Page last updated: 2024-12-07

3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione: isolated from Streptomyces griseoluteus fermentation broth; RN given refers to cpd without isomeric designation; structure [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID114728
CHEMBL ID512223
SCHEMBL ID11670768
MeSH IDM0045028

Synonyms (16)

Synonym
3,6-bis(5-chloro-2-piperidinyl)-2,5-piperazinedione
NEURO_000069
593a
2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidinyl)-
3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione
64474-15-3
CHEMBL512223
3,6-bis(5-chloropiperidin-2-yl)piperazine-2,5-dione
GVATXFBCMPDLPO-UHFFFAOYSA-N
3,6-bis(5-chloro-2piperidinyl)-2,5-piperazinedione
SCHEMBL11670768
3,6-bis-(5-chloro-2-piperidinyl)2,5-piperazinedione
DTXSID60983047
3,6-bis(5-chloropiperidin-2-yl)-3,6-dihydropyrazine-2,5-diol
593 a
piperazinedione di-hcl

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
" This study indicates that low doses of piperazinedione can produce variable and severe myelosuppression when used in combination with other myelosuppressive agents, and that only small increments in dosage may produce marked increases in the degree of myelosuppression."( Severe myelosuppression from piperazinedione, (NSC No. 135758), cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC).
Klahr, C; Presant, CA, 1977
)
0.26
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID409953Inhibition of mouse liver MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID409954Inhibition of mouse brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (47)

TimeframeStudies, This Drug (%)All Drugs %
pre-199031 (65.96)18.7374
1990's4 (8.51)18.2507
2000's4 (8.51)29.6817
2010's7 (14.89)24.3611
2020's1 (2.13)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.55

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index10.55 (24.57)
Research Supply Index4.04 (2.92)
Research Growth Index4.60 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.55)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (14.29%)5.53%
Reviews2 (4.08%)6.00%
Case Studies1 (2.04%)4.05%
Observational0 (0.00%)0.25%
Other39 (79.59%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Treatment of Children With All Stages of Hepatoblastoma With Temsirolimus (NSC#683864) Added to High Risk Stratum Treatment [NCT00980460]Phase 3236 participants (Actual)Interventional2009-09-14Active, not recruiting
A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma [NCT06172296]Phase 3478 participants (Anticipated)Interventional2024-02-14Not yet recruiting
A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma [NCT03786783]Phase 242 participants (Actual)Interventional2019-01-14Active, not recruiting
A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma [NCT01231906]Phase 3642 participants (Actual)Interventional2010-11-22Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00980460 (5) [back to overview]Event-free Survival
NCT00980460 (5) [back to overview]Feasibility of Referral for Liver Transplantation
NCT00980460 (5) [back to overview]Number of Deaths
NCT00980460 (5) [back to overview]Disease Status at the End of 2 Courses of Therapy
NCT00980460 (5) [back to overview]Number of Cycles on Which Grade 3 or Higher Adverse Events Coded According to CTC AE Version 5 Were Observed
NCT01231906 (1) [back to overview]Event-Free Survival
NCT03786783 (5) [back to overview]"Percentage of Participants Who Are Feasibility Failure"
NCT03786783 (5) [back to overview]Event-free Survival
NCT03786783 (5) [back to overview]Overall Survival
NCT03786783 (5) [back to overview]Percentage of Participants With Unacceptable Toxicity
NCT03786783 (5) [back to overview]Response Rate

Event-free Survival

Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT00980460)
Timeframe: Time from patient enrollment to progression, treatment failure, death from any cause, diagnosis of a second malignant neoplasm, or last follow-up, assessed up to 5 years

InterventionPercent Probability (Number)
Very Low-risk Group100
Low-risk Group (Regimen T)87.21
Intermediate-risk Group (Regimen F)87.03
High-risk Group (Regimen W)43.61
High-risk Group (Regimen H)46.38

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Feasibility of Referral for Liver Transplantation

A patient for whom referral is considered appropriate who receives a consultation after enrollment will be considered a success with respect to feasibility. (NCT00980460)
Timeframe: 3 cycles of therapy - up to 3 months after enrollment

InterventionParticipants (Count of Participants)
Intermediate-risk Group (Regimen F)37
High-risk Group (Regimen H)16

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Number of Deaths

Number of patients who experience on-protocol-therapy death possibly, probably or likely related to systemic chemotherapy. This outcome measure applies to INTERMEDIATE RISK patients only. (NCT00980460)
Timeframe: During protocol therapy or within 30 days of the termination of protocol therapy up to 1 year after enrollment

InterventionParticipants (Count of Participants)
Intermediate-risk Group (Regimen F)1

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Disease Status at the End of 2 Courses of Therapy

RECIST v 1.1 and serum alphafetoprotein responses are evaluated separately. RECIST v 1.1 complete response (CR) is defined as disappearance of all target lesions and partial response (PR) is defined as reduction of at last 30% in the sum of the longest dimension of all target lesions (CR and PR measured by CT or MRI) between enrollment. Serum alphafetoprotein response is a decrease of at least 90% from the last serum alphafetoprotein measurement from the baseline prior to the start of chemotherapy to the end of cycle 2. This is calculated for HIGH RISK regimen W and HIGH RISK regimen H only. (NCT00980460)
Timeframe: First two cycles of therapy- up to 42 days after enrollment

,
Interventionparticipants (Number)
RECIST PR, no AFP responseAFP response, no RECIST responseRECIST response, AFP responseno AFP response, no RECIST response
High-risk Group (Regimen H)310418
High-risk Group (Regimen W)35616

