(8R,9S,10R,13S,14S)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one | 6533-00-2

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 避孕药
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (8R,9S,10R,13S,14S)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
• CAS: 6533-00-2
• 化学式: C₂₁H₂₈O₂
• 分子量: 312.4
• InChiKey: WWYNJERNGUHSAO-CULCCENASA-N

物化性质

• 熔点：
  239-241 °C(lit.)
• 沸点：
  392.36°C (rough estimate)
• 密度：
  1.0697 (rough estimate)
• 溶解度：
  氯仿（少量，超声处理）、二氯甲烷（少量溶解）、甲醇（少量溶解）
• 颜色/状态：
  Crystals from methanol
• 蒸汽压力：
  1.0X10-9 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition, it emits acrid smoke and irritating fumes.

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

(14)C-Norgestrel 给七名受试者服用后，5天内尿液中排出了剂量的43%... 酶水解仅释放了尿液中放射性活度的32%，另外25%以硫酸盐结合物的形式排出。尿液中排出的代谢物比服用相关化合物如norethisterone或lynestrenol后的代谢物极性要小得多。从尿液中分离出了四氢诺孕酮的3alphaOH,5beta和3betaOH,5beta异构体（13beta-ethyl-17alpha-ethynyl-5beta-gonane-3alpha,17beta-二醇），并通过质谱、薄层色谱和气液色谱进行了鉴定。血浆中的放射性活度下降速度比服用norethisterone和lynestrenol后要快。大约2%的服用剂量转化为了酸性化合物。无论是口服还是静脉给药，norgestrel的放射性活度排出速率或代谢物似乎没有明显差异。

(14)C-Norgestrel was administered to seven human subjects and 43% of dose was excreted in the urine within 5 days ... Enzymic hydrolysis released only 32% of the urinary radioactivity and a further 25% was excreted as sulphate conjugates. The metabolites excreted in the urine were much less polar than those following the administration of the related compounds, norethisterone or lynestrenol. The 3alphaOH,5beta and 3betaOH,5beta isomers of the tetrahydronorgestrel (13beta-ethyl-17alpha-ethynyl-5 beta-gonane-3alpha,17beta-diol) were isolated from urine and identified by mass spectrometry and thin-layer and gas-liquid chromatography. Plasma radioactivity decreased more rapidly than after the administration of norethisterone and lynestrenol. About 2% of the administered dose was converted to acidic compounds. There was no apparent difference in the rate of excretion of radioactivity or in the metabolites after either oral or intravenous administration of norgestrel.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在非洲绿猴（Cercopithecus aethiops）中研究了dl-、d-和l-诺孕醇的相对代谢情况。单次口服给予(14)C-dl-诺孕醇（1 mg/kg）后，尿液中的总(14)C排泄量（51.4 +/- 5.0%）显著高于给予d-对映体后的排泄量（37.5 +/- 5.4%），但与给予l-对映体后的排泄量（44.2 +/- 8.9%）无显著差异。在所有情况下，尿液中放射性物质的主要部分以游离分数存在（48-62%），而另外13-27%的放射性物质可以通过β-葡萄糖醛酸酶制剂释放。未检测到硫酸盐结合物。至少有一个主要（16beta-羟基化）和一个次要（16alpha-羟基化）的代谢途径具有立体选择性，即它们作用于l-对映体而非d-对映体。三种代谢物，16beta-羟基诺孕醇、16alpha-羟基诺孕醇和16-羟基四氢诺孕醇（认为是16beta）仅在给予(14)C-dl-和-l-诺孕醇的动物尿样中检测到。在给予(14)C-d-诺孕醇后，3alpha, 5beta-四氢诺孕醇被发现是主要的尿液代谢物。这些观察结果与之前在女性中报道的dl-诺孕醇尿液代谢物进行了比较。

