20011-17-0Relevant articles and documents
Arylpiperazines for management of benign prostatic hyperplasia: Design, synthesis, quantitative structure-activity relationships, and pharmacokinetic studies
Sarswat, Amit,Kumar, Rajeev,Kumar, Lalit,Lal, Nand,Sharma, Smriti,Prabhakar, Yenamandra S.,Pandey, Shailendra K.,Lal, Jawahar,Verma, Vikas,Jain, Ashish,Maikhuri, Jagdamba P.,Dalela, Diwakar,Kirti,Gupta, Gopal,Sharma, Vishnu L.
experimental part, p. 302 - 311 (2011/03/20)
A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47%. Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction). QSAR suggested structures with more cyclic and branched moieties, increased topological separation of O and N therein, and reduced solvation connectivity index for better activity. Pharmacokinetic study with compound 10 at an oral dose of 10.0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood-brain barrier. A 10-fold decrease in PSA and 15-fold increase in ER-β gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-β mediated actions. The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia.
