替勃龙3-乙烯缩酮 | 677299-58-0

• 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
• 中文名称: 替勃龙3-乙烯缩酮
• 中文别名: 替勃龙-13CD33-乙烯缩酮
• 英文名称: 7α-methylnorethynodrel ethylene ketal
• 英文别名: 3,3-ethylenedioxy-17α-ethynyl-17β-hydroxy-7α-methyl-5(10)-estren；Tibolone 3-Ethylene Ketal；(7R,8R,9S,13S,14S,17R)-17-ethynyl-7,13-dimethylspiro[1,2,4,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-ol
• CAS: 677299-58-0
• 化学式: C₂₃H₃₂O₃
• 分子量: 356.505
• InChiKey: CEZIIFYCFVQGAR-LADQHVHVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  替勃龙3-乙烯缩酮 在 1,3'-联吡咯烷 、 氧气 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 四氯化碳 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 160.3h， 生成 17α-ethynyl-10β-hydroxy-7α-methyl-3-oxo-4-estren-17-yl heptanoate
  参考文献：
  名称：

  7α-methylnorethindrone enanthate 10β-hydroperoxide: Isolation and characterization

  摘要：

  10 beta-Hydroperoxy-7 alpha-methylnorethindrone 17-heptanoate (II), a product of allylic autoxidation of 7 alpha-methylnorethindrone enanthate (I), has been isolated and characterized. The synthesis of the hydroperoxide (II) from the 3-ethylene ketal of 7 alpha-methylnorethynodrel (III) was achieved. Esterification of alcohol (III), subsequent deketalization, and photochemical oxygenation resulted in the hydroperoxide (II). Reduction of the hydroperoxide (II) to the 10 beta-alcohol (VI) and acetylation of (II) to the 10 beta-acetoxyperoxide (VII) are described. A single subcutaneous injection of the compounds (II), (VI), and (VII) to rats failed to produce long term inhibition of fertility in contrast to the parent compound (I) which is at least five times more effective than norethindrone enanthate as measured by suppression of vaginal cornification and estrous cycles.

  DOI：

  10.1016/0039-128x(83)90138-1
• 作为产物：
  描述：

  17-乙炔基-17-羟基-7,13-二甲基-1,2,6,7,8,9,10,11,12,14,15,16-十二氢环戊烯并[a]菲-3-酮 、 乙二醇 在 对甲苯磺酸 、 原甲酸三乙酯 、 碳酸氢钠 作用下， 以 水 、 甲苯 为溶剂， 反应 1.03h， 以62%的产率得到替勃龙3-乙烯缩酮
  参考文献：
  名称：

  [EN] PROCESS AND INTERMEDIATES TO PREPARE 17.BETA.-HYDROXY-7.ALFA.-METHYL-19-NOR-17.ALFA.-PREGN-5(10)-EN-20-YN-3-ONE
  [FR] PROCEDE ET INTERMEDIAIRES POUR LA PREPARATION DE L7ss-HYDROXY-7 DOLLAR G(A)-METHYL-19-NOR-1720040701DINUNNO, CECIL M. ET AL: "7.alpha.-Methylnorethindrone enanthate 10.beta.-hydroperoxide: isolation and characterization", STEROIDS (1983), 42(4), 401-8, XP009027390DINUNNO, CECIL M. ET AL7.alpha.-Methylnorethindrone enanthate 10.beta.-hydroperoxide: isolation and characterizationSTEROIDS (1983), 42(4), 401-840410-214062,3compound IIIX17-20XHOYTE, ROBERT M. ET AL: "7.alpha.-Methyl-17.alpha.-(E-2'[125I]iodovinyl)-19-nortestosterone: a new radioligand for the detection of androgen receptor", STEROIDS, vol. 58, no. 1, 1993, pages 13 - 23, XP009027391HOYTE, ROBERT M. ET AL7.alpha.-Methyl-17.alpha.-(E-2'[125I]iodovinyl)-19-nortestosterone: a new radioligand for the detection of androgen receptorSTEROIDS1993581132315111X17-20Y1-8,12-16,21-23XYUS4308265ABLYE RICHARD, et al198112292653133DX17,18Y1-8,12-16,21-23DXYVAN VLIET N P ET AL: "An alternative synthesis of 17.beta.-hydroxy-7.alpha.-methyl-19-nor -17.alpha.-pregn-5(10)-en-20-yn-3-one (Org OD 14)", RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, ELSEVIER SCIENCE PUBLISHERS. AMSTERDAM, NL, vol. 105, no. 4, April 1986 (1986-04-01), pages 111 - 115, XP002099865, ISSN: 0165-0513VAN VLIET N P ET ALAn alternative synthesis of 17.beta.-hydroxy-7.alpha.-methyl-19-nor -17.alpha.-pregn-5(10)-en-20-yn-3-one (Org OD 14)RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, ELSEVIER SCIENCE PUBLISHERS. AMSTERDAM, NL19860410540165-05131111151151311521Scheme 2, compounds 4, 13 and 21YD1-8,12-16,21-23YDWO0023460A1AKZO NOBEL NV [NL], et al2000042726321-3YD1-8,12-16,21-23YDUS3534139ABUCOURT ROBERT, et al197010131Y1-8,12-16,21-23YUS4945064AHOFMEISTER HELMUT [DE], et al19900731333-384YD14-16YD

