公开(公告)号：US09085589B2

公开(公告)日：2015-07-21

申请号：US13642959

申请日：2011-04-27

申请人： Hiroki Kusano ,  Kenji Yamawaki

发明人： Hiroki Kusano ,  Kenji Yamawaki

IPC分类号： A61K31/546 ,  C07D501/56 ,  C07D501/42 ,  C07D501/44 ,  C07D501/46 ,  C07D519/00 ,  C07D519/06 ,  C07D501/54

CPC分类号： C07D501/56 ,  C07D501/42 ,  C07D501/44 ,  C07D501/46 ,  C07D501/54 ,  C07D519/00 ,  C07D519/06

摘要： Provided is a cephem compound which has a wide antimicrobial spectrum, and in particular exhibits potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and a pharmaceutical composition comprising the same. The cephem compound has the formula (I): where W and U are as defined in the specification; R1 is as defined in the specification; R2A and R2B are as defined in the specification, provided that R2A and R2B are not taken together to form an optionally substituted oxime group when R1 is aminothiazole or aminothiadiazole optionally protected at the amino group; ring A is a benzene ring or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; R3 is a hydrogen atom, —OCH3 or —NH—CH(═O); k is an integer from 0 to 2; R4 is as defined in the specification; and D and E are as defined in accordance with a) or b) described in the specification.

摘要翻译： 本发明提供一种具有广谱抗菌谱的头孢烯化合物，特别是对产生β-内酰胺酶的革兰氏阴性细菌表现出有效的抗微生物活性，以及​​包含其的药物组合物。 头孢烯化合物具有式（I）：其中W和U如说明书中所定义; R1如规范中所定义; R2A和R2B如说明书中所定义，条件是当R 1为氨基噻唑或氨基噻二唑任选在该氨基保护时，R2A和R2B不一起形成任选取代的肟基; 环A是苯环或具有1-3个氮原子的6元芳族杂环基; R3是氢原子，-OCH3或-NH-CH（= O）; k是0至2的整数; R4如规范中所定义; 和D和E如在说明书中描述的a）或b）所定义。

公开(公告)号：US20130096299A1

公开(公告)日：2013-04-18

申请号：US13642959

申请日：2011-04-27

申请人： Hiroki Kusano ,  Kenji Yamawaki

发明人： Hiroki Kusano ,  Kenji Yamawaki

IPC分类号： C07D501/56 ,  C07D519/06 ,  C07D501/54

CPC分类号： C07D501/56 ,  C07D501/42 ,  C07D501/44 ,  C07D501/46 ,  C07D501/54 ,  C07D519/00 ,  C07D519/06

摘要： Provided is a cephem compound which has a wide antimicrobial spectrum, and in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical composition comprising the same.A Compound of the formula (I): wherein W and U are as defined in the specification; R1 is as defined in the specification; R2A and R2B are as defined in the specification, provided that R2A and R2B are not taken together to form an optionally substituted oxime group when R1 is aminothiazole or aminothiadiazole optionally protected at the amino group; ring A is a benzene ring or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; R3 is a hydrogen atom, —OCH3 or —NH—CH(═O); k is an integer from 0 to 2; R4 is as defined in the specification; and D and E are as defined in accordance with a) or b) described in the specification.

摘要翻译： 提供了具有广谱抗菌谱的头孢烯化合物，并且特别表现出对产生β-内酰胺酶的革兰氏阴性细菌具有强力的抗微生物活性，以及​​包含其的药物组合物。 式（I）的化合物：其中W和U如说明书中所定义; R1如规范中所定义; R2A和R2B如说明书中所定义，条件是当R 1为氨基噻唑或氨基噻二唑任选在该氨基保护时，R2A和R2B不一起形成任选取代的肟基; 环A是苯环或具有1-3个氮原子的6元芳族杂环基; R3是氢原子，-OCH3或-NH-CH（= O）; k是0至2的整数; R4如规范中所定义; 和D和E如在说明书中描述的a）或b）所定义。

