专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

WO2009016132A1 PYRROLOPYRIMIDINES 审中-公开
标题翻译：的吡咯
公开(公告)号：WO2009016132A1
公开(公告)日：2009-02-05
申请号：PCT/EP2008/059833
申请日：2008-07-25
申请人： JANSSEN PHARMACEUTICA NV , DIELS, Gaston Stanislas Marcella , TEN HOLTE, Peter , FREYNE, Eddy Jean Edgard , GRAND-PERRET, Thierry Andre Regis , VAN EMELEN, Kristof , EMBRECHTS, Werner Constant Johan , BONNET, Pascal Ghislain André
发明人： DIELS, Gaston Stanislas Marcella , TEN HOLTE, Peter , FREYNE, Eddy Jean Edgard , GRAND-PERRET, Thierry Andre Regis , VAN EMELEN, Kristof , EMBRECHTS, Werner Constant Johan , BONNET, Pascal Ghislain André
IPC分类号： C07D487/08 , C07D498/08 , A61K31/529 , A61P35/02
CPC分类号： C07D498/08 , C07D487/08
摘要： The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumour growth, rheumatoid arthritis, restenosis and atherosclerosis.
摘要翻译：本发明涉及其化合物或药学上可接受的盐，其制备方法，含有它们的药物组合物及其在治疗中的用途。本发明特别涉及可用于治疗由PLK，特别是PLK4介导的疾病状态的polo样激酶（PLK）抑制剂的化合物，特别是可用于治疗涉及异常细胞增殖的病理过程的此类化合物，如肿瘤生长，类风湿关节炎，再狭窄和动脉粥样硬化。

2. 发明申请

WO2003015776A1 2,4,5-TRISUBSTITUTED THIAZOLYL DERIVATIVES AND THEIR ANTIINFLAMMATORY ACTIVITY 审中-公开
标题翻译： 2,4,5-三唑衍生物及其抗炎活性
公开(公告)号：WO2003015776A1
公开(公告)日：2003-02-27
申请号：PCT/EP2002/008956
申请日：2002-08-09
申请人： JANSSEN PHARMACEUTICA N.V. , LOVE, Christopher, John , VAN WAUWE, Jean, Pierre, Frans , DE BRABANDER, Marc, J. , MOSES, Roger, Clive , GONCHARENKO, Mykhalyo , COOYMANS, Ludwig, Paul , VANDERMAESEN, Nele , DIELS, Gaston, Stanislas, Marcella , SIBLEY, Anthony, William , NOULA, Caterina
发明人： LOVE, Christopher, John , VAN WAUWE, Jean, Pierre, Frans , DE BRABANDER, Marc, J. , MOSES, Roger, Clive , GONCHARENKO, Mykhalyo , COOYMANS, Ludwig, Paul , VANDERMAESEN, Nele , DIELS, Gaston, Stanislas, Marcella , SIBLEY, Anthony, William , NOULA, Caterina
IPC分类号： A61K31/426
CPC分类号： C07D417/04 , C07D277/28 , C07D417/14
摘要： This invention concerns the use of a compound of formula (I), a N -oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein Z is halo; C 1-6 alkyl; C 1-6 alkyl substituted with hydroxy, carboxyl, cyano, amino, mono -or di(C 1-6 alkyl)amino, aminocarbonyl, mono -or di(C 1-6 alkyl)aminocarbonyl, C 1-6 alkyloxycarbonyl or C 1-6 alkyloxy; polyhaloC 1-4 alkyl; C 1-4 alkyloxy; cyano; amino; aminocarbonyl; mono -or di(C 1-6 alkyl)aminocarbonyl; C 1-6 alkyloxycarbonyl; C 1-6 alkylcarbonyloxy; H 2 N-S(=O) 2 -; mono -or di(C 1-6 alkyl)amino-S(=O) 2 ; -C(=N-R x )NR y R z ; Q is an optionally substituted carbocycle or an optionally substituted heterocycle; L is substituted phenyl or an optionally substituted monocyclic 5 or 6-membered partially saturated or aromatic heterocycle or a bicyclic partially saturated or aromatic heterocycle; aryl is optionally substituted phenyl; for the manufacture of a medicament for the prevention or the treatment of diseases mediated through TNF-α and/or IL-12.
摘要翻译：本发明涉及式（I）化合物，其N-氧化物，其药学上可接受的加成盐，季胺及其立体化学异构体形式的用途，其中Z为卤素; C1-6烷基; 被羟基，羧基，氰基，氨基，单 - 或二（C 1-6烷基）氨基，氨基羰基，单 - 或二（C 1-6烷基）氨基羰基，C 1-6烷氧基羰基或C 1-6烷氧基取代的C 1-6烷基; polyhaloC1-4alkyl; C1-4alkyloxy; 氰基; 氨基; 羰基; 单 - 或二（C 1-6烷基）氨基羰基; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; H 2 N-S（= O）2 - ; 单 - 或二（C 1-6烷基）氨基-S（= O）2; -C（= NR ）NR - [R ; Q是任选取代的碳环或任选取代的杂环; L是取代的苯基或任选取代的单环5或6元部分饱和或芳族杂环或双环部分饱和或芳族杂环; 芳基是任选取代的苯基; 用于制备用于预防或治疗通过TNF-α和/或IL-12介导的疾病的药物。

