公开(公告)号：US09034856B2

公开(公告)日：2015-05-19

申请号：US12810858

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hübner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hübner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/58 ,  C07J21/00 ,  C07J41/00 ,  C07J53/00

CPC分类号： C07J21/00 ,  C07J41/0016 ,  C07J53/001 ,  C07J53/007

摘要： The invention relates to 17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivatives with the general chemical formula I, where the residues Z, R4, R6a, R6b, R7, R15, R16a, R16b and R18 have the meanings stated in Claim 1, and their solvates, hydrates and salts, including all stereoisomers of these compounds. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives, and in particular application in the aforementioned indications. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

摘要翻译： 本发明涉及具有一般化学式I的17-（1'-丙烯基）-17-3'-氧代雌-4-烯-3-酮衍生物，其中残基Z，R4，R6a，R6b，R7，R15， R16a，R16b和R18具有权利要求1所述的含义，及其溶剂合物，水合物和盐，包括这些化合物的所有立体异构体。 本发明还涉及这些衍生物用于生产口服避孕用药物和用于治疗绝经前，绝经期和绝经后的投诉和含有所述衍生物的药用产品的用途，特别是在上述适应症中的应用。 根据本发明的衍生物具有促孕作用，在优选情况下另外具有抗皮质激素和中性至轻度雄激素作用。

公开(公告)号：US20110015162A1

公开(公告)日：2011-01-20

申请号：US12811002

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/58 ,  C07J53/00 ,  A61K31/56

CPC分类号： C07J53/008

摘要： The invention relates to 15,16-methylene-17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivatives with the general chemical formula I, and R4, R6a, R6b, R7 and Z have the meanings stated in claim 1, and their solvates, hydrates, stereoisomers and salts. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

摘要翻译： 本发明涉及具有一般化学式I的15,16-亚甲基-17-羟基-19-去甲-21-羧酸 - 类固醇γ-内酯衍生物，且R4，R6a，R6b，R7和Z具有以下含义： 权利要求1及其溶剂合物，水合物，立体异构体和盐。 本发明还涉及这些衍生物用于生产口服避孕用药物和用于治疗前，绝经前和绝经后的投诉和含有所述衍生物的药用产品的用途。 根据本发明的衍生物具有促孕作用，在优选情况下另外具有抗皮质激素和中性至轻度雄激素作用。

公开(公告)号：US20100311702A1

公开(公告)日：2010-12-09

申请号：US12810860

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/585 ,  C07J21/00 ,  A61P15/18 ,  A61P5/24 ,  A61P5/42 ,  A61P5/26

CPC分类号： C07J21/003 ,  C07J53/008

摘要： The 15α,16α-methylene-17-hydroxy-19-nor-17-pregna-4-en-3-one-21-carboxylic acid γ-lactone derivatives of the present invention possess progestational efficacy. They have the general chemical formula I, in which Z is selected from the group comprising an oxygen atom, two hydrogen atoms, NOR and NNHSO2R, where R is hydrogen, C1-C10-alkyl, aryl or C7-C20-aralkyl, R4 is hydrogen or halogen, and moreover either: R6a, R6b together form methylene or 1,2-ethanediyl or R6a is hydrogen and R6b is selected from the group comprising hydrogen, C1-C10-alkyl, C2-C10-alkenyl or C2-C10-alkynyl, and R7 is selected from the group comprising hydrogen, C1-C10-alkyl, C3-C6-cycloalkyl, C2-C10-alkenyl or C2-C10-alkynyl, or: R6a is hydrogen and R6b and R7, together, denote a bond, an oxygen or form methylene, R18 represents hydrogen or C1-C3-alkyl and in addition include their solvates, hydrates, stereoisomers and salts.

摘要翻译： 本发明的15α，16α-亚甲基-17-羟基-19-去甲-17-前 - 孕-4-烯-3-酮-21-羧酸γ-内酯衍生物具有促进功效。 它们具有一般化学式I，其中Z选自氧原子，两个氢原子，NOR和NNHSO 2 R，其中R是氢，C 1 -C 10 - 烷基，芳基或C 7 -C 20 - 芳烷基，R 4是 氢或卤素，此外：R6a，R6b一起形成亚甲基或1,2-乙二基或R6a为氢，R6b选自氢，C1-C10-烷基，C2-C10-烯基或C2-C10-烯基， 炔基，R 7选自氢，C 1 -C 10 - 烷基，C 3 -C 6 - 环烷基，C 2 -C 10 - 烯基或C 2 -C 10 - 炔基，或者：R 6a是氢，R 6b和R 7一起表示 键，氧或亚甲基，R 18表示氢或C 1 -C 3 - 烷基，并且还包括它们的溶剂合物，水合物，立体异构体和盐。

