Delving into the Latest Updates on Piperazine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Diethylenediamine, Piperazidine, Piperazime Phosphate

+ [10]

Target-

Mechanism-

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

AscariasisCoughEnterobiasis

Inactive Indication-

Originator Organization

Sichuan Emeishan Pharmaceutical Co Ltd.

Active Organization

Sichuan Emeishan Pharmaceutical Co Ltd.

Chengdu Pharmaceutical Co. Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure

Molecular FormulaC4H10N2

InChIKeyGLUUGHFHXGJENI-UHFFFAOYSA-N

CAS Registry110-85-0

The protein arginine methyltransferase 5 (PRMT5) has emerged as potential target for the treatment of cancer. Many efforts have been made to develop potent and selective PRMT5 inhibitors targeting either S-adenosyl methionine (SAM) pocket or substrate binding pocket. Here, we rationally designed a series of nucleoside derivatives incorporated with piperazine as novel PRMT5 inhibitors occupying both pockets. The representative compound 36 exhibited highly potent PRMT5 inhibition activity as well as good selectivity over other methyltransferases. Further cellular experiments revealed that compound 36 potently reduced the level of symmetric dimethylarginines (sDMA) and inhibited the proliferation of MOLM-13 cell lines by inducing apoptosis and cell cycle arrest. Moreover, compound 36 had more favorable metabolic stability and aqueous solubility than JNJ64619178 (9). Meanwhile, it obviously suppressed the tumor growth in a MOLM-13 tumor xenograft model. These results clearly indicate that 36 is a highly potent and selective PRMT5 inhibitor worthy for further development.

01 Jan 2025·Mini-Reviews in Medicinal Chemistry

Pharmaceutical Studies on Piperazine-based Compounds Targeting Serotonin Receptors and Serotonin Reuptake Transporters

Article

Author: Kaplan, Hasan Alper ; Nenni, Merve ; Sakarya, Mehtap Tugrak ; Yamali, Cem

Depression is a debilitating mental illness that has a significant impact on an individual's psychological, social, and physical life. Multiple factors, such as genetic factors and abnormalities in neurotransmitter levels, contribute to the development of depression. Monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotoninnoradrenaline reuptake inhibitors, and atypical and new-generation antidepressants are well-known drug classes. SSRIs are the commonly prescribed antidepressant medications in the clinic. Genetic variations impacting serotonergic activity in people can influence susceptibility to diseases and response to antidepressant therapy. Gene polymorphisms related to 5-hydroxytryptamine (5-HT) signaling and subtypes of 5-HT receptors may play a role in the development of depression and the response to antidepressants. SSRIs binding to 5-HT reuptake transporters help relieve depression symptoms. Research has been conducted to identify a biomarker for detecting depressive disorders to identify new treatment targets and maybe offer novel therapy approaches. The pharmacological potentials of the piperazine-based compounds led researchers to design new piperazine derivatives and to examine their pharmacological activities. Structure-activity relationships indicated that the first aspect is the flexibility in the molecules, where a linker of typically a 2-4 carbon chain joins two aromatic sides, one of which is attached to a piperazine/phenylpiperazine/benzyl piperazine moiety. Newly investigated compounds having a piperazine core show a superior antidepressant effect compared to SSRIs <i>in vitro/in vivo</i>.

31 Dec 2024·Journal of Enzyme Inhibition and Medicinal Chemistry

Design, synthesis, and biological evaluation of piperazine derivatives involved in the 5-HT _1A R/BDNF/PKA pathway

Article

Author: Liu, Zheng ; Liu, Hui ; Zhou, Hao ; Wang, Shiben ; Li, Mengjiao ; Wang, Xuekun

In this study, four series of piperazine derivatives were designed, synthesised and subjected to biological test, and compound 6a with potential antidepressant activity was obtained. An affinity assay of compound 6a with 5-hydroxytryptamine (serotonin, 5-HT)_1A receptor (5-HT_1AR) was undertaken, and the effects on the 5-HT level in the brains of mice were also tested. The results showed that compound 6a had the best affinity with 5-HT_1AR (K_i = 1.28 nM) and significantly increased the 5-HT level. The expression levels of 5-HT_1AR, BDNF, and PKA in the hippocampus were analysed by western blot and immunohistochemistry analyses. The results showed that the expression of 5-HT_1AR, BDNF, and PKA in the model group was reduced compared to that of the control group, and compound 6a could reverse this phenomenon. Molecular docking was performed to investigate the interactions of the studied compound 6a with 5-HT_1AR on the molecular level.

100 Deals associated with Piperazine

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External Link

KEGG	Wiki	ATC	Drug Bank
D00807	Piperazine	P02CB01	DB00592

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Ascariasis	CN	Sichuan Emeishan Pharmaceutical Co Ltd.	-
Cough	CN	Chengdu Pharmaceutical Co. Ltd.	-
Enterobiasis	CN	Sichuan Emeishan Pharmaceutical Co Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AAIC2016	Not Applicable	Cognitive Dysfunction	-	Novel Piperazine Derivatives	tikhnpoigr(qwswyafjvf) = gccksomrnj tftyeplgxb (wuzpyelcbk )	-	01 Jul 2016
NCT02083406 (CTgov)	Phase 1	Malaria	22	800mg OZ439 prototype formulation 1+960mg PQP (Treatment A: OZ439 Prototype 1)	nmrdmtghhl(hchcegouso) = tezacdwqdk lxsoayqhhj (lclogywceg, kfprbjgegn - tabatrioeg) View more	-	23 Mar 2015
NCT02083406 (CTgov)	Phase 1	Malaria	22	800mg OZ439 prototype formulation 2+960mg PQP (Treatment B: OZ439 Prototype 2)	nmrdmtghhl(hchcegouso) = wuvmeogfxv lxsoayqhhj (lclogywceg, ryfhknsrto - ervayoypwc) View more	-	23 Mar 2015