公开(公告)号：US20070082895A1

公开(公告)日：2007-04-12

申请号：US10596386

申请日：2005-01-21

申请人： Jerome Guillemont ,  Elisabeth Pasquier

发明人： Jerome Guillemont ,  Elisabeth Pasquier

IPC分类号： A61K31/541 ,  A61K31/5377 ,  C07D417/14 ,  C07D413/14

CPC分类号： C07D413/06 ,  C07D413/14

摘要： The present invention relates to novel substituted quinoline derivatives according to the general formula (Ia) or the general formula (Ib) salts, quaternary amines, stereochemically isomeric forms, tautomeric forms and N-oxide forms thereof, wherein R1 is hydrogen, halo, haloalkyl, cyano, hydroxy, Ar, Het, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; p is 1, 2, 3 or 4; R2 is hydrogen, hydroxy, thio, alkyloxy, alkyloxyalkyloxy, alkylthio, mono or di(alkyl)amino or a radical of formula R3 is alkyl, Ar, Ar-alkyl, Het or Het-alkyl; R4 is hydrogen, alkyl or benzyl; R5 is hydrogen, halo, haloalkyl, hydroxy, Ar, alkyl, alkyloxy, alkylthio, alkyloxyalkyl, alkylthioalkyl, Ar-alkyl or di(Ar)alkyl; or two vicinal R5 radicals may be taken together to form together with the phenyl ring to which they are attached a naphthyl; r is 1, 2, 3, 4 or 5; R6 is hydrogen, alkyl, Ar or Het; R7 is hydrogen or alkyl; R8 is oxo; or R7 and R8 taken together form the radical CH═CH—N═; Z is CH2 or C(═O). The claimed compounds are useful for the treatment of mycobacterial diseases, particularly those diseases caused by pathogenic mycobacteria such as M. tuberculosis, M. bovis, M. avium, M. smegmatis and M. marinum. Also claimed is a pharmaceutical composition containing a compound of the present invention, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of mycobacterial diseases and a process for preparing the claimed compounds.

摘要翻译： 本发明涉及根据通式（Ia）或通式（Ib）的新的取代喹啉衍生物，其盐，季胺，立体化学异构形式，互变异构形式和N-氧化物形式，其中R 1， 烷基，烷氧基，烷硫基，烷氧基烷基，烷硫基烷基，芳烷基或二（Ar）烷基; p为1,2,3或4; R 2是氢，羟基，硫代，烷氧基，烷氧基烷氧基，烷硫基，一或二（烷基）氨基或式R 3的基团是烷基，Ar，Ar- 烷基，Het或Het-烷基; R 4是氢，烷基或苄基; R 5是氢，卤素，卤代烷基，羟基，Ar，烷基，烷氧基，烷硫基，烷氧基烷基，烷硫基烷基，芳烷基或二（Ar）烷基; 或两个邻位R 5个基团可以与它们所连接的苯环一起形成萘基; r为1,2,3,4或5; R 6是氢，烷基，Ar或Het; R 7是氢或烷基; R 8是氧代; 或R 7和R 8一起形成基团CH-CH-N-; Z是CH 2或C（-O）。 所要求保护的化合物可用于治疗分枝杆菌疾病，特别是由致病性分枝杆菌引起的疾病如结核分枝杆菌，牛分枝杆菌，鸟分枝杆菌，耻垢分枝杆菌和马氏海马。 还要求保护的是含有本发明化合物，所要求保护的化合物或组合物在制备用于治疗分枝杆菌疾病的药物中的用途的药物组合物及其制备方法。

公开(公告)号：US20070021449A1

公开(公告)日：2007-01-25

申请号：US10544735

申请日：2004-02-04

申请人： Jan Heeres ,  Paulus Lewi ,  Paul Janssen ,  Marc de Jonge ,  Lucien Koymans ,  Frederik Daeyaert ,  Hendrik Vinkers ,  Jerome Guillemont ,  Elisabeth Pasquier ,  Frank Xavier Arts

发明人： Jan Heeres ,  Paulus Lewi ,  Paul Janssen ,  Marc de Jonge ,  Lucien Koymans ,  Frederik Daeyaert ,  Hendrik Vinkers ,  Jerome Guillemont ,  Elisabeth Pasquier ,  Frank Xavier Arts

IPC分类号： A61K31/513 ,  C07D239/47

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 (I) 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; and pharmaceutical compositions comprising them.

