美沙雌酸 | 517-18-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 雌激素及孕激素类药
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 美沙雌酸
• 英文名称: (+-)-2.2-dimethyl-3-(6-methoxy-naphthyl-(2))-valeric acid
• 英文别名: (+/-)-2.2-dimethyl-3-(6-methoxy-naphthyl-(2))-valeric acid；(+/-)-2.2-Dimethyl-3-(6-methoxy-naphthyl-(2))-valeriansaeure；rac.-α.α-Dimethyl-β-<6-methoxy-naphthyl-(2)>-valeriansaeure；2-<1-Aethyl-2-carboxy-2-methyl-propyl>-6-methoxy-naphthalin；O-Methyl-allenolsaeure；Methallenestril；3-(6-methoxynaphthalen-2-yl)-2,2-dimethylpentanoic acid
• CAS: 517-18-0
• 化学式: C₁₈H₂₂O₃
• 分子量: 286.371
• InChiKey: KHLJKRBMZVNZOC-UHFFFAOYSA-N

物化性质

• 熔点：
  139-140°
• 沸点：
  437.0±20.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)
• 颜色/状态：
  CRYSTALS FROM DIL METHANOL
• 溶解度：
  SOL IN ETHER & VEGETABLE OILS; INSOL IN WATER; FREELY SOL IN CHLOROFORM

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 人类毒性摘录

乳腺增大和结节在男女孩食用了含有雌激素的维生素胶囊后都发生了。/雌激素/

BREAST ENLARGEMENT & NODULARITY OCCURRED IN BOTH MALE & FEMALE CHILDREN AFTER CONSUMPTION OF VITAMIN CAPSULES CONTAMINATED WITH ESTROGENS. /ESTROGEN/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

不适、易怒和抑郁...即使是小剂量也会出现，而且...大剂量时更是如此。对性欲的影响不稳定，有的人增加，有的人减少。...血液中某些凝血因子浓度的变化...增加血栓性静脉炎和血栓栓塞在...浅表和深静脉的发生率。/雌激素/

MALAISE, IRRITABILITY, & DEPRESSION...OCCUR WITH SMALL DOSES &...WITH LARGE DOSES. EFFECT ON LIBIDO IS ERRATIC, BEING INCR IN SOME & DECR IN OTHERS. ... CHANGES IN CONCN OF SOME OF CLOTTING FACTORS IN BLOOD...INCR INCIDENCE OF THROMBOPHLEBITIS & THROMBOEMBOLISM IN...SUPERFICIAL & DEEP VEINS. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

肺栓塞，脑栓塞并伴有中风和肠系膜血管阻塞发生。冠状动脉血栓形成...增加...改变肝功能，这会改变...肝脏功能的测试以及各种合成和生物转化过程。...降低葡萄糖耐量，并且可能加剧糖尿病。/雌激素/

PULMONARY EMBOLISM, CEREBRAL EMBOLISM WITH STROKE & MESENTERIC VASCULAR OCCULSION OCCUR. CORONARY THROMBOSIS...INCR... ALTER HEPATIC FUNCTION, WHICH... ALTER...TESTS OF LIVER FUNCTION AS WELL AS VARIOUS SYNTHETIC & BIOTRANSFORMATION PROCESSES. ...DECR IN GLUCOSE TOLERANCE, & DIABETES MELLITUS MAY BE EXACERBATED. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

血清甘油三酯升高，可能会发生高脂血症...成分被改变...胆结石增加...可能会引发卟啉症。血液蛋白浓度可能会发生变化；甲状腺素和糖皮质激素结合蛋白增加，这可能会改变内分泌关系。/雌激素/

SERUM TRIGLYCERIDES RISE, &...HYPERLIPIDEMIA MAY OCCUR... COMPOSITION IS ALTERED...INCR OF GALL STONES... PORPHYRIA MAY BE PROVOKED. CHANGES IN CONCN OF BLOOD PROTEINS MAY OCCUR; THYROXINE- & GLUCOCORTICOID-BINDING PROTEINS ARE INCR, WHICH MAY ALTER ENDOCRINE RELATIONSHIPS. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

治疗中使用的雌激素很容易通过皮肤和粘膜被吸收。当它们用于局部作用时，吸收往往足以引起系统效应，实际上，在没有戴手套的情况下处理己烯雌酚的工厂工人中已经出现了男性乳房发育的情况。

ESTROGENS USED IN THERAPY ARE...READILY ABSORBED THROUGH SKIN & MUCOUS MEMBRANES. WHEN THEY ARE APPLIED FOR LOCAL ACTION, ABSORPTION IS OFTEN SUFFICIENT TO CAUSE SYSTEMIC EFFECTS, & IN FACTORY WORKERS GYNECOMASTIA HAS FOLLOWED HANDLING OF DIETHYLSTILBESTROL WITHOUT GLOVES. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

