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HCID 5694Erstellt: 3. November 2026

Pirinixic Acid

PIRINIXIC ACID · CS-737 · WY-14643 · Pirinixic · NSC 310038 · wyeth14,643 · Chloro Acid · pirnixicacid

https://huagongshe.com/de/chemical/5694

Molekülstruktur von Pirinixic Acid

Identifikatoren & physikalische Daten

CAS No.50892-23-4
SummenformelC14H14ClN3O2S
Durchschnittliche Molmasse323,8 g/mol
Monoisotopische Masse323,0495256 g/mol
SMILESCc1cccc(Nc2cc(Cl)nc(SCC(=O)O)n2)c1C
InChIKeySZRPDCCEHVWOJX-UHFFFAOYSA-N
PubChem CID5694
ChEMBLCHEMBL295416
ChEBICHEBI:32509
EC No.621-657-5
DTXSIDDTXSID4020290

Chemische & physikalische Eigenschaften

XLogP4,2
Polarare Oberfläche (TPSA)100
H-Brücken-Donoren2
H-Brücken-Akzeptoren6
Frei drehbare Bindungen5
Schwere Atome21
Formalladung0
Komplexität361
DecompositionWhen heated to decomposition it emits very toxic fumes of /chlorine, oxides of nitrogen, and oxides of sulfur/.
Collision Cross Section178.2 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID4020290]
Schmelzpunkt155°C
Siedepunkt514.4±50.0 °C(Predicted)
Dichte1.2984 (rough estimate)
Brechungsindex1.5630 (estimate)
LagerbedingungenKeep in dark place,Sealed in dry,Room Temperature
LöslichkeitSoluble in DMSO (up to 40 mg/ml).
AggregatzustandWhite crystalline solid
pKa (Säurekonstante)2.99±0.10(Predicted)
FarbeOff-white
StabilitätStable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 6 months.
InChI1S/C14H14ClN3O2S/c1-8-4-3-5-10(9(8)2)16-12-6-11(15)17-14(18-12)21-7-13(19)20/h3-6H,7H2,1-2H3,(H,19,20)(H,16,17,18)
InChIKeySZRPDCCEHVWOJX-UHFFFAOYSA-N
SMILESCC1=C(C)C=CC=C1NC2=NC(SCC(O)=O)=NC(Cl)=C2

Sicherheit & Vorschriften

GHS-EinstufungDangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and CategoriesAcute Tox. 4 (100%)
EntsorgungsverfahrenSRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
WechselwirkungenInflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other systemic effects of PPARalpha activators.

Anwendungen & Verwendung

Verwenden

WY-14643 has been used:as a positive control for transfection and luciferase assayto stimulate bone marrow–derived macrophages (BMDM) for autophagic flux analysisto analyze the regulation of fatty acid metabolism-immune nexus (FAMIN) expression in cell culture

