公开(公告)号：US4542159A

公开(公告)日：1985-09-17

申请号：US039436

申请日：1979-05-15

申请人： Jurgen Engel ,  Axel Kleemann ,  Klaus Posselt ,  Fritz Stroman ,  Klaus Thiemer

发明人： Jurgen Engel ,  Axel Kleemann ,  Klaus Posselt ,  Fritz Stroman ,  Klaus Thiemer

IPC分类号： A61K31/135 ,  A61K20060101 ,  A61K31/13 ,  A61K31/137 ,  A61K31/43 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P29/00 ,  C07C20060101 ,  C07C67/00 ,  C07C213/00 ,  C07C213/02 ,  C07C213/08 ,  C07C215/30 ,  C07C215/60 ,  C07C221/00 ,  C07C225/06 ,  C07C225/10 ,  C07C225/14 ,  C07C91/23 ,  C07C91/34 ,  C07C97/10

CPC分类号： Y10S514/929

摘要： There are prepared compounds of the formula: ##STR1## wherein X is the group >C.dbd.O or >CH(OH), Y is the group ##STR2## R.sub.2 is hydrogen or C.sub.1 to C.sub.6 alkyl, R.sub.3 is hydrogen or a hydroxy group and R.sub.1 is the adamantyl group or a saturated or single unsaturated C.sub.3 to C.sub.16 cycloalkyl group where the C.sub.3 to C.sub.16 cycloalkyl group can be substituted by a C.sub.1 -C.sub.4 alkyl group or a halogen atom and their salts. The compounds are useful in dilating the peripheral blood vessels and in lowering blood pressure.

摘要翻译： 制备下式的化合物：其中X是基团> C = O或> CH（OH），Y是基团R 2是氢或C 1至C 6烷基，R 3是氢或羟基 R1是金刚烷基或饱和或不饱和的C 3〜C 16环烷基，其中C 3〜C 16环烷基可被C 1 -C 4烷基或卤原子及其盐取代。 该化合物可用于扩张外周血管和降低血压。

公开(公告)号：US4283405A

公开(公告)日：1981-08-11

申请号：US112099

申请日：1980-01-14

申请人： Jurgen Engel ,  Axel Kleemann ,  Fritz Stroman ,  Klaus Thiemer

发明人： Jurgen Engel ,  Axel Kleemann ,  Fritz Stroman ,  Klaus Thiemer

IPC分类号： C07D409/14 ,  A61K20060101 ,  A61K31/38 ,  A61K31/4433 ,  A61K31/445 ,  A61P7/06 ,  A61P9/02 ,  A61P25/04 ,  C07D20060101

CPC分类号： A61K31/38 ,  A61K31/4433 ,  A61K31/445 ,  C07D409/14

摘要： There are prepared compounds of the formula ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen or together represent a second bond between the carbon atom carrying R.sub.1 and R.sub.2, R.sub.1 also can be a hydroxy group, R.sub.3 is hydrogen, a C.sub.3 -C.sub.8 cycloalkyl group or a C.sub.1 -C.sub.20 alkyl group, which optionally can also contain one or two hydroxy groups and the groups R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are the same or different and are hydrogen, C.sub.1 -C.sub.6 -alkyl groups or halogen atoms, their N-oxide, their quaternary salts and their acid addition salts. There are also described processes for their production. The compounds possess especially an antischemic and blood pressure increasing activity.

