公开(公告)号：US5541175A

公开(公告)日：1996-07-30

申请号：US301619

申请日：1994-09-07

申请人： Jae H. Yeo ,  Chan S. Bang ,  Jong C. Lim ,  Young M. Woo ,  Deog H. Yang ,  Se H. Kim ,  Jae H. Jeon ,  Mu Y. Kim ,  Sam S. Kim ,  Tae H. Lee ,  Yong Z. Kim ,  Hun S. Oh

发明人： Jae H. Yeo ,  Chan S. Bang ,  Jong C. Lim ,  Young M. Woo ,  Deog H. Yang ,  Se H. Kim ,  Jae H. Jeon ,  Mu Y. Kim ,  Sam S. Kim ,  Tae H. Lee ,  Yong Z. Kim ,  Hun S. Oh

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/00 ,  C07D501/04 ,  C07D501/24 ,  C07D501/60 ,  A01K31/545

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： The present invention relates to a cephalosporin compound represented by the following general formula (I): ##STR1## its pharmaceutically acceptable non-toxic salt, physiologically hydrolyzable ester, hydrate or solvate, or isomers thereof, in whichR.sup.1 represents hydrogen or an amino-protecting group,R.sup.2 and R.sup.3 can be identical or different and independently of one another represent hydrogen or a hydroxy-protecting group, orR.sup.2 and R.sup.3 together can form a cyclic diol-protecting group,R.sup.4 represents hydrogen or a carboxyl-protecting group,R.sup.5, R.sup.6 and R.sup.7 independently of one another represent hydrogen, amino or substituted amino, hydroxy, alkoxy, C.sub.1-4 alkyl, carboxyl or alkoxycarbonyl, orR.sup.5 and R.sup.6 together with the carbon atoms to which they are attached can form a C.sub.3-7 cycle, andQ represents CH or N,and to a process for preparation thereof and a pharmaceutical composition containing the compound (I) as an active ingredient.

摘要翻译： 本发明涉及由以下通式（I）表示的头孢菌素化合物：其药学上可接受的无毒盐，生理上可水解的酯，水合物或溶剂合物或其异构体，其中R 1 表示氢或氨基保护基，R2和R3可以相同或不同，彼此独立地表示氢或羟基保护基，或者R2和R3一起可以形成环状二醇保护基，R4表示氢或 羧基保护基，R 5，R 6和R 7彼此独立地表示氢，氨基或取代的氨基，羟基，烷氧基，C 1-4烷基，羧基或烷氧基羰基，或者R 5和R 6与它们所连接的碳原子一起可以 形成C3-7周期，Q表示CH或N，以及其制备方法和含有化合物（I）作为活性成分的药物组合物。

公开(公告)号：US5571804A

公开(公告)日：1996-11-05

申请号：US303930

申请日：1994-09-09

申请人： Chan S. Bang ,  Jae H. Yeo ,  Young M. Woo ,  Jong C. Lim ,  Deog H. Yang ,  Se H. Kim ,  Jae H. Jeon ,  Mi K. Seo ,  Sam S. Kim ,  Tae H. Lee ,  Yong Z. Kim ,  Hun S. Oh

发明人： Chan S. Bang ,  Jae H. Yeo ,  Young M. Woo ,  Jong C. Lim ,  Deog H. Yang ,  Se H. Kim ,  Jae H. Jeon ,  Mi K. Seo ,  Sam S. Kim ,  Tae H. Lee ,  Yong Z. Kim ,  Hun S. Oh

IPC分类号： A61K31/546 ,  C07D501/00 ,  C07D501/04 ,  C07D501/36 ,  C07D501/60 ,  A61K31/545

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： Cephalosporin compounds of formula (I): ##STR1## wherein: R.sup.1 is a hydrogen or an amino protecting group;R.sup.2 and R.sup.3 are, independently, a hydrogen or a hydroxy protecting group, or form together a cyclic diol protecting group;R.sup.4 and R.sup.5 are, independently, a hydrogen or a carboxyl protecting group;X and Y are a nitrogen and a carbon atom, respectively, or a carbon and a nitrogen atom, respectively;R.sup.6 and R.sup.7 are, independently, a hydrogen or an amino, substituted amino, hydroxy, alkoxy, C.sub.1-4 alkyl, carboxyl or alkoxy carbonyl group, or jointly form a C.sub.3-7 cycloalkyl group together with the carbon to which they are attached, when X and Y are a nitrogen and a carbon, respectively, or R.sup.7 is a hydrogen or an amino group when X and Y are a carbon and a nitrogen, respectively; andQ is .dbd.CH-- or .dbd.N--, or pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates and isomers thereof, and isomers thereof possess potent and broad antibacterial activities.

