PROTECT TABLETS FROM EXCESSIVE HEAT & LIGHT TO PREVENT DISCOLORATION & DEGRADATION.
保留指数：
1860;1860
计算性质
辛醇/水分配系数(LogP)：
2
重原子数：
17
可旋转键数：
3
环数：
2.0
sp3杂化的碳原子比例：
0.214
拓扑面积：
42.8
氢给体数：
0
氢受体数：
3
ADMET
代谢
肝脏的。主要的生物转化是将酮还原为甲吡酮，这是一种活性醇代谢物。甲吡酮和甲吡醇都与葡萄糖醛酸结合。
Hepatic. The major biotransformation is reduction of the ketone to metyrapol, an active alcohol metabolite. Metyrapone and metyrapol are both conjugated with glucuronide.
/METYRAPONE IS METABOLIZED BY/ ONE ENZYME, PRESENT IN MICROSOMAL FRACTION OF RAT LIVER, IS NADPH-DEPENDENT & IS ACTIVE UNDER AEROBIC CONDITIONS, REDUCING COMPD TO 2-METHYL-1,2-BIS-(3-PYRIDYL)PROPAN-1-OL...SECOND ENZYME...HAS NOT BEEN IDENTIFIED...
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今天，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按在人类中发展药物诱导肝损伤风险排名的最大参考药物清单。药物发现今天2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
◉ Summary of Use during Lactation:Evidence from two patients indicate that amounts of metyrapone and its active metabolite in breastmilk are very small and unlikely to adversely affect a breastfed infant. Exposure of the infant can be markedly decreased by avoiding nursing for 2 to 2.5 hours after each dose.
◉ Effects in Breastfed Infants:A woman was taking metyrapone 250 mg 3 times daily, as well as bisoprolol 10 mg and captopril 12.5 mg twice a day postpartum. She breastfed her preterm infant about 50% milk and 50% formula. At 5 weeks postpartum, infant blood was collected. ACTH was 160 ng/L, cortisol was 98 nmol/L, 11-deoxycortisol was 2 nmol/L, sodium was 133 mmol/L, and potassium was 4.8 mmol/L. All values were within normal limits and his pediatric team found his growth and development to be appropriate.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date. Women taking metyrapone chronically for suppression of hypercorticism associated with Cushing's syndrome may have other hormonal abnormalities that might interfere with lactation.
来源:Drugs and Lactation Database (LactMed)
吸收、分配和排泄
吸收
口服给药吸收迅速且良好。通常在给药后1小时达到血浆峰浓度。
Absorbed rapidly and well when administered orally. Peak plasma concentrations are usually reached 1 hour after administration.
After administration of 4.5 g metyrapone (750 mg every 4 hours), an average of 5.3% of the dose was excreted in the urine in the form of metyrapone (9.2% free and 90.8% as glucuronide) and 38.5% in the form of metyrapol (8.1% free and 91.9% as glucuronide) within 72 hours after the first dose was given.
GASTROINTESTINAL ABSORPTION OF METYRAPONE IS VARIABLE. FOLLOWING ORAL ADMIN OF 750 MG OF METYRAPONE EVERY 4 HR TO NORMAL PT, PEAK PLASMA LEVELS OF ABOUT 1.2 UG M/L...REACHED AFTER THIRD DOSE...0.4 UG/ML...PRESENT IMMEDIATELY AFTER SIXTH DOSE.
...PLASMA LEVELS OF METYRAPONE...IN RATS WERE SHOWN TO EXHIBIT A CIRCADIAN PATTERN WHEN ANIMALS WERE KEPT IN ALTERNATING 12-HR LIGHT-12 HR DARK REGIMEN. HALF-LIFE...OBSERVED @ 10:00 PM WAS APPROX 2.5 TIMES LONGER THAN THAT OBSERVED @ 10:00 AM...
...WITHIN 2 DAYS FOLLOWING ORAL ADMIN OF 750 MG...EVERY 4 HR FOR 6 DOSES, APPROX 0.5%...IS EXCRETED IN URINE UNCHANGED, 3% IS EXCRETED AS REDUCED METABOLITE, & 37% AS GLUCURONIDE CONJUGATES OF METYRAPONE & ITS METABOLITES.