The comparative metabolism of dl-, d-, and l-norgestrel was investigated in African Green Monkeys (Cercopithecus aethiops). Total (14)C excretion in urine after a single oral dose of (14)C-dl-norgestrel (1 mg/kg) was significantly higher (51.4 +/- 5.0%) than that observed after administration of the d-enantiomer (37.5 +/- 5.4%) but not the l-enantiomer (44.2 +/- 8.9%). In all cases, the major part of the urinary radioactivity was present in a free fraction (48-62%), while an additional 13-27% was released by beta-glucuronidase preparations. No sulfate conjugates were detected. At least one major (16beta-hydroxylation) and one minor (16alpha-hydroxylation) metabolic pathway were stereoselective, i.e., they are operative with the I-but not the d-enantiomer. Three metabolites, 16beta-hydroxynorgestrel, 16alpha-hydroxynorgestrel, and 16-hydroxytetrahydronorgestrel (believed to be 16beta) were only detected in urine samples obtained from (14)C-dland -l-norgestrel-dosed animals. Following (14)C-d-norgestrel administration, 3alpha, 5beta-tetrahydronorgestrel was found to be the major urinary metabolite. These observations are compared with those reported earlier on the urinary metabolites of dl-norgestrel in women.

来源:Hazardous Substances Data Bank (HSDB)

代谢

体外对诺孕醇立体异构体（D型、L型以及外消旋混合物DL）的代谢进行了研究，使用的是兔肝微粒体部分。生物活性较强的L-诺孕醇的代谢速度比生物活性较低的D-诺孕醇快。这主要是由于L-诺孕醇更容易转化为环A还原代谢物。两种异构体在羟基化方面的量没有差异；大约30%的每种异构体在30分钟孵化后被转化为羟基化代谢物。然而，两种异构体之间存在差异，L-诺孕醇主要转化为16beta-羟基甾体，而D-诺孕醇转化为16alpha-羟基甾体。两种异构体在C-6位置上羟基化的量相似。外消旋混合物的代谢速度介于D型和L型异构体之间。

The in vitro metabolism of stereo-isomers (d, l and the racemic mixture dl) of norgestrel by a microsomal fraction from rabbit liver was investigated. The metabolism of the biologically active l-norgestrel was more rapid than that of d-norgestrel (sic.) which is biologically inactive. This was mainly due to the more ready conversion of l-norgestrel to ring-A reduced metabolites. There was no difference between the two isomers in respect of the amount undergoing hydroxylation; about 40% of each isomer was converted to hydroxylated metabolites after 30 min incubation. However, there were differences between the isomers, l-norgestrel being converted mainly to the 16beta-hydroxysteroid and d-norgestrel to the 16alpha-hydroxysteroid. Similar amounts of both isomers were hydroxylated at C-6. The metabolism of the racemic mixture was intermediate between that of the d and l isomers.

来源:Hazardous Substances Data Bank (HSDB)

代谢

19-诺睾酮衍生的合成孕激素在大白兔体外肝脏组织中的代谢速率进行了比较。在1小时的时间范围内，炔雌醇的代谢速度与19-诺睾酮相当，而d-诺孕酯和利奈孕醇的代谢速率略低。不到5%的l-诺孕酯被代谢。在所有情况下，反应产物都是四氢孕激素。利奈孕醇通过炔雌醇进行代谢。骨骼肌、肺和小肠也能代谢炔雌醇和d-诺孕酯，但速率比肝脏组织慢。少量炔雌醇被脂肪组织代谢，但心脏和脾脏无活性。利奈孕醇和l-诺孕酯没有被所研究任何的肝外组织代谢。

The rates of metabolism of synthetic gestagens derived from 19-nortestosterone by rabbit liver tissue in vitro were compared. Over a period of 1 hr norethisterone was metabolized as rapidly as 19-nortestosterone whereas d-norgestrel and lynestrenol were metabolized at a slightly lower rate. Less than 5% of l-norgestrel was metabolized. In all cases the reaction product was the tetrahydrosteroid. Lynestrenol was metabolised through norethisterone. Skeletal muscle, lung and small intestine also metabolized norethisterone and d-norgestrel but at a slower rate than liver tissue. Small amounts of norethisterone were metabolized by adipose tissue but heart and spleen were inactive. Lynestrenol and l-norgestrel were not metabolized by any of the extra-hepatic tissues studied.