公开(公告)号：US20100292184A1

公开(公告)日：2010-11-18

申请号：US12664099

申请日：2008-06-12

申请人： Joachim Kuhnke ,  Jan Huebner ,  Rolf Bohlmann ,  Thomas Frenzel ,  Ulrich Klar ,  Frederik Menges ,  Sven Ring ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Joachim Kuhnke ,  Jan Huebner ,  Rolf Bohlmann ,  Thomas Frenzel ,  Ulrich Klar ,  Frederik Menges ,  Sven Ring ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/56 ,  C07J53/00 ,  C07J41/00 ,  A61K31/695 ,  A61K31/565 ,  A61P15/18 ,  A61P5/24 ,  A61P5/34 ,  A61P5/42

CPC分类号： C07J41/0094 ,  C07J53/007 ,  C07J53/008

摘要： The 17β-cyano-19-androst-4-ene derivatives of the present invention possess gestagenic activity. They have the general chemical formula 1, in which Z is selected from the group comprising O, two hydrogen atoms, NOR and NNHSO2R, in which R is hydrogen or C1-C4-alkyl, R1, R2 are each independently hydrogen or methyl, or R1 and R2 together form methylene or are omitted with formation of a double bond between C1 and C2, R4 is hydrogen or halogen, furthermore either: R6a, R6b together form methylene or 1,2-ethanediyl or R6a is hydrogen and R6b is selected from the group comprising hydrogen, methyl and hydroxymethylene, and R7 is selected from the group comprising hydrogen, C1-C4-alkyl, C2-C3-alkenyl and cyclopropyl, or: R6a hydrogen and R6b and R7 together form methylene or are omitted with formation of a double bond between C6 and C7 or: R6a is methyl and R6b and R7 are omitted with formation of a double bond between C6 and C7, R15, R16 are hydrogen or together form methylene, R17 is selected from the group comprising hydrogen, C1-C4-alkyl and allyl, and moreover comprise their solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts, with the proviso that particular compounds are excluded.

摘要翻译： 本发明的17α-氰基-19-雄甾-4-烯衍生物具有孕激活作用。 它们具有一般化学式1，其中Z选自O，两个氢原子，NOR和NNHSO 2 R，其中R是氢或C 1 -C 4烷基，R 1，R 2各自独立地是氢或甲基，或 R1和R2一起形成亚甲基或被省略，在C1和C2之间形成双键，R4是氢或卤素，此外：R6a，R6b一起形成亚甲基或1,2-乙二基或R6a是氢，R6b选自 包括氢，甲基和羟基亚甲基的基团，并且R 7选自氢，C 1 -C 4 - 烷基，C 2 -C 3 - 烯基和环丙基，或者：R 6a氢和R 6b和R 7一起形成亚甲基或被形成 C6和C7之间的双键或：R6a是甲基，R6和C7之间形成双键，R6b和R7被省略，R15，R16是氢或一起形成亚甲基，R17选自氢，C1- C4-烷基和烯丙基，并且还包含它们的溶剂化物 es，水合物，立体异构体，非对映体，对映异构体和盐，条件是排除特定的化合物。

公开(公告)号：US20110003779A1

公开(公告)日：2011-01-06

申请号：US12810857

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/58 ,  C07J21/00 ,  A61P15/18 ,  A61P15/12 ,  A61P15/00

CPC分类号： C07J53/008

摘要： The invention relates to 15,16-methylene-17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivatives with the general chemical formula I, where the Z, R4, R6a, R6b, R7 and R18 have the meanings stated in claim 1, and solvates, hydrates and salts thereof, including all crystal modifications and all stereoisomers of these compounds. The invention also relates to the use of these derivatives for the production of a drug for oral contraception and for the treatment of pre-, peri- and postmenopausal problems and drugs which contain such derivatives, in particular use in the aforesaid indications. The derivatives according to the invention have a progestational and in preferable cases also an antimineralcorticoid and neutral to slight androgenic activity.

