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17 条记录 (耗时 0.034 秒)

    Piperazine oxime dervatives having NK-1 receptor antagonistic activity
    1.
    发明授权
    Piperazine oxime dervatives having NK-1 receptor antagonistic activity 有权
    具有NK-1受体拮抗活性的哌嗪肟衍生物

    公开(公告)号：US07094779B2

    公开(公告)日：2006-08-22

    申请号：US10480542

    申请日：2002-07-03

    申请人： Wouter I. Iwema Bakker ,  Jan H. van Maarseveen ,  Hein K. A. C. Coolen ,  Martinus Th. M. Tulp ,  Arnoldus H. J. Herremans ,  Andrew C. Mccreary ,  Gustaaf J. M. van Scharrenburg ,  Adrianus van den Hoogenband

    发明人： Wouter I. Iwema Bakker ,  Jan H. van Maarseveen ,  Hein K. A. C. Coolen ,  Martinus Th. M. Tulp ,  Arnoldus H. J. Herremans ,  Andrew C. Mccreary ,  Gustaaf J. M. van Scharrenburg ,  Adrianus van den Hoogenband

    IPC分类号： A61K31/496 ,  C07D403/06 ,  C07D413/14 ,  C07D471/04

    CPC分类号： C07D401/14 ,  C07D241/04 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/14 ,  C07D409/06 ,  C07D471/04

    摘要： The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH3, CF3, OCH3, halogen, cyano and 5-CF3-tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1–3C); n has the value 0–3; m has the value 0–2; R1 represents NH2, NH-alkyl (1–3C), dialkyl (1–3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH3-piperazinyl; R2 is hydrogen, alkyl (1–4C) or phenyl, or R2 together with (CH2)m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R3 and R4 independently represent hydrogen or methyl, or R3 and R4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved

    摘要翻译： 本发明涉及一组具有有趣的NK-1拮抗活性的新型哌嗪肟衍生物。 本发明涉及通式（1）的化合物，其中：X表示苯基或被1或2个取代基取代的吡啶基，其中CH 3，CF 3，OCH 3， N 3，卤素，氰基和5-CF 3 - 四唑-1-基; Y代表2-或3-吲哚基，苯基，7-氮杂 - 吲哚-3-基或3-吲唑基，2-萘基，3-苯并[b]噻吩基，2-苯并呋喃基，它们可以被一个或多个 卤素或烷基（1-3C）; n的值为0-3; m的值为0-2; R 1表示NH 2，NH-烷基（1-3C），（1-3C）二烷基，吗啉代或吗啉基，被一或两个甲基和/或甲氧基甲基 基团，硫代吗啉代，1,1-二氧代硫代吗啉代，2-，3-或4-吡啶基或4- CH 3 - 哌嗪基; R 2是氢，烷基（1-4C）或苯基，或R 2和（CH 2 CH 2）m， 其中m为1，中间碳，氮和氧原子形成异恶唑基或4,5-二氢异恶唑基; R 3和R 4独立地代表氢或甲基，或R 3和R 4一起是氧。 本发明还涉及一种制备新化合物的方法，以及包含式（1）化合物作为活性成分的药物组合物，以及这些化合物用于治疗涉及神经激肽-1受体的疾病的用途

    Diazabicyclo alkane derivatives with NK1 antagonistic activity
    3.
    发明授权
    Diazabicyclo alkane derivatives with NK1 antagonistic activity 有权
    具有NK1拮抗活性的二氮杂双环烷烃衍生物

    公开(公告)号：US07202238B2

    公开(公告)日：2007-04-10

    申请号：US10490364

    申请日：2003-04-02

    申请人： Dirk de Boer ,  Hein K. A. C. Coolen ,  Mayke B. Hesselink ,  Wouter I. Iwema Bakker ,  Gijsbert D. Kuil ,  Jan H. van Maarseveen ,  Andrew C. McCreary ,  Gustaaf J. M. van Scharrenburg

    发明人： Dirk de Boer ,  Hein K. A. C. Coolen ,  Mayke B. Hesselink ,  Wouter I. Iwema Bakker ,  Gijsbert D. Kuil ,  Jan H. van Maarseveen ,  Andrew C. McCreary ,  Gustaaf J. M. van Scharrenburg