来源:Hazardous Substances Data Bank (HSDB)

代谢

体外研究对口服避孕药中使用的3种类固醇（炔雌醇、左炔诺孕酮和甲孕酮）通过小块人空肠粘膜进行了代谢研究。这样做是因为已知人类胃肠粘膜能代谢多种药物。在孵化后，炔雌醇代谢了几乎40%，左炔诺孕酮代谢了9.8%，甲孕酮代谢了7%。所有这些代谢反应与对照组有显著差异。研究结果表明，炔雌醇的代谢与所用组织的重量有关。这些结果与已知的炔雌醇明显的一过效应相一致。已知诺孕酮的一过效应很小或没有，因此没有显示出高的肠道代谢率。在实验条件下，炔雌醇或左炔诺孕酮的I相代谢不明显。

In vitro studies were conducted on the metabolism of 3 steroids used in OCs (oral contraceptives) by small pieces of human jejunal mucosa. This was done because the gastrointestinal mucosa of humans is known to metabolize a number of drugs. Almost 40% of the ethinyl estradiol, 9.8% of the levonorgestrel, and 7% of the mestranol were metabolized after incubation. All these metabolic responses were significantly different from those in the control groups. Results of the study show that the metabolism of the ethinyl estradiol was related to the weight of the tissue used. These results are consistent with the known marked 1st pass effect of ethinyl estradiol. Norgestrel, known to have little or no 1st pass effect, did not show a high rate of gut metabolism. Under the experimental conditions employed, no Phase 1 metabolism of either ethinyl estradiol or levonorgestrel was apparent.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

与已知能诱导药物代谢酶（特别是细胞色素P450酶）的物质同时使用时，可能会增加雌激素和黄体激素的代谢，例如抗惊厥药（如苯巴比妥、苯妥英、卡马西平）和抗感染药（如利福平、利福布丁、奈韦拉平、依非韦伦）。

The metabolism of estrogens and progestagens may be increased by concomitant use of substances known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes, such as anticonvulsants (eg phenobarbital, phenytoin, carbamazepine), and anti-infectives (eg rifampicin, rifabutin, nevirapine, efavirenz).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

利托那韦和奈非那韦虽然被认为是强烈的抑制剂，但与之相反，当与类固醇激素同时使用时，它们表现出诱导性质。

Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

含有圣约翰草（金丝桃）的草药制剂可能会诱导雌激素和黄体激素的代谢。

Herbal preparations containing St John's Wort (Hypericum Perforatum) may induce the metabolism of estrogens and progestagens.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

苯妥英和利福平增加性激素结合球蛋白（SHBG）的血清浓度；这显著降低了一些孕激素的自由药物血清浓度，这对于使用孕激素进行避孕的患者来说是一个特别关注的问题。/孕激素/

Phenytoin and rifampin increase the serum concentrations of sex hormone-binding globulin (SHBG); this significantly decreases the serum concentration of free drug for some progestins, which is a special concern in patients using progestins for contraception. /Progestins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

药物相互作用数据对于利福布汀尚不可用，但由于其结构与利福平相似，因此在与孕激素联合使用时可能需要类似的谨慎措施。

Drug interaction data are not available for rifabutin, but because its structure is similar to that of rifampin, similar precautions with its use with progestins may be warranted. ... /Progestins/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

左炔诺孕酮从胃肠道吸收，由肝脏代谢，并以葡萄糖醛酸和硫酸盐结合物的形式通过尿液和粪便排出体外。

Norgestrel is absorbed from the gastrointestinal tract, metabolised by the liver and excreted in the urine and faeces as glucuronide and sulphate conjugates.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(14)C-Norgestrel 给七名受试者服用后，5天内尿液中排出了剂量的43%；放射性物质的生物半衰期是24小时。酶促水解仅释放出32%的尿液放射性，另外25%以硫酸结合物的形式排出。尿液中排出的代谢物相比服用相关化合物如norethisterone或lynestrenol后的代谢物极性要小得多。从尿液中分离出了四氢诺孕醇的3alphaOH,5beta和3betaOH,5beta异构体（13beta-ethyl-17alpha-ethynyl-5beta-雄烷-3alpha,17beta-二醇），并通过质谱、薄层色谱和气液色谱进行了鉴定。血浆中放射性物质的下降速度比服用norethisterone和lynestrenol后要快。大约2%的服用剂量转化为了酸性化合物。无论是口服还是静脉给药，norgestrel的放射性物质排出速率或代谢物没有明显差异。