摘要翻译： 制备式Ⅰ的化合物，其中R1和R2是氢或一起代表携带R1和R2的碳原子之间的第二个键，R1也可以是羟基，R3是氢，C3-C8环烷基 或C 1 -C 20烷基，其任选地还可以含有一个或两个羟基，并且基团R 4，R 5，R 6和R 7相同或不同，并且是氢，C 1 -C 6 - 烷基或卤素原子， 氧化物，它们的季盐和它们的酸加成盐。 还描述了其生产方法。 这些化合物特别具有抗缺血和增压活性。

公开(公告)号：US4335126A

公开(公告)日：1982-06-15

申请号：US193482

申请日：1980-10-03

申请人： Axel Kleemann ,  Vladimir Jakovlev ,  Klaus Thiemer ,  Jurgen Engel

发明人： Axel Kleemann ,  Vladimir Jakovlev ,  Klaus Thiemer ,  Jurgen Engel

IPC分类号： C07D295/092 ,  A61K31/495 ,  C07D295/08

CPC分类号： C07D295/088

摘要： There are prepared compounds corresponding to the general formula ##STR1## in which R.sup.1 is a hydrogen atom, a C.sub.2 to C.sub.6 -alkanoyl group, a C.sub.3 to C.sub.6 -alkenoyl group, a C.sub.3 to C.sub.6 -cycloalkyl carbonyl group, a benzoyl group, an alkoxybenzoyl group, a nicotinoyl group, a thienyl carbonyl group, a furyl carbonyl group, a phenylacetyl group or a C.sub.1 to C.sub.4 -alkoxyphenyl acetyl group and R.sup.2 represents a phenyl, naphthyl or pyridyl group or such group substituted by the groups R.sup.3 and R.sup.4, the groups R.sup.3 and R.sup.4, which may be the same or different, each representing hydrogen, hydroxyl, fluorine, chlorine, bromine, a nitro group, a trifluoromethyl group, a C.sub.1 to C.sub.6 -alkyl group, a C.sub.1 to C.sub.6 -alkoxy group, a C.sub.1 to C.sub.6 -alkyl thio group, a C.sub.1 to C.sub.6 -alkyl sulphonyl group, a C.sub.2 to C.sub.6 -alkanoyl group, an amino group, an acylamino group or an acyloxy group in which the acyl is of the type defined in respect to R.sup.1, and their salts. The compounds are pharmacodynamically active.

摘要翻译： 制备相应于通式Ⅰ的化合物，其中R 1为氢原子，C 2至C 6烷酰基，C 3至C 6链烯酰基，C 3至C 6环烷基羰基，苯甲酰基， 烷氧基苯甲酰基，烟酰基，噻吩基羰基，呋喃基羰基，苯乙酰基或C1〜C4烷氧基苯基乙酰基，R2表示苯基，萘基或吡啶基，或被基团R3和R4取代的基团 ，可以相同或不同的各自表示氢，羟基，氟，氯，溴，硝基，三氟甲基，C1至C6烷基，C1至C6-烷氧基的基团R3和R4 ，C 1至C 6烷基硫基，C 1至C 6烷基磺酰基，C 2至C 6烷酰基，氨基，酰氨基或酰氧基，其中酰基是关于 R1及其盐。 该化合物具有药效学活性。

公开(公告)号：US4263308A

公开(公告)日：1981-04-21

申请号：US112100

申请日：1980-01-14

申请人： Jurgen Engel ,  Axel Kleemann ,  Ute-Achterrath Tuckermann ,  Klaus Thiemer

发明人： Jurgen Engel ,  Axel Kleemann ,  Ute-Achterrath Tuckermann ,  Klaus Thiemer

IPC分类号： C07D409/14 ,  A61K31/4433 ,  A61K31/445 ,  C07D333/00 ,  C07D417/14

CPC分类号： C07D333/00

摘要： There are prepared compounds of the formula ##STR1## where R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydrogen or R.sub.1 and R.sub.2 together represent a second bond between the carbon atoms carrying R.sub.1 and R.sub.2, Alk is a C.sub.2 -C.sub.6 alkylene group, R.sub.3 is a C.sub.3 -C.sub.8 -cycloalkyl group, a C.sub.1 -C.sub.6 -alkyl group, a C.sub.1 -C.sub.6 -hydroxyalkyl group or a C.sub.2 -C.sub.6 -hydroxyalkoxy-C.sub.1 -C.sub.6 -alkyl group and the groups R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are the same or different and are hydrogen, C.sub.1 -C.sub.6 -alkyl group or halogen atoms, their N-oxides, their quaternary salts and their acid addition salts. There are also described processes for their production. The compounds have a strong bronchospasmolytic activity, antianaphylactic activity and an antihistamine-antiserotonine activity.