3. 发明申请

WO1992006086A1 NOVEL 4-PIPERIDINYLCARBONYL DERIVATIVES 审中-公开
标题翻译：新型4-哌啶子基衍生物
公开(公告)号：WO1992006086A1
公开(公告)日：1992-04-16
申请号：PCT/EP1991001782
申请日：1991-09-17
申请人： JANSSEN PHARMACEUTICA N.V. , JANSSENS, Frans, Eduard , DIELS, Gaston, Stanislas, Marcella , SOMMEN, François, Maria
发明人： JANSSEN PHARMACEUTICA N.V.
IPC分类号： C07D401/06
CPC分类号： C07D401/06 , C07D401/14 , C07D405/14 , C07D413/14 , C07D471/04 , C07D473/08 , C07D513/04
摘要： 4-piperidinylcarbonyl derivatives having formula (I), wherein -A =A -A =A - is a bivalent radical having the formula -CH=CH-CH=CH- (a-1), -N=CH-CH=CH- (a-2), -CH=N-CH=CH- (a-3), -CH=CH-N=CH- (a-4), -CH=CH-CH=N- (a-5), -N=CH-N=CH- (a-6) or -CH=N-CH=N- (a-7); R is aryl or a radical of formula -D-R wherein D is O or S; R is C1-6alkyl optionally substituted with hydroxy, C1-6alkyloxy, carboxyl or C1-6alkyloxy-carbonyl; m is 1, 2, 3 or 4; n is 0, 1 or 2; L is hydrogen; C1-12alkyl; C3-6cycloalkyl; C3-6alkenyl optionally substituted with aryl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; arylcarbonyl; arylC1-6alkyloxycarbonyl; -Alk-R (b-1); -Alk-Y-R (b-2); -Alk-Z -C(=X)-Z -R (b-3); -CH2-CHOH-CH2-O-R (b-4) or -Alk-CHOH-R (b-5); wherein Alk is C1-6alkanediyl; R is cyano, aryl or Het; R and R are hydrogen, aryl, Het or C1-6alkyl optionally substituted with aryl or Het; R is aryl or naphthalenyl; R is aryl; Y is O, S, NR ; said R being hydrogen, C1-6alkyl or C1-6alkylcarbonyl; Z and Z independently are O, S, NR or a direct bond; R being hydrogen or C1-6alkyl; X is O, S or NR ; said R being hydrogen, C1-6alkyl or cyano; provided that when -A =A -A =A - is a radical of formula (a-1) and R is phenyl optionally substituted with C1-6alkyl, C1-6alkyloxy, halo or hydroxy; then L is other than hydrogen, C1-6alkyloxycarbonyl or other than a radical of formula -Alk-R (b-1), -Alk-O-R (b-2-a), -Alk-C(=O)-R (b-3-a) or -Alk-CHOH-R (b-5) wherein R , R , R and R are phenyl optionally substituted with halo, hydroxy, C1-6alkyl, C1-6alkyloxy, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof having antihistaminic properties, compositions containing the same and methods of treating warm-blooded animals suffering from allergic diseases.
摘要翻译：具有式（I）的4-哌啶基羰基衍生物，其中-A 1 = A 2 -A 3 = A 4 - 是式-CH = CH-CH = CH-的二价基团（a -1），-N = CH-CH = CH-（a-2），-CH = N-CH = CH-（a-3），-CH = CH-N = CH-（a-4） CH = CH-CH = N-（a-5），-N = CH-N = CH-（a-6）或-CH = N-CH = N-（a-7） R 1是芳基1或式-D-R 2的基团，其中D是O或S; R 2是任选被羟基，C 1-6烷氧基，羧基或C 1-6烷氧基 - 羰基取代的C 1-6烷基; m为1,2,3或4; n为0,1或2; L是氢; C1-12烷基; 3-6环; 任选被芳基取代的C 3-6烯基; C1-6烷基; C1-6alkyloxycarbonyl; 基羰基; arylC1-6alkyloxycarbonyl; -Alk-R 3（b-1）; -Alk-Y-R 4（b-2）; -Alk-Z 1 -C（= X）-Z 2 -R 5（b-3）; -CH 2 -CHOH -CH 2 -O-R 6（b-4）或-Alk-CHOH-R 14（b-5）; 其中Alk是C1-6烷二基; R 3是氰基，芳基或Het; R 4和R 5是氢，芳基，Het或任选被芳基或Het取代的C 1-6烷基; R 6是芳基或萘基; R 14是芳基; Y是O，S，NR 7; 所述R 7为氢，C 1-6烷基或C 1-6烷基羰基; Z 1和Z 2独立地是O，S，NR 8或直接键; R 8是氢或C 1-6烷基; X是O，S或NR 9; 所述R 9为氢，C 1-6烷基或氰基; 条件是当-A 1 = A 2 -A 3 3 = A 4 - 是式（a-1）的基团时，R 1是任选被C 1-6烷基取代的苯基，C 1〜 6-烷氧基，卤素或羟基; 那么L不是氢，C 1-6烷氧基羰基或不同于式-Alk-R 3（b-1），-Alk-OR 4（b-2-a），-Alk-C（ = O）-R 5（b-3-a）或-Alk-CHOH-R 14（b-5）其中R 3，R 4，R 5和R 14，任选被卤素，羟基，C 1-6烷基，C 1-6烷氧基，具有抗组氨酸性质的药学上可接受的酸加成盐和立体化学异构体形式，含有该组合物的组合物和治疗患有过敏性疾病的温血动物的方法的苯基。

