Taurocholic acid has known human metabolites that include 2-[[(4R)-4-[(3R,5R,7R,10S,12S,13R)-7,12-Dihydroxy-10,13-dimethyl-3-sulfooxy-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonic acid.
Chickens receiving taurocholate iv did not show active tubular excretion; however, it inhibited tubular excretioN of phenolsulfonphthaleiN & of n-methylnicotinamide.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
在麻醉大鼠中，消炎痛（吲哚美辛）引起的糜烂发生率较低，但通过与酸性和牛磺胆酸盐的胃灌注显著增加。
In the anesthetized rat, the low incidence of erosions with indomethacin was markedly increased by concurrent gastric perfusion with acid saline & taurocholate.
When a combination of aspirin & taurocholic acid was introduced to 8 subjects the mean electrical potential difference also fell significantly from 38.6 1.8 mv to 17.9 1.8 mv, but mean duration of this change (27 min) was significantly longer than found after individual admin.
/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/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
通过载体介导的过程在哺乳动物近端小管双向传输。
Transported by carrier-mediated processes bidirectionally across mammalian proximal tubule.
After secretion into the biliary tract, bile acids are largely (95%) reabsobed in the intestine (mainly in the terminal ileum), returned to the liver, and then again secreted in bile (enterohepatic circulation).
The disposition kinetics of [(3)H]taurocholate ([(3)H]TC) in perfused normal and cholestatic rat livers were studied using the multiple indicator dilution technique and several physiologically based pharmacokinetic models. The serum biochemistry levels, the outflow profiles and biliary recovery of [(3)H]TC were measured in three experimental groups: (i) control; (ii) 17 alpha-ethynylestradiol (EE)-treated (low dose); and (iii) EE-treated (high dose) rats. EE treatment caused cholestasis in a dose-dependent manner. A hepatobiliary TC transport model, which recognizes capillary mixing, active cellular uptake, and active efflux into bile and plasma described the disposition of [(3)H]TC in the normal and cholestatic livers better than the other pharmacokinetic models. An estimated five- and 18-fold decrease in biliary elimination rate constant, 1.7- and 2.7-fold increase in hepatocyte to plasma efflux rate constant, and 1.8- and 2.8-fold decrease in [(3)H]TC biliary recovery ratio was found in moderate and severe cholestasis, respectively, relative to normal. There were good correlations between the predicted and observed pharmacokinetic parameters of [(3)H]TC based on liver pathophysiology (e.g. serum bilirubin level and biliary excretion of [(3)H]TC). In conclusion, these results show that altered hepatic /taurocholate/ pharmacokinetics in cholestatic rat livers can be correlated with the relevant changes in liver pathophysiology in cholestasis.
It has been reported that the adjuvant-induced inflammation could affect drug metabolism in liver. /The authors/ further investigated the effect of inflammation on drug transport in liver using taurocholate as a model drug. The hepatic disposition kinetics of [(3)H]taurocholate in perfused normal and adjuvant-treated rat livers were investigated by the multiple indicator dilution technique and data were analyzed by a previously reported hepatobiliary taurocholate transport model. Real-time RT-PCR was also performed to determine the mRNA expression of liver bile salt transporters in normal and diseased livers. The uptake and biliary excretion of taurocholate were impaired in the adjuvant-treated rats as shown by decreased influx rate constant k(in) (0.65 +/- 0.09 vs. 2.12 +/- 0.30) and elimination rate constant k(be) (0.09 +/- 0.02 vs. 0.17 +/- 0.04) compared with control rat group, whereas the efflux rate constant k(out) was greatly increased (0.07 +/- 0.02 vs. 0.02 +/- 0.01). The changes of mRNA expression of liver bile salt transporters were found in adjuvant-treated rats. Hepatic taurocholate extraction ratio in adjuvant-treated rats (0.86 +/- 0.05, n = 6) was significantly reduced compared with 0.93 +/- 0.05 (n = 6) in normal rats. Hepatic extraction was well correlated with altered hepatic ATP content (r(2) = 0.90). In conclusion, systemic inflammation greatly affects hepatic ATP content/production and associated transporter activities and causes an impairment of transporter-mediated solute trafficking and pharmacokinetics.
