公开(公告)号：US20080167464A1

公开(公告)日：2008-07-10

申请号：US12031011

申请日：2008-02-14

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jerome Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jerome Emile Georges Guillemont

IPC分类号： C07D239/48

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US07563922B2

公开(公告)日：2009-07-21

申请号：US11738688

申请日：2007-04-23

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

IPC分类号： C07C255/42 ,  C07C253/30 ,  C07C253/20 ,  C07D239/48 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III)  in the presence of a suitable solvent; b) reacting an intermediate of formula (IV)  with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US07399856B2

公开(公告)日：2008-07-15

申请号：US10523753

申请日：2003-08-07

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

IPC分类号： C07D239/48 ,  C07C255/42 ,  C07C253/30 ,  C07C253/20 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III)  in the presence of a suitable solvent; b) reacting an intermediate of formula (IV)  with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US07705148B2

公开(公告)日：2010-04-27

申请号：US12031011

申请日：2008-02-14

申请人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

发明人： Didier Philippe Robert Schils ,  Joannes Josephus Maria Willems ,  Bart Petrus Anna Maria Jozef Medaer ,  Elisabeth Therese Jeanne Pasquier ,  Paul Adriaan Jan Janssen ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Jérôme Emile Georges Guillemont

IPC分类号： C07D239/48 ,  C07C255/42 ,  C07C253/30 ,  C07C253/20 ,  A61K31/505 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07C253/20 ,  C07C253/30 ,  C07C255/42

摘要： Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile of formula (I), a N-oxide, a pharmaceutically acceptable acid addition salt, a quaternary amine or a stereochemically isomeric form thereof are provided, said processes comprise: a) reacting 4-(2-cyanoethenyl)-2,6-dimethylbenzenamine with an intermediate of formula (III) in the presence of a suitable solvent; b) reacting an intermediate of formula (IV) with acrylonitrile in the presence of a suitable palladium catalyst, a suitable base and a suitable solvent; c) dehydrating the corresponding amide of the compound of formula (I).

摘要翻译： 用于制备式（I）的4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基] - 氨基] -2-嘧啶基]氨基]苄腈的方法，N-氧化物， 提供药学上可接受的酸加成盐，季胺或其立体化学异构形式，所述方法包括：a）使4-（2-氰基乙烯基）-2,6-二甲基苯胺与式（III）的中间体在 合适的溶剂; b）在合适的钯催化剂，合适的碱和合适的溶剂的存在下使式（Ⅳ）的中间体与丙烯腈反应; c）使相应的式（I）化合物的酰胺脱水。

公开(公告)号：US07585861B2

公开(公告)日：2009-09-08

申请号：US10544584

申请日：2004-02-05

申请人： Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Jozef Herwig Arts, legal representative ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Georges Joseph Cornelius Hoomaert ,  Amuri Kilonda ,  Donald William Ludovici

发明人： Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Ruben Gerardus George Leenders ,  Georges Joseph Cornelius Hoomaert ,  Amuri Kilonda ,  Donald William Ludovici

IPC分类号： C07D253/075 ,  A61K31/53 ,  A61P31/18 ,  C07D403/12 ,  C07D403/14

CPC分类号： A61K31/53 ,  C07D253/07 ,  C07D253/075

摘要： The present invention relates to HIV replication inhibitors of formula (I) as defined in the specification their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及如本说明书中定义的式（I）的HIV复制抑制剂，其用作药物，其制备方法和包含它们的药物组合物。

公开(公告)号：US07276510B2

公开(公告)日：2007-10-02

申请号：US10275931

申请日：2001-05-03

申请人： Michael Joseph Kukla ,  Donald William Ludovici ,  Robert William Kavash ,  Bart Lieven Daniel De Corte ,  Jan Heeres ,  Paul Adriaan Jan Janssen ,  Lucien Maria Henricus Koymans ,  Marc René de Jonge ,  Koen Jeanne Alfons Van Aken ,  Alain Krief ,  Ruben Gerardus George Leenders

发明人： Michael Joseph Kukla ,  Donald William Ludovici ,  Robert William Kavash ,  Bart Lieven Daniel De Corte ,  Jan Heeres ,  Paul Adriaan Jan Janssen ,  Lucien Maria Henricus Koymans ,  Marc René de Jonge ,  Koen Jeanne Alfons Van Aken ,  Alain Krief ,  Ruben Gerardus George Leenders

IPC分类号： C07D239/46 ,  C07D239/48 ,  A61K31/505 ,  C07D401/12

CPC分类号： C07D239/47 ,  C07D239/48 ,  C07D251/16 ,  C07D251/50 ,  C07D401/12

摘要： This invention concerns HIV replication inhibitors of formula the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, provided that when Q is halo then Z is N; or when Q is polyhaloC1-6alkyl then Y is hydrogen or C1-6alkyl; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及具有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的式的HIV复制抑制剂，条件是当Q为卤素时，Z为N; 或当Q为多卤C 1-6烷基时，则Y为氢或C 1-6烷基; 它们作为药物的用途，其制备方法和包含它们的药物组合物。

公开(公告)号：US08026245B2

公开(公告)日：2011-09-27

申请号：US10573364

申请日：2004-09-21

申请人： Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts, legal representative ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

发明人： Paul Adriaan Jan Janssen ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Hendrik Maarten Vinkers ,  Ruben Gerardus George Leenders ,  Dirk Alfons Leo Vandenput

IPC分类号： C07D473/16 ,  C07D473/18 ,  A61K31/52 ,  A61K31/522 ,  A61P31/18 ,  C07D473/40

CPC分类号： A61K31/52 ,  C07D473/00 ,  C07D473/16 ,  C07D473/18

摘要： The present invention relates to the use of a compound of formula (I) for the manufacture of a medicament for the prevention or the treatment of HIV infection wherein the compound of formula (I) is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein A and B each represents a radical of formula and wherein —C-D- represents a bivalent radical of formula —N═CH—NR17—  (c-1); or —NR17—CH═N—  (c-2); provided that when A represents a radical of formula (a) then B represents a radical of formula (b) and when A represents a radical of formula (b) then B represents a radical of formula (a).

摘要翻译： 本发明涉及式（I）化合物在制备用于预防或治疗HIV感染的药物中的用途，其中式（I）化合物为式I化合物，N-氧化物，药学上 其中A和B各自表示式的基团，其中-CD-表示式-N = CH-NR 17 - （c-1）的二价基团; 或-NR17-CH = N-（c-2）; 条件是当A表示式（a）的基团时，B表示式（b）的基团，并且当A表示式（b）的基团时，B表示式（a）的基团。