4. 发明申请

WO1996031487A1 1,3-DIHYDRO-2H-IMIDAZOL-2-ONE DERIVATIVES HAVING PDE IV AND CYTOKININ INHIBITING ACTIVITY 审中-公开
标题翻译：具有PDE IV和细胞因子抑制活性的1,3-二氢-2H-咪唑-2-酮衍生物
公开(公告)号：WO1996031487A1
公开(公告)日：1996-10-10
申请号：PCT/EP1996001393
申请日：1996-03-28
申请人： JANSSEN PHARMACEUTICA N.V. , FREYNE, Eddy, Jean, Edgard , DIELS, Gaston, Stanislas, Marcella , ANDRES-GIL, José, Ignacio , FERNANDEZ-GADEA, Francisco, Javier
发明人： JANSSEN PHARMACEUTICA N.V.
IPC分类号： C07D233/70
CPC分类号： C07D405/04 , C07D233/32 , C07D233/70
摘要： The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R and R each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; R is hydrogen, halo or C1-6alkyloxy; =C=X is a bivalent radical of formula =C=O; =C=CH-R ; =C=N-O-R ; or formula (a-4); Alk is C1-4alkanediyl; -A-B- is a bivalent radical of formula: -CR =CR - or -CHR -CHR -; L is hydrogen; optionally substituted C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; optionally substituted C3-6alkenyl; optionally substituted piperidinyl; C1-6alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het is morpholinyl or optionally substituted pyridinyl, -furanyl, -thienyl, -hydroxypyridinyl, -imidazolyl, -thiazolyl, -oxazolyl, -isoquinolinyl, -quinolinonyl, -piperidinyl, -piperazinyl; and Het is morpholinyl or optionally substituted piperidinyl, -piperazinyl, -pyridinyl, -furanyl or -thienyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的酸或碱加成盐及其立体化学异构形式，其中R 1和R 2各自独立地为氢; C1-6烷基; 二氟; 三氟甲基; 3-6环; 含有一个或两个选自氧，硫或氮的杂原子的饱和的5-，6-或7-元杂环; 二氢化茚基; 二环[2.2.1] -2-庚烯基; 二环[2.2.1]庚烷基; C1-6alkylsulfonyl; 芳基磺酰基; 或取代的C 1-10烷基; R 3是氢，卤素或C 1-6烷氧基; = C = X是式= C = O的二价基团; = C = CH-R <4>; = C = N-O-R <5>; 或式（a-4）; Alk是C1-4烷二基; -A-B-是下式的二价基团：-CR 6 = CR 7 - 或-CHR 6 -CHR 7 - ; L是氢; 任选取代的C 1-6烷基; C1-6烷基; C1-6alkyloxycarbonyl; 任选取代的C 3-6烯基; 任选取代的哌啶基; C 1-6烷基磺酰基或芳基磺酰基; 芳基是任选取代的苯基; - Het 1是吗啉基或任选取代的吡啶基， - 呋喃基， - 噻吩基， - 羟基吡啶基， - 咪唑基， - 噻唑基， - 恶唑基， - 异喹啉基， - 喹啉酮基， - 哌啶基 - 和Het 2是吗啉基或任选取代的哌啶基，哌嗪基， - 吡啶基， - 呋喃基或 - 噻吩基; 具有PDE IV和细胞因子抑制活性。本发明还涉及制备式（I）化合物及其药物组合物的方法。

