Sa dd eae phan wng tdng hap 5-eloroisatin va dan chit<br /> P h i IR eua t i t ca cac c h i t (2-12) d i u x u i t (2951-2803 em"') d i i u nay ehCpng to da x u i t<br /> hien dai h i p thu dac trung NH amid (3433- hien lien k i t N-CH2 cua hgp phin<br /> 3048 cm"') d i i u nay chCpng to cac phan Cpng aminomethyl dugc tao ra sau phan Cpng<br /> Mannich d i u ehi thu duge d i n x u i t mono Mannich. Dai h i p thu cua 4 c h i t (5, 6, 7, 8) co<br /> Mannich. P h i IR eua 9 d i n c h i t mono Manich dai h i p thu -NH- a hgp p h i n amin tham<br /> (4-12) x u i t hien dai h i p thu cua nhom >CH2 (3420-3413 cm"').<br /> <br /> <br /> TAP CHI DUOC HOC - 11/2010 (SO 415 NAM 50) 31<br />  Nghien CLPU - Ky thuat<br /> Bang 1 : Kit qui tdng hap cic chit (1 - 12)<br /> Thoi gian Dung moi Nhi^t dp Hieu suit<br /> Chat CTPT PTL<br /> phan wng (gia) ket tinh nong ehay (°C) '(%)<br /> 1 C8H4O2NCI 181,5 1 EtOH 252-254 80,6<br /> 2 C11H5O2N2CIS2 296,5 6 EtOH 336-338 85,6<br /> 3 C11H6O3N3CI 263,5 6 EtOH:DMF(2:1) 396-398 58,1<br /> 4 Cl7H,602N3ClS2 393,5 2 EtOH:CHCl3(2:1) 198-199 55,9<br /> 5 C19H1402N3CIS2 415,5 3,5 EtOH:CHCl3(2:1) 196-197 78,2<br /> 6 C18H1202N3CIS2 401,5 4 EtOH 260-261 61,0<br /> 7 Ci8Hi,02N3ClFS2 419,5 4 EtOH:CHCl3(5:1) 258-259 75,1<br /> 8 C18H1102N3C12S2 435 4 EtOH:CHCl3(2:1) 306-308 65,4<br /> 9 C18H1202N3CIS2 353,5 3 EtOH 215-216 44,8<br /> 10 C1SH1403N3C1S2 395,5 2 EtOH 228-230 84,7<br /> 11 C16H1504N4CI 362,5 2,5 EtOH:CHCl3(5:1) 256-258 78,4<br /> 12 C17H1703N4C1 360,5 2,5 EtOH:CHCl3(5:1) 234-235 51,6<br /> <br /> Rieng phi IR cua chit (7) eon xuit hien dai hip tu* VO'I s i khii dung b i n g khii lugng phan tCp<br /> thu cua lien kit Carom-F (1188 cm"'). P h i IR cua eae tinh theo c6ng thCpc c h i t du kiin va phu hgp vo'i<br /> chit (2,4-10) diu co dai h i p thu eua lien kit C=S quy t i c Nita. Ngoai ra, tren p h i d i MS cua 11<br /> (1266-1227 cm"') dac tnj'ng cua vong Rhodanin. chit CO cac pie cua cac ion manh dae trung phu<br /> Muo'i mot chit dugc ghi p h i d i u co pie phan hgp VO'I sa d i phan manh.<br /> <br /> Bang 2: Sd lieu phd IR va MS cue cic chat tdng hap<br /> Bien giai Pho khoi<br /> Chat VNH VCH2 Vc=0 vc=s (M*)<br /> V C^^Carom ^C^rom-CI<br /> <br /> 3048 1719 1638, 1455 1243 724 295/297<br /> 2<br /> 1692 1421 768<br /> 3215 1779 1681, 1641 768 262/264<br /> 3<br /> 1739 1458 688<br /> 3109 2951 1692 1604, 1456 1266 754 393<br /> 4<br /> 2812 1662 1436 1257 687<br /> 3420 2920 1694 1615, 1524 1241 750 414/416<br /> 5<br /> 3115 2851 1454<br /> 3178 2927 1693 1603, 1512 1238 748 400/402<br /> 6<br /> 3114 2851 1455 686<br /> 3419 2923 1693 1615, 1513 1227 726 418/420<br /> 7<br /> 1445<br /> 3413 2851 1615,1602 1241 703 435<br /> 8<br /> 3176 1692 1455<br /> 3433 2851 1693 1616, 1455 1253 753<br /> 9<br /> 3178 1438 1235 676 352<br /> 3059 2918 1701 1606, 1475 1244 703<br /> 10<br /> 2857 1461 684 394/396<br /> 3438 2958 1776 1691, 1645 771<br /> 11<br /> 3281 2863 1724 1460 692 361/363<br /> 3283 2935 1787 1685, 1465 766<br /> 12<br /> 2803 1731 1649 692 359<br /> Chung t6i da phan tich p h i 'H-NMR 11 chat djch chuyen phu hgp vo'i c6ng thCpc du kien.<br /> ting hgp duge v^ p h i '^C-NMR eua c h i t 2 va P h i '^C-NMR eua c h i t 2 va 3 cho cac gia tri cua<br /> 3. K i t qua phan tich p h i ' H - N M R eho t h i y tren d6 djch chuyin ho^ hpc 5 cua cac vj tri carbon<br /> p h i d i eua eae c h i t ( 2 - 1 2 ) co s i proton va dp phu hgp vgi e6ng thu'c du kiin.<br /> <br /> 32 TAP CHI DUQC HQC- 11/2010 (SO 415 NAM 50)<br />  Nghien CLPU - Ky thuat<br /> Bang 3: Sd lipu phd ^H-NMR cua 11 chit<br /> Ki hieu ehat ^H-NMR (DMSO-de), 5 (ppm)<br /> 11,30(s, 1H, H-3); 8,77(s, 1H, H-1'); 7,93(s, 1H, H-7'); 7,43(m, 1H, H-4'); 6,94(q, 1H, H-6')<br /> 11,98(s, 1H, H-3); 10,97(s, 1H, H-1'); 10,53(s, 1H, H-1); 8,53(s, 1H, H-7'); 7,94(m, 1H, H-4');<br /> 6,91 (q, 1H, H-6')<br /> 11,06(d, 1H, H-1'); 7,41 (s, 1H, H-7'); 7,29(m, 1H, H-4'); 7,22(m, 1H, H-6'); 4,33(s, 2H, CH2-N);<br /> 3,34(m, 4H, H-3",5"); 2,50(m,4H, H-2",6"); 1,39(t, 2H, H-4")<br /> 11,24(8, I N , H-1');8.56(d, 1H, NH-Ar); 7,49(s, 1H, H-7'); 7,20(m, 1H, H-4'); 6,90(m, 1H, H-6');<br /> 5,11(d, 2H, CH2-N); 6,52-6,98(m, 4H, H-2",6",3",5"); 2,12(m, 3H, -CH3)<br /> 11,31(s, 1H, H-1');8.56(d, 1H, NH-Ar); 7,43(s, 1H, H-7'); 7,08(m, 1H, H-4'); 6,94(m, 1H, H-6');<br /> 5,10(d, 2H, CH2-N); 6,51-6,88(m, 4H, H-2",6",3",5")<br /> 11,23(8, 1H, H-1'); 8.58(d, 1H, NH-Ar); 8,50(s, 1H, H-7'); 7,24(m, 1H, H-4'); 7,05(m, 1H, H-6');<br /> 5,10(d, 2H, CH2-N); 6,51-6,99(m, 4H, H-2",6",3",5")<br /> 11,31(8, 1H, H-1'); 8.78(d, 1H, NH-Ar); 7,57(8, 1H, H-7'); 7,09(m, 1H, H-4'); 7,03(m, 1H, H-6');<br /> 5,18(d, 2H, CH2-N); 6,71-6,88(m, 4H, H-2",6",3",5")<br /> 11,31(8, 1H, H-1'); 7,49(8, 1H, H-7'); 7,28(m, 1H, H-4'); 6,98(m, 1H, H-6'); 4,58(s, 2H, CH2-N);<br /> 2,29(m, 6H, -CH3)<br /> 11,29(8, 1H, H-1'); 7,51(8, 1H, H-7'); 7,42(m, 1H, H-4'); 7,29(m, 1H, H-6'); 4,49(8, 2H, CH2-N);<br /> 10 3,34(m, 4H, H-3",5"); 2,51 (m,4H, H-2",6"); 1,39(t, 2H, H-4")<br /> 11,01(8, 1H, H-1'); 10,97(8, 