摘要翻译： 式（I）的头孢菌素化合物： R2和R3独立地是氢或羟基保护基，或者一起形成环状二醇保护基; R4和R5独立地是氢或羧基保护基; X和Y分别是氮和碳原子，或分别是碳和氮原子; R 6和R 7独立地是氢或氨基，取代的氨基，羟基，烷氧基，C 1-4烷基，羧基或烷氧基羰基，或者与它们所连接的碳一起共同形成C 3-7环烷基， 当X和Y分别为氮和碳时，或当X和Y分别为碳和氮时，R 7为氢或氨基; 并且Q是= CH-或= N-，或药学上可接受的无毒盐，生理上可水解的酯，水合物和溶剂合物及其异构体及其异构体具有有效和广泛的抗菌活性。

公开(公告)号：US5605895A

公开(公告)日：1997-02-25

申请号：US277629

申请日：1994-07-20

申请人： Chan S. Bang ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Young M. Woo ,  Hun S. Oh ,  Duk H. Yang ,  Sam S. Kim ,  Se H. Kim ,  Jae H. Jeon ,  Tae H. Lee ,  Sung I. Kim ,  Mi K. Seo ,  Jae W. Lee

发明人： Chan S. Bang ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Young M. Woo ,  Hun S. Oh ,  Duk H. Yang ,  Sam S. Kim ,  Se H. Kim ,  Jae H. Jeon ,  Tae H. Lee ,  Sung I. Kim ,  Mi K. Seo ,  Jae W. Lee

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/00 ,  C07D501/36

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： The present invention relates to a cephalosporin compound represented by the following general formula (I), its pharmaceutically acceptable non-toxic salt, physiologically hydrolyzable ester, hydrate or solvate, or isomers thereof, which is useful as an antibiotic agent: ##STR1## in which R.sup.1 represents hydrogen or an amino-protecting group,R.sup.2 and R.sup.3 can be identical or different and each represent hydrogen or a hydroxy-protecting group, orR.sup.2 and R.sup.3 together can form a diol-protecting cyclic group,R.sup.4 represents hydrogen or a carboxyl-protecting group,R.sup.5 represents hydrogen, C.sub.1-4 alkyl, alkoxycarbonyl, carboxyl or sulfomethyl,R.sup.6 represents hydrogen, amino or substituted amino, andR.sup.7 represents C.sub.1-4 alkyl, amino or substituted amino, orR.sup.5 and R.sup.6 together with the carbon atoms to which they are attached can form a 3 to 7-membered cyclic group, orR.sup.6 and R.sup.7 together with the carbon and nitrogen atoms to which they are attached can form a 3 to 7-membered heterocyclic ring which may optionally contain additional heteroatoms such as nitrogen and/or oxygen and which may be substituted with the substituents selected from C.sub.1-4 alkyl, amino and substituted amino, andQ represents CH or N.

摘要翻译： 本发明涉及以下通式（I）表示的头孢菌素化合物，其药学上可接受的无毒盐，生理上可水解的酯，水合物或溶剂化物或其异构体，其可用作抗生素： I），其中R 1表示氢或氨基保护基，R 2和R 3可以相同或不同，各自表示氢或羟基保护基，或者R 2和R 3一起可以形成二醇保护的环状基团，R 4表示氢 或羧基保护基，R5表示氢，C1-4烷基，烷氧基羰基，羧基或磺基甲基，R6表示氢，氨基或取代的氨基，R7表示C1-4烷基，氨基或取代的氨基，或R5和R6连同 它们连接的碳原子可以形成3至7元环基，或者R6和R7与它们所连接的碳原子和氮原子一起可以形成3至7元杂环，其可以 任选地含有另外的杂原子如氮和/或氧并且可以被选自C 1-4烷基，氨基和取代的氨基的取代基取代，Q代表CH或N.