    IPC分类号： A01N43/00 ,  A01N43/58 ,  A01N43/50 ,  A61K31/55 ,  C07D241/36

    CPC分类号： C07D471/04 ,  C07D487/04

    摘要： The present invention relates to a group of unique diazabicyclo alkane derivatives having interesting neurokinin-NK1 receptor antagonistic activity represented by the general formula (1) wherein: R1 represents phenyl, 2-indolyl, 3-indolyl, 3-indazolyl or benzo[b]thiophen-3-yl, which groups may be substituted with halogen or alkyl (1–3C), R2 and R3 independently represent halogen, H, OCH3, CH3 and CF3, R4, R5 and R6 independently represent H, OH, O-alkyl(1–4C), CH2OH, NH2, dialkyl(1–3C)N, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or morpholin-4-yl substituted with one or two methyl or methoxymethyl groups, morpholin-4-ylamino, morpholin-4-ylmethyl, imidazol-1-yl, thiomorpholin-4-yl, 1,1-dioxothiomorpholin-4-yl or 3-oxa-8-azabicyclo[3.2.1]oct-8-yl; R4 and R5 together may represent a keto, a 1,3-dioxan-2-yl or a 1,3-dioxolan-2-yl group, X represents either O or S, n has the value of 1, 2 or 3, a is the asymmetrical carbon atom 8a, 9a or 10a when n equals 1, 2 or 3 respectively The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions containing at least one of these compounds as an active ingredient

    摘要翻译： 本发明涉及具有由通式（1）表示的具有感兴趣的神经激肽NK 1受体拮抗作用的独特的二氮杂双环烷烃衍生物组，其中：R 1表示苯基， 2-吲哚基，3-吲哚基，3-吲唑基或苯并[b]噻吩-3-基，该基团可被卤素或烷基（1-3C），R 2和R 2 > 3个独立地表示卤素，H，OCH 3，CH 3和CF 3，R 4， >，R 5和R 6独立地表示H，OH，O-烷基（1-4C），CH 2 OH，NH （1-3C）N，吡咯烷-1-基，哌啶-1-基，吗啉-4-基或被一个或两个甲基或甲氧基甲基取代的吗啉-4-基，吗啉代 - 吡啶-4-基氨基，吗啉-4-基甲基，咪唑-1-基，硫代吗啉-4-基，1,1-二氧代硫代吗啉-4-基或3-氧杂-8-氮杂双环[3.2.1]辛-8-基; R 4和R 5一起可以表示酮基，1,3-二氧杂环戊烷-2-基或1,3-二氧戊环-2-基，X表示 O或S，n的值为1,2或3，当n分别为1,2或3时，a为非对称碳原子8a，9a或10a。本发明还涉及一种制备新化合物的方法 以及含有这些化合物中的至少一种作为活性成分的药物组合物

    Bisaryl (thio)morpholine derivatives as S1P modulators
    7.
    发明授权
    Bisaryl (thio)morpholine derivatives as S1P modulators 有权
    二芳基（硫代）吗啉衍生物作为S1P调节剂

    公开(公告)号：US09029371B2

    公开(公告)日：2015-05-12

    申请号：US13808900

    申请日：2011-07-08

    申请人： Wouter I. Iwema Bakker ,  Raymond Bronger

    发明人： Wouter I. Iwema Bakker ,  Raymond Bronger

    IPC分类号： C07D295/15 ,  C07D265/30 ,  C07D413/10 ,  A61K31/5377 ,  A61K31/5375

    CPC分类号： A61K31/5375 ,  A61K31/5377 ,  A61K31/54 ,  C07D265/30 ,  C07D295/15 ,  C07D413/10

    摘要： The present invention relates to bisaryl (thio)morpholine derivatives of the formula (I) or a pharmaceutically acceptable salt, a solvate or hydrate thereof, with the proviso that the derivative of formula (I) is not 2-[4-(4-chlorophenoxy)-2-chlorophenyl]-4 -morpholineethanol. The compounds of the invention have affinity to S1 Preceptors and may be used in the treatment, alleviation or prevention of S1 Preceptor mediated diseases and conditions.

    摘要翻译： 本发明涉及式（I）的二芳基（硫代）吗啉衍生物或其药学上可接受的盐，溶剂合物或水合物，条件是式（I）的衍生物不是2- [4-（4- 氯苯氧基）-2-氯苯基] -4-吗啉乙醇。 本发明的化合物对S1受体具有亲和力，可用于治疗，缓解或预防S1受体介导的疾病和病症。

    BISARYL (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS
    9.
    发明申请
    BISARYL (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS 有权