1H, H-1); 7,39(8, 1H, H-7'); 7,35(m, 1H, H-4'); 7,28(m, 1H, H-6');<br /> 11<br /> 4,50(8, 2H, CH2-N); 2,50(m, 4H, H-3",5"); 3,54(m,4H, H-2",6")<br /> 11,08(8, 1H, H-1'); 11,01(8, 1H, H-1); 7,37(s, 1H, H-7'); 7,28(m, 1H, H-4'); 7,20(m, 1H, H-6');<br /> 12<br /> 4,32(8, 2H, CH2-N); 2,34(m, 4H, H-3",5"); 3,45(m,4H, H-2",6"); 1,37(t, 2H, H-4")<br /> <br /> Bang 4: Sd lieu phd "C-NMR cua chit 2vi 3<br /> Ki hieu ehat 'C-NMR (DMSO-de), 5 (ppm)<br /> 199,64(C-2); 167,75(C-4); 169,67(C-2'); 143,04(C-7a'); 123,02(C-7'); 127,03(C-6'); 162,31(0-3');<br /> 135,99(C-5'); 131,81(C-5); 121.14(C-3a'); 125,89(C-4')<br /> 154,07(C-2); 164,89(C-4); 169,19(C-2'); 140,08(C-7a'); 121,91(C-7'); 125,36(C-6'); 105,92(0-3');<br /> 128,83(0-5'); 135,55(C-5); 111,08(C-3a'); 124,83(C-4')<br /> <br /> Thip tac dung sinh hoc Bub'c 1. S^ng Ipc sa bp tim chit c6 hoat<br /> Thw hoat tinh khang khuan, khang nam tfnh.<br /> ThLP hoat tinh khang khuin, khang nim Bu6'e 2. Tim ning dp CPC chi tii thiiu (MIC)<br /> duge tiin hanh tai phong Sinh hpc thuc nghiem cua eae chit eo hoat tfnh.<br /> (Vien hoa hpc eae hgp chit thien nhien - Vien Kit qua thCp hoat tfnh kh^ng khuin, kh^ng<br /> Khoa hpc va C6ng nghe Viet Nam) theo phuang nim duge trinh bay 6' bang 5.<br /> phap eua Vanden Bergher va Vlietlinck ''°' tren<br /> Kit qua thCp hoat tfnh khang khuin cua 7<br /> 96 giing vi lugng. Cac chung vi sinh vat kiim<br /> chit eho thiy ca 7 chit diu c6 hoat tfnh khang<br /> djnh bao gim: 2 chung vi khuin Gram (-):<br /> Escherichia coli, Pseudomonas aeruginosa; 2 khuin tren chung 6. subtillis a ning dp<br /> Chung vi khuin Gram (+): Bacillus subtilis, 50p.g/ml. Chit (2, 4, 5) c6 hoat tfnh khSng<br /> Staphylococcus aureus; 2 chung nim sgi: khuin tren chung S. aureus a ning dp 25pg/ml.<br /> Aspergillus niger, Fusarium oxysporum; 2 chung Chit (5, 6, 7, 8, 9) eo hoat tfnh khang khuin<br /> nim men: Candida albicans, Saeeharomyees tren chung E. coli va F. oxysporum. Cac chit<br /> cerevisiae. Khang sinh kiim djnh bao gim: diu kh6ng c6 tac dung tren 2 chung nim men.<br /> ampicilin dii vai vi khuin Gram (+), tetracyclin TLP kit qua thu dugc co thi thiy ring viec gin<br /> dii VO'I vi khuin Gram (-). ThCp nghiem hoat tinh them hgp phan base Mannich l^m tang hoat<br /> sinh hpc dugc tiin hanh dii vo'i 7 chit ( 2, 4 - phi kh^ng khuin v^ kh^ng nim so v6'i chit<br /> 9) theo 2 buac: ngung tu.