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：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。

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：US08828982B2

公开(公告)日：2014-09-09

申请号：US12567051

申请日：2009-09-25

申请人： Jan Heeres ,  Paulus Joannes Lewi ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Jéròme Emile Georges Guillemont ,  Elisabeth Therese Jeanne Pasquier ,  Frank Xavier Jozef Herwig Arts

发明人： Jan Heeres ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Marc René de Jonge ,  Lucien Maria Henricus Koymans ,  Frederik Frans Desiré Daeyaert ,  Hendrik Maarten Vinkers ,  Jéròme Emile Georges Guillemont ,  Elisabeth Therese Jeanne Pasquier

IPC分类号： A01N43/00 ,  A61K31/33 ,  A61K39/395

CPC分类号： A61K31/513 ,  C07D239/47 ,  C07D239/48 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： This invention concerns the use of a compound for the manufacture of a medicament for the prevention of HIV infection via sexual intercourse and related intimate contact between partners, wherein the compound is a compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein the ring containing -a1=a2-a3=a4- and -b1=b2-b3=b4- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyloxy; substituted C1-6alkyloxyC1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)pR6, —NH—S(═O)pR6, —C(═O)R6, —NHC(═O)H, —C(═O)NHNH2, —NHC(═O)R6, —C(═NH)R6 or a 5-membered heterocycle; X1 is —NR5—, —NH—NH—, —N═N—, —O—, —C(═O)—, C1-4alkanediyl, —CHOH—, —S—, —S(═O)p—, —X2—C1-4alkanediyl- or —C1-4alkanediyl-X2—; R3 is NHR13; NR13R14; —C(═O)—NHR13; —C(═O)—NR13R14; —C(═O)—R15; —CH═N—NH—C(═O)—R16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; C1-6alkyl substituted with hydroxy and a second substituent; —C(═N—O—R8)—C1-4alkyl; R7; or —X3—R7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl)amino; and pharmaceutical compositions comprising them.

公开(公告)号：US20080262007A1

公开(公告)日：2008-10-23

申请号：US11576315

申请日：2005-09-29

申请人： Jerome Emile Georges Guillemont ,  Jan Heeres ,  Paulus Joannes Lewi

发明人： Jerome Emile Georges Guillemont ,  Jan Heeres ,  Paulus Joannes Lewi

IPC分类号： A61K31/505 ,  C07D239/32 ,  A61P31/18

CPC分类号： C07D239/48 ,  C07D239/50

摘要： HIV replication inhibitors of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein A is —CH2—CH2—, —CH═CH—, —C≡C—; R1 is hydrogen, aryl, formyl, C1-6alkylcarbonyl, C1-6alkyl, C1-6alkyloxycarbonyl, R2 hydroxy, halo, C1-6alkyl, carboxyl, cyano, —C(═O)R6, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl; X1 is —NR1—, —O—, —S—, —S(═O)p—; R3 is H, C1-6alkyl, halo; R4 is H, C1-6alkyl, halo; R5 is nitro, amino, mono- and diC1-4alkylamino, aryl, halo, —CHO, —CO—R6, —COOR7, —NH—C(═O)H, —NH—C(═O)R6, —CH═N—O—R8; R6 is C1-4alkyl, amino, mono- or di(C1-4alkyl)amino or polyhaloC1-4alkyl; R7 is hydrogen, C1-6alkyl, arylC1-6alkyl; R8 is hydrogen, C1-6alkyl, aryl; p is 1 or 2; aryl is optionally substituted phenyl; pharmaceutical compositions containing these compounds as active ingredient and processes for preparing said compounds and compositions.

摘要翻译： 式I的N-复合抑制剂N-氧化物，药学上可接受的加成盐，季胺或其立体化学异构形式，其中A为-CH 2 -CH 2 - ，-CH-CH-，-C≡C-; R 1是氢，芳基，甲酰基，C 1-6烷基羰基，C 1-6烷基，C 1-6烷基， 烷基氧基羰基，R 2羟基，卤素，C 1-6烷基，羧基，氰基，-C（-O）R 6， ，硝基，氨基，一或二（C 1-6烷基）氨基，多卤代甲基; X 1是-NR 1 - ， - O - ， - S - ， - S（-O）p - 。 R 3是H，C 1-6烷基，卤素; R 4是H，C 1-6烷基，卤素; R 5是硝基，氨基，单和二C 1-4烷基氨基，芳基，卤素，-CHO，-CO-R 6， -COOR 7，-NH-C（-O）H，-NH-C（-O）R 6，-CH-NOR 8 >; R 6是C 1-4烷基，氨基，单或二（C 1-4烷基）氨基或多卤代1 -4 烷基; R 7是氢，C 1-6烷基，芳基C 1-6烷基; R 8是氢，C 1-6烷基，芳基; p为1或2; 芳基是任选取代的苯基; 含有这些化合物作为活性成分的药物组合物和制备所述化合物和组合物的方法。

公开(公告)号：US20120076835A1

公开(公告)日：2012-03-29

申请号：US13249796

申请日：2011-09-30

申请人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

发明人： Jérôme Emile Georges Guillemont ,  Patrice Palandijian ,  Marc René De Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desiré Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen ,  Frank Xavier Jozef Herwig Arts

IPC分类号： A61K9/14 ,  A61K31/505 ,  C07D405/12 ,  A61K31/506 ,  C07D417/12 ,  A61K31/541 ,  C07D401/12 ,  C07D409/12 ,  C07D413/12 ,  A61K31/5377 ,  C07D403/12 ,  A61K31/551 ,  C07D401/14 ,  C07D403/14 ,  C07D239/47 ,  A61P31/18 ,  C07D239/48 ,  B82Y5/00

CPC分类号： C07D239/48 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07C255/42 ,  C07C257/12 ,  C07D239/47 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

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; 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II的HIV复制抑制剂; 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。