When heated to decomposition it emits acrid smoke and irritating fumes.
计算性质
辛醇/水分配系数(LogP)：
3.1
重原子数：
22
可旋转键数：
1
环数：
4.0
sp3杂化的碳原子比例：
0.8
拓扑面积：
40.5
氢给体数：
2
氢受体数：
2
ADMET
代谢
口服给药后，醋酸炔诺酮和双醋酸炔诺雌醇通过肝脏首过代谢中的酯酶迅速转化为炔诺酮。
After oral administration, norethisterone acetate and ethynodiol diacetate are rapidly converted to norethisterone by esterases during hepatic first-pass metabolism.
On administration of a single oral dose of [4-(14)C]ethynodiol diacetate (0.15 mg/kg) to rhesus monkey, plasma concentration of total 14C peaked after about 4 hr. About 60% of the plasma radioactivity was present as glucuronide conjugates and no unchanged drug was detected. Some 67 +/- 6% (mean +/- S.D.) of the dose of 14C was excreted in 4 days, 50 +/- 6% in urine and 18 +/- 2% in feces. Most of the urinary excretion occurred within 24 hr of dosage. Glucuronide conjugates accounted for 60% of the urinary 14C, and 46% of the fecal 14C was free steroids. Norethisterone and its tetrahydro metabolites were identified in the free, glucuronide and sulphate fractions of plasma and urine. Keto-4,5-dihydronorethisterones and trihydroxy metabolites were identified in the conjugated fractions of urine, and a complex mixture of polar metabolites was detected in feces.
All of the 17beta-ethynyl progestins reviewed follow similar metabolic paths. For three of these, norethynodrel, ethynodiol diacetate and lynestrenol, a principal metabolite is norethindrone. Biotransformation to more polar metabolites and conjugation proceed rapidly for these three precursor drugs and norethindrone. ... The compounds appear to be readily absorbed, and they and their metabolites are excreted to a greater extent in the urine than in the feces.
来源:Hazardous Substances Data Bank (HSDB)
代谢
乙炔诺醇二醋酸酯被广泛代谢成更具极性的产物及其结合物。
... The ethynodiol diacetate was metabolized extensively to more polar products and their conjugates. ...
There is limited information on the metabolism of levonorgestrel, norethindrone and structurally related contraceptive steroids. Both levonorgestrel and norethindrone undergo extensive reduction of the alpha, beta-unsaturated ketone in ring A. Levonorgestrel also undergoes hydroxylation at carbons 2 and 16. The metabolites of both compounds circulate predominantly as sulfates. In urine, levonorgestrel metabolites are found primarily in the glucuronide form, whereas norethindrone metabolites are present in approximately equal amounts as sulfates and glucuronides. Of the progestogens structurally related to norethindrone, norethindrone acetate, ethynodiol diacetate, norethindrone enanthate, and perhaps lynestrenol, undergo rapid hydrolysis and are converted to the parent compound and its metabolites. There is no convincing evidence that norethynodrel is converted to norethindrone. Of the progestogens structurally related to levonorgestrel, it appears that neither desogestrel nor gestodene are transformed to the parent compound. However, there is evidence that norgestimate can be, at least partly, converted to levonorgestrel. ...
... Rifampicin treatment (7.5 mg/kg/day, orally) for 8 days decreased the half-life of total 14C in plasma following a single oral dose of 4-[14C]ethynodiol diacetate (0.15 mg/kg) from 44 +/- to 24 +/- 2 hr. Fecal elimination of total 14C was significantly increased to 29 +/- 5% of the dose following rifampicin treatment, but urinary excretion was unchanged. Rifampicin treatment increased the amount of polar metabolites and decreased the amount of norethisterone in the free and conjugated fractions of plasma and urine. The amounts of sulphate and non-hydrolysed conjugates in feces were increased after rifampicin treatment.
Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested for barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.
Administration of troglitazone concomitantly with a combination oral contraceptive (estrogen and progestin) reduced the plasma concentrations of both hormones by approximately 30%. This could result in loss of contraceptive efficacy.
/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/
Absorption, distribution, excretion and metabolism of SC-11800EE, a combined steroid preparation consisting of SC-11800(ethynodiol diacetate)as gestagen and ethinyl estradiol (EE)as estrogen in 20:1 (w:w), were studied with the use of 14C-SC-11800 and 3H-EE by radiometry in female rats and by the whole body autoradiography in female normal and pregnant mice. The gestagen orally given with EE was rapidly absorbed from digestive tracts and distributed in tissues in various levels. Gestagen levels in liver and kidney exceeded that in plasma. About 75% of dosed radioactivity was excreted in feces largely via bile and more than 20% in urine within 72 hr after administration. The gestagen was metabolized extensively to more polar products and their conjugates. The pharmacokinetic behavior of the gestagen given with EE did not alter after repeated administrations for 7 days, but was slightly different from that without EE, possibly due to the estrogen effect. The pharmacokinetic behavior of the estrogen was independent from the gestagen given simultaneously. The distribution of the gestagen given with EE revealed by the whole body autoradiography in normal mice were essentially consistent with the radiometric results in rats and that in the pregnant mice showed that the gestagen in fetus was virtually nil under the present conditions.