我们公开了三磷酸标记的非钳型钨络合物的合成、表征和催化应用。相关的基于 W 的半夹心化合物用于酮和酯的均相氢化以提供相应的醇。此外，引入的贱金属催化剂促进了烯酸酯的共轭还原，从而产生相应的无 C-C 键的酯。大多数应用的底物酮在非常温和的反应条件（室温，5 bar H 2）下在t –BuONa 存在下可转化。辅助碱基中的阳离子从Na +到Li +的交换结果证明对于成功还原羰基酯基团至关重要。部署的有机金属复合物很容易称重，可以在密封手套箱系统外的实验室工作台上处理。
Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol
摘要：
17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis. This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione. Indeed, our data show that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone. This fact allowed us to infer that this new pathway is closely related to the activity of the 11-beta-hydroxylase that is responsible for the synthesis of cortisol. Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals. This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency.
Photocatalytic decarboxylative alkylations mediated by triphenylphosphine and sodium iodide
作者：Ming-Chen Fu、Rui Shang、Bin Zhao、Bing Wang、Yao Fu
DOI：10.1126/science.aav3200
日期：2019.3.29
variety of alkylations. Science, this issue p. 1429 A cheap combination of sodium iodide and triphenylphosphine can act as an electron-transfer catalyst under visible light. Most photoredox catalysts in current use are precious metalcomplexes or synthetically elaborate organic dyes, the cost of which can impede their application for large-scale industrial processes. We found that a combination of triphenylphosphine
[EN] PEPTIDOMIMETICS FOR THE TREATMENT OF CORONAVIRUS AND PICORNAVIRUS INFECTIONS<br/>[FR] PEPTIDOMIMÉTIQUES POUR LE TRAITEMENT D'INFECTIONS PAR CORONAVIRUS ET PICORNAVIRUS
申请人：UNIV EMORY
公开号：WO2020247665A1
公开（公告）日：2020-12-10
Compounds, compositions and methods for preventing, treating or curing a coronavirus, picornavirus, and/or Hepeviridae virus infection in human subjects or other animal hosts. Specific viruses that can be treated include enteroviruses. In one embodiment, the compounds can be used to treat an infection with a severe acute respiratory syndrome virus, such as human coronavirus 229E, SARS, MERS, SARS-CoV-1 (OC43), and SARS-CoV- 2. In another embodiment, the methods are used to treat a patient co-infected with two or more of these viruses, or a combination of one or more of these viruses and norovirus.
[EN] GLUCOCORTICOID RECEPTOR LIGANDS FOR THE TREATMENT OF METABOLIC DISORDERS<br/>[FR] LIGANDS DE RECEPTEURS GLUCOCORTICOIDES POUR LE TRAITEMENT DE TROUBLES METABOLIQUES
申请人：ABBOTT LAB
公开号：WO2004000869A1
公开（公告）日：2003-12-31
This invention relates to novel compounds that are liver selective glucocorticoid receptor antagonists, to methods of preparing such compounds, and to methods for using such compounds in the regulation of metabolism, especially lowering serum glucose levels, insulin levels, or lipid levels, and/or decreasing body weight.
METHODS AND SYSTEMS FOR DESIGNING AND/OR CHARACTERIZING SOLUBLE LIPIDATED LIGAND AGENTS
申请人：TUFTS MEDICAL CENTER
公开号：US20160052982A1
公开（公告）日：2016-02-25
The present application provides methods for preparing soluble lipidated ligand agents comprising a ligand entity and a lipid entity, and in some embodiments, provides relevant parameters of each of these components, thereby enabling appropriate selection of components to assemble active agents for any given target of interest.
[EN] BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS AND USES THEREOF<br/>[FR] ACIDES BÊTA-AMINÉS SUBSTITUÉS EN BÊTA ET ANALOGUES À UTILISER EN TANT QU'AGENTS DE CHIMIOTHÉRAPIE ET LEURS UTILISATIONS
申请人：QUADRIGA BIOSCIENCES INC
公开号：WO2017024009A1
公开（公告）日：2017-02-09
β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.