公开(公告)号：US09476087B2

公开(公告)日：2016-10-25

申请号：US14326215

申请日：2014-07-08

申请人： Nanyang Technological University

发明人： Bengang Xing ,  Xianfeng Huang ,  Tingting Jiang ,  Rongrong Liu

IPC分类号： C12Q1/34 ,  C07D501/04 ,  C07D501/18 ,  C07D501/16 ,  C07D519/06

CPC分类号： C12Q1/34 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D519/06 ,  G01N2333/986

摘要： The present invention relates to compounds for and a method of detecting beta-lactamase activity in a sample. The sample is contacted with a nanoparticulate tag. The nanoparticulate tag comprises a metal or a combination of metals, or it comprises a nanotube of a metal, boron nitride and/or carbon. The respective metal is capable of forming one of a covalent bond, a coordinative bond and a non-covalent interaction with a thio or a seleno group. The sample is contacted with a compound of one of general formulas (I)-(III) and (VII)-(IX). At least one beta-lactam moiety of the compound is cleaved by the beta-lactamase activity in the sample. As a result a cleavage moiety Z-A-Z, Z-A-Z—R15, Z-A-Z—R16, Z-A-Z—R17, Z-A-Z—R18 or Z-G-N(R8)R9 is released that is immobilized on the surface of the nanoparticulate tag by a covalent bond via a Z atom. The presence of beta-lactamase activity is determined based on the presence of the cleavage moiety immobilized onto the surface of the nanoparticulate tag.

摘要翻译： 本发明涉及用于检测样品中β-内酰胺酶活性的化合物和方法。 样品与纳米颗粒标签接触。 纳米颗粒标签包括金属或金属的组合，或者它包括金属，氮化硼和/或碳的纳米管。 相应的金属能够形成共价键，配位键和与硫代或硒基的非共价相互作用之一。 将样品与通式（I） - （III）和（VII） - （IX）之一的化合物接触。 化合物的至少一个β-内酰胺部分被样品中的β-内酰胺酶活性切割。 结果，通过Z原子通过共价键将解离部分Z-A-Z，Z-A-Z-R15，Z-A-Z-R16，Z-A-Z-R17，Z-A-Z-R18或Z-G-N（R8）R9释放固定在纳米颗粒标签的表面上。 基于固定在纳米颗粒标签表面上的切割部分的存在来确定β-内酰胺酶活性的存在。

公开(公告)号：US09145425B2

公开(公告)日：2015-09-29

申请号：US13639412

申请日：2011-04-04

申请人： Shinya Hisakawa ,  Yasushi Hasegawa ,  Toshiaki Aoki ,  Hiroki Kusano ,  Masayuki Sano ,  Jun Sato ,  Kenji Yamawaki

发明人： Shinya Hisakawa ,  Yasushi Hasegawa ,  Toshiaki Aoki ,  Hiroki Kusano ,  Masayuki Sano ,  Jun Sato ,  Kenji Yamawaki

IPC分类号： C07D471/08 ,  C07D501/56 ,  C07D505/24 ,  C07D501/46 ,  C07D519/06

CPC分类号： C07D505/24 ,  C07D471/08 ,  C07D501/46 ,  C07D501/56 ,  C07D519/06

摘要： This invention provides Cephem compounds having the formula: or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof, a pharmaceutical composition thereof, and a method for treating a bacterial infectious disease with the compound, the ester, the protected compound, the salt, or the solvate thereof, wherein the symbols in the formula are defined in the specification. The compounds exhibit potent antimicrobial spectrum against a variety of bacteria including Gram negative bacteria and/or Gram positive bacteria, preferably beta-lactamase producing Gram negative bacteria, more preferably, multi-drug resistant microbials, in particular, Class B type metallo-beta-lactamase producing Gram negative bacteria, and still preferably extended-spectrum beta-lactamase (ESBL) producing bacteria. The compounds most preferably do not exhibit cross-resistance against known Cephem drugs or Carbapenem drugs.