摘要翻译： 制备式为“IMAGE”的化合物，其中R 1为氢或羟基，R 2为氢或R 1和R 2一起代表携带R1和R2的碳原子之间的第二个键，Alk为C2-C6亚烷基，R3为 C 3 -C 8 - 环烷基，C 1 -C 6烷基，C 1 -C 6羟基烷基或C 2 -C 6羟基烷氧基-C 1 -C 6 - 烷基，R 4，R 5，R 6和R 7基团相同或 不同的是氢，C 1 -C 6烷基或卤原子，它们的N-氧化物，它们的季盐和它们的酸加成盐。 还描述了其生产方法。 该化合物具有强的支气管痉挛分解活性，抗过敏活性和抗组织胺 - 抗血清素活性。

公开(公告)号：US4643995A

公开(公告)日：1987-02-17

申请号：US682773

申请日：1984-12-17

申请人： Jurgen Engel ,  Vladimir Jakovlev ,  Bernd Nickel ,  Klaus Thiemer ,  Gerhard Scheffler

发明人： Jurgen Engel ,  Vladimir Jakovlev ,  Bernd Nickel ,  Klaus Thiemer ,  Gerhard Scheffler

IPC分类号： C07D401/12 ,  A61K31/435 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/46 ,  A61K31/55 ,  A61P25/04 ,  A61P29/00 ,  C07D211/54 ,  C07D213/643 ,  C07D213/70 ,  C07D213/71 ,  C07D213/89 ,  C07D243/00 ,  C07D317/00 ,  C07D405/12 ,  C07D405/14 ,  C07D451/02 ,  C07D451/06 ,  C07D453/02

CPC分类号： C07D213/70 ,  C07D211/54 ,  C07D213/89 ,  C07D401/12 ,  C07D405/14 ,  C07D451/06 ,  C07D453/02

摘要： There are disclosed pyridine-2-ethers and pyridine-2-thioethers having a nitrogen-containing cycloaliphatic ring corresponding to the formula ##STR1## the pyridine-N-oxides and/or amine oxides thereof and the pharmaceutically acceptable salts thereof. The compounds show analgesic activity.

摘要翻译： 公开了具有对应于式I的吡啶-N-氧化物和/或氧化胺及其药学上可接受的盐的含氮脂环族的吡啶-2-醚和吡啶-2-硫醚。 化合物显示止痛活性。

公开(公告)号：US4547505A

公开(公告)日：1985-10-15

申请号：US583324

申请日：1984-02-24

申请人： Gerhard Oepen ,  Jurgen Engel ,  Vladimir Jakovlev ,  Klaus Thiemer

发明人： Gerhard Oepen ,  Jurgen Engel ,  Vladimir Jakovlev ,  Klaus Thiemer

IPC分类号： C07D295/18 ,  A61K31/495 ,  A61K31/496 ,  A61P25/04 ,  A61P29/00 ,  C07D213/74 ,  C07D239/42 ,  C07D241/20 ,  C07D295/185 ,  A61K31/505 ,  C07D241/02 ,  C07D403/00