Bioavailability and pharmacokinetics of norethisterone (NE) were studied in 12 women, aged 21-37 years, after oral doses of ethynodiol diacetate (EDA). Plasma NE levels, measured by radioimmunoassay, were used to compare the bioavailability of EDA tablets (Ovulen 50; 1 mg EDA plus .05 mg ethinyl estradiol) with that of a standard oral solution of EDA. The 3 different batches of tablets studied showed different in vitro dissolution rates, 82.6%, 94.6%, and 99% at 3 hours. No marked differences were seen in the bioavailability of the tablet formulations, which were essentially bioequivalent to the solution. Peak plasma NE levels were reached within 4 hours of EDA administration in solution or tablets. Following the peak, NE plasma levels declined in 2 phases, with mean terminal elimination 1/2-lives of 4-6.9 hours. These results have shown that small variations in in vitro dissolution rates do not affect the bioavailability of NE from tablets containing EDA.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
小剂量的口服避孕药激素已经在哺乳期母亲的乳汁中被识别出来...
Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers ...
Synthesis of 5,17-dihydroxy-5α, 17α, -19-norpregn-20-yn-3-one, a major photodegradation product of norethindrone
摘要：
A convenient synthesis of 5,17-dihydroxy-5 alpha,17 alpha-19-norpregn-20-yn-3-one in multigram quantities from norethindrone is reported. Confirmation of the structural assignment of this major photodegradation product of norethindrone is thus made.
Synthesis of 5,17-dihydroxy-5α, 17α, -19-norpregn-20-yn-3-one, a major photodegradation product of norethindrone
摘要：
A convenient synthesis of 5,17-dihydroxy-5 alpha,17 alpha-19-norpregn-20-yn-3-one in multigram quantities from norethindrone is reported. Confirmation of the structural assignment of this major photodegradation product of norethindrone is thus made.
[EN] ATAZANAVIR (ATV) ANALOGUES FOR TREATING HIV INFECTIONS<br/>[FR] ANALOGUES D'ATAZANAVIR (ATV) POUR TRAITER DES INFECTIONS PAR LE VIH
申请人：GILEAD SCIENCES INC
公开号：WO2018145021A1
公开（公告）日：2018-08-09
The invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, the compound of formula (I) for use in therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS symptoms in a mammal using compounds of Formula I. Preferred compounds are N-[(2S) -1-[2-[(2S,3S)-2-hydroxy-3-[[(2S)-2-(methoxycarbonylamino) -3,3-dimethylbutanoyl]amino]-4-phenylbutyl]-2-[(phenyl) methyl]hydrazinyl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate atazanavir (ATV) analogues substituted by several heterocycles, such as e.g. pyrazole (Rl); e.g. oxetane (substituent of X2); e.g. pyridine or pyrimidine (X1); e.g. piperazine or 3,8-diazabicyclo[3.2.1]octan (X2).
The invention provides compounds having Formula (I):
or a pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions comprising the same, processes for their preparation, and methods of treating and preventing HIV infection by their administration.
Nitric Oxide Releasing Prodrugs of Therapeutic Agents
申请人：SATYAM Apparao
公开号：US20110263526A1
公开（公告）日：2011-10-27
The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.
[EN] DIACYLGLYCEROL KINASE MODULATING COMPOUNDS<br/>[FR] COMPOSÉS MODULANT LA DIACYLGLYCÉROL KINASE
申请人：CARNA BIOSCIENCES INC
公开号：WO2021130638A1
公开（公告）日：2021-07-01
The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.
Molybdenum-Catalyzed Hydroxyl-Directed <i>Anti</i>-Dihydroxylation of Allylic and Homoallylic Alcohols
作者：Pei Fan、Shixia Su、Chuan Wang
DOI：10.1021/acscatal.8b01449
日期：2018.8.3
A catalytic hydroxyl-directed anti-dihydroxylation of allylic and homoallylic alcohols has been developed. This operationally simple method was successfully applied to the direct anti-monodihydroxylation of allylic alcohols containing at least one distal olefinic unit. Under the catalysis of commercially available MoO2(acac)2, an array of hydroxylated dienes were successfully converted into various
