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1. 发明授权

US07709498B2 Quinoline derivatives as antibacterial agents 有权
标题翻译：喹啉衍生物作为抗菌剂
公开(公告)号：US07709498B2
公开(公告)日：2010-05-04
申请号：US11296918
申请日：2005-12-08
申请人： Koenraad Jozef Lodewijk Marcel Andries , Anil Koul , Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier
发明人： Koenraad Jozef Lodewijk Marcel Andries , Anil Koul , Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier
IPC分类号： C07D215/38
CPC分类号： C07D215/227 , A61K31/47 , A61K31/4709 , A61K31/496 , A61K31/497 , A61K31/501 , A61K31/506 , A61K31/53 , A61K31/5377 , A61K31/541 , C07D215/36 , C07D401/04 , C07D401/06 , C07D401/12 , C07D405/04 , C07D405/06 , C07D409/06 , Y02A50/473
摘要： The present invention relates to a method for the treatment of a bacterial infection comprising administering a therapeutically effective amount of a compound of formula or a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof or a N-oxide form thereof, wherein R1 is hydrogen, halo, polyhaloC1-6alkyl, C1-6alkyl, Ar or Het; p is an integer equal to 1 or 2; R2 is C1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy or C1-6alkylthio; R3 is Ar, Het or Het1; R4 and R5 each independently are hydrogen, C1-6alkyl or benzyl; or R4 and R5 together and including the N to which they are attached may form a radical selected from the group of pyrrolidinyl, 2-pyrrolinyl, 3-pyrrolinyl, pyrrolyl, imidazolidinyl, pyrazolidinyl, 2-imidazolinyl, 2-pyrazolinyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, morpholinyl and thiomorpholinyl, each of said rings may optionally be substituted with C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, hydroxyC1-6alkyl, C1-6alkyloxy, amino, mono- or di(C1-6alkyl)amino, C1-6alkylthio, C1-6alkyloxyC1-6alkyl, C1-6alkylthioC1-6alkyl or pyrimidinyl; R6 is hydrogen, halo, polyhaloC1-6alkyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio; or two vicinal R6 radicals may be taken together to form a bivalent radical of formula —CH═CH—CH═CH—; r is an integer equal to 1 or 2; R7 is hydrogen, C1-6alkyl, Ar, Het or Het1; provided that to bacterial infection is other than a Mycobacterial infection.
摘要翻译：本发明涉及一种治疗细菌感染的方法，包括给予治疗有效量的式的化合物或其药学上可接受的酸或碱加成盐，其立体化学异构形式或其N-氧化物形式，其中 R 1是氢，卤素，多卤代C 1-6烷基，C 1-6烷基，Ar或Het; p是等于1或2的整数; R2是C1-6烷氧基，C1-6烷氧基C1-6烷氧基或C1-6烷硫基; R3是Ar，Het或Het1; R 4和R 5各自独立地为氢，C 1-6烷基或苄基; 或R4和R5一起并且包括它们所连接的N可以形成选自吡咯烷基，2-吡咯啉基，3-吡咯啉基，吡咯基，咪唑烷基，吡唑烷基，2-咪唑啉基，2-吡唑啉基，咪唑基，吡唑基三唑基，哌啶基，吡啶基，哌嗪基，哒嗪基，嘧啶基，吡嗪基，三嗪基，吗啉基和硫代吗啉基，每个所述环可任选被C 1-6烷基，卤素，多卤代C 1-6烷基，羟基，羟基C 1-6烷基，C 1-6烷氧基，氨基，单或二（C 1-6烷基）氨基，C 1-6烷硫基，C 1-6烷氧基C 1-6烷基，C 1-6烷硫基C 1-6烷基或嘧啶基; R 6是氢，卤素，多卤代C 1-6烷基，C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基; 或两个连位的R6基团可以一起形成式-CH = CH-CH = CH-的二价基团; r是等于1或2的整数; R7是氢，C1-6烷基，Ar，Het或Het1; 只要细菌感染不是分枝杆菌感染。

2. 发明授权

US07563922B2 Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile 有权
标题翻译：制备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
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。

3. 发明授权

US07399856B2 Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-2pyrimidinyl]amino]benzonitrile 有权
标题翻译：制备4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基苯基]氨基] -2-2嘧啶基]氨基]苄腈的方法
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。

4. 发明授权

US07338949B2 Mycobacterial inhibitors 有权
标题翻译：分枝杆菌抑制剂
公开(公告)号：US07338949B2
公开(公告)日：2008-03-04
申请号：US10596386
申请日：2005-01-21
申请人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier
发明人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier
IPC分类号： C07D413/06 , C07D413/14 , A61K31/5355 , A61P31/10
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。

5. 发明授权

US07705148B2 Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile 有权
标题翻译：制备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
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。

6. 发明授权

US07902225B2 Mycobacterial inhibitors 有权
标题翻译：分枝杆菌抑制剂
公开(公告)号：US07902225B2
公开(公告)日：2011-03-08
申请号：US10596270
申请日：2005-01-21
申请人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier , David Francis Alain Lancois
发明人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier , David Francis Alain Lancois
IPC分类号： C07D215/38 , A61K31/04
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 tautomeric 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 r 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）的新的取代喹啉衍生物，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R1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R3的基团是任选取代的Ar或Het; q = 1，R4和R5各自独立地为烷基; R6是氢或式r的基团等于0或1，而R7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。