CPC分类号： C07D239/42 ,  C07D213/74 ,  C07D241/20 ,  C07D295/185

摘要： There are prepared new pharmacologically active compounds of the formula: ##STR1## In formula I R.sub.1 is a phenyl radical, pyridyl radical, a pyrimidyl group, or pyrazinyl radical, or a phenyl radical, pyridiyl radical, pyrimidyl radical, or pyrazinyl radical substituted by the radicals R.sub.3 and R.sub.4 which are the same or different and are hydrogen, fluorine, chlorine, bromine, trifluoromethyl, hydroxyl, C.sub.1 -C.sub.6 -alkyl groups C.sub.1 -C.sub.6 -alkoxy groups, C.sub.3 -C.sub.6 -alkenyloxy groups, C.sub.3 -C.sub.6 -cycloalkyloxy groups, phenyl-C.sub.1 -C.sub.4 -alkoxy groups, C.sub.1 -C.sub.6 -alkylmercapto groups, the nitro group, the amino group, C.sub.1 -C.sub.6 -dialkylamino groups, C.sub.2 -C.sub.6 -alkanoyl groups, C.sub.2 -C.sub.6 -alkanoylamino groups, or C.sub.2 -C.sub.6 -alkanoyloxy groups and R.sub.2 is the adamantyl group, the 3,3-dimethyl-bicyclo[2.2.1]hept-2-yl radical, a saturated C.sub.3 -C.sub.16 -cycloalkenyl radical and alk is a straight or branched C.sub.1 -C.sub.6 alkyl chain.

摘要翻译： 制备下式的新的药理学活性化合物：在式Ⅰ中R1是苯基，吡啶基，嘧啶基或吡嗪基，或苯基，吡啶基，嘧啶基或吡嗪基自由基取代基 由相同或不同且为氢，氟，氯，溴，三氟甲基，羟基，C 1 -C 6烷基，C 1 -C 6 - 烷氧基，C 3 -C 6 - 烯氧基，C 3 -C 6 - C 1 -C 6烷基巯基，C 1 -C 6烷基巯基，硝基，氨基，C 1 -C 6二烷基氨基，C 2 -C 6烷酰基，C 2 -C 6烷酰基氨基或C 2 -C 6烷酰基氨基 -C 6 - 烷酰氧基，R 2是金刚烷基，3,3-二甲基 - 双环[2.2.1]庚-2-基，饱和C 3 -C 16 - 环烯基，alk是直链或支链C 1 -C 6 烷基链。

公开(公告)号：US4946836A

公开(公告)日：1990-08-07

申请号：US399439

申请日：1989-08-28

申请人： Jurgen Engel ,  Axel Kleemann ,  Bernd Nickel ,  Istvan Szelenyi

发明人： Jurgen Engel ,  Axel Kleemann ,  Bernd Nickel ,  Istvan Szelenyi

IPC分类号： A61K31/4427 ,  A61K31/445 ,  A61P25/04 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D401/12

摘要： Compounds of formula ##STR1## wherein the radicals R.sub.1 and R.sub.2 are the same or different and represent hydrogen, halogen atoms, a trifluoromethyl group, a cyano, a nitro group, an amino group, a mono-C.sub.1 -C.sub.6 -alkylamino group, a di-C.sub.1 -C.sub.6 -alkylamino group, an amino group that is substituted by a phenyl C.sub.1 -C.sub.4 -alkyl radical, a C.sub.2 -C.sub.6 -alkanoyl-amino group, a C.sub.1 -C.sub.6 -alkoxycarbonyl amino group, a C.sub.1 -C.sub.6 -alkyl group optionally substituted by a phenyl radical, a hydroxy group, a C.sub.1 -C.sub.6 -alkoxy group, a C.sub.2 -C.sub.6 -alkanoyloxy group, a phenoxy group or represent a carbamoyl group optionally substituted by one or two C.sub.1 -C.sub.6 -alkyl groups and the radical A is an acyl group which is derived from an amino acid as well as processes for their preparation.