5. 发明申请

WO1994013680A1 ANTIALLERGIC IMIDAZO[1,2-a](PYRROLO, THIENO OR FURANO)[2,3-d]AZEPINE DERIVATIVES 审中-公开
标题翻译： [1,2-a]（吡咯，三苯或呋喃）[2,3-d]亚胺衍生物
公开(公告)号：WO1994013680A1
公开(公告)日：1994-06-23
申请号：PCT/EP1993003321
申请日：1993-11-25
申请人： JANSSEN PHARMACEUTICA N.V. , JANSSENS, Frans, Eduard , DIELS, Gaston, Stanislas, Marcella , LEENAERTS, Joseph, Elisabeth
发明人： JANSSEN PHARMACEUTICA N.V.
IPC分类号： C07D495/14
CPC分类号： C07D495/14
摘要： Antiallergic imidazo[1,2-a](pyrrolo, thieno or furano)[2,3-d]azepines of formula (I), the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein each of the dotted lines independently represents an optional bond; R represents hydrogen, C1-4alkyl, halo, ethenyle substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, formyl, hydroxycarbonyl or hydroxycarbonylC1-4alkyl; R represents hydrogen, C1-4alkyl, ethenyl substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, C1-4alkyl substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, formyl or hydroxycarbonyl; R represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl, phenyl or halo; X represents O, S or NR ; L represents hydrogen; C1-6alkyl; substituted C1-6alkyl; C3-6alkenyl; C3-6alkenyl substituted with aryl; or a radical of the formula: -Alk-Y-Het (a-1), -Alk-NH-CO-Het (a-2) or Alk-Het (a-3). Compositions comprising said compounds, processes of preparing the same and intermediates in the preparation thereof.
摘要翻译：式（I）的抗过敏咪唑并[1,2-a]（吡咯并噻吩并或呋喃）[2,3-d]吖庚因，其药学上可接受的加成盐和立体化学异构形式，其中每条虚线独立地表示可选债券; R 1表示氢，C 1-4烷基，卤素，被羟基羰基或C 1-4烷氧基羰基取代的亚乙烯基，羟基C 1-4烷基，甲酰基，羟基羰基或羟基羰基C 1-4烷基; R 2表示氢，C 1-4烷基，被羟基羰基或C 1-4烷氧基羰基取代的乙烯基，被羟基羰基或C 1-4烷氧基羰基取代的C 1-4烷基，羟基C 1-4烷基，甲酰基或羟基羰基; R 3表示氢，C 1-4烷基，羟基C 1-4烷基，苯基或卤素; X表示O，S或NR 4; L表示氢; C1-6烷基; 取代的C 1-6烷基; C3-6alkenyl; 被芳基取代的C 3-6烯基; 或下式的基团：-Alk-Y-Het 1（a-1），-Alk-NH-CO-Het 2（a-2）或Alk-Het 3（a-3）。包含所述化合物的组合物，其制备方法及其制备中的中间体。