Ongoing Test StatusThe following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from, as of June 21, 2012: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=50892-23-4]
Human Toxicity Excerpts/GENOTOXICITY/ The ability of peroxisome proliferators to induce hepatocellular carcinomas in rodents has been known since the mid 1970's, but the mechanism of tumor formation is still poorly understood. In this study, we have used primary cultures of both rat and human hepatocytes to address the question of whether the peroxisome proliferator, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643), causes genotoxic damage in hepatocytes as measured by sister chromatid exchange (SCE), micronuclei formation, and chromosomal aberrations. We have found that in rat hepatocytes the number of SCEs per chromosome increased in a dose-dependent manner from a background level of 0.7 to a maximum of 1.1 in cells exposed for 48 hr to 100 microM of Wy-14,643. In contrast, no increase in SCE frequency was observed in rat hepatocytes exposed to Wy-14,643 for 3 hr. A dose-dependent increase in micronuclei formation was also seen in the 48 hr but not in the 3 hr cultures. The maximum frequency of micronuclei formation after a 48 hr exposure occurred at 20 microM Wy-14,643 and was 2.3 times that for control cells. At this concentration of Wy-14,643, the frequency of chromosomal aberrations was increased by more than 10-fold. A 48 hr exposure to Wy-14,643 also significantly increased micronuclei formation in human hepatocytes, but it was less effective than in rat hepatocytes. To investigate the potential role of peroxisome proliferation in these genotoxic responses, we measured the activities of palmitoyl-CoA beta-oxidase in hepatocytes exposed for 48 hr to Wy-14,643. A dose-dependent increase in palmitoyl-CoA beta-oxidase activity was observed in rat hepatocytes, but not in human hepatocytes. The SCE frequency in rat hepatocytes correlated well with the degree of peroxisome proliferation, however, the increased formation of micronuclei in both rat and human hepatocytes occurred by a mechanism that appeared to be independent of peroxisome induction. In summary, these results demonstrate that the peroxisome proliferator, Wy-14,643, causes genotoxic damage in primary cultures of both rat and human hepatocytes./ALTERNATIVE and IN VITRO TESTS/ Peroxisome proliferator-activated receptor alpha (PPARalpha) agonism in ocular inflammation has not been thoroughly investigated. The objective of this investigation was to determine the effect of WY-14 643, a selective PPARalpha agonist, on inflammatory cytokine release in human ocular cells. Stimulation of primary human corneal epithelial cells, keratocytes, and retinal endothelial cells with 1 to 10 ng/mL interleukin 1beta (IL-1beta) resulted in a significant increase in numerous inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha)and dexamethasone was able to significantly inhibit these effects. However, WY-14 643 did not effectively block IL-1beta-induced cytokine release in ocular cellsrather, significant increases in IL-1beta-induced inflammatory cytokines were observed in these cells but not in aortic smooth muscle cells. WY-14 643 also significantly upregulated vascular endothelial growth factor (VEGF) expression in corneal epithelial cells and keratocytes. These studies demonstrate for the first time that PPARalpha agonism may be proinflammatory and proangiogenic in a variety of ocular cells and suggest that therapeutic applications of such agents in ophthalmology may be limited.
Non-Human Toxicity Excerpts/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ...In this study, male CD and F344 rats were fed diets containing 0, 50, or 1000 ppm WY for 21 days. Peroxisome proliferation in the liver and testis was determined biochemically by measuring beta-oxidation activity and was confirmed ultrastructurally. Serum hormone levels and cell proliferation rates in the liver and testis were also measured. In addition, basal beta-oxidation activity and cell proliferation rates were compared between the CD and F344 rats. A significant decrease in final body weight was observed in the 1000 ppm WY groups for both CD and F344 rats./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Peroxisome proliferators (PPs) cause hepatomegaly, peroxisome proliferation, and hepatocarcinogenesis in rats and mice, whereas hamsters are less responsive to PPs. PPs increase the activities of enzymes involved in peroxisomal beta-oxidation and omega-hydroxylation of fatty acids, which has been hypothesized to result in oxidative stress. The hypothesis of this study was that differential modulation of antioxidant enzymes and vitamins might account for differences in species susceptibility to PPs. Accordingly, we measured the activities of DT-diaphorase and superoxide dismutase (SOD) and the hepatic content of ascorbic acid and alpha-tocopherol in male Sprague-Dawley rats and Syrian hamsters fed 2 doses of 3 known peroxisome proliferators (dibutyl phthalate [DBP], gemfibrozil, and [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) for 6, 34, or 90 days. In untreated animals, the activity of DT-diaphorase was much higher in hamsters than in rats, but the control levels of SOD, ascorbic acid and alpha-tocopherol were similar. In rats and hamsters treated with Wy-14,643, we observed decreases in alpha-tocopherol content and total SOD activity. DT-diaphorase was decreased in activity following Wy-14,643 treatment in rats at all time points and doses, but only sporadically affected in hamsters. Rats and hamsters treated with DBP demonstrated increased SOD activity at 6 dayshowever, in the rat, DBP decreased SOD activity at 90 days and alpha-tocopherol content was decreased throughout. In gemfibrozil treated rats and hamsters, a decrease in alpha-tocopherol content and an increase in DT-diaphorase activity were observed. In either species, no consistent trend was observed in total ascorbic acid content after treatment with any of the PPs. In conclusion, these data suggest that both rats and hamsters are compromised in antioxidant capabilities following PP treatment.../LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ We investigated whether chronic in vivo treatment with the peroxisome proliferator-activated receptor alpha agonist Wy-14,643 attenuates cardiac contractile function by impairing mitochondrial respiration. Wy-14,643 (25 mg/kg/day) was administered to Wistar rats by oral gavage for 14 consecutive days, after which ex vivo heart function, myocardial mitochondrial respiratory capacity, and metabolic gene expression were determined. Body