(14)C-Norgestrel was administered to seven human subjects and 43% of dose was excreted in the urine within 5 days; the biological half-life of the radioactivity was 24 hr. Enzymic hydrolysis released only 32% of the urinary radioactivity and a further 25% was excreted as sulphate conjugates. The metabolites excreted in the urine were much less polar than those following the administration of the related compounds, norethisterone or lynestrenol. The 3alphaOH,5beta and 3betaOH,5beta isomers of the tetrahydronorgestrel (13beta-ethyl-17alpha-ethynyl-5 beta-gonane-3alpha,17beta-diol) were isolated from urine and identified by mass spectrometry and thin-layer and gas-liquid chromatography. Plasma radioactivity decreased more rapidly than after the administration of norethisterone and lynestrenol. About 2% of the administered dose was converted to acidic compounds. There was no apparent difference in the rate of excretion of radioactivity or in the metabolites after either oral or intravenous administration of norgestrel.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

不同合成类固醇（用于激素避孕）与性激素结合球蛋白（SHBG）的结合能力通过测量它们在竞争性蛋白结合系统中取代放射性标记的睾酮的能力进行研究。只有19-去甲睾酮衍生物具有显著取代睾酮的能力，d-诺孕酯（d-Ng）是最强的取代剂。在SHBG水平增加的女性中，之前恒定的血浆d-Ng水平增加了两到六倍。因此，可以得出结论，SHBG是d-Ng的主要载体蛋白。d-Ng强烈的睾酮取代活性也可能解释含d-Ng的口服避孕药观察到的雄激素样副作用。

The binding of different synthetic steroids, used in hormonal contraception, to Sex Hormone Binding Globulin (SHBG) was studied by measuring their ability to displace tritiated testosterone from SHBG in a competitive protein binding system. Only 19-nortestosterone derivates had any significant ability to displace testosterone from SHBG, d-norgestrel (d-Ng) being the strongest displacer. Increasing the SHBG levels in women with previous constant plasma d-Ng levels increased these levels two- to sixfold. It is concluded that SHBG is the main carrier protein for d-Ng. The strong testosterone displacing activity of d-Ng might also explain androgenic side effects observed with d-Ng containig oral contraceptives.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S22,S36
• 危险类别码：
  R20/21/22,R40
• WGK Germany：
  3
• 海关编码：
  2937230000
• 危险品运输编号：
  OTH
• RTECS号：
  JF8259000

制备方法与用途

概述

左炔诺孕酮是一种速效、短期口服避孕药，通过显著抑制排卵和阻止孕卵着床，并使宫颈黏液稠度增加，精子穿透阻力增大，从而发挥速效避孕作用。目前，单用孕激素或与雌激素配伍的左炔诺孕酮已制成多种类型的女性避孕药，以口服、外用及注射等方式达到避孕目的。

药理作用

左炔诺孕酮是一种强效孕激素，其孕激素作用约为炔诺酮的5～10倍，并具有雄激素和抗雌激素活性。该药物主要通过抑制排卵来发挥作用。此外，它还能改变宫颈黏液性质，使精子难以穿透；同时，它还可以使子宫内膜变薄，不利于受精卵着床。

用法用量

• 短效口服避孕药：从月经第5天开始，每天服1片（丸），连服22天。停药后2～4天来月经，然后于第5天继续服用下一个月的药。
• 探亲避孕药：于探亲当晚开始服炔诺孕酮探亲避孕药，每天1片，服法同短效口服避孕药。
• 事后避孕药：房事后72小时内口服2片复方炔诺孕酮事后避孕片，12小时后再服2片。

不良反应

常见不良反应包括胃纳差、痤疮、液体潴留和水肿、体重增加、过敏性皮肤炎症、精神压抑、乳房疼痛、女性性欲改变、月经紊乱、不规则出血或闭经。少见的不良反应有头痛，胸、臀、腿特别是腓肠肌处疼痛，手臂和脚无力、麻木或疼痛，突然的或原因不明的呼吸短促，突然语言发音不清，突然视力改变、复视、不同程度失明等。长期应用可能引起肝功能异常，缺血性心脏病发生率上升，妊娠早期时应用可能导致雄激素活性高引起的后代女婴男性化以及生殖道畸形（多见为尿道下裂）。

