chapter10antiparasiticdrugs

1、Chapter 10Antiparasitic drugs Parasitic diseases is common in the past.The incidence of parasitic diseases in China has decreased significantly as a result of economic development and peoples living standards improved.10.1 AntimalarialAn ancient disease, especially in South America, Africa, South As

2、ia and the old China,seriously affected the peoples health. Cinchona was early used to treat the disease of malaria in which Quinine was the active constituent.奎寧 Quinine 6-甲氧基-（5-乙烯基-2-奎寧環(huán)基）-4-羥甲基喹啉甲醇6-Methoxy-（5-vinyl-2-quiniclidinyl）-4-quinoline methanolQuinine的結(jié)構(gòu)特點(diǎn)兩部分組成喹啉及通過醇與哌啶雙環(huán)相連部分四個(gè)手性碳C-3、C-

3、4、C-8、C-9 Distribution: It can be absorbed rapidly and completely after oral administration, widely distributed. Mechanism:hydroxylation at 2 in quinoline ring is the main way, then at 2 in anohter ring.Metabolism of Quinine 甲氟喹 （ Mefloquine） 磷酸氯喹Chloroquine phophate N4-（7-氯-4-喹啉基）-N1，N1-二乙基-1，4-戊二胺

4、二磷酸鹽N4-（7-Chloro-4-quinolinyl）-N1，N1-diethyl-1，4-pentanediamine diphosphateMechanism: 1. Disturb replication of DNA.Inserted DNA double chains to form a stable complex to disturb replication of DNA, transcription of RNA and synthesis of protein2, Changes pH value of cell.Much alkalescence Chloroquin

5、e enter the body of plasmodium so that the pH value of solution increased, so produce abnormal environment for protein enzyme, reduce the decomposition ability of hemoglobin, lead to a lack of essential amino acids, at last interfere with parasite reproduction.Absorption and distribution：Rapid and c

6、omplete absorption in intestinal by oral administration, 1-2 hours up to the peak plasma concentration, concentrated Chloroquine inside red blood cells in malaria parasites is conducive to kill propagules.青蒿素Artemisinin3R-（3，5a，6，8a，9，12，12aR*） 八氫-3，6，9-三甲基-3，12-橋氧-12H吡喃4，3-j -1，2-苯并二氧卓-10（3H）-酮.Low

7、 activity and solubility by oral administration, shortcoming of high relapse rate. so restriction of expanding application.SAR: (1) Endoperoxide is necessary for activity, deoxy artemisinin, a total loss of antimalarial activity, the activity attributed to the endoperoxide - ketal - Acetal - lactone

8、 segment. (2) Carbonyl at 10 was reduced to dihydroartemisinin, greater activity than Artemisinin. (3) Ether, ester and carboxylic acid derivatives of dihydroartemisinin all have anti-malarial activity. (4) The introduction of hydrophilic groups will increase the polarity and reduced activity, lipop

9、hilic characteristic is very important .Metabolism 二氫蒿素脫氧二氫蒿素3-羥基脫氧二氫青蒿素9，10-二羥基二氫青蒿素10.2 Helminthic drugEffect in intestinal: to kill or drive away parasites such as roundworm, hookworm, pinworm and other insects out of the body.阿苯達(dá)唑 Albendazole（5-丙硫基）-1H-苯并咪唑-2-基 氨基甲酸甲酯（5-Propylthio）-1H-benzimidaz

10、ol-2-yl carbamicacid methyl esterSynthesis of AlbendazoleForbidden for women - side effects of teratogenicity and embryotoxicity10.3 Anti-schistosomiasis drugs吡喹酮 Praziquantel2-（環(huán)己甲?；?1，2，3，6，7，11b-六氫-4H-吡嗪并2，1-a異喹啉-4-酮2-（Cydohexylcarbonyl）-1，2，3，6，7，11b-hexahydro-4H-pyrazino2,1-aisoquinolin-4- one廣譜抗寄生蟲藥，對(duì)日本血吸蟲有殺滅作用低濃度時(shí)（5g/ml），可刺激血吸蟲使其活性加強(qiáng)較高濃度時(shí)（5mg/ml）蟲體即孿縮療效高、療程短、代謝快、毒性低Mecha