摘要翻译： 本发明涉及化合物在制备药物中的用途，所述药物通过性交和伴侣之间的相关紧密接触来预防HIV感染，其中所述化合物是式（I）的化合物，N-氧化物，药学上可接受的添加剂 盐，季胺及其立体化学异构形式，其中含-a 1〜 > 4 - 和 - b 1 - b 2 - b 3 - b 4 - 表示 苯基，吡啶基，嘧啶基，吡嗪基，哒嗪基; 和包含它们的药物组合物。

公开(公告)号：US20060194804A1

公开(公告)日：2006-08-31

申请号：US10545358

申请日：2004-02-20

申请人： Jerome Guillemont ,  Elisabeth Pasquier ,  Jan Heeres ,  Kurt Hertogs ,  Eva Bettens ,  Paulus Lewi ,  Marc De Jonge ,  Lucien Maria Koymans ,  Frederik Daeyaert ,  Hendrik Vinkers ,  Adriaan Janssen ,  Frank Zavier Jozef Arts

发明人： Jerome Guillemont ,  Elisabeth Pasquier ,  Jan Heeres ,  Kurt Hertogs ,  Eva Bettens ,  Paulus Lewi ,  Marc De Jonge ,  Lucien Maria Koymans ,  Frederik Daeyaert ,  Hendrik Vinkers ,  Adriaan Janssen ,  Frank Zavier Jozef Arts

IPC分类号： A61K31/53 ,  A61K31/506 ,  C07D405/14

CPC分类号： C07D239/47 ,  C07D239/48 ,  C07D413/12

摘要： This invention concerns HIV replication inhibitors of formula (I), 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： 本发明涉及式（I）的N-复制抑制剂，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，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：US20070093478A1

公开(公告)日：2007-04-26

申请号：US10596270

申请日：2005-01-21

申请人： Jerome Guillemont ,  Elisabeth Pasquier ,  David Lancois

发明人： Jerome Guillemont ,  Elisabeth Pasquier ,  David Lancois

IPC分类号： A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/4709 ,  C07D417/02 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D215/14 ,  C07D215/227 ,  C07D215/38 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14

摘要： The present invention relates to novel substituted quinoline derivatives according to the general Formula (Ia) or the general Formula (Ib) the pharmaceutically acceptable acid or base addition salts thereof, the quaternary amines thereof, the stereochemically isomeric forms thereof the tautomers forms thereof and the N-oxide forms thereof. The claimed compounds are useful for the treatment of mycobacterial diseases. In particular, compounds are claimed in which, independently from each other, R1 is halo; p=1; R2 is optionally substituted alkyloxy, alkyl, Ar, Het, or a radical of formula R3 is optionally substituted Ar or Het; q=1, R4 and R5 each independently are alkyl; R6 is hydrogen or a radical of formula is equal to 0 or 1 and R7 is hydrogen or Ar. Also claimed is a composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of the claimed compounds, the use of the claimed compounds or compositions for the manufacture of a medicament for the treatment of mycobacterial diseases and a process for preparing the claimed compounds.

摘要翻译： 本发明涉及根据通式（Ia）或通式（Ib）的其取代的喹啉衍生物，其药学上可接受的酸或碱加成盐，其季胺，其互变异构体形式的立体化学异构形式和 N-氧化物形式。 所要求保护的化合物可用于治疗分枝杆菌病。 特别地，要求保护的化合物，其中R 1彼此独立地为卤素; p = 1; R 2是任选取代的烷氧基，烷基，Ar，Het或式R 3的基团是任选取代的Ar或Het; q = 1，R 4和R 5各自独立地为烷基; R 6是氢或式的基团等于0或1，R 7是氢或Ar。 还要求保护的是包含药学上可接受的载体和作为活性成分的治疗有效量的要求保护的化合物的组合物，所要求保护的化合物或组合物在制备用于治疗分枝杆菌疾病的药物中的用途以及制备方法 要求保护的化合物。

公开(公告)号：US20060167253A1

公开(公告)日：2006-07-27

申请号：US10523753

申请日：2003-08-07

申请人： Didier Philippe Schils ,  Joannes Josephus Willems ,  Bart Petrus Anna Medaer ,  Elisabeth Pasquier ,  Paul Janssen ,  Jan Heeres ,  Ruben Gerardus Leenders ,  Jerome Guillemont

发明人： Didier Philippe Schils ,  Joannes Josephus Willems ,  Bart Petrus Anna Medaer ,  Elisabeth Pasquier ,  Paul Janssen ,  Jan Heeres ,  Ruben Gerardus Leenders ,  Jerome 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。