7. 发明授权

US07790894B2 Mycobacterial inhibitors 有权
标题翻译：分枝杆菌抑制剂
公开(公告)号：US07790894B2
公开(公告)日：2010-09-07
申请号：US11422152
申请日：2006-06-05
申请人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier , David Francis Alain Lancois
发明人： Jérôme Emile Georges Guillemont , Elisabeth Therese Jeanne Pasquier , David Francis Alain Lancois
IPC分类号： C07D215/00 , C07D215/12 , C07D215/04
CPC分类号： C07D215/18
摘要： The present invention relates to novel substituted quinoline derivatives according to the general Formula (I) and pharmaceutically acceptable addition salts thereof, wherein the variable moieties are as defined in the specification. The invention also relates to a method of treating of mycobacterial diseases through administration of the claimed compounds and a process for preparing the claimed compounds.
摘要翻译：本发明涉及根据通式（I）的新的取代喹啉衍生物及其药学上可接受的加成盐，其中可变部分如说明书中所定义。本发明还涉及通过施用所要求保护的化合物治疗分枝杆菌疾病的方法和制备所要求保护的化合物的方法。

8. 发明授权

US07956063B2 Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile 有权
标题翻译： 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
公开(公告)号：US07956063B2
公开(公告)日：2011-06-07
申请号：US12168540
申请日：2008-07-07
申请人： Jérôme Emile Georges Guillemont , Paul Theodoor Agnes Stevens , Alex Herman Copmans , Jozef Peeters , Alfred Elisabeth Stappers , Roger Petrus Gerebern Vandecruys , Paul Stoffels
发明人： Jérôme Emile Georges Guillemont , Paul Theodoor Agnes Stevens , Alex Herman Copmans , Jozef Peeters , Alfred Elisabeth Stappers , Roger Petrus Gerebern Vandecruys , Paul Stoffels
IPC分类号： A61K31/505 , A61P31/18 , C07D239/48
CPC分类号： A61K31/505 , C07D239/48
摘要： The present invention relates to a pharmaceutical composition comprising as active ingredient the hydrochloric acid salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethyl-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile and to processes for their preparation.
摘要翻译：本发明涉及药物组合物，其包含4 - [[4 - [[4-（2-氰基乙烯基）-2,6-二甲基 - 苯基]氨基] -2-嘧啶基]氨基] 苄腈和其制备方法。

9. 发明授权

US07879857B2 6-substituted 2-quinolinones and 2-quinoxalinones as poly (adp-ribose) polymerase inhibitors 有权
标题翻译： 6-取代的2-喹啉酮和2-喹喔啉酮作为聚（adp-核糖）聚合酶抑制剂
公开(公告)号：US07879857B2
公开(公告)日：2011-02-01
申请号：US10596086
申请日：2004-11-18
申请人： Dominique Jean-Pierre Mabire , Jérôme Emile Georges Guillemont , Jacobus Alphonsus Josephus Van Dun , Maria Victorina Francisca Somers , Walter Boudewijn Leopold Wouters
发明人： Dominique Jean-Pierre Mabire , Jérôme Emile Georges Guillemont , Jacobus Alphonsus Josephus Van Dun , Maria Victorina Francisca Somers , Walter Boudewijn Leopold Wouters
IPC分类号： C07D241/44 , C07D215/227 , A61K31/498 , A61K31/4704 , A61P25/28
CPC分类号： C04B35/632 , C07D241/44 , C07D401/12 , C07D407/06 , C07D409/14
摘要： The present invention provides compounds of formula (I), their use as PARP inhibitors as well as pharmaceutical compositions comprising said compounds of formula (I) wherein n, R1, R2, R3, R4 and X have defined meanings.
摘要翻译：本发明提供式（I）化合物，它们作为PARP抑制剂的用途以及包含所述式（I）化合物的药物组合物，其中n，R1，R2，R3，R4和X具有定义的含义。

10. 发明申请

US20100204270A1 Quinoline Derivatives as Antibacterial Agents 审中-公开
标题翻译：喹啉衍生物作为抗菌剂
公开(公告)号：US20100204270A1
公开(公告)日：2010-08-12
申请号：US11917923
申请日：2006-06-26
申请人： Koenraad Jozef Lodewijk Marcel Andries , Anil Koul , Jérôme Emile Georges Guillemont , Magali Madeleine Simone Motte
发明人： Koenraad Jozef Lodewijk Marcel Andries , Anil Koul , Jérôme Emile Georges Guillemont , Magali Madeleine Simone Motte
IPC分类号： A61K31/47 , C07D215/16 , A61P31/04
CPC分类号： C07D215/227 , A61K31/4353 , A61K45/06 , C07D215/36 , A61K2300/00
摘要： Use of a compound for the manufacture of a medicament for the treatment of a bacterial infection provided that the bacterial infection is other than a Mycobacterial infection, said compound being a compound of formula (Ia) or (Ib) a pharmaceutically acceptable acid or base addition salt thereof, a stereochemically isomeric form thereof, a tautomeric form thereof or a N-oxide form thereof. Several of these compounds are also claimed as such. Further the combination of the above compounds with other antibacterial agents is described
摘要翻译：使用化合物制造用于治疗细菌感染的药物，只要细菌感染不是分枝杆菌感染，所述化合物是式（Ia）或（Ib）的化合物，其药学上可接受的酸或碱加成其盐，其立体化学异构形式，其互变异构形式或其N-氧化物形式。这些化合物中的几种也是这样声称的。此外，还描述了上述化合物与其它抗菌剂的组合

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