6. 发明申请

WO1993014088A1 ANTIHISTAMINIC PIPERAZINYL DERIVATIVES 审中-公开
标题翻译：抗生素哌嗪衍生物
公开(公告)号：WO1993014088A1
公开(公告)日：1993-07-22
申请号：PCT/EP1992003000
申请日：1992-12-29
申请人： JANSSEN PHARMACEUTICA N.V. , JANSSENS, Frans, Eduard , LEENAERTS, Joseph, Elisabeth , DIELS, Gaston, Stanislas, Marcella , SOMMEN, François, Maria
发明人： JANSSEN PHARMACEUTICA N.V.
IPC分类号： C07D405/06
CPC分类号： C07D405/04 , C07D405/06 , C07D405/14 , C07D413/06 , C07D413/14 , C07D471/04 , C07D513/04
摘要： Antihistaminic piperazinyl derivatives having formula (I) wherein R is (hydroxyC1-6alkyl)furanyl, (C1-6alkyl)oxazolyl or (hydroxyC1-6alkyl)oxazolyl; -A =A -A =A - is a bivalent radical having the formula -CH=CH-CH=CH- (a-1), -N=CH-CH=CH- (a-2), -CH=N-CH=CH- (a-3), -CH=CH-N=CH- (a-4), -CH=CH-CH=N- (a-5), -N=CH-N=CH- (a-6) or -CH=N-CH=N- (a-7); m is 1, 2, 3 or 4; L is hydrogen; C1-12alkyl; C3-6cycloalkyl; C3-6alkenyl optionally substituted with aryl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; arylcarbonyl; arylC1-6alkyloxycarbonyl; or a radical of formula: -Alk-R (b-1); -Alk-Y-R (b-2); -Alk-Z -C(=X)-Z -R (b-3); or -CH2-CHOH-CH2-O-R (b-4). Process for preparing the same, compositions containing said antihistaminic derivatives and a method of treating allergic diseases.
摘要翻译：式（I）的抗组胺哌嗪衍生物，其中R 1为（羟基C 1-6烷基）呋喃基，（C 1-6烷基）恶唑基或（羟基C 1-6烷基）恶唑基; -A 1 = A 2 -A 3 3 = A 4是具有式-CH = CH-CH = CH-（a-1），-N = CH-CH = CH-（a-2），-CH = N-CH = CH-（a-3），-CH = CH-N = CH-（a-4），-CH = CH-CH = 5），-N = CH-N = CH-（a-6）或-CH = N-CH = N-（a-7）; m为1,2,3或4; L是氢; C1-12烷基; 3-6环; 任选被芳基取代的C 3-6烯基; C1-6烷基; C1-6alkyloxycarbonyl; 基羰基; arylC1-6alkyloxycarbonyl; 或式-Alk-R 3（b-1）的基团; -Alk-Y-R 4（b-2）; -Alk-Z 1 -C（= X）-Z 2 -R 5（b-3）; 或-CH 2 -CHOH-CH 2 -O-R 6（b-4）。制备该组合物的方法，含有所述抗组胺衍生物的组合物和治疗过敏性疾病的方法。

7. 发明申请

WO1992022553A1 IMIDAZO[1,2-a](PYRROLO, THIENO OR FURANO)[3,2-d]AZEPINE DERIVATIVES, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：咪唑（1,2-A）（吡咯烷，三苯或呋喃）（3,2-D）亚胺衍生物，组合物和使用方法
公开(公告)号：WO1992022553A1
公开(公告)日：1992-12-23
申请号：PCT/EP1992001331
申请日：1992-06-09
申请人： JANSSEN PHARMACEUTICA N.V. , JANSSENS, Frans, Eduard , DIELS, Gaston, Stanislas, Marcella , LEENAERTS, Joseph, Elisabeth , COOYMANS, Ludwig, Paul
发明人： JANSSEN PHARMACEUTICA N.V.
IPC分类号： C07D487/14
CPC分类号： C07D487/14 , C07D491/14 , C07D495/14
摘要： The present invention is concerned with novel imidazo[1,2-a](pyrrolo, thieno or furano)[3,2-d]azepines of formula (I), the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein each of the dotted lines independently represents an optional bond; R1 represents hydrogen, C¿1-4?alkyl, halo, ethenyl substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, formyl, hydroxycarbonyl or hydroxycarbonylC1-4alkyl; R?2¿ represents hydrogen, C¿1-4?alkyl, ethenyl substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, C1-4alkyl substituted with hydroxycarbonyl or C1-4alkyloxycarbonyl, hydroxyC1-4alkyl, formyl or hydroxycarbonyl; R?3¿ represents hydrogen, C¿1-4?alkyl, hydroxyC1-4alkyl, phenyl or halo; L represents hydrogen; C1-6alkyl; C1-6alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C1-4alkyloxy, hydroxycarbonyl, C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyloxy, hydroxycarbonylC1-4alkyloxy, C1-4alkyloxycarbonylamino, C1-4alkylaminocarbonyl, C1-4alkylaminocarbonylamino, C1-4alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C1-6alkyl substituted with both hydroxy and aryloxy; C3-6alkenyl; C3-6alkenyl substituted with aryl; L represents a radical of formula -Alk-Y-Het?1¿ (a-1), -Alk-NH-CO-Het2 (a-2) or -Alk-Het3 (a-3); which are useful antiallergic compounds. Compositions comprising said compounds, methods of using, and processes for preparing the same.