摘要翻译： 本发明提供具有下式的Cephem化合物：或酯，7-侧链上的环上的氨基上的被保护的化合物，其药学上可接受的盐或溶剂合物，其药物组合物和 化合物，酯，受保护化合物，盐或其溶剂化物的细菌感染性疾病，其中式中的符号在说明书中定义。 该化合物对各种细菌（包括革兰氏阴性细菌和/或革兰氏阳性细菌，优选β-内酰胺酶产生革兰氏阴性细菌，更优选多药耐药性微生物，特别是B类金属β- 产生革兰氏阴性细菌的内酰胺酶，更优选延长的β-内酰胺酶（ESBL）产生细菌。 该化合物最优选不表现出对已知的Cephem药物或碳青霉烯类药物的抗药性。

公开(公告)号：US09334289B2

公开(公告)日：2016-05-10

申请号：US14113459

申请日：2012-04-25

申请人： Yasuhiro Nishitani ,  Toshiaki Aoki ,  Jun Sato ,  Kenji Yamawaki ,  Katsuki Yokoo ,  Masayuki Sano

发明人： Yasuhiro Nishitani ,  Toshiaki Aoki ,  Jun Sato ,  Kenji Yamawaki ,  Katsuki Yokoo ,  Masayuki Sano

IPC分类号： C07D501/16 ,  C07D501/60 ,  C07D501/18 ,  C07D501/46 ,  C07D519/06 ,  C07D519/00

CPC分类号： C07D501/60 ,  C07D501/18 ,  C07D501/46 ,  C07D519/00 ,  C07D519/06

摘要： The present invention provides a novel compound which has a wide antimicrobial spectrum, and in particular exhibits potent antimicrobial activity against beta-lactamase producing Gram negative bacteria. Specifically, the present invention provides a compound of the formula (I): wherein each symbol is as defined in the specification, or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same.

摘要翻译： 本发明提供了具有广谱抗菌谱的新型化合物，并且特别表现出对产生β-内酰胺酶的革兰氏阴性菌具有强效的抗微生物活性。 具体而言，本发明提供了式（I）化合物：其中各符号如说明书中所定义，或氨基保护的化合物，当氨基存在于7-侧链的环上时，或药学上 可接受的盐，以及包含其的药物组合物。

公开(公告)号：US20150344502A1

公开(公告)日：2015-12-03

申请号：US14655893

申请日：2013-12-26

申请人： SHIONOGI & CO., LTD.

发明人： Kenji YAMAWAKI ,  Hiroki KUSANO

IPC分类号： C07D519/06 ,  C07D501/46

CPC分类号： C07D519/06 ,  A61K9/0019 ,  C07D501/46 ,  Y02A50/473

摘要： A compound of the formula: wherein, W is —CH2− etc.; U is —S− etc.; R1 is substituted or unsubstituted carbocyclyl etc.; R2A and R2B is a) or b) described in the specification; R3 is a hydrogen atom etc.; R11 is carboxylate anion (—COO−) etc.; L is substituted or unsubstituted lower alkylene etc., E is a substituted or unsubstituted divalent group containing quaternary ammonium ion; G is a single bond etc.; D is —C(═O)—C(═O)—NR6— etc.; R10 1) to 3) described in specification; or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof.