<br /> <br /> TAP CHi DUOC HQC - 11/2010 (SO 415 NAM 50) 33<br />  Nghien CLPU - Ky thuat<br /> Bang 5: Kit qui thw hoat tinh khing khuin, khing nim cua mpt sd chit tdng hap dwac<br /> Nong dp wc ehe toi thieu (MIC: pg/ml)<br /> Vi khuan Gr(-) Vi khuan Gr(+) Nam moe Nam men<br /> Chat<br /> E. P. B. S. Asp. F. S. C.<br /> coli aeruginosa subtillis aureus niger oxysporum cerevisiae albicans<br /> 2 (-) (-) 50 25 (-) (-) (-) (-)<br /> 4 (-) (-) 50 25 (-) (-) (-) (-)<br /> 5 50 (-) •<br /> 50 25 (-) 50 (-) (-)<br /> 6 50 (-) 50 (-) (-) 50 (-) (-)<br /> 7 50 (-) 50 (-) (-) 50 (-) (-)<br /> 8 50 (-) 50 (-) (-) 50 (-) (-)<br /> 9 25 (-) 25 (-) (-) 50 (-) (-)<br /> ThCp hoat tinh chdng ung thu' Chit 3: tuang tu c h i t 2 nhung thay 0,04 moi<br /> Phuang phap thCp nghiem hoat tinh khang t i 2-thioxo-4-thiazolidinon bing 0,04 moi<br /> bao ung thu dugc tiin hanh theo mo hinh thCr imidazolidin-2,4-dion, dung m6i k i t tinh Ethanol:<br /> nghiem eua Vien nghien CCPU ung thu Q u i e gia DMF(1:1).<br /> eua My (NCI) theo phuang phap Sulforhodanin K i t qua t i n g hgp duge ghi 6' bang 1.<br /> B (SRB) eua Likhiwitayawuid '®' va dugc thuc Qui trinh chung tdng hgp cac base<br /> hien tai phong sinh hpc thuc nghiem (Vien hoa Mannich:<br /> hpc cac hgp chit thien nhien - Vien khoa hpc Cho vao binh e i u 0,0045 moi amin trong<br /> va C6ng nghe Viet Nam). 40ml ethanol, khuiy trpn d i u , them 0,5ml formol<br /> Chung t6i da tiin hanh thCp kha nang gay dpc (0,006 moi HCHO). Them tCp tCp 0,002 moi chit<br /> t i bao eua eae chit ting hgp dugc d i i vo'i cac ngung tu (2) hoac (3) khuiy a nhiet d6 phong<br /> dong t i bao ung thu gan nguo'i (Hep-2) Kit qua trong vong 1h. Sau do tang nhiet dp h i n hgp<br /> eho thiy eae chit dem thCp nghiem d i u kh6ng co phan Cpng to'i nhiet dp thich hgp 40-60°C, theo<br /> tac dung khang dong t i bao ung thu thu' nghiem. doi phan Cpng bing SKLM vo'i he dung m6i thich<br /> ThiFC nghiem hgp 6e xac djnh tho'i gian phan Cpng t i i uu, do<br /> SKLM duge thuc hien tren ban mong ra c i c thuy tinh, d i k i t tua. Lpc hut chan khong,<br /> silieagel Kieselgel 6OF254 (Merck). D i i m chay rCpa tua bing ethanol lanh. K i t tinh lai trong<br /> dugc ghi tren may Electrothermal digital. P h i IR dung m6i thich hgp (bang 1), d i k i t tua 1 ngay<br /> duge ghi tren may Perkin Elmer. P h i MS dugc dem, Ipe hut, s i y kh6 thu san pham. Kit qua<br /> ghi tren eae may HP - 989B - MS, LC-MSD- ting hgp duge ghi g bang 1.