and heart weights were not significantly altered following 14 days of Wy-14,643 administration. Heart perfusion studies showed significantly reduced systolic and developed pressures, while the rate pressure product declined by 36 +/- 2.6% (P < 0.01 vs. vehicle) after 14 days of Wy-14,643 treatment. State 3 mitochondrial respiration was lower in the Wy-14,643 group (P = 0.06 vs. vehicle). State 4 respiration and oligomycin-insensitive proton leak were significantly increased compared with matched controls. The rate of ADP phosphorylation was also decreased by 44.9 +/- 1.9% (P < 0.05 vs. vehicle). Pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling protein 3 (UCP3) transcript levels were upregulated, while cytochrome oxidase II (COXII) expression was decreased following Wy-14,643 treatment. This study demonstrates that chronic in vivo Wy-14,643 administration impaired cardiac contractile function in parallel with decreased mitochondrial respiratory function and increased uncoupling./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Several peroxisome proliferators have been shown to produce pancreatic acinar cell hyperplasia/adenocarcinomas in 2-year bioassays with rats: ammonium perfluorooctanoate (C8), clofibrate, methylclofenapate, HCFC-123, and Wyeth-14,643 (WY). ...Two types of in vivo experiments were conducted. The subchronic study (2-month duration) was designed primarily to detect early changes in pancreatic growth such as those mediated by compounds that inhibit trypsin or act as CCK(A) receptor agonists. The chronic study (6 months) was designed primarily to evaluate whether the pancreatic lesions were secondary to hepatic changes such as cholestasis and/or altered bile flow/composition. In the in vivo experiments, male Crl:CDBR rats were fed diets containing 0 or 100 ppm WY. In the subchronic study WY-treated rats had a twofold increase in mean relative liver weights, an eightfold increase in hepatic peroxisomal proliferation, and a fourfold increase in hepatocyte cell proliferation after 1 week which remained elevated throughout the 2 months of treatment. In contrast, no pancreatic weight effects, increases in plasma CCK, or acinar cell proliferation was seen through 2 months in the WY group when compared to the control group. Fecal fat concentrations were also measured at 2 months and demonstrated no difference between control and WY-treated animals. The absence of any early pancreas changes in the subchronic study is consistent with the in vitro data which demonstrated that WY is not a CCK(A) agonist or a trypsin inhibitor. The chronic study demonstrated increases in pancreatic weights at 3 months (6% above control) and 6 months (17% above control), as well as increased CCK plasma levels in the WY-treated group. Liver effects in the chronic study paralleled those of the subchronic time points. Clinical pathology endpoints including increased serum concentrations of bile acids, alkaline phosphatase, and bilirubin were indicative of cholestasis in the chronic WY-treated group. The cholestasis may be responsible for the downward trend in total bile acid output, both of which may contribute to the modest increases in plasma CCK levels. These results indicate that chronic exposure to WY causes liver alterations such as cholestasis, which may increase plasma concentrations of CCK. Hence, WY may induce pancreatic acinar cell adenomas/adenocarcinomas via a mild but sustained increase in CCK levels secondary to hepatic cholestasis.For more Non-Human Toxicity Excerpts (Complete) data for Pirinixic acid (13 total), please visit the HSDB record page.
Antidote and Emergency Treatment/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B//SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B//SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
National Toxicology Program StudiesWyeth-14,643 is a chemical that was developed by the pharmaceutical industry to lower serum cholesterol. It is not used in clinical applications. We studied the effects of Wyeth-14,643 on rats, mice, and hamsters because it was known that this chemical promotes the production of peroxisomes, organelles that contain a variety of enzymes involved in metabolism of lipids and cholesterol. We gave groups of male rats, mice, and hamsters Wyeth-14,643 mixed in their food for three months. In each species, groups of 25 animals received either 5, 10, 50, 100, or 500 parts per million (ppm) of Wyeth-14,643 in feed. Other groups receiving undosed feed served as the control groups. Tissues from 35 sites were examined for each animal and measures of sperm motility were performed. All the animals survived until the end of the studies. All of the animal groups exposed to the chemical, except the groups receiving 5 ppm and the mice receiving 10 ppm, had lower body weights than their control groups although the feed consumption was generally similar in the various groups of each species. However, the liver weights of rats, mice, and hamsters fed Wyeth-14,643 were generally greater than those of the controls and liver foci were observed in three 100 ppm mice and one 500 ppm mouse. In all groups of animals exposed to Wyeth-14,643, there were significant increases in cytoplasmic alteration of the liver. In the examination of sperm motility, the weights of the cauda epididymis were decreased in all three species of rodents receiving 500 ppm, and in hamsters the testis weights and spermatid counts were decreased in all dosed groups. Exposure to Wyeth-14,643 caused several changes in the livers of male rats, mice, and hamsters, including increased liver weights, increases in cytoplasmic alteration of the liver, and some liver foci. Wyeth-14,643 also had effects on the testes of exposed male rodents, decreasing the spermatid counts and the weights of the cauda epididymis.No increase in the frequency of micronucleated normochromatic erythrocytes was observed in the peripheral blood of male or female Tg.AC mice exposed to Wy-14,643 in feed or via dermal application for 6 months. In neither study was a significant alteration in the percent polychromatic erythrocytes induced by chemical treatment, indicating no toxic effects in the bone marrow of treated animals.
Non-Human Toxicity ValuesLD50 Rat oral 4150 mg/kgLD50 Mouse oral 1600 mg/kg
Wassergefährdungsklasse (WGK)3
Zollcode2933.59.9500
RTECS-Nr.AG2915000
R-Sätze (R)45-22-36/37/38
GefahrensymboleT
Sicherheitshinweise (S)53-26-36/37/39-45
Lagerklasse6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Gefahrstoffdaten50892-23-4(Hazardous Substances Data)
GefahrenklasseAcute Tox. 4 OralCarc. 1BEye Irrit. 2Skin Irrit. 2STOT SE 3