8. 发明申请

WO2004105765A1 MACROCYCLIC QUINAZOLINE DERIVATIVES AS ANTIPROLIFERATIVE AGENTS 审中-公开
标题翻译：大环喹诺酮衍生物作为抗增生剂
公开(公告)号：WO2004105765A1
公开(公告)日：2004-12-09
申请号：PCT/EP2004/005621
申请日：2004-05-25
申请人： JANSSEN PHARMACEUTICA N.V. , FREYNE, Eddy, Jean, Edgard , PERERA, Timothy, Pietro, Suren , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , WILLEMS, Marc , DIELS, Gaston, Stanislas, Marcella , EMBRECHTS, Werner, Constant, Johan , TEN HOLTE, Peter
发明人： FREYNE, Eddy, Jean, Edgard , PERERA, Timothy, Pietro, Suren , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , WILLEMS, Marc , DIELS, Gaston, Stanislas, Marcella , EMBRECHTS, Werner, Constant, Johan , TEN HOLTE, Peter
IPC分类号： A61K31/529
CPC分类号： C07D498/06 , C07C229/16 , C07C229/40 , C07D239/88 , C07D239/93 , C07D239/94
摘要： The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents O, CH 2 , NH or S; in particular Z represents NH; Y represents -C 3-9 alkyl-, -C 3-9 alkenyl-, -C 3-9 alkynyl-, -C 3-7 alkyl-CO-NH- optionally substituted with amino, mono- or di(C 1-4 alkyl)amino or C 1-4 alkyloxycarbonylamino-, -C 3-7 alkenyl-CO-NH- optionally substituted with amino, mono- or di(C 1-4 alkyl)amino- or C 1-4 alkyloxycarbonylamino-, C 1-5 alkyl-oxy-C 1-5 alkyl-, -C 1-5 alkyl NR 13 -, -C 1-5 alkyl-, -C 1-5 alkyl-NR 14 -CO-C 1-5 alkyl-, -C 1-5 alkyl-CO NR 15 -C 1-5 alkyl-, -C 1-6 alkyl-CO-NH-, -C 1-6 alkyl-NH-CO-, -C 1-3 alkyl-NH-CS-Het 20 -, -C 1-3 alkyl-NH-CO-Het 20 -, -C 1-2 alkyl-CO-Het 21 -CO-, -Het 22 -CH 2 -CO-NH-C 1-3 alkyl-, -CO-NH-C 1-6 alkyl-, -NH-CO-C 1-6 alkyl-, -CO-C 1-7 alkyl-, -C 1-7 alkyl-CO-, -C 1-6 alkyl-CO-C 1-6 alkyl-, -C 1-2 alkyl-NH-CO-CR 16 R 17 -NH-, -C 1-2 alkyl-CO-NH-CR 18 R 19 -CO-, -C 1-2 alkyl-CO-NR 20 -C 1-3 alkyl-CO-, C 1-2 alkyl-NR 21 -CH 2 -CO-NH-C 1-3 alkyl-, or -NR 22 -CO-C 1-3 alkyl-NH-; X 1 represents a direct bond, O or -O-C 1-2 alkyl-, CO, -CO-C 1-2 alkyl-, NR 11 , -NR 11 -C 1-2 alkyl-, CH 2 -, -O-N=CH- or -C 1-2 alkyl-; X 2 represents a direct bond, O, -O-C 1-2 alkyl-, CO, -CO-C 1-2 alkyl-, NR 12 , -NR 12 -C 1-2 alkyl-, -CH 2 -, -O-N=CH- or -C 1-2 alkyl-. The growth inhibitory effect anti-tumour activity of the present compounds has been demonstrated in vitro , in enzymatic assays on the receptor tyrosine kinase EGFR.
摘要翻译：本发明涉及式（I）化合物的N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中Z代表O，CH2，NH或S; 特别是Z表示NH; 一个或多个（C 1-4烷基）氨基或C 1-4烷氧基羰基氨基 - 取代的C 1-3烷基 - ， - C 3-9烯基 - ， - C 3-9炔基 - ， - 一个或多个（C 1-4烷基）氨基 - 或C 1-4烷氧基羰基氨基 - ，C 1-5烷基 - 氧基-C 1-5烷基 - ， - C 1-5烷基NR 13取代的-C 3-7烯基-CO-NH- - ， - C 1-5烷基 - ， - C 1-5烷基-NR 14 -CO-C 1-5烷基 - ， - C 1-5烷基-CO NR 15 -C 1-6烷基 - ， - C 1-6烷基-CO-NH - ，-C 1-6烷基-NH-CO - ， - C 1-3烷基-NH-CS-Het 20 - ， - C 1-3烷基-NH-CO-Het 20 - ， - C 1-2烷基-CO-Het -CO-，-Het 22，-CH 2 -CO-NH-C 1-3烷基 - ， - CO-NH-C 1-6烷基 - ， - -NH-CO-C 1-6烷基 - ， - CO-C 1-7烷基 - ， - C 1-7烷基-CO - ， - C 1-6烷基-CO-C 1-6烷基 - ， - C 1-2烷基-NH-CO-CR 16 R 17 -NH-，-C 1-2烷基-CO- NH-CR 18 R 19 -CO - ， - C 1-2烷基-CO-NR 20 -C 1-3烷基-CO-，C 1-2烷基-NR 21 -CH 2 -CO-NH-C1- 3-烷基 - 或-NR 22 -CO-C 1-3烷基-NH-; X 1表示直接键，O或-O-C 1-2烷基 - ，CO，-CO-C 1-2烷基 - ，NR 11，-NR 11 -C 1-2烷基 - ，CH 2 - ，--ON = CH-或-C1-2烷基 - ; X 2表示直接键，O，-O-C 1-2烷基 - ，CO，-CO-C 1-2烷基 - ，NR 12，-NR 12 -C 1-2烷基 - ， - CH 2 - ON = CH-或-C1-2烷基。在体外，在受体酪氨酸激酶EGFR的酶学测定中已经证明了本发明化合物的生长抑制作用抗肿瘤活性。

