500-92-5
基本信息
氯胍-D6盐酸
N-(4-氯苯基)-N'-(异丙基)-双胍
PROGUANIL
paludrine
Aids008307
Aids-008307
chlorguanide
chloroguanide
ChlorguanideCl
Chlorguanide-D6Cl
Chlorguanide-d6 HCl
物理化学性质
| 熔点 | 129° |
| 沸点 | 399.65°C (rough estimate) |
| 密度 | 1.2039 (rough estimate) |
| 折射率 | 1.6110 (estimate) |
| 储存条件 | Store at -20°C, protect from light |
| 溶解度 | DMF: 2mg/mL; DMSO: 3mg/mL; DMSO:PBS (pH 7.2) (1:10): 0.09mg/mL; Ethanol: 1mg/mL |
| 酸度系数(pKa) | 11.15±0.10(Predicted) |
| 形态 | 固体 |
| 颜色 | White to off-white |
安全数据
| 危险性符号(GHS) |  GHS07 |
| 警示词 | 警告 |
| 危险性描述 | H302-H315-H319-H335 |
| 防范说明 | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
制备方法
由硫氯酸钠与水合肼加成、重排，最后经甲醛在乙醇中缩合而制得。
常见问题列表
Proguanil per se has only weak antimalarial activity
in vitro
(IC
50
=2.4-19 μM), and its effectiveness depends on the active metabolite Cycloguanil (IC
50
=0.5-2.5 nM). The Cycloguanil is a dihydrofolate reductase (DHFR) inhibitor. The combination of Atovaquone and Proguanil is synergistic
in vitro
. Both drugs also have activity against gametocytes and pre-erythrocytic (hepatic) stages of malaria parasites.
Proguanil acts as a biguanide rather than as its metabolite Cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the Atovaquone effect. Proguanil-mediated enhancement is specific for Atovaquone, since the effects of other mitochondrial electron transport inhibitors, such as Myxothiazole and Antimycin, are not altered by inclusion of Proguanil.
5-HT
3
receptor responses are reversibly inhibited by Proguanil, the metabolite 4-chlorophenyl-1-biguanide (CPB) and the active metabolite Cycloguanil (CG), with an IC
50
of 1.81, 1.48 and 4.36 μM, respectively.
Proguanil (p.o.; 2.9 mg/kg body weight; daily for 5 days and 6 weeks respectively) shows mild degenerative changes for five days, while shows severe degenerative changes for six weeks in wistar strain albino rats.
Serum testosterone level is significantly decreased for proguanil treatment rats.
Administration of Malarone (atovaquone and proguanil) to experimentally
B. gibsoni
infected two dogs in chronic stage and three dogs in acute stage results in decrease in parasitemia, and clinical improvements are observed.