摘要翻译： 本发明涉及具有一般化学式I的15,16-亚甲基-17-（1'-丙烯基）-17-3'-氧代雌-4-烯-3-酮衍生物，其中Z，R4，R6a，R6b R 7和R 18具有权利要求1所述的含义，并溶剂合物，其水合物和盐，包括这些化合物的所有晶体改性和所有立体异构体。 本发明还涉及这些衍生物用于生产口服避孕药物和用于治疗绝经前，绝经期和绝经后问题的药物以及含有此类衍生物的药物，特别是在上述适应症中使用。 根据本发明的衍生物具有促孕作用，并且在优选情况下还具有抗铁皮质激素和中性至轻度雄激素活性。

公开(公告)号：US20100317632A1

公开(公告)日：2010-12-16

申请号：US12810858

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Hubner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/58 ,  C07J21/00 ,  A61P15/18

CPC分类号： C07J21/00 ,  C07J41/0016 ,  C07J53/001 ,  C07J53/007

摘要： The invention relates to 17-(1′-propenyl)-17-3′-oxidoestra-4-en-3-one derivatives with the general chemical formula I, where the residues Z, R4, R6a, R6b, R7, R15, R16a, R16b and R18 have the meanings stated in Claim 1, and their solvates, hydrates and salts, including all stereoisomers of these compounds. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives, and in particular application in the aforementioned indications. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

摘要翻译： 本发明涉及具有一般化学式I的17-（1'-丙烯基）-17-3'-氧代雌-4-烯-3-酮衍生物，其中残基Z，R4，R6a，R6b，R7，R15， R16a，R16b和R18具有权利要求1所述的含义，及其溶剂合物，水合物和盐，包括这些化合物的所有立体异构体。 本发明还涉及这些衍生物用于生产口服避孕用药物和用于治疗绝经前，绝经期和绝经后的投诉和含有所述衍生物的药用产品的用途，特别是在上述适应症中的应用。 根据本发明的衍生物具有促孕作用，在优选情况下另外具有抗皮质激素和中性至轻度雄激素作用。

公开(公告)号：US20110021472A1

公开(公告)日：2011-01-27

申请号：US12810991

申请日：2008-12-23

申请人： Ulrich Klar ,  Jooachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Jooachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/585 ,  C07J21/00 ,  A61P15/18

CPC分类号： C07J53/00 ,  C07J19/00

摘要： The invention relates to 17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivatives with the chemical formula I, where R4, R6a, R6b, R7, R15, R16a, R16b, R18 and Z have the meanings stated in claim 1, and their solvates, hydrates, stereoisomers and salts. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

摘要翻译： 本发明涉及具有化学式I的17-羟基-19-去甲-21-羧酸 - 类固醇γ-内酯衍生物，其中R4，R6a，R6b，R7，R15，R16a，R16b，R18和Z具有以下含义： 权利要求1及其溶剂合物，水合物，立体异构体和盐。 本发明还涉及这些衍生物用于生产口服避孕用药物和用于治疗前，绝经前和绝经后的投诉和含有所述衍生物的药用产品的用途。 根据本发明的衍生物具有促孕作用，在优选情况下另外具有抗皮质激素和中性至轻度雄激素作用。

公开(公告)号：US20090029953A1

公开(公告)日：2009-01-29

申请号：US11813251

申请日：2005-12-30

申请人： Rolf Bohlmann ,  Dieter Bittler ,  Hermann Kuenzer ,  Peter Esperling ,  Hans Peter Muhn ,  Karl Heinrich Fritzemeier ,  Ulrike Fuhrmann ,  Katja Prelle ,  Steffen Borden

发明人： Rolf Bohlmann ,  Dieter Bittler ,  Hermann Kuenzer ,  Peter Esperling ,  Hans Peter Muhn ,  Karl Heinrich Fritzemeier ,  Ulrike Fuhrmann ,  Katja Prelle ,  Steffen Borden

IPC分类号： A61K31/585 ,  C07J21/00 ,  A61P15/00

CPC分类号： C07J21/00 ,  C07J53/008

摘要： The invention relates to novel 18-methyl-19-nor-17-pregn-4-en-21,17-carbolactones of general formula (I), where Z=O, H2, ═NOR or ═NNHSO2R, where R=H, a straight- or branched-chain 1-4 or 3-4 C alkyl group, R4=H, halogen, methyl or trifluoromethyl, R6 and/or R7 can be α- or β-positioned and independently=branched- or straight-chain 1-4 or 3-4 alkyl, or R6=H and R7=a- or β-positioned, straight- or branched-chain 1-4 or 3-4 C alkyl, or R6 and R7=H, or R6 and R7 together=a- or β-positioned methylene or an additional bond. The novel compounds have gestagenic and antimineralocorticoid activity and are suitable for the production of pharmaceutical preparations, for example, for oral contraception and the treatment of pre-, peri- and post-menopausal pain.