Chemical modifications of bile acids under high-intensity ultrasound or microwave irradiation
摘要：
High-intensity ultrasound (HIU) and microwave (MW) irradiation, having emerged as effective promoters of organic reactions, were exploited for the synthesis of bile acids derivatives. Esterification, amidation, hydrolysis, oxidation, and reduction were investigated. Compared to conventional methods, both techniques proved much more efficient, increasing product yields and dramatically cutting down reaction times. Scaled-up studies are now under way. (C) 2004 Elsevier Inc. All rights reserved.
DOI：
10.1016/j.steroids.2004.09.007
作为试剂：
描述：
(R)-N-(4-methyl-2-oxo-2H-chromen-7-yl)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide 在
N-(3Alpha,7Alpha,12Alpha)三羟基-5β-胆甾烷-24-酰基牛黄酸 、 bacterial bile salt hydrolase from Clostridium perfringens 作用下，
以
aq. phosphate buffer 为溶剂，
生成 7-氨基-4-甲基香豆素
[EN] HORMONE RECEPTOR MODULATORS FOR TREATING METABOLIC MUTAGENIC AND FIBROTIC CONDITIONS AND DISORDERS<br/>[FR] MODULATEURS DU RÉCEPTEUR HORMONAL POUR LE TRAITEMENT D'ÉTATS ET DE TROUBLES MÉTABOLIQUES MUTAGÈNES ET FIBROTIQUES
申请人：ARDELYX INC
公开号：WO2019055808A1
公开（公告）日：2019-03-21
The invention relates to activators of FXR useful in the treatment of autoimmune disorders, liver disease, intestinal disease, kidney disease, cancer, and other diseases in which FXR plays a role, having the Formula (I): wherein L1, A, X1, X2, Y1, Y2, Y3, Y4, R1, R2, and R3 are described herein.
Pharmaceutical compositions of drug-oligomer conjugates and methods of treating diseases therewith
申请人：——
公开号：US20030069170A1
公开（公告）日：2003-04-10
Pharmaceutical compositions that include a drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating diseases in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.
[EN] TARGETING COMPOUNDS<br/>[FR] COMPOSÉS DE CIBLAGE
申请人：ZAFGEN INC
公开号：WO2019118612A1
公开（公告）日：2019-06-20
The disclosure provides, at least in part, liver, intestine and/or kidney-targeting compounds and their use in treating liver, intestine and/or kidney disorders, such as non-alcoholic steatohepatitis, alcoholic steatohepatitis, hepatocellular carcinoma, liver cirrhosis, and hepatitis B; and/or chronic kidney disease, glomerular disease such as IGA nephropathy, lupus nephritis, or polycystic kidney disease. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
[EN] NOVEL COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR THE TREATMENT OF HEPATITIS B<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS PHARMACEUTIQUES DE CEUX-CI POUR LE TRAITEMENT DE L'HÉPATITE B
申请人：GALAPAGOS NV
公开号：WO2020239656A1
公开（公告）日：2020-12-03
The present invention discloses compounds according to Formula (I), wherein X, G, R1, R2a, R2b, R3, R4, and R5 are as defined herein. The present invention relates to compounds, methods for their production, pharmaceutical compositions comprising the same, and methods of treatment using the same, for the prophylaxis and/or treatment of diseases involving hepatitis B by administering the compound of the invention.
[EN] NOVEL DIHYDROQUINOLIZINONES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION<br/>[FR] NOUVELLES DIHYDROQUINOLIZINONES POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B
申请人：HOFFMANN LA ROCHE
公开号：WO2015173164A1
公开（公告）日：2015-11-19
The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5, R6, X and Y are as described in the description and in the claims, as well as or pharmaceutically acceptable salts, or enantiomers, or diastereomers thereof. The invention also contains compositions including the compounds and methods of using the compounds.