<br /> Trap - SL va tren may Autospec Premier. P h i K§t luan<br /> ' H - N M R va '^C-NMR duge ghi tren may Avance 1. Da t i n g hgp duge 12 c h i t bao g i m 5-<br /> 500 MHz (Bruker). eloroisatin (1), d i n chit ngung tu eua 5-<br /> Qui trinh t i n g hap chit 1: cloroisatin vo'i 2-thioxo-4-thiazolidinon (2); vd'i<br /> Theo tai lieu tham khao '^'. imidazolidin-2,4-dion (3) va 9 d i n c h i t Mannich<br /> Qui trinh t i n g hap chit ngu'ng tu 2, 3: cua (2) va (3) la eae c h i t tCp (4 -12).<br /> Chat 2: Cho vao binh eiu 0,04mol chat 1, 0,12 2. Da thCp tac dung khang khuin, khang nim<br /> moi natri acetat khan, 0,04 moi 2-thioxo-4- eua 7 c h i t t i n g hgp duge (2, 4, 5, 6, 7, 8, 9) voi<br /> thiazolidinon va 80ml acid acetic bang. Dun hii luu 4 chung vi khuin (6. subtillis, S. aureus, E. coli,<br /> each eat. Hin hgp s6i 6' 117 - 121°C thi b i t d i u P. aeruginosa) va 4 chung vi n i m {A. niger, F.<br /> tfnh gia. Theo doi qua trinh tiin trien phan Cpng oxysporum, C. albicans, S cerevisiae). K i t qua<br /> bing SKLM vo'i he dung m6i CHCl3:MeOH (13:1) eho thiy cac chit d i u co hoat tfnh khang nim<br /> de xac djnh tho'i gian phan Cpng thich hgp (6h). khang khuin. Cu the ca 7 c h i t d i u co hoat tfnh<br /> De ngupi, eho k i t tinh sau d6 dem Ipe hut khang chung vi khuin B. subtillis. Cac c h i t (2),<br /> chan khong, rCpa bing nuo'c da d i n khi h i t acid. (4) va (5) CO hoat tfnh khang chung vi khuin<br /> S i y kh6 va k i t tinh lai trong EtOH. S.aureus. Cac chit (5), (6), (7), (8) va (9) con co<br /> <br /> <br /> 34 TAP CHi DUQC HQC - 11/2010 (SO 415 NAM 50)<br />  Nghien CLPU - Ky thuat<br /> hoat tfnh kh^ng vi khuin chung E.coli v^ kh^ng Keywords: 5-ehloroisatin, rhodanine,<br /> chung vi nam F.oxysporum hydantoin, Mannich bases, antibacterial activity,<br /> 3. Da thLP t^e dung khang d6ng t i b^o ung antifungal activity.<br /> thu nguo'i (Hep-G2) eua 7 chit t i n g hgp dugc. Tai lieu tham khao<br /> Kit qua eho thiy ca 5 chit d i u eho k i t qua am 1. Eshba N. H., Salama H. M. Eshba N. H., Salama<br /> tinh vai dong t i bao thCp nghiem. H. M., Phanvazle , (1985), 40, 5, p. 530 - 532<br /> Summary 2. B. A. Grinberg, B. Mazylis, Chemija ,(1990), 2,<br /> p. 8 7 - 9 2 , vol 114.<br /> From 5-Chloroisatin (1) (introduced by<br /> 3. K. C. Josi, V. N. Pathak, S. K. Jain, J. Indian.<br /> Sandmayer, 1919), by condensation with 2- ChemSoe, (1980), 57 (12),vol 95, p. 1176-1180.<br /> thioxo-4-thiazolidinon and imidazolidine-2,4- 4. Pop F. D., J. Med. Chem, (1969), 12 (5), p. 182 -184.<br /> dion, compounds 2 and 3 were obtained. 5. S.N. Pandeya, P. Yogeesnari, D. Siram,<br /> Compound 2 and 3 underwent Mannich reaction Chemotherapy , (1999), 45, 1 9 2 - 1 9 6<br /> to give nine Mannich base derivatives (4 - 12). 