雌激素的尿排泄率无论是口服还是静脉给药都相当相似，这表明大多数雌激素从胃肠道吸收迅速且相当完全。

URINARY EXCRETION RATE OF ESTROGENS IS QUITE SIMILAR WHETHER AGENTS ARE GIVEN ORALLY OR INTRAVENOUSLY, WHICH SUGGESTS THAT ABSORPTION OF MOST ESTROGENS FROM GI TRACT IS PROMPT & QUITE COMPLETE. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

自然雌激素在水溶液中溶解，当溶于油中注射时，能被迅速吸收并快速代谢。雌激素在体内的灭活主要在肝脏进行。

NATURAL ESTROGENS ARE SOL IN WATER, &, WHEN INJECTED DISSOLVED IN OIL, ARE RAPIDLY ABSORBED & QUICKLY METABOLIZED. ... INACTIVATION OF ESTROGEN IN BODY IS CARRIED OUT MAINLY IN THE LIVER. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一定比例的雌激素到达肝脏后被排入胆汁，然后从肠道再次被吸收并通过门静脉返回肝脏。/雌激素/

CERTAIN PROPORTION OF ESTROGEN REACHING.../THE LIVER/ IS EXCRETED INTO THE BILE, ONLY TO BE REABSORBED FROM THE INTESTINE & CARRIED BACK AGAIN TO THE LIVER BY THE PORTAL VEIN. /ESTROGENS/

来源:Hazardous Substances Data Bank (HSDB)

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3-(6-methoxy-[2]naphthyl)-2,2-dimethyl-valeric acid methyl ester	22290-97-7	C19H24O3	300.398
  ——	3-(6-methoxy-[2]naphthyl)-2,2-dimethyl-valeric acid ethyl ester	873390-88-6	C20H26O3	314.425
  乙基3-羟基-3-(6-甲氧基-2-萘基)-2,2-二甲基戊酸酯	3-hydroxy-3-(6-methoxy-[2]naphthyl)-2,2-dimethyl-valeric acid ethyl ester	85536-81-8	C20H26O4	330.424
  ——	2-Methyl-2-<6-methoxy-naphthoyl-(2)>-propionsaeure-aethylester	101743-90-2	C18H20O4	300.354
  ——	3-(6-methoxy-[2]naphthyl)-2,2-dimethyl-pent-3-enoic acid methyl ester	——	C19H22O3	298.382

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(S)-2.2-dimethyl-3-(6-methoxy-naphthyl-(2))-valeric acid	20756-70-1	C18H22O3	286.371
  ——	(R)-2.2-dimethyl-3-(6-methoxy-naphthyl-(2))-valeric acid	20664-44-2	C18H22O3	286.371
  ——	(S)-2.2-dimethyl-3-(6-hydroxy-naphthyl-(2))-valeric acid	17660-00-3	C17H20O3	272.344
  ——	alpha,alpha-Dimethyl-beta-ethyl allenolic acid	20664-58-8	C17H20O3	272.344
  ——	α,α-dimethyl-β-ethyl allenolic acid	15372-37-9	C17H20O3	272.344

反应信息

• 作为反应物：
  描述：

  美沙雌酸 在 奎宁 作用下， 生成 (S)-2.2-dimethyl-3-(6-methoxy-naphthyl-(2))-valeric acid
  参考文献：
  名称：

  Post-translational regulation of Saccharomyces cerevisiae proteins tagged with the hormone-binding domains of mammalian nuclear receptors

  摘要：

  In the post-genome sequencing era the functional analysis of newly discovered proteins becomes more and more important. In this report we describe a genetic approach to the post-translational regulation of protein function in Saccharomyces cerevisiae by creating conditional lethal mutants. The yeast ORFs YDL139c, YDL147w, ERG3 and ERG11 were tagged with sequences encoding the hormone-binding domains of mammalian steroid receptors by PCR-mediated, targeted integration into the yeast genome. We found that se the function of the chimeric proteins is regulated in a hormone-dependent way. This technique provides another important tool for the functional analysis of the yeast preteome.

