626219-18-9

Upstream product

• 445-27-2 2'-Fluoroacetophenone 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 

Downstream Products

• 678995-25-0 4-[2-(1-ethylamino-ethyl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 626219-27-0 (R)-1-[4-(2-Acetyl-phenyl)-piperazin-1-yl]-2-amino-3-(4-chloro-phenyl)-propan-1-one 
• 626219-24-7 [2-[4-(2-acetyl-phenyl)-piperazin-1-yl]-1-(4-chloro-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester 
• 748808-87-9 3-[2-[4-(2-acetyl-phenyl)-piperazin-1-yl]-1-(4-chloro-benzyl)-2-oxo-ethylcarbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression

Depression is one of the most frequent comorbid psychiatric symptoms of Alzheimer's disease (AD), and no efficacious drugs have been approved specifically for this purpose thus far. Herein, we proposed a novel therapeutic strategy that merged the key pharmacophores of the antidepressant vilazodone (5-HT1A receptor partial agonist and serotonin transporter inhibitor) and the anti-AD drug donepezil (acetylcholinesterase inhibitor) together to develop a series of multi-target-directed ligands for potential therapy of the comorbidity of AD and depression. Accordingly, 55 vilazodone-donepezil chimeric derivatives were designed and synthesized, and their triple-target activities against acetylcholinesterase, 5-HT1A receptor, and serotonin transporter were systematically evaluated. Among them, compound 5 displayed strong triple-target bioactivities in vitro, low hERG potassium channel inhibition and acceptable brain distribution. Importantly, oral intake of 5 mg/kg of the compound 5 dihydrochloride significantly alleviated the depressive symptoms and ameliorated cognitive dysfunction in mouse models. In brief, these results highlight vilazodone-donepezil chimeras as a prospective therapeutic approach for the treatment of the comorbidity of AD and depression.

Structure-activity relationship studies on a series of piperazinebenzylalcohols and their ketone and amine analogs as melanocortin-4 receptor ligands

A series of piperazinebenzylalcohols were prepared and studied to compare with their ketone and amine analogs as MC4R antagonists. Several benzylalcohols such as 14a and 14g displayed low nanomolar binding affinities (Ki 10 nM), and high sele

Identification of agonists and antagonists of the human melanocortin-4 receptor from piperazinebenzylamines

SAR studies of a series of piperazinebenzylamines resulted in identification of potent agonists and antagonists of the human melanocortin-4 receptor. Thus, the 1,2,3,4-tetrahydroisoquinolin-1-ylacetyl compound 12e and the quinolin-3-ylcarbonyl analogue 12l possessed Ki values of 6.3 and 4.5 nM, respectively. Interestingly, 12e was a full agonist with an EC 50 value of 31 nM, and 12l was a weak partial agonist (IA = 17%) and functioned as an antagonist (IC50 = 300 nM).

Structure-activity relationships of piperazinebenzylamines as potent and selective agonists of the human melanocortin-4 receptor

SAR studies on a series of piperazinebenzenes directed toward the human melanocortin-4 receptor resulted in potent MC4R agonists. Replacement of the triazole moiety of an initial lead 4 by a basic nitrogen baring a lipophilic side-chain increased the binding affinities of these compounds. Analogs bearing an additional hetero-atom in the side-chain possessed good agonist potency. Thus, 11h had a Ki of 11 nM, and 13g exhibited an EC50 of 3.8 nM and a Ki of 6.4 nM.

Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor

SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had Ki values of 21, 14, and 15 nM, respectively, possessed low efficacy