环氯胍
化合物
环氯胍（英语：Cycloguanil），又称氯胍三嗪[1]或氯苯三嗪[2]，化学上是一种胺缩醛，药理学上属二氢叶酸还原酶抑制剂[3]，是抗疟疾药物氯胍的经肝脏细胞色素P450代谢产物，并被认为是氯胍在体内发挥抗疟作用的活性成分（即氯胍是环氯胍的前体药物）[1][4]。然而最新研究表明，在抗疟药物马拉隆（Malarone，即复方氯胍/阿托伐醌）中，氯胍与阿托伐醌虽然有协同作用，但代谢成环氯胍后对阿托伐醌是拮抗的，表明氯胍与环氯胍不同，除了抑制二氢叶酸还原酶之外，可能还具备另一种抗疟作用机制[5]。
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| CAS号 | 516-21-2  |
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| 化学信息 | |
| 化学式 | C11H14ClN5 |
| 摩尔质量 | 251.72 g·mol−1 |
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尽管环氯胍目前并未被广泛用作抗疟药，但随着现有抗疟药物的耐药性不断增强，人们对环胍与其他药物联合使用的研究重新产生了兴趣[6]。
合成
环氯胍制备路线如图，采用对氯苯胺(1)与双氰胺(2)反应得到对氯苯基双胍 (3)，对氯苯基双胍在丙酮作用下发生缩合即可得到环氯胍。
参考文献
- ^ 1.0 1.1 卢爱华，舒焱，黄松林，等. 体外中国成人肝微粒体中氯胍活化为氯胍三嗪由CYP2C19和CYP3A4介导. 中国药理学报（英文版）. 2000, 21 (8): 747-752.
- ^ 唐汝愚，姚丹帆，周文正. 国产新抗疟药——氯苯三嗪抗疟作用的研究. 中华医学杂志. 1957, 43 (4): 286-291.
- ^ Srivastava IK, Vaidya AB. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrobial Agents and Chemotherapy. June 1999, 43 (6): 1334–9. PMC 89274
. PMID 10348748. doi:10.1128/AAC.43.6.1334.
- ^ Watkins WM, Sixsmith DG, Chulay JD. The activity of proguanil and its metabolites, cycloguanil and p-chlorophenylbiguanide, against Plasmodium falciparum in vitro (Free full text). Annals of Tropical Medicine and Parasitology. June 1984, 78 (3): 273–8 [2024-09-16]. PMID 6385887. doi:10.1080/00034983.1984.11811816. （原始内容存档于2010-03-07）.
- ^ Thapar MM, Gupta S, Spindler C, Wernsdorfer WH, Björkman A. Pharmacodynamic interactions among atovaquone, proguanil and cycloguanil against Plasmodium falciparum in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene. May 2003, 97 (3): 331–7. PMID 15228254. doi:10.1016/S0035-9203(03)90162-3 .
- ^ Walzer PD, Foy J, Steele P, White M. Synergistic combinations of Ro 11-8958 and other dihydrofolate reductase inhibitors with sulfamethoxazole and dapsone for therapy of experimental pneumocystosis. Antimicrobial Agents and Chemotherapy. July 1993, 37 (7): 1436–43. PMC 187990 . PMID 8363372. doi:10.1128/AAC.37.7.1436.
- ^ Modest, Edward J. (1956). "Chemical and Biological Studies on 1,2-Dihydro-s-triazines. II. Three-Component Synthesis". The Journal of Organic Chemistry 21 (1): 1–13. doi:10.1021/jo01107a001.
- ^ Modest, Edward J.; Levine, Philip. (1956). "Chemical and Biological Studies on 1,2-Dihydro-s-triazines. III. Two-Component Synthesis". The Journal of Organic Chemistry. 21(1): 14–20. doi:10.1021/jo01107a002.
- ^ Carrington, H. C.; Crowther, A. F.; Stacey, G. J. (1954). "Synthetic antimalarials. Part XLIX. The structure and synthesis of the dihydrotriazine metabolite of proguanil". Journal of the Chemical Society (Resumed): 1017. doi:10.1039/jr9540001017.
- ^ Modest, Edward J.; Foley, George E.; Pechet, Maurice M.; Farber, Sidney (1952). "A SERIES OF NEW, BIOLOGICALLY SIGNIFICANT DIHYDROTRIAZINES". Journal of the American Chemical Society. 74 (3): 855–856. doi:10.1021/ja01123a532.
- ^ Loo, Ti Li (1954). "1-p-Chlorophenyl-2,4-diamino-6,6-dimethyl-1,6-dihydro-1,3,5- triazine". Journal of the American Chemical Society. 76 (20): 5096–5099. doi:10.1021/ja01649a026.
- ^ Edward J. Modest, 美国专利第2,900,385号 (1959 to Children s Cancer Research Foundation).
- ^ Donald F. Worth, 美国专利第3,074,947号 (1963 to Parke).
