78923-90-7Relevant articles and documents
Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists
Wang, Wenli,Zheng, Lan,Li, Wei,Zhu, Chen,Peng, Weiqing,Han, Bing,Fu, Wei
, p. 235 - 248 (2020/02/18)
5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.
Comparative metabolism and elimination of acetanilide compounds by rat
Davison,Larsen,Feil
, p. 1003 - 1012 (2007/10/03)
1. 14C-labelled propachlor, alachlor, butachlor, metolachlor, methoxypropachlor and some of their mercapturic acid pathway metabolites (MAP) were given to rat either by gavage or by perfusion into a renal artery MAP metabolites were isolated from bile and urine. 2. Rat gavaged with propachlor and methoxypropachlor eliminated 14C mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminated 14C about equally divided between urine and faeces When bile ducts were cannulated, the gavaged rat eliminated most of the 14C in bile for all compounds The amount of 14C in bile from the propachlor-gavaged rat was less than that for the other acetanilides, with the difference being in the urine 3. The mercapturic acid metabolites 2-methylsulphinyl-N-(1-methylhydroxyethyl)-N-phenylacetamide and 2-methylsulphinyl-N-(1-methylmethoxyethyl)-N-phenylacetamide were isolated from the urine and bile of the methoxypropachlor-gavaged rat 4. Bile was the major route for 14C elimination when MAP metabolites of alachlor, butachlor and metolachlor were perfused into a renal artery Urine was the major route for 14C elimination when MAP metabolites of propachlor and methoxypropachlor were perfused Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused 5. We conclude that alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination
