1,2-diphenyl-3,5-pyrazolidinedione, also known as **phenylbutazone**, is a non-steroidal anti-inflammatory drug (NSAID) that is **no longer widely used in the United States** due to concerns about its potential for serious side effects. However, it remains relevant in research for several reasons:
**Historical Importance:**
* **Early NSAID:** Phenylbutazone was one of the **first NSAIDs** developed, and its discovery was crucial in the understanding of NSAID mechanisms.
* **Pioneer in Anti-inflammatory Therapy:** It played a significant role in revolutionizing pain and inflammation management, particularly in conditions like rheumatoid arthritis.
**Research Applications:**
* **Model for Drug Discovery:** It serves as a **structural template** for the design and development of newer, safer NSAIDs. Understanding its structure-activity relationship helps researchers create improved anti-inflammatory medications with fewer side effects.
* **Pharmacokinetic Studies:** Its unique properties, such as long half-life and high plasma protein binding, make it a useful tool in studying **pharmacokinetic processes** (absorption, distribution, metabolism, and excretion) of drugs.
* **Animal Models:** It's used in **animal models** to investigate the mechanisms of inflammation and to test the efficacy of new anti-inflammatory therapies.
**Caution:**
* **Limited Clinical Use:** While phenylbutazone remains relevant in research, it's important to remember that it's no longer widely used clinically due to its **potential for serious side effects**, including gastrointestinal bleeding, blood disorders, and liver damage.
**In summary**, 1,2-diphenyl-3,5-pyrazolidinedione, though not commonly used clinically, holds historical and research significance. It serves as a foundation for the development of safer NSAIDs and remains valuable in studying pharmacokinetic properties and investigating inflammation mechanisms.
1,2-diphenyl-3,5-pyrazolidinedione: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 17561 |
| SCHEMBL ID | 181607 |
| MeSH ID | M0146352 |
| Synonym |
|---|
| HMS1485E19 |
| 1,2-diphenyl-3,5-pyrazolidinedione |
| MLS000676764 |
| smr000271773 |
| difenildichetopirazolidina [italian] |
| 1,2-diphenyl-3,5-dioxopyrazolidin [german] |
| brn 0210835 |
| da 339 |
| diphenyldiketopyrazolidine |
| g 14744 |
| 3,5-pyrazolidinedione, 1,2-diphenyl- |
| OPREA1_113769 |
| CHEMDIV3_004331 |
| IDI1_022241 |
| 1,2-diphenylpyrazolidine-3,5-dione |
| BRD-K49636304-001-01-0 |
| 2652-77-9 |
| 1,2-diphenyl-pyrazolidine-3,5-dione |
| FT-0650905 |
| AB00554261-02 |
| NCGC00245656-01 |
| HMS2540H07 |
| difenildichetopirazolidina |
| 1,2-diphenyl-3,5-dioxopyrazolidin |
| 5-24-05-00186 (beilstein handbook reference) |
| AKOS016001945 |
| F1151-0006 |
| 1,2-diphenyl-3,5-dioxopyrazolidine |
| SCHEMBL181607 |
| diphenyldioxopyrazolidine |
| mfcd00179924 |
| AS-62588 |
| A877200 |
| DTXSID60877699 |
| 2,5-pyrazolidindione,1,2-diphenyl |
| CS-0156127 |
| SY056699 |
| CAA65277 |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Chain A, ATP-DEPENDENT DNA HELICASE Q1 | Homo sapiens (human) | Potency | 39.8107 | 0.1259 | 19.1169 | 125.8920 | AID2549 |
| thioredoxin reductase | Rattus norvegicus (Norway rat) | Potency | 25.1189 | 0.1000 | 20.8793 | 79.4328 | AID588453 |
| Microtubule-associated protein tau | Homo sapiens (human) | Potency | 8.9125 | 0.1800 | 13.5574 | 39.8107 | AID1460 |
| DNA polymerase beta | Homo sapiens (human) | Potency | 22.3872 | 0.0224 | 21.0102 | 89.1251 | AID485314 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| FAD-linked sulfhydryl oxidase ALR | Homo sapiens (human) | AC50 | 4.3710 | 0.0050 | 3.2126 | 22.7870 | AID493248 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| regulation of cell shape | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| peptidoglycan biosynthetic process | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| cell wall organization | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| regulation of cell shape | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| peptidoglycan biosynthetic process | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| cell division | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| cell wall organization | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| UDP-N-acetylmuramate dehydrogenase activity | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| oxidoreductase activity | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| flavin adenine dinucleotide binding | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| FAD binding | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Process | via Protein(s) | Taxonomy |
|---|---|---|
| cytoplasm | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| cytosol | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| cytosol | UDP-N-acetylenolpyruvoylglucosamine reductase | Escherichia coli K-12 |
| [Information is prepared from geneontology information from the June-17-2024 release] | ||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588501 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID504810 | Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588497 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID504812 | Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign | 2010 | Endocrinology, Jul, Volume: 151, Issue:7 | A small molecule inverse agonist for the human thyroid-stimulating hormone receptor. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Current protocols in cytometry, Oct, Volume: Chapter 13 | Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2006 | Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5 | Microsphere-based protease assays and screening application for lethal factor and factor Xa. |
| AID588499 | High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set | 2010 | Assay and drug development technologies, Feb, Volume: 8, Issue:1 | High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors. |
| AID651635 | Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression | |||
| AID1745845 | Primary qHTS for Inhibitors of ATXN expression | |||
| AID540299 | A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis | 2010 | Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21 | Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis. |
| AID588519 | A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities | 2011 | Antiviral research, Sep, Volume: 91, Issue:3 | High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors. |
| AID1159607 | Screen for inhibitors of RMI FANCM (MM2) intereaction | 2016 | Journal of biomolecular screening, Jul, Volume: 21, Issue:6 | A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway. |
| AID272840 | Inhibition of MurB activity | 2006 | Journal of medicinal chemistry, Oct-05, Volume: 49, Issue:20 | Pyrazolidine-3,5-diones and 5-hydroxy-1H-pyrazol-3(2H)-ones, inhibitors of UDP-N-acetylenolpyruvyl glucosamine reductase. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 3 (25.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 2 (16.67) | 29.6817 |
| 2010's | 6 (50.00) | 24.3611 |
| 2020's | 1 (8.33) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
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.
| This Compound (11.45) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 13 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||