药物相互作用

• 与利福平、氯霉素、氨苄西林、苯巴比妥、苯妥英钠、扑米酮、甲丙氨酯、氯氮平、对乙酰氨基酚及吡唑酮类镇痛药（保泰松）等同服可产生肝微粒体酶效应，加速炔酮在体内的代谢，导致避孕失败、突破性出血发生率增高。
• 维生素C能增强口服避孕药的作用，每天口服1g维生素C可使炔雌醇生物利用度从40%提高到60%～70%。
• 与环孢素合用，可抑制环孢素的代谢清除，致其毒性增强，应避免合用。

规格

• 复方炔诺孕酮一号片（或滴丸）：每片（丸）含炔诺孕酮0.3mg和炔雌醇0.03mg。
• 炔诺孕酮探亲避孕片：每片含炔诺孕酮3mg。
• 复方炔诺孕酮事后避孕片：每片含炔诺孕酮1mg和炔雌醇0.1mg。

化学性质

左炔诺孕酮为白色或类白色结晶性粉末，无臭、无味。不溶于水，溶于氯仿，微溶于甲醇。

用途

用于避孕药。

反应信息

• 作为反应物：
  描述：

  、 炔诺酮醋酸酯 、 、 异炔诺酮 、 、 双醋炔诺醇 、 、 (8R,9S,10R,13S,14S)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one 、 生成 炔诺酮
  参考文献：
  名称：

  Follicular phase estrogen or progestin with physiologic

  摘要：

  本发明涉及一种用于月经周期调节的性激素类固醇药物的给药方法、配方和递送系统。该发明在临床应用中用于妊娠间隔和月经功能障碍的治疗。孕激素和雌激素在治疗周期中被给予，模拟正常月经周期中的性激素激素。类固醇治疗周期被分为任意和离散的卵泡期和黄体期段，从月经开始时开始。在卵泡期的早期段，不给予外源性类固醇。根据患者的临床和/或生理情况，随后给予不受抵抗的孕激素或雌激素。在首选实施例中，随后是早期黄体期，以低剂量的联合雌激素/孕激素给药；中期黄体期给予足以抑制垂体FSH和LH并维持子宫内膜的雌激素和孕激素；最后，给予减少剂量的联合雌激素/孕激素。该方法和配方的临床成功不仅取决于给予的孕激素分子的生物学效力，还取决于外源性雌激素、孕激素和联合雌激素/孕激素的给药剂量和时间关系。因此，任何FDA批准的合成雌激素或孕激素，在药理学上适当剂量下，均适用于本发明的配方。通过下丘脑-垂体节律而非持续的FSH、LH、内源性雌激素抑制实现月经周期调节和有效避孕。同时，还实现了减少同时给予高剂量雌激素和孕激素的不良内分泌和代谢影响的暴露。在停止使用本发明的给药后，迅速的FSH和随后的LH恢复发生，为正常排卵患者提供适当的排卵和适当的月经。该方法和配方还允许医生采取生理纠正措施，治疗可能或可能不寻求避孕的月经功能障碍患者，这些患者表现为低雌激素、正常雌激素或高雌激素的排卵功能障碍或无排卵。

  公开号：

  US04292315A1

文献信息

• Dibenzyl Amine Compounds and Derivatives
  申请人：Chang George

  公开号：US20070213371A1

  公开（公告）日：2007-09-13

  Dibenzyl amine compounds and derivatives, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans.

  二苯基胺化合物及其衍生物，含有这种化合物的药物组合物以及使用这种化合物提高某些血浆脂质水平，包括高密度脂蛋白胆固醇，并降低其他一些血浆脂质水平，如低密度脂蛋白胆固醇和甘油三酯，并据此治疗由高密度脂蛋白胆固醇水平低和/或低密度脂蛋白胆固醇和甘油三酯水平高加重的疾病，如动脉粥样硬化和心血管疾病在某些哺乳动物，包括人类。
• SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
  申请人：Ohio State Innovation Foundation

  公开号：US20140155577A1

  公开（公告）日：2014-06-05

  Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.