9. 发明申请

WO2004033428A1 SUBSTITUTED 1,4-DI-PIPERIDIN-4-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS 审中-公开
标题翻译：取代的1,4-二哌啶-4-基哌嗪衍生物及其作为神经营养因子拮抗剂的用途
公开(公告)号：WO2004033428A1
公开(公告)日：2004-04-22
申请号：PCT/EP2003/050697
申请日：2003-10-07
申请人： JANSSEN PHARMACEUTICA N.V. , JANSSENS, Frans, Eduard , SOMMEN, François, Maria , DE BOECK, Benoît, Christian, Albert, Ghislain , LEENAERTS, Joseph, Elisabeth , VAN ROOSBROECK, Yves, Emiel, Maria , DIELS, Gaston, Stanislas, Marcella
发明人： JANSSENS, Frans, Eduard , SOMMEN, François, Maria , DE BOECK, Benoît, Christian, Albert, Ghislain , LEENAERTS, Joseph, Elisabeth , VAN ROOSBROECK, Yves, Emiel, Maria , DIELS, Gaston, Stanislas, Marcella
IPC分类号： C07D211/58
CPC分类号： C07D401/14 , C07D211/58 , C07D405/14 , C07D409/14 , C07D413/14 , C07D417/14 , C07D471/04
摘要： The invention concerns substituted 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK 1 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of emesis, anxiety, depression, pain, pancreatitis and IBS. The compounds according to the invention can be represented by general Formula (I), and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N -oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1. In view of their capability to antagonize the actions of neurokinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P by blocking the NK 1 receptor, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of neurokinin-mediated conditions, such as, for instance CNS disorders, in particular depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, schizoaffective disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions; inflammation; allergic disorders; emesis; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders; vasospastic diseases; fibrosing and collagen diseases; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.
摘要翻译：本发明涉及具有神经激肽拮抗活性的取代的1,4-二哌啶-4-基 - 哌嗪衍生物，特别是NK1拮抗活性，其制备方法，包含它们的组合物及其作为药物的用途，特别是用于治疗呕吐，焦虑，抑郁，疼痛，胰腺炎和IBS。根据本发明的化合物可以由通式（I）表示，并且还包括其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式和其前药，其中所有取代基被定义鉴于它们通过阻断神经激肽受体拮抗神经激肽的作用的能力，特别是通过阻断NK1受体拮抗物质P的作用，根据本发明的化合物可用作药物，在特别是在神经激肽介导的病症例如中枢神经系统疾病，特别是抑郁症，焦虑障碍，应激相关疾病，睡眠障碍，认知障碍，人格障碍，分裂情感障碍，进食障碍，神经变性疾病中的预防和治疗治疗中，成瘾症，情绪障碍，性功能障碍，疼痛等CNS相关c onditions; 炎; 过敏性疾病; 呕吐; 胃肠道疾病，特别是肠易激综合征（IBS）; 皮肤病; 血管痉挛性疾病; 纤维化和胶原病; 与免疫增强或抑制相关的疾病和风湿性疾病和体重控制。