  摘要：

  公开号：

  WO2004031204A3

文献信息

• Process and intermediates to prepare17beta-hydroxy-7alpha-methyl-19-nor-17alpha-pregn -5(10)-en-20-yn-3-one
  申请人：Martynow Jacek

  公开号：US20060111332A1

  公开（公告）日：2006-05-25

  The present invention is a process for the preparation of 17β-hydroxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-3-one (17α-ethynyl-17β-hydroxy-7α-methyl-5(10)-estren-3-one, tibolone) of formula 1, which comprises hydrolysis of 17α-ethynyl-17β-hydroxy-7α-methyl-5(10)-estrene 3,3 -cyclic ketals of formula 2, where groups R 1 , R 2 , R 3 and R 4 are hydrogen atoms or alkyl groups, or R 1 and R 3 , taken together with the carbon atoms within the dioxolane ring to which they are attached, form an alicyclic ring fused to the dioxolane ring, with R 2 and R 4 being hydrogen atoms, or R 1 and R 3 together with the carbon atoms to which they are attached form an aromatic ring fused to the dioxolane ring, where R 2 and R 4 , taken together, form a chemical bond within said aromatic ring. In addition, the present invention includes an intermediate, compound of formula 2 and two processes to prepare 17α-ethynyl-17β-hydroxy-7α-methyl-5(10)-estrene 3,3 -cyclic ketals of formula 2: (a) by contacting 17α-ethynyl-17β-hydroxy-7α-methyl-4-estren-3-one with vicinal diols in the presence of a protic acid, and (b) by contacting 7α-methyl-5(10)-estrene-17-one 3,3-cyclic ketals of formula 4, where R 1 -R 4 are defined as above, with metal acetylides, in inert solvents.

  本发明涉及一种制备17β-羟基-7α-甲基-19-去氢-17α-孕-5（10）-烯-20-炔-3-酮（17α-乙炔基-17β-羟基-7α-甲基-5（10）-雌甾-3-酮，替泼酮）的方法，其包括对式2的17α-乙炔基-17β-羟基-7α-甲基-5（10）-雌甾-3,3-环糊精酮进行水解，其中基团R1、R2、R3和R4是氢原子或烷基，或者R1和R3与它们所附着的二氧兰环内的碳原子一起形成螺环并与二氧兰环融合，其中R2和R4是氢原子，或者R1和R3与它们所附着的碳原子一起形成与二氧兰环融合的芳香环，其中R2和R4一起在该芳香环内形成化学键。此外，本发明还包括一个中间体，化合物的式子为2，并且还包括两种制备式2的17α-乙炔基-17β-羟基-7α-甲基-5（10）-雌甾-3,3-环糊精酮的方法：（a）通过在质子酸存在下与邻二醇接触17α-乙炔基-17β-羟基-7α-甲基-4-雌甾-3-酮，和（b）通过在惰性溶剂中与金属乙炔基化合物接触式4的7α-甲基-5（10）-雌甾-17-酮3,3-环糊精酮，其中R1-R4的定义如上。
• 7α-Methyl-17α-(E-2'-[125I]iodovinyl)-19-nortestosterone: a new radioligand for the detection of androgen receptor
  作者：Robert M. Hoyte、Theodore J. Brown、Neil J. MacLusky、Richard B. Hochberg