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Number of Cycles on Which Grade 3 or Higher Adverse Events Coded According to CTC AE Version 5 Were Observed

All grade 3 or 4 or greater non-hematological toxicities. The frequency of each toxicity type will be quantified as the number of reporting periods on which the toxicity of the relevant grade is reported. This measure does not apply to patients enrolled in the VERY LOW RISK group. (NCT00980460)
Timeframe: During protocol therapy up to 1 year after enrollment

,,,
InterventionCycles (Number)
Hearing impairedDiarrheaEnterocolitisNauseaSmall intestinal obstructionVomitingAbdominal distensionAbdominal painColitisAnal mucositisAscitesMalabsorptionMucositis oralConstipationDental cariesTyphlitisDuodenal obstructionEsophageal hemorrhageGastritisIlleusOral painSmall intestinal mucositisColonic hemorrhageDysphagiaEsophagitisGastroparesisGastric fistulaGastrointestinal disorders - Other, specifyObstruction gastricRectal mucositisFeverGeneral disorders and administration site conditions - Other, specifyPainMulti-organ failureIrritabilityInfusion related reactionHypothermiaCatheter related infectionInfections and infestations - Other, specifyMucosal infectionOtitis mediaUrinary tract infectionBiliary tract infectionAbdominal infectionBladder infectionEnterocolitis infectiousDuodenal infectionUpper respiratory infectionEye infectionWound infectionSepsisLung infectionPeritoneal infectionSkin infectionSmall intestine infectionPeriorbital infectionAlanine aminotransferase increasedAspartate aminotransferase increasedActivated partial thromboplastin time prolongedAlkaline phosphatase increasedBlood bilirubin increasedCreatinine increasedGGT increasedWeight lossFibronogen decreasedEjection fraction decreasedInvestigations - Other, specifyWhite blood cell decreasedINR increasedCPK increasedCholesterol highElectrocardiogram QT corrected interval prolongedLipase increasedSerum amylase increasedAnorexiaDehydrationHyperglycemiaHyperkalemiaHypermagnesemiaHypernatremiaHypokalemiaHyponatremiaAcidosisAlkalosisHypocalcemiaHypoalbuminemiaHypomagnesemiaHypophosphatemiaTumor lysis syndromeHypercalcemiaHypoglycemiaHypertriglyceridemiaMetabolism and nutrition disorders - Other, specifyPeripheral sensory neuropathyOculomotor nerve disorderAbducens nerve disorderPeripheral motor neuropathySyncopeDysphasiaDepressed level of consciousnessSeizureApneaAtelectasisDyspneaBronchospasmHypoxiaPleural effusionPulmonary edemaStridorRespiratory failureEpistaxisWheezingHypertensionHematomaHypotensionVascular disorders - Other, specifyThromboembolic eventLeft ventricular systolic dysfunctionCardiac arrestRight ventricular dysfunctionVentricular tachycardiaCardiac disorders - Other, specifySinus tachycardiaHeart failureMyocardial infarctionBiliary fistulaHepatobiliary disorders - Other, specifyHepatic hemorrhagePortal vein thrombosisPortal hypertensionBiliary anastomotic leakPostoperative hemorrhageGastrointestinal anastomotic leakIntraoperative hemorrhageArthralgiaGeneralized muscle weaknessBack painBone painMuscle weakness lower limbAgitationHallucinationsInsomniaAcute kidney injuryRenal and urinary disorders - Other, specifyRenal calculiProteinuriaErythema multiformeSkin and subcutaneous tissue disorders - Other, specifyRash maculo-papularEye disorders - Other, specifySurgical and medical procedures - Other, specifyTumor painAllergic reactionAnaphylaxisImmune system disorders - Other, specify
High-risk Group (Regimen H)4151305061000600100000000001111904211109003000502003107016191151661100011111171210503291013212190014110020011003061001114050100000410011000001000000010001012000221
High-risk Group (Regimen W)415010013391000810200141011110000101000012711000040200000100910302014000110000020353001260043370110020230100001022000202131113001111001011120000001000100001001000
Intermediate-risk Group (Regimen F)20150101241103111442121113410000000091610008380031128141152111028372173762110000000301315124148224173112120000531710000221102112006132011210000112101100121114109310123110000
Low-risk Group (Regimen T)14111200000000000000000000000010000001411100000000000000110000000000000000132222410000000000020000000100000000003000000000000000000000000000000000000000000

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Event-Free Survival

Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT01231906)
Timeframe: 5 years after enrollment

InterventionPercent Probability (Number)
Arm A (Combination Chemotherapy)77.64
Arm B (Combination Chemotherapy, Topotecan Hydrochloride)78.79

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"Percentage of Participants Who Are Feasibility Failure"

"Feasibility failures were defined as patients that did not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility failure rate together with a 95% confidence interval." (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

InterventionPercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)0.0

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Event-free Survival

Per the revised INRC, progressive disease is: 1) > 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬> increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with > 20% increase in longest diameter, taking as reference the smallest sum on study, and with > 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬> 1.2, 8) Bone marrow without tumor infiltration that becomes >5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by > 2-fold and has > 20% tumor infiltration on reassessment. (NCT03786783)
Timeframe: Up to 1 year

InterventionPercent Probability (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)82.6

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Overall Survival

Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided. (NCT03786783)
Timeframe: Up to 1 year

InterventionPercent Probability (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)95.0

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Percentage of Participants With Unacceptable Toxicity

Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval. (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

Interventionpercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)0.0

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Response Rate

Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD. (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

InterventionPercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)78.6

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