Design, synthesis and antihistamine evaluations of several N-hydroxyalkyl desloratadine analogues.
Several N-hydroxyalkyl desloratadines and N-methoxyl ethyl desloratadine were prepared and evaluated for H1 antihistamine activity. The effects on isolated ileum smooth muscle tension in guinea pigs in vitro and asthma-relieving effects on the histamine-induced asthmatic reaction in guinea-pigs in vivo were examined. Most of them exhibited satisfactory H1 antihistamine activity and were obviously more potent than loratadine. Among these, Compound 3, N-(3-hydroxy)propyl desloratadine was the most active one. And it was chosen as a candidate for evaluation of acute toxicity (LD(50)= 0.876(0.784-0.980) g/kg), significantly superior to that of desloratadine (LD(50)=0.353 g/kg). Meanwhile, the experimental results demonstrated that the oxygen atom in the side carbon chain is crucial for enhancing the antihistamine activities.
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.
Yan
Y
Lin
Yue
Y
Wang
Li-feng
LF
Sima
Dong-hua
DH
Wang
Li-gong
LG
Chen
Lei
L
Li
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000009:adverse effects; D006633:Histamine Antagonists / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017336:Loratadine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology
D006633:Histamine Antagonists; D017336:Loratadine; D006632:Histamine