  DOI：10.1016/0039-128x(93)90012-c

  日期：1993.1

  We have synthesized two gamma-emitting, I-125-labeled steroids, E- and Z-7alpha-methyl-17alpha-(2'-[I-125]iodovinyl)-19-nortestosterone [I-125](E- and Z-MIVNT) for specific labeling of androgen receptors. [I-125]E- and [I-125]Z-MIVNT were synthesized stereospecifically from E- and Z-7alpha-methyl-17alpha-(2'-tri-n-butylstannyl-vinyl)-19-nortestosterone. The tin adducts were prepared by addition of tri-n-butyltin hydride to 7alpha-methyl-17alpha-ethynyl-19-nortestosterone, and after purification they were converted in high yield to the [I-125]MIVNT isomers by reaction with I-125 (generated in situ by oxidation of[I-125]iodide with chloramine T). The I-125-labeled products were purified by high-performance liquid chromatography, and their mass determined with an ultraviolet detector (specific activity of both, approximately 2,200 Ci/mmol). In rat prostate cytosol, [I-125]E-MIVNT bound with high affinity to a single class of binding sites. Nonspecific binding in the presence of 5alpha-dihydrotestosterone was relatively low, and compared favorably with that obtained in parallel studies with [H-3]methyltrienolone (R1881). The E-isomer bound prostate cytosol with at least twice the affinity of the Z-isomer; therefore, the interaction of the E-isomer with the androgen receptor as well as other steroid receptors was studied in greater detail. Complexes of the androgen receptor with [I-125]E-MIVNT as well as [H-3]R1881 dissociate very slowly at 4C (k(diss) for both = 0.04 h-1). Displacement studies showed that the interaction of[I-125]E-MIVNT with the androgen receptor is highly specific. Competition studies showed that unlabeled E-MIVNT binds poorly to other steroid receptors in rat tissue cytosols. These binding properties make [I-125]E-MIVNT a promising ligand for study of the androgen receptor, and [I-125] E-MIVNT a potential imaging agent for the detection of androgen-dependent tumors, such as prostate cancer.
• PROCESS AND INTERMEDIATES TO PREPARE 17.BETA.-HYDROXY-7.ALFA.-METHYL-19-NOR-17.ALFA.-PREGN-5(10)-EN-20-YN-3-ONE
  申请人：INSTYTUT FARMACEUTYCZNY

  公开号：EP1556407A2

  公开（公告）日：2005-07-27
• [EN] PROCESS AND INTERMEDIATES TO PREPARE l7ß-hydroxy-7alpha-methyl-19-nor-17alpha-pregn-5(10)-en-20-yn-3-one<br/>[FR] PROCEDE ET INTERMEDIAIRES POUR LA PREPARATION DE L7ss-HYDROXY-7 DOLLAR G(A)-METHYL-19-NOR-1720040415
  申请人：PRZED FARMACEUTYCZNE ANPHARM S

  公开号：WO2004031204A2

  公开（公告）日：2004-04-15

  The present invention is a process for the preparation of l7ß-hydroxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-3-one (17α-ethynyl-l7ß-hydroxy-7α-methyl-5(10)-estren-3-one, tibolone) of formula 1, which comprises hydrolysis of 17α-ethynyl-l7ß-hydroxy-7α-methyl-5(10)-estrene 3,3-cyclic ketals of formula 2, where groups R1, R2, R3 and R4 are hydrogen atoms or alkyl groups, or R1 and R3, taken together with the carbon atoms within the dioxolane ring to which they are attached, form an alicyclic ring fused to the dioxolane ring, with R2 and R4 being hydrogen atoms, or R1 and R3 together with the carbon atoms to which they are attached form an aromatic ring fused to the dioxolane ring, where R2 and R4, taken together, form a chemical bond within said aromatic ring. In addition, the present invention includes an intermediate, compound of formula 2 and two processes to prepare 17α-ethynyl-17(3-hydroxy-7α-methyl-5(10)-estrene 3,3-cyclic ketals of formula 2: (a) by contacting 17α-ethynyl-l7ßhydroxy-7α-methyl-4-estren-3-one with vicinal diols in the presence of a protic acid, and (b) by contacting 7α-methyl-5(10)-estrene-17-one 3,3-cyclic ketals of formula 4, where R1-R4 are defined as above, with metal acetylides, in inert solvents.
• 7α-methylnorethindrone enanthate 10β-hydroperoxide: Isolation and characterization
  作者：Cecil M. DiNunno、James E. Burdett、P. Narasimha Rao、Hyun K. Kim、Richard P. Blye

  DOI：10.1016/0039-128x(83)90138-1

  日期：1983.10

  10 beta-Hydroperoxy-7 alpha-methylnorethindrone 17-heptanoate (II), a product of allylic autoxidation of 7 alpha-methylnorethindrone enanthate (I), has been isolated and characterized. The synthesis of the hydroperoxide (II) from the 3-ethylene ketal of 7 alpha-methylnorethynodrel (III) was achieved. Esterification of alcohol (III), subsequent deketalization, and photochemical oxygenation resulted in the hydroperoxide (II). Reduction of the hydroperoxide (II) to the 10 beta-alcohol (VI) and acetylation of (II) to the 10 beta-acetoxyperoxide (VII) are described. A single subcutaneous injection of the compounds (II), (VI), and (VII) to rats failed to produce long term inhibition of fertility in contrast to the parent compound (I) which is at least five times more effective than norethindrone enanthate as measured by suppression of vaginal cornification and estrous cycles.