    公开(公告)号：US20130203745A1

    公开(公告)日：2013-08-08

    申请号：US13808900

    申请日：2011-07-08

    申请人： Wouter I. Iwema Bakker ,  Raymond Bronger

    发明人： Wouter I. Iwema Bakker ,  Raymond Bronger

    IPC分类号： C07D295/15

    CPC分类号： A61K31/5375 ,  A61K31/5377 ,  A61K31/54 ,  C07D265/30 ,  C07D295/15 ,  C07D413/10

    摘要： The present invention relates to bisaryl(thio)morpholine derivatives of the formula (I) wherein R1 is an aryl substitutent selected from phenyl, pyridyl, pyrimidinyl, biphenyl and naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino, —SO2-(1-4C)alkyl, —CO-(1-4C)alkyl, —CO—O-(1-4C)alkyl and —NH—CO-(1-4C)alkyl, or substituted with phenoxy, benzyl, benzyloxy, phenylethyl or morpholinyl, each optionally substituted with (1-4C)alkyl, and (8-10C)bicyclic group, bicyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms or oxo; A is selected from —CO—, —NH—, —O—, —S—, —SO— or —SO2—; ring structure B optionally contains one nitrogen atom; R2 is H, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, or halogen; and R3 is (1-4C)alkylene-R6 wherein the alkylene group may be substituted with (CH2)2 to form a cyclopropyl moiety or with one or more halogen atoms, or R3 is (3-6C)cycloalkylene-R5 or —CO—CH2—R6, wherein R6 is —OH, —PO3H2, —OPO3H2, —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; R4 is H or (1-4C)alkyl; R5 is one or more substituents independently selected from H, (1-4C)alkyl or oxo; W is —O—, —S—, —SO— or —SO2—; or a pharmaceutically acceptable salt, a solvate or hydrate thereof, with the proviso that the derivative of formula (I) is not 2-[4-(4-chlorophenoxy)-2-chloro-phenyl]-4-morpholineethanol. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of S1P receptor mediated diseases and conditions.

    FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS
    10.
    发明申请
    FUSED HETEROCYCLIC DERIVATIVES AS S1P MODULATORS 有权

    公开(公告)号：US20130203737A1

    公开(公告)日：2013-08-08

    申请号：US13808908

    申请日：2011-07-08

    申请人： Pieter Smid ,  Wouter I. Iwema Bakker ,  Hein K.A.C. Coolen ,  Leonardus A.J.M. Sliedregt ,  Maria J.P. van Dongen ,  Jacobus A.J. den Hartog

    发明人： Pieter Smid ,  Wouter I. Iwema Bakker ,  Hein K.A.C. Coolen ,  Leonardus A.J.M. Sliedregt ,  Maria J.P. van Dongen ,  Jacobus A.J. den Hartog

    IPC分类号： C07D513/04 ,  C07D495/04 ,  C07D487/04 ,  C07D471/04 ,  C07D491/048 ,  C07D498/04

    CPC分类号： C07D491/048 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04

    摘要： The present invention relates to a fused heterocyclic derivative of the formula (I) wherein R1 is selected from cyano, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl, each optionally substituted with CN or one or more fluoro atoms, (3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, dimethylamino, and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen, and phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl, Z is a linking group —W—(Cn-alkylene)-T- wherein W is attached to R1 and selected from a bond, —O—, —CO—, —S—, —SO—, —SO2—, —NH—, —CH═CH—, —C(CF3)═CH—, —C≡C—, —CH2—O—, —O—CO—, —CO—O—, —CO—NH—, —NH—CO— and trans-cyclopropylene; n is an integer from 0 to 10; and T is attached to the phenylene/pyridyl moiety and selected from a bond, —O—, —S—, —SO—, —SO2—, —NH—, —CO—, —C═C—, —C≡C—, and trans-cyclopropylene; R2 is H or one or more substituents independently selected from cyano, halogen, (1-4C)alkyl optionally substituted with one or more halogen atoms, or (1-4C)alkoxy optionally substituted with one or more halogen atoms; ring structure A may contain one nitrogen atom; X is selected from C or N; if X is C, R3 is selected from H and (1-4C)alkyl, otherwise R3 is not present; Y is selected from NH, O and S; structure Q is a 5-, 6- or 7-membered cyclic amine; and R4 is (1-4C)alkylene-R5 wherein one or more carbon atoms in the alkylene group may independently be substituted with one or more halogen atoms or with (CH2)2 to form a cyclopropyl moiety, or R4 is (3-6C)cycloalkylene-R5, —CH2-(3-6C)cycloalkylene-R5, (3-6C)cycloalkylene-CH2-R5 or —CO—CH2-R5, wherein R5 is —OH, —PO3H2, —OPO3H2, —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof. The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (any) S1P receptor(s) is (are) involved or in which modulation of the endogenous S1P signaling system via any S1P receptor is involved.