Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives.
In our efforts to discover more potent and lasting NHE1 inhibitors, we designed and synthesized a series of substituted indan-1-ylidene aminoguanidine derivatives (5). NHE1 inhibitory activity of twenty-one compounds 5 was evaluated in a rat platelet swelling assay. It is found that most of the tested compounds possess NHE1 inhibitory effects. 2-(5-methoxybenzimidazol-2-ylthio)-5-chloro-2,3-dihydroinden-1-ylidene aminoguanidine hydrobromide (5m) proved to be sixty-nine times more potent than cariporide. Furthermore, when tested in vivo, compound 5m also displayed superior cardioprotective effects against SD rat myocardial ischemic-reperfusion injury over those of cariporide.
Zhang
Rui
R
Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
Dong
Jin
J
Xu
Yun-gen
YG
Hua
Wei-yi
WY
Wen
Na
N
You
Qi-dong
QD
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002316:Cardiotonic Agents; D006146:Guanidines; D007189:Indans; C452850:Slc9a1 protein, rat; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; C004479:pimagedine