10. 发明申请

WO2003037891A1 HETEROARYL AMINES AS GLYCOGEN SYNTHASE KINASE 3BETA INHIBITORS (GSK3 INHIBITORS) 审中-公开
标题翻译：杂多胺作为糖原合成酶激酶3β抑制剂（GSK3抑制剂）
公开(公告)号：WO2003037891A1
公开(公告)日：2003-05-08
申请号：PCT/EP2002/012077
申请日：2002-10-29
申请人： JANSSEN PHARMACEUTICA N.V. , FREYNE, Eddy, Jean, Edgard , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , WILLEMS, Marc , EMBRECHTS, Werner, Constant, Johan , LOVE, Christopher, John , JANSSEN, Paul, Adriaan, Jan , LEWI, Paulus, Joannes , HEERES, Jan , DE JONGE, Marc, René , KOYMANS, Lucien, Maria, Henricus , VINKERS, Hendrik, Maarten , VAN AKEN, Koen, Jeanne, Alfons , DIELS, Gaston, Stanislas, Marcella
发明人： FREYNE, Eddy, Jean, Edgard , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , WILLEMS, Marc , EMBRECHTS, Werner, Constant, Johan , LOVE, Christopher, John , JANSSEN, Paul, Adriaan, Jan , LEWI, Paulus, Joannes , HEERES, Jan , DE JONGE, Marc, René , KOYMANS, Lucien, Maria, Henricus , VINKERS, Hendrik, Maarten , VAN AKEN, Koen, Jeanne, Alfons , DIELS, Gaston, Stanislas, Marcella
IPC分类号： C07D403/12
CPC分类号： C07D213/74 , C07D239/42 , C07D239/48 , C07D401/04 , C07D401/12 , C07D403/04 , C07D403/12 , C07D405/12 , C07D409/12 , C07D417/12
摘要： This invention concerns a compound of formula (I), a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A is a 6-membered heterocycle; R 1 is hydrogen; aryl; formyl; C 1-6 alkylcarbonyl; optionally substituted C 1-6 alkyl; C 1-6 alkyloxycarbonyl; optionally substituted C 1-6 alkyloxy C 1-6 alkylcarbonyl; X is a direct bond or a linker atom or group; Z is a direct bond or a linker atom or group; R 2 is hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R 3 is hydrogen; hydroxy; halo; optionally substituted C 1-6 alkyl or C 1-6 alkenyl or C 2-6 alkynyl; C 1-6 alkyloxy; C 1-6 alkylthio; C 1-6 alkyloxycarbonyl; C 1-6 alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C 1-6 alkyl)amino; polyhaloC 1-6 alkyl; polyhaloC 1-6 alkyloxy; polyhaloC 1-6 alkylthio; R 21 ; R 21 -C 1-6 alkyl; R 21 -O-; R 21 -S-; R 21 -C(=0)-; R 21 -S(=0)p-; R 7 -S =O R 7 -S(=O)p-NH-; R 21 -S(=O)p-NH-; R 7 -C(=0)-; -NHC(=0)H; -C(=O)NHNH2; R 7 -C(=O)-NH-; R 21 -C(=O)-NH-; -C(=NH)R 7 ; -C(=NH)R 21 ; R° is an optionally substituted heterocycle provided that -X-R 2 and/or R 3 is other than hydrogen;their use, pharmaceutical compositions comprising them and processes for their preparation.
摘要翻译：本发明涉及式（I）化合物，其N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式，其中环A为6-元杂环; R 1是氢; 芳基; 甲酰基; ç<子> 1-6 烷基羰基; 任选取代的C 1-6烷基; ç<子> 1-6 烷氧基羰基; 任选取代的C 1-6烷氧基C 1-6烷基羰基; X是直接键或连接基原子或基团; Z是直接键或连接基原子或基团; R 2是氢，C 1-10烷基，C 2-10烯基，C 2-10炔基，碳环或杂环，每个所述基团可以任选被取代; R 3是氢; 羟基; 光环; 任选取代的C 1-6烷基或C 1-6链烯基或C 2-6炔基; ç<子> 1-6 烷氧基; ç<子> 1-6 烷硫基; ç<子> 1-6 烷氧基羰基; ç<子> 1-6 烷基羰基氧基; 羧基; 氰基; 硝基; 氨基; 单 - 或二（C 1-6烷基）氨基; 多卤代<子> 1-6 烷基; 多卤代<子> 1-6 烷氧基; 多卤代<子> 1-6 烷硫基; [R ^{21 ; [R ^{21 -C <子> 1-6 烷基; [R ^{21 -O-; [R ^{21 -S-; [R ^{21 -C（= O） - ; [R ^{21 -S（= O）p - ; R 7 -S = O R 7 -S（= O）p -NH-; [R ^{21 -S（= O）P-NH-; [R ^{7 -C（= O） - ; -NHC（= O）H; -C（= O）NHNH 2; [R ^{7 C（= O）-NH-; [R ^{21 C（= O）-NH-; -C（= NH）R ^{7 ; -C（= NH）R ^{21 ; R＆度; 是任选取代的杂环，条件是-XR 2和/或R 3不为氢;它们的用途，包含它们的药物组合物及其制备方法。}}}}}}}}}}}}

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式