摘要翻译： 其中基团R 1和R 2相同或不同并表示氢，卤原子，三氟甲基，氰基，硝基，氨基，单C 1 -C 6 - 烷基氨基， 二C1-C6烷基氨基，被苯基C1-C4-烷基取代的氨基，C2-C6-烷酰基 - 氨基，C1-C6-烷氧基羰基氨基，C1-C6-烷基 任选被苯基，羟基，C 1 -C 6 - 烷氧基，C 2 -C 6 - 烷酰氧基，苯氧基取代的基团，或表示任选被一个或两个C 1 -C 6 - 烷基取代的氨基甲酰基， 基团A是衍生自氨基酸的酰基以及它们的制备方法。

公开(公告)号：US4716242A

公开(公告)日：1987-12-29

申请号：US704465

申请日：1985-02-22

申请人： Jurgen Engel ,  Axel Kleemann ,  Ulf Niemeyer ,  Peter Hilgard ,  Joerg Pohl

发明人： Jurgen Engel ,  Axel Kleemann ,  Ulf Niemeyer ,  Peter Hilgard ,  Joerg Pohl

IPC分类号： C07F9/24 ,  A61K31/675 ,  A61P35/00 ,  A61P35/02 ,  C07F9/22 ,  C07F9/6584 ,  C07F9/40

CPC分类号： C07F9/65846

摘要： There are provided new antitumor salts of oxazaphosphorine derivatives of the formula ##STR1## where R.sub.1, R.sub.2, and R.sub.3 are the same or different and represent hydrogen, methyl, ethyl, 2-chloroethyl, or 2-methanesulfonyloxyethyl and wherein at least two of these residues are 2-chloroethyl and/or 2-methanesulfonyl-oxyethyl and A is the group --S--alk--SO.sub.3 H or --N(OH)--CONH--alk--CO.sub.2 H and alk represents a C.sub.2 -C.sub.6 -alkylene residue optionally containing a mercapto group, whereby alk also can be --CH.sub.2 -- in case there is a carboxy group attached to the alk group, with homocysteinethiolactone or .alpha.-amino-.epsilon.-caprolactam or a basic compound of the formula: ##STR2## wherein R.sub.4 is a hydroxy group, an amino group or a C.sub.1 -C.sub.6 -alkoxy group, R.sub.5 is hydrogen or a difluoromethyl group, R.sub.6 is hydrogen, an indolyl-(3)-methyl residue, imidazolyl-(4)-methyl residue, a C.sub.1 -C.sub.10 -alkyl group or a C.sub.1 -C.sub.10 -alkyl group which is substituted by a hydroxy group, a C.sub.1 -C.sub.6 -alkoxy group, a mercapto group, a C.sub.1 -C.sub.6 -alkylmercapto group, a phenyl group, a hydroxy phenyl group, an amino-C.sub.1 -C.sub.6 -alkylmercapto group, an amino-C.sub.1 -C.sub.6 -alkoxy group, an amino group, an aminocarbonyl group, a ureido group (H.sub.2 NCONH--), a guanidino group or a C.sub.1 -C.sub.6 -alkoxycarbonyl group, or wherein R.sub.6 together with the structured portion >CR.sub.5 (NR.sub.7 R.sub.8) forms the proline residue, the 4-hydroxy-proline residue or the 2-oxo-3-amino-3-difluoromethyl-piperidine and the residues R.sub.7 and R.sub.8 represent hydrogen or C.sub.1 -C.sub.6 -alkyl residues.

摘要翻译： 提供了新的式（ⅩⅧ）的恶唑烷磷衍生物的抗肿瘤盐，其中R 1，R 2和R 3相同或不同，代表氢，甲基，乙基，2-氯乙基或2-甲磺酰氧基乙基，其中这些 残基是2-氯乙基和/或2-甲磺酰氧基乙基，A是-S-烷基-SO 3 H或-N（OH）-CONH-烷基-CO 2 H，烷基代表任选含有巯基的C 2 -C 6亚烷基 其中烷基也可以是-CH 2 - ，如果存在与烷基连接的羧基，具有同半胱氨酸硫内酯或α-氨基 - ε-己内酰胺或下式的碱性化合物：其中R 4是羟基 基团，氨基或C1-C6-烷氧基，R5是氢或二氟甲基，R6是氢，吲哚基 - （3） - 甲基残基，咪唑基 - （4） - 甲基残基，C1-C10- 烷基或被羟基，C1-C6-烷氧基，巯基，C1-C6烷基巯基取代的C1-C10-烷基 基团，苯基，羟基苯基，氨基-C 1 -C 6烷基巯基，氨基-C 1 -C 6烷氧基，氨基，氨基羰基，脲基（H 2 NCONH-），胍基 或C 1 -C 6烷氧基羰基，或其中R 6与结构部分> CR 5（NR 7 R 8）一起形成脯氨酸残基，4-羟基 - 脯氨酸残基或2-氧代-3-氨基-3-二氟甲基 - 哌啶和 残基R7和R8表示氢或C1-C6烷基残基。