摘要翻译： 下式的化合物：其中，W是-CH 2 - 等; U是-S-等; R1是取代或未取代的碳环基等; R2A和R2B是说明书中描述的a）或b） R3是氢原子等。 R11是羧酸根阴离子（-COO-）等; L是取代或未取代的低级亚烷基等，E是取代或未取代的含二价基团的季铵离子; G是单键等; D是-C（= O）-C（= O）-NR 6 - 等; R10 1）〜3） 或当氨基存在于7-侧链的环上时的氨基保护的化合物或其药学上可接受的盐。

公开(公告)号：US20140322739A1

公开(公告)日：2014-10-30

申请号：US14326215

申请日：2014-07-08

申请人： Nanyang Technological University

发明人： Bengang Xing ,  Xianfeng Huang ,  Tingting Jiang ,  Rongrong Liu

IPC分类号： C12Q1/34 ,  C07D501/16 ,  C07D501/04 ,  C07D519/06

CPC分类号： C12Q1/34 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D519/06 ,  G01N2333/986

摘要： The present invention relates to compounds for and a method of detecting beta-lactamase activity in a sample. The sample is contacted with a nanoparticulate tag. The nanoparticulate tag comprises a metal or a combination of metals, or it comprises a nanotube of a metal, boron nitride and/or carbon. The respective metal is capable of forming one of a covalent bond, a coordinative bond and a non-covalent interaction with a thio or a seleno group. The sample is contacted with a compound of one of general formulas (I)-(III) and (VII)-(IX). At least one beta-lactam moiety of the compound is cleaved by the beta-lactamase activity in the sample. As a result a cleavage moiety Z-A-Z, Z-A-Z—R15, Z-A-Z—R16, Z-A-Z—R17, Z-A-Z—R18 or Z-G-N(R8)R9 is released that is immobilized on the surface of the nanoparticulate tag by a covalent bond via a Z atom. The presence of beta-lactamase activity is determined based on the presence of the cleavage moiety immobilized onto the surface of the nanoparticulate tag.

摘要翻译： 本发明涉及用于检测样品中β-内酰胺酶活性的化合物和方法。 样品与纳米颗粒标签接触。 纳米颗粒标签包括金属或金属的组合，或者它包括金属，氮化硼和/或碳的纳米管。 相应的金属能够形成共价键，配位键和与硫代或硒基的非共价相互作用之一。 将样品与通式（I） - （III）和（VII） - （IX）之一的化合物接触。 化合物的至少一个β-内酰胺部分被样品中的β-内酰胺酶活性切割。 结果，通过Z原子通过共价键将解离部分Z-A-Z，Z-A-Z-R15，Z-A-Z-R16，Z-A-Z-R17，Z-A-Z-R18或Z-G-N（R8）R9释放固定在纳米颗粒标签的表面上。 基于固定在纳米颗粒标签表面上的切割部分的存在来确定β-内酰胺酶活性的存在。

公开(公告)号：US20090275065A1

公开(公告)日：2009-11-05

申请号：US12113109

申请日：2008-04-30

申请人： Bengang XING ,  Xianfeng Huang ,  Tingting Jiang ,  Rongrong Liu

发明人： Bengang XING ,  Xianfeng Huang ,  Tingting Jiang ,  Rongrong Liu

IPC分类号： C12Q1/34 ,  C07D501/00 ,  C07D499/00 ,  C07D487/00

CPC分类号： C12Q1/34 ,  C07D501/04 ,  C07D501/16 ,  C07D501/18 ,  C07D519/06 ,  G01N2333/986

摘要： The present invention relates to compounds for and a method of detecting beta-lactamase activity in a sample. The sample is contacted with a nanoparticulate tag. The nanoparticulate tag comprises a metal or a combination of metals, or it comprises a nanotube of a metal, boron nitride and/or carbon. The respective metal is capable of forming one of a covalent bond, a coordinative bond and a non-covalent interaction with a thio or a seleno group. The sample is contacted with a compound of one of general formulas (I)-(III) and (VII)-(IX). At least one beta-lactam moiety of the compound is cleaved by the beta-lactamase activity in the sample. As a result a cleavage moiety Z-A-Z, Z-A-Z-R15, Z-A-Z-R16, Z-A-Z-R17, Z-A-Z-R18 or Z-G-N(R8)R9 is released that is immobilised on the surface of the nanoparticulate tag by a covalent bond via a Z atom. The presence of beta-lactamase activity is determined based on the presence of the cleavage moiety immobilized onto the surface of the nanoparticulate tag.