摘要翻译： 本发明涉及通式（I）的新颖的18-甲基-19-去甲-17-孕-4-烯-21,17-碳内酯，其中Z = O，H 2，-NOR或-NNHSO 2 R，其中R = H 直链或支链1-4或3-4C烷基，R4 = H，卤素，甲基或三氟甲基，R6和/或R7可以是α-或β-位置，并且独立地为支链或直链， 链1-4或3-4烷基，或R6 = H和R7 =α-或β-位置的直链或支链1-4或3-4C烷基，或R6和R7 = H或R6和 R7一起= a-或β-位置的亚甲基或另外的键。 新化合物具有孕激素和抗皮质激素活性，并且适用于制备药物制剂，例如用于口服避孕和治疗绝经前，绝经期和绝经后疼痛。

公开(公告)号：US20090099250A1

公开(公告)日：2009-04-16

申请号：US12249056

申请日：2008-10-10

申请人： Ralf WYRWA ,  Olaf Peters ,  Rolf Bohlmann ,  Peter Droescher ,  Katja Prelle ,  Karl Heinrich Fritzemeier ,  Hans Peter Muhn

发明人： Ralf WYRWA ,  Olaf Peters ,  Rolf Bohlmann ,  Peter Droescher ,  Katja Prelle ,  Karl Heinrich Fritzemeier ,  Hans Peter Muhn

IPC分类号： A61K31/381 ,  C07C39/17 ,  A61K31/122 ,  A61K31/05 ,  A61P5/00 ,  C07C49/747 ,  C07D333/16

CPC分类号： C07C39/23 ,  C07C39/17 ,  C07C43/23 ,  C07D333/16

摘要： The present invention describes non-steroidal compounds of the general formula (I) in which A is in which X1 means one or more groups on the phenyl ring and represents independently of one another a halogen, OH, (C1-C4)alkyl, (C1-C4)alkyl-O, (C3-C6)cycloalkyl-O, (C1-C14)acyl-O, (C1-C4)alkenyl, (C1-C4)alkynyl, perfluoro(C1-C4)alkyl radical, —CHO or CN, and X2 means one or more groups on the phenyl ring and represents independently of one another an H, halogen, OH, (C1-C4)alkyl, (C1-C4)alkyl-O, (C1-C4)alkenyl, (C1-C4)alkynyl, perfluoro-(C1-C4)alkyl radical, —CHO or CN, as Estrogens.

摘要翻译： 本发明描述了通式（I）的非甾体化合物，其中A是其中X 1表示苯基上的一个或多个基团并且彼此独立地表示卤素，OH，（C 1 -C 4）烷基，（ C1-C4）烷基-O，（C3-C6）环烷基-O，（C1-C14）酰基-O，（C1-C4）烯基，（C1-C4）炔基，全氟（C1-C4）烷基， CHO或CN，X2表示苯基上的一个或多个基团，并且彼此独立地表示H，卤素，OH，（C1-C4）烷基，（C1-C4）烷基-O，（C1-C4）烯基 ，（C 1 -C 4）炔基，全氟 - （C 1 -C 4）烷基，-CHO或CN作为雌激素。

公开(公告)号：US20090075987A1

公开(公告)日：2009-03-19

申请号：US12178325

申请日：2008-07-23

申请人： Lars Wortmann ,  Marcus Koppitz ,  Hans Peter Muhn ,  Thomas Frenzel ,  Florian Peter Liesener ,  Anna Schrey ,  Ronald Kuehne

发明人： Lars Wortmann ,  Marcus Koppitz ,  Hans Peter Muhn ,  Thomas Frenzel ,  Florian Peter Liesener ,  Anna Schrey ,  Ronald Kuehne

IPC分类号： A61K31/541 ,  C07D209/18 ,  A61K31/404 ,  A61P15/08 ,  A61P19/10 ,  C07D417/02

CPC分类号： C07D209/14 ,  C07D405/12

摘要： The present invention relates to acyltryptophanols of the general formula I, in which R1, R2, R3, Q and X have the meaning as defined in the description.The compounds according to the invention are effective FSH antagonists and can be used for example for fertility control in men or in women, or for the prevention and/or treatment of osteoporosis.

摘要翻译： 本发明涉及通式Ⅰ的酰基色氨酸，其中R1，R2，R3，Q和X具有说明书中定义的含义。 根据本发明的化合物是有效的FSH拮抗剂，可用于例如男性或女性的生育控制，或用于预防和/或治疗骨质疏松症。