公开(公告)号：US08173592B1

公开(公告)日：2012-05-08

申请号：US09523455

申请日：2000-03-10

申请人： Jurgen Engel ,  Hilde Riethmuller-Winzen

发明人： Jurgen Engel ,  Hilde Riethmuller-Winzen

IPC分类号： A61K38/00 ,  A61K38/24 ,  A61K38/09 ,  A61P15/08 ,  A61P15/16 ,  A61P15/18 ,  A61P5/06 ,  A61P5/24 ,  A61P5/02 ,  C07K14/59

CPC分类号： A61K38/24 ,  Y10S514/841 ,  A61K38/09 ,  A61K31/565 ,  A61K2300/00

摘要： A method of therapeutic management of infertility by programming of controlled ovarian stimulation and assisted reproductive procedures is disclosed containing the steps of a) suppression of premature ovulation with an LHRH-antagonist in controlled ovarian stimulation and assisted reproductive techniques with multiple follicle and oocyte development; b) programming the start of controlled ovarian stimulation by the administration to a patient of progestogen only-preparations or, alternatively, combined oral contraceptive preparations; c) exogenous stimulation of the ovarian follicle growth; d) ovulation induction with HCG, native LHRH, LHRH-agonists or recombinant LH; and e) application of assisted reproduction techniques, especially of IVF, ICSI, GIFT, ZIFT or by intrauterine insemination by sperm injection, wherein onset of the patient's menstrual cycle and of controlled ovarian stimulation are programmed in order to perform oocyte pickup and fertilization procedures during Mondays to Fridays.

摘要翻译： 公开了通过编程控制的卵巢刺激和辅助生殖过程治疗不育症的方法，其包括以下步骤：a）在受控的卵巢刺激中抑制LHRH拮抗剂的过早排卵和具有多次卵泡和卵母细胞发育的辅助生殖技术; b）通过给予仅孕激素制剂的患者或替代地联合的口服避孕制剂来编程控制卵巢刺激的开始; c）外源性刺激卵泡生长; d）用HCG，天然LHRH，LHRH激动剂或重组LH排卵诱导; 和e）应用辅助生殖技术，特别是IVF，ICSI，GIFT，ZIFT或通过精子注射子宫内授精的辅助生殖技术的应用，其中对患者的月经周期和受控的卵巢刺激的发​​作进行编程以在卵母细胞摄取和施肥过程中进行 周一至周五

公开(公告)号：US20070161571A1

公开(公告)日：2007-07-12

申请号：US11711235

申请日：2007-02-27

申请人： Werner Sarlikiotis ,  Horst Bauer ,  Matthias Rischer ,  Jurgen Engel ,  Frank Guthlein ,  Dominique Di Stefano

发明人： Werner Sarlikiotis ,  Horst Bauer ,  Matthias Rischer ,  Jurgen Engel ,  Frank Guthlein ,  Dominique Di Stefano

IPC分类号： A61K38/09 ,  A61K31/19

CPC分类号： A61K31/19 ,  A61K9/0019 ,  A61K38/09 ,  A61K47/26

摘要： An aqueous injectable solution of an LHRH antagonist, such as Cetrorelix, in an organic, pharmaceutically acceptable acid, such as gluconic acid.

摘要翻译： LHRH拮抗剂的注射用水溶液，例如Cetrorelix，在有机的药学上可接受的酸如葡萄糖酸中。