摘要翻译： 本发明涉及用于检测样品中β-内酰胺酶活性的化合物和方法。 样品与纳米颗粒标签接触。 纳米颗粒标签包括金属或金属的组合，或者它包括金属，氮化硼和/或碳的纳米管。 相应的金属能够形成共价键，配位键和与硫代或硒基的非共价相互作用之一。 将样品与通式（I） - （III）和（VII） - （IX）之一的化合物接触。 化合物的至少一个β-内酰胺部分被样品中的β-内酰胺酶活性切割。 结果，通过Z原子通过共价键将解离部分Z-A-Z，Z-A-Z-R15，Z-A-Z-R16，Z-A-Z-R17，Z-A-Z-R18或Z-G-N（R8）R9释放固定在纳米颗粒标签的表面上。 基于固定在纳米颗粒标签表面上的切割部分的存在来确定β-内酰胺酶活性的存在。

公开(公告)号：US20170246300A1

公开(公告)日：2017-08-31

申请号：US15516076

申请日：2015-09-28

申请人： Shuwen HE ,  Jared N. CUMMING ,  Jack D. SCOTT ,  Merck Sharp & Dohme Corp.

发明人： Shuwen He ,  Jared N. Cumming ,  Jack D. Scott

IPC分类号： A61K45/06 ,  C07D519/06 ,  C07D513/04 ,  C07D417/12 ,  A61K31/54 ,  A61K31/549

CPC分类号： A61K45/06 ,  A61K31/54 ,  A61K31/549 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04 ,  C07D519/00 ,  C07D519/06

摘要： In its many embodiments, the present invention provides certain C5-C6 fused tricyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R2, R3, RA, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

公开(公告)号：US09238657B2

公开(公告)日：2016-01-19

申请号：US13063878

申请日：2009-10-27

申请人： Yasuhiro Nishitani ,  Kenji Yamawaki ,  Yusuke Takeoka ,  Hideki Sugimoto ,  Shinya Hisakawa ,  Toshiaki Aoki

发明人： Yasuhiro Nishitani ,  Kenji Yamawaki ,  Yusuke Takeoka ,  Hideki Sugimoto ,  Shinya Hisakawa ,  Toshiaki Aoki

IPC分类号： C07D501/46 ,  C07D505/24 ,  C07D519/06 ,  A61K31/546

CPC分类号： C07D501/46 ,  C07D505/24 ,  C07D519/06

摘要： The present disclosure describes Cephem compounds of the formula: wherein, X is N, CH or C—Cl; T is S or the like; A and G are lower alkylene or the like; B is a single bond or the like; D is optionally present, and when present is, —NR7—, —CO—, —CO—NR7—, —NR7—CO—, —NR7—CO—NR7—, or the like; F is optionally present, and when present is or phenylene; R3 and R4 are —OR8; R5 and R6 each is independently hydrogen, halogen, nitrile, or —OR8; or an ester at the carboxyl at the 7-position side chain or at the 4-position, a compound protected at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof, which have a wide antimicrobial spectrum and have potent antimicrobial activity against beta-lactamase producing Gram negative bacteria.

摘要翻译： 本公开内容描述了具有下式的Cephem化合物：其中X是N，CH或C-Cl; T是S等; A和G是低级亚烷基等; B是单键等; D是任选存在的，并且当存在时为-NR 7 - ， - CO - ， - CO-NR 7 - ， - NR 7 -CO-，-NR 7 -CO-NR 7 - 等; F任选存在，当存在时为或亚苯基; R3和R4是-OR8; R5和R6各自独立地为氢，卤素，腈或-OR8; 或在7-位侧链或4-位的羧基处的酯，在7-侧链的环上的氨基保护的化合物，其药学上可接受的盐或溶剂合物，其具有宽的 抗菌谱，对抗β-内酰胺酶产生革兰氏阴性细菌具有有效的抗菌活性。