  揭示了与受保护或未受保护的氨基酸或肽连接的疏水药物的共轭物。所述的共轭物是两性的，可以自组装成纳米管。还描述了包含这些共轭物的纳米管，可以具有高药物载荷并保护药物免受降解或排泄。这些纳米管非常适合向个体输送疏水和不稳定的药物。
• [EN] TARGETED DRUG DELIVERY THROUGH AFFINITY BASED LINKERS<br/>[FR] ADMINISTRATION CIBLÉE D'UN MÉDICAMENT FAISANT APPEL À DES COUPLEURS FONDÉS SUR L'AFFINITÉ
  申请人：INVICTUS ONCOLOGY PVT LTD

  公开号：WO2015148126A1

  公开（公告）日：2015-10-01

  The current invention discloses targeted drug delivery conjugates comprising a targeting moiety linked to a drug via a molecule having an affinity for the targeting moiety. Typically, the conjugate comprises a targeting ligand and a molecule of interest, e.g., a therapeutic agent. The targeting ligand and the molecule of interest are linked to each other via an affinity ligand. The affinity ligand is further covalently or non-covalently linked to a drug or therapeutic agent. The drug can be modified to make it more soluble and so that it cleaves from the linking molecule at the target site.

  当前的发明揭示了包括通过具有与靶向基团亲和力的分子连接到药物的靶向药物传递共轭物。通常，该共轭物包括一个靶向配体和一个感兴趣的分子，例如，一个治疗剂。靶向配体和感兴趣的分子通过一个亲和配体相互连接。该亲和配体进一步以共价或非共价方式连接到药物或治疗剂。药物可以被修改以使其更溶解，并使其在靶点处从连接分子中解离。
• Pyrrolidine and related derivatives useful as PR modulators
  申请人：Commons Thomas Joseph

  公开号：US20080045560A1

  公开（公告）日：2008-02-21

  Compounds of the following structure are described: wherein R 1 -R 6 , R 11 , R 12 , m, V, X, Y, Z and Q are described herein, or a pharmaceutically acceptable salt, tautomer, metabolite or prodrug thereof. These compounds are useful for treating a variety of hormone-related conditions including contraception, treating or preventing fibroids, endometriosis, dysfunctional bleeding, uterine leiomyomata, polycystic ovary syndrome, or hormone-dependent carcinomas, providing hormone replacement therapy, stimulating food intake or synchronizing estrus.

  以下结构的化合物被描述如下： 其中R1-R6，R11，R12，m，V，X，Y，Z和Q在此处描述，或其药学上可接受的盐、异构体、代谢物或前药。这些化合物可用于治疗各种激素相关疾病，包括避孕、治疗或预防子宫肌瘤、子宫内膜异位症、功能性出血、子宫平滑肌瘤、多囊卵巢综合征、激素依赖性癌症、提供激素替代疗法、促进食欲或同步发情。
• Tricyclic oxazolidone derivatives useful as PR modulators
  申请人：Commons Thomas Joseph

  公开号：US20080045578A1

  公开（公告）日：2008-02-21

  Compounds of the following structure are described: wherein R 1 -R 6 , R 16 , m, V, W, X, Y, and Q are described herein, or a pharmaceutically acceptable salt, tautomer, metabolite or prodrug thereof. These compounds are useful for treating a variety of hormone-related conditions including contraception, treating or preventing fibroids, endometriosis, dysfunctional bleeding, uterine leiomyomata, polycystic ovary syndrome, or hormone-dependent carcinomas, providing hormone replacement therapy, stimulating food intake or synchronizing estrus.

  以下结构的化合物被描述如下： 其中R1-R6，R16，m，V，W，X，Y和Q在此处描述，或其药学上可接受的盐，异构体，代谢物或前药。这些化合物可用于治疗各种激素相关疾病，包括避孕，治疗或预防子宫肌瘤，子宫内膜异位症，功能性出血，子宫平滑肌瘤，多囊卵巢综合征，或激素依赖性癌症，提供激素替代疗法，刺激食欲或同步发情。