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Synthesis and Biological Activities of 2,4‐Diaminopteridine Derivatives
Author(s) -
Ma Fei,
Lü Gang,
Zhou WeiFen,
Wang QiuJuan,
Zhang YiHua,
Yao QiZheng
Publication year - 2009
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200800192
Subject(s) - nitric oxide , chemistry , in vivo , nitric oxide synthase , in vitro , chemical synthesis , pharmacology , septic shock , inhibitory postsynaptic potential , proton nmr , stereochemistry , biochemistry , medicine , organic chemistry , biology , microbiology and biotechnology , sepsis
Abstract Substituted 2,4‐diaminopteridine derivatives 10a – 10l were prepared in moderate to good yield. Their structures were confirmed by 1 H‐NMR and MS spectroscopy, as well as by elemental analysis. Their inhibitory properties against inducible nitric oxide synthase (iNOS) were evaluated in vitro . Biological tests indicated that compound 10a , 10d , 10e , 10h , 10i , and 10l showed potent inhibitory activities similar to that of methotrexate (MTX), while the activities of compound 10b , 10c , 10f , 10g , 10j , and 10k are stronger than MTX. Two compounds, i. e., 10b (IC 50 = 18.85 μM) and 10i (IC 50 = 24.08 μM) were further studied for their effect on septic shock in rats and immunologically liver injured mice ( in vivo ). The results demonstrated that 10b and 10i had the capacity to increase the blood pressure in septic shock and showed notable protective activities on immunological hepatic injury.