Chenodesoxycholsure
CDCA · CHENODIOL · CHENODEOXYCHOLATE · 3ALPHA,7ALPHA-DIHYDROXY-5BETA-CHOLANIC ACID · Chenix · ChenodeoxychoL · URSODEOXYCHOLOC ACID · 3a,7a-Dihydroxy-5b-cholanoic acid
Identifikatoren & physikalische Daten
| CAS No. | 474-25-9 |
|---|---|
| Summenformel | C24H40O4 |
| Durchschnittliche Molmasse | 392,6 g/mol |
| Monoisotopische Masse | 392,29265975 g/mol |
| SMILES | C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C |
| InChIKey | RUDATBOHQWOJDD-BSWAIDMHSA-N |
| PubChem CID | 10133 |
| ChEMBL | CHEMBL240597 |
| ChEBI | CHEBI:16755 |
| EC No. | 207-481-8 |
| DTXSID | DTXSID2020260 |
| Lokaler Name | Chenodesoxycholsure |
Chemische & physikalische Eigenschaften
| XLogP | 4,9 |
|---|---|
| Polarare Oberfläche (TPSA) | 77,8 |
| H-Brücken-Donoren | 3 |
| H-Brücken-Akzeptoren | 4 |
| Frei drehbare Bindungen | 4 |
| Schwere Atome | 28 |
| Formalladung | 0 |
| Komplexität | 605 |
| LogP (Verteilungskoeffizient) | 4.15 |
| Löslichkeit | 89.90.0899 mg/mLPRACTICALLY INSOLUBLE |
| Schmelzpunkt | 168-171165 - 167 °C165-167 °C (lit.) |
| Physical Description | Solid |
| Collision Cross Section | 203.3 Ų [M-H]- [CCS Type: DTBuffer gas: N2Ionization: ESI-Dataset: Bile Acids]202.8 Ų [M+H-H2O]+ [CCS Type: DTMethod: single field calibrated]208.5 Ų [M+K-H+HCOO]- [CCS Type: DT224.5 Ų [M+K-H+HCOO]- [CCS Type: DT205.8 Ų [M+Na-H+HCOO]- [CCS Type: DT199.2 Ų [M+Na-H+Cl]- [CCS Type: DT202.3 Ų [M-H]- [CCS Type: DT186.9 Ų [M+H-2H2O]+ [CCS Type: DT201.9 Ų [M+HCOO]- [CCS Type: DT192.83 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]198.15 Ų [M+K]+ [CCS Type: TW195.52 Ų [M+Na]+ [CCS Type: TW206.57 Ų [M-H]- [CCS Type: DTMethod: stepped-field]201.51 Ų [M-H]- [CCS Type: DTMethod: single field calibrated with Agilent tune mix (Agilent)]205.9 Ų [M-H]- |
| Siedepunkt | 437.26°C (rough estimate) |
| Dichte | 0.9985 (rough estimate) |
| Brechungsindex | 1.4460 (estimate) |
| Flammpunkt | 9℃ |
| Lagerbedingungen | room temp |
| pKa (Säurekonstante) | pKa 4.34 (Uncertain) |
| Aggregatzustand | Powder |
| Farbe | White to off-white |
| Merck | 13,2062 |
| BRN | 3219887 |
| Hauptanwendungen | pharmaceutical (small molecule) |
| InChIKey | RUDATBOHQWOJDD-BSWAIDMHSA-N |
| SMILES | C[C@H](CCC(O)=O)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C |
| LogP (Verteilungskoeffizient) | 3.05 at 20℃ |
| CAS Datenbank | 474-25-9(CAS DataBase Reference) |
| EPA chemische Informationen | Chenodiol (474-25-9) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 8.3% (1 of 12) of reports.WarningH302 (16.7%): Harmful if swallowed [Warning Acute toxicity, oral]H312 (16.7%): Harmful in contact with skin [Warning Acute toxicity, dermal]H315 (41.7%): Causes skin irritation [Warning Skin corrosion/irritation]H319 (41.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]H332 (16.7%): Harmful if inhaled [Warning Acute toxicity, inhalation]H335 (16.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposureRespiratory tract irritation]H361 (33.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, 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 12 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Reported as not meeting GHS hazard criteria per 1 of 12 reports by companies.There are 7 notifications provided by 11 of 12 reports by companies with hazard statement code(s).Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Regulatorische Informationen | Hazard Traits - Developmental ToxicityAuthoritative List - Prop 65Report - regardless of intended function of ingredient in the productStatus: Active Update: 19-04-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/5782 |
| Weitere Sicherheitsinformationen | IMAP assessments - Cholan-24-oic acid, 3,7-dihydroxy-, (3.alpha.,5.beta.,7.alpha.)-: Environment tier I assessmentIMAP assessments - Cholan-24-oic acid, 3,7-dihydroxy-, (3.alpha.,5.beta.,7.alpha.)-: Human health tier I assessment |
| Hazard Classes and Categories | Acute Tox. 4 (16.7%)Skin Irrit. 2 (41.7%)Eye Irrit. 2 (41.7%)STOT SE 3 (16.7%)Repr. 2 (33.3%) |