  DOI：

  10.1007/s004380000325
• 作为产物：
  描述：

  2-Methyl-2-<6-methoxy-naphthoyl-(2)>-propionsaeure-aethylester 在 sodium hydroxide 、 甲酸 、 乙醚 、 1-methoxyethanol 、 铂 、 苯 作用下， 生成 美沙雌酸
  参考文献：
  名称：

  spo12 is a multicopy suppressor of mcs3 that is periodically expressed in fission yeast mitosis

  摘要：

  Hyperactivation of Cdc2 in fission yeast causes cells to undergo a lethal premature mitosis, a phenomenon called mitotic catastrophe. This phenotype is observed in cdc2-3w wee1-50 cells at high temperature and is suppressed by a single recessive mutant, mcs3-12. Mcs3 acts independently of the Wee1 kinase and Cdc25 phosphatase, two major regulators of Cdc2. We have isolated multicopy suppressors of the cell cycle arrest phenotype of mcs3-12 wee1-50 cdc25-22 cells, but did not identify the mcs3 gene itself. Instead several known mitotic regulators were isolated, including the Cdc25 phosphatase, Wis2 cyclophilin, Cek1 kinase. and an Hsp90 homologue, Swo1. We also isolated clones encoding non-functional, truncated forms of the Wee1 kinase and Dis2 type 1 phosphatase. In addition we identified a multicopy suppressor that encodes a structural homologue of the budding yeast SPO12 gene. We find that overexpression of fission yeast spo12 not only suppresses the phenotype of the mcs3-12 wee1-50 cdc25-22 strain, but also that of a win1-1 wee1-50 cdc25-22 strain at high temperature, indicating that the function of spo12 is not directly related to mcs3. We show that spo12 mRNA is periodically expressed during the fission yeast cell cycle, peaking at the G2/M transition coincidently with cdc15. Deletion of spo12, however, has no overt effect on either the mitotic or meiotic cell cycles, except when the function of the major B type cyclin, Cdc13, is compromised.

  DOI：

  10.1007/s004380000324

文献信息

• [EN] NITRIC OXIDE RELEASING PRODRUGS OF THERAPEUTIC AGENTS<br/>[FR] PROMÉDICAMENTS D'AGENTS THÉRAPEUTIQUES LIBÉRANT DE L'OXYDE NITRIQUE
  申请人：SATYAM APPARAO

  公开号：WO2014111957A1

  公开（公告）日：2014-07-24

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其中所述药物或治疗剂至少含有一个羧酸基团。发明还涉及制备这些一氧化氮释放前药的方法，包含它们的药物组合物以及使用这些前药的方法。
• 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.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• CONJUGATES OF WATER SOLUBLE POLYMER-AMINO ACID OLIGOPEPTIDE-DRUG, PREPARATION METHOD AND USE THEREOF
  申请人：JENKEM TECHNOLOGY CO. LTD. TIANJIN BRANCH

  公开号：US20150359900A1

  公开（公告）日：2015-12-17

  A conjugate of water soluble polymer-amino acid oligopeptide-drug of Formula (I) below and a pharmaceutical composition comprising the conjugate are provided. In the conjugate, P is a water soluble polymer; X is a linking group, wherein the linking group links P and A 1 ; each of A 1 , A 2 and A 3 is independently same or different amino acid residue or amino acid analogue residue; each of D 1 and D 2 is independently same or different drug molecule residue; a is 0 or 1; b is an integer of 2-12; c is an integer of 0-7; d is 0 or 1. The conjugate could improve drug load capacity, water solubility, stability and activity of the drug.

  提供一种水溶性聚合物-氨基酸寡肽-药物的共轭物，其化学式（I）如下，并提供包含该共轭物的制药组合物。在该共轭物中，P是水溶性聚合物；X是一个连接基团，连接基团连接P和A1；A1、A2和A3中的每一个独立地是相同或不同的氨基酸残基或氨基酸类似物残基；D1和D2中的每一个独立地是相同或不同的药物分子残基；a为0或1；b是2-12的整数；c是0-7的整数；d为0或1。该共轭物能够提高药物的载荷能力、水溶性、稳定性和活性。
• Technology for the Preparation of Microparticles
  申请人：Malakhov Michael

  公开号：US20090098207A1

  公开（公告）日：2009-04-16

  Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

  微球是通过将溶液中的大分子或小分子与抗溶剂和对离子接触，并冷却溶液而制备的。这些微球可用于制备具有明确定义尺寸的药物、营养保健品、化妆品等产品。
• 19-NOR-PROGESTERONE FOR CONTRACEPTION
  申请人：PFAFF TAMARA

  公开号：US20090093448A1

  公开（公告）日：2009-04-09

  The invention relates to compounds of the general formula (I) to a method for the production thereof, to pharmaceutical, cosmetic compositions or dosage forms which contain these compounds, and to a method for contraception by administration of these compounds.

  该发明涉及通式（I）化合物，涉及其生产方法，包含这些化合物的药用、化妆品组合物或剂型，以及通过给予这些化合物进行避孕的方法。