6. Likhiwitayawid K., Angerhofer O.K et al, J. Nat<br /> The structures of the synthesized compounds prod, (1993), 56(1), 3 0 - 3 8 .<br /> were confirmed by IR, ^H-NMR, ^^C-NMR and 7. Nguyin Quang Dat, Tr§n Viet Hung va cpng<br /> su. Tap chiDwoe hoc, (1998), so 12, trang 8 - 1 0 .<br /> MS. Biological activity screening showed<br /> 8. Nguyen Quang Dat, Tran Viit Hung, Ha Quoc<br /> compounds 2, 4, 5 antibacterially active against<br /> Khanh , Tap chi DWQC hoc, (2007), 86 4, trang 2 6 - 2 8 .<br /> Bacillus subtilis. Staphylococcus aureus and<br /> 9. Tran V i i t Hung, Nguyin Quang Dat va cpng<br /> compounds 5, 6, 7, 8, 9 antibacterial against su, Tap ehi Dwac hoe , (2000), s6 8, trang 1 5 - 1 7 ,<br /> Escherichia coli, Bacillus subtilis and antifungal 10. Nguyen Le Hien, Nguyen Quang Oat, T r i n Viit<br /> against Fusarium oxyporum. Hung, T^p chiDwpfc hpc, (2009), so 8, trang 35 - 39.<br /> <br /> <br /> <br /> <br /> Nghien ciru tong hop terazosin hydroclorid<br /> Nguyen Hai Nam', Nguyen Tien Vimg^<br /> ' Truang dai hoc Duac Ha Noi<br /> ^ Vien Phap Y Quoc gia<br /> <br /> Dat van de dugc ke dan kha nhiiu. Tuy nhien, tai tho'i diim<br /> 6' Viet Nam trong eae nam g i n day ty le nam hien tai, t i t eae cac thuic tren d i u chua eo san<br /> gio'i m i c benh phi dai tiin liet tuyin lanh tinh xuit trong nuo'c va eung chua co ca so' nao san<br /> (BPH) dang eo chiiu huo'ng gia tang. Co hai xuit eung c i p nguyen lieu hoa duge dung d i<br /> nhom thuic hien dang 6\sac dung diiu tri BPH la san xuit cac thuic nay. Chfnh vi vay, chung t6i<br /> da tiin hanh nghien CCPU trien khai quy trinh ting<br /> cac chit CPC c h i enzym 5a-reduetase va eae chit<br /> hgp terazosin hydroclorid, mot trong nhu'ng thuic<br /> CPC e h i thu t h i al-adrenergic. Chit CPC c h i<br /> CO hieu qua diiu trj cao thuoc nhom nay, huo'ng<br /> enzym 5a-reductase hien nay ehi eo finasterid<br /> to'i SU' dung lam nguyen lieu san xuit thuie diiu<br /> dugc su* dung trong khi do cac chit u'C c h i ccl-<br /> trj tang huyit ap va phi dai tiin liet tuyin lanh tinh<br /> adrenergie hien co kha nhiiu thuic tren lam sang<br /> trong nuac. Bai bao nay e6ng b i e^c k i t qua ban<br /> nhu doxazosin, terazosin, prazosin va<br /> d i u thu duge tCp nghien CCPU nay.<br /> tamsulosin. Dae biet, cac chit u'C c h i a 1 -<br /> adrenergic c6n eo tac dung ha huyit ap, vi vay / \<br /> e6n dugc dung d i diiu trj tang huyit ap. Hien<br /> N N-