| Hepatotoxicity | In multiple clinical trials of chenodiol therapy for dissolution of gallstones, serum aminotransferase elevations occurred in up to 30% of patients. The elevations generally arose within 2 months of starting therapy and were typically mild, transient and not accompanied by symptoms or jaundice. Liver biopsies done during chenodiol therapy generally showed mild, nonspecific changes. Clinically apparent liver injury with jaundice was not reported. The liver enzyme elevations were generally dose related and usually did not recur on restarting chenodiol at lower doses. While the serum enzyme abnormalities that occurred on chenodiol therapy generated considerable concern, they appeared to be relatively benign. Since the approval of chenodiol and its more widespread use, at least four instances of liver injury with jaundice have been reported to the sponsor, but the clinical features and outcomes of these cases have not been published. Nevertheless, the product label for chenodiol includes a boxed warning about hepatotoxicity although it does not provide advice on the frequency or how to respond to abnormalities. Thus, the reliability of reports of clinically apparent liver injury with chenodiol therapy remains unclear. Once ursodiol was found to be equally as effective as chenodiol, even at lower doses, and was rarely associated with serum enzyme elevations, it rapidly replaced chenodiol as medical therapy for gallstones.Likelihood score: E* (Suspected but unproven cause of clinically apparent liver injury). |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)ChenodiolAmbiguous-DILI-concern8Warnings & precautionsDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationChenodiol (chenodeoxycholic acid) and its conjugates are naturally present in human milk, with higher milk levels of chenodiol conjugates in obesity. Chenodiol has not been measured in milk after administration as a drug. Chenodiol in the infant’s gastrointestinal tract enhances intestinal motility. No special precautions are required if mothers are taking chenodiol, but observe the infant for diarrhea.◉ Effects in Breastfed InfantsChenodiol acts directly on enterochromaffin cells in the gastrointestinal tract to stimulate 5-hydroxytryptamine secretion, which regulates gastrointestinal motility. Chenodiol stool levels were higher in breastfed infants with increased defecation frequency than in infants with normal or lower frequency.◉ Effects on Lactation and BreastmilkRelevant published information was not found as of the revision date. |
| Wassergefährdungsklasse (WGK) | 2 |
| UN-Transportnummer | UN1230 - class 3 - PG 2 - Methanol, solution |
| Zollcode | 29181990 |
| RTECS-Nr. | FZ1980000 |
| R-Sätze (R) | 63 |
| Gefahrensymbole | Xn |
| Sicherheitshinweise (S) | 22-24/25-45-36/37 |
| Gefahrenklasse | Eye Irrit. 2Skin Irrit. 2 |
Anwendungen & Verwendung
Beschreibung
Chenodeoxycholic acid is the first agent to be introduced into the US market for the treatment of radiolucent gallstones. Large scale clinical trials have demonstrated the safety and efficacy of this agent. Chenodeoxycholic acid reduces the biliary concentration of cholesterol relative to that of bile acids and phospholipid, reducing the saturation and thus the lithogenicity of the bile. Success rates in dissolving gallstones are in the range of 50-70% within 4-24 months of treatment. Continuation of the drug after stone dissolution may be required to prevent reoccurrence. Chenodeoxycholic acid is the 7α-isomer of ursodeoxycholic acid which was introduced into the European market in 1978. chenodeoxycholic acid structure
History
Chenodeoxycholic acid was isolated in 1924 from goose gall by Adolf Windaus and human gall by Heinrich Wieland.Its complete structural configuation was elucidated by Hans Lettre at the University of Gottingen. In 1968, William Admirand and Donald Small at Boston University Medical School established that in patients with gallstones their bile was saturated with cholesterol, sometimes even exhibiting microcrystals, whereas this was not the case in normal people.It was then found that biliary levels of cholic acid and chenodeoxycholic acid were lower in patients with cholesterol gallstones than in normal people. Leslie Thistle and John Schoenfield at the Mayo Clinic in Rochester, Minnesota, then administered individual bile salts by mouth for four months and found that chenodeoxycholic acid reduced the amount of cholesterol in the bile.This led to a national collaborative study in the United States, which confirmed the effectiveness of chenodeoxycholic acid in bringing about dissolution of gallstones in selected patients. However, recent developments such as laparoscopic cholecystectomy and endoscopic biliary techniques have curtailed the role of chenodeoxycholic acid and ursodeoxycholic acid in the treatment of cholelithiasis.
Verwenden
A major bile acid in many vertebrates, occurring as the N-glycine and/or N-taurine conjugate. With other bile acids, forms mixed micelles with lecithin in bile which solubilize cholesterol and thus fa cilitates its excretion. Fcilitates fat absorption in the small intestine by micellar solubilization of fatty acids and monoglycerides. Anticholelithogenic. Epimeric with Ursodiol.