公开(公告)号：US5416081A

公开(公告)日：1995-05-16

申请号：US171535

申请日：1993-12-22

申请人： Chan S. Bang ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Hun S. Oh ,  Young M. Woo ,  Duk H. Yang ,  Sam S. Kim ,  Hyeon J. Yim

发明人： Chan S. Bang ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Hun S. Oh ,  Young M. Woo ,  Duk H. Yang ,  Sam S. Kim ,  Hyeon J. Yim

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/00 ,  C07D501/36

CPC分类号： C07D501/00

摘要： The present invention relates to novel cephalosporin compounds, pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates and isomers thereof which possess potent and broad antibacterial activities. The compounds of the present invention have a (4-amino-1-substituted-alkapyrimidinium-4-yl)thiomethyl group in 3-position of the cephem nucleus and is specifically represented by the following formula(I): ##STR1## wherein: R.sup.1 is a hydrogen atom or a C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl or --C(R.sup.A)(R.sup.B)COOH group wherein R.sup.A and R.sup.B are independently a hydrogen atom or a C.sub.1-4 alkyl group, or form a C.sub.3-7 cycloalkyl group together with the carbon atom to which they are attached;R.sup.2 is an unsubstituted or substituted amino, C.sub.1-4 alkyl or C.sub.3-7 cycloalkyl group; andn is an integer ranging from 2 to 7.

摘要翻译： 本发明涉及具有有效和广泛的抗菌活性的新型头孢菌素化合物，药学上可接受的无毒盐，生理上可水解的酯，水合物和溶剂合物及其异构体。 本发明的化合物在头孢烯核的3位具有（4-氨基-1-取代 - 烷基嘧啶鎓-4-基）硫代甲基，具体由下式（I）表示：C 1-4烷基 ，C 2-4的链烯基，C 2-4炔基或-C（RA）（R B）COOH基，其中RA和RB独立地为氢原子或C 1-4烷基，或与碳原子一起形成C 3-7环烷基 它们所附着的原子; R2是未取代或取代的氨基，C1-4烷基或C3-7环烷基; n为2〜7的整数。

公开(公告)号：US5202315A

公开(公告)日：1993-04-13

申请号：US494163

申请日：1990-03-15

申请人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang ,  Hyeon J. Yim

发明人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang ,  Hyeon J. Yim

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/36

CPC分类号： C07D501/36

摘要： The present invention relates to new cephalosporin compounds of the formula(I), pharmaceutically acceptable non-toxic salts thereof, and physiologically hydrolyzable esters and solvates thereof, which have potent and broad antibacterial activities ##STR1## wherein R.sup.1 is a C.sub.1.about.4 alkyl, C.sub.3.about.4 alkenyl, C.sub.3.about.4 alkynyl group, or --C(R.sup.a)(R.sup.b)CO.sub.2 H.sub.1 wherein R.sup.a and R.sup.b are the same or different, and each is a hydrogen atom or a C.sub.1.about.4 alkyl group, or R.sup.a and R.sup.b form a C.sub.3.about.7 cycloalkyl group with the carbon atom to which they are linked;R.sup.2 is a C.sub.1.about.4 alkyl, C.sub.3.about.4 alkenyl or C.sub.3.about.4 cycloalkyl group, a substituted or unsubstituted amino group, or a substituted or unsubstituted phenyl group;R.sup.3 is hydrogen or a C.sub.1.about.4 alkyl group; andQ is N or CH.The invention further relates to a process for preparing said compounds, and to pharamaceutical compositions containing said compounds.

公开(公告)号：US4971962A

公开(公告)日：1990-11-20

申请号：US350617

申请日：1989-05-11

申请人： Hun S. Oh ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Soon H. An ,  Chan S. Bang ,  Hyeon J. Yim

发明人： Hun S. Oh ,  Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Soon H. An ,  Chan S. Bang ,  Hyeon J. Yim

IPC分类号： C07D501/00 ,  C07D501/34 ,  C07D501/36 ,  C07D501/46

CPC分类号： C07D501/00 ,  Y02P20/55

摘要： The present invention relates to novel cephalosporin compounds having high antimicrobial activity, which are shown by the formula(I), and to a process for preparing them ##STR1## wherein R.sup.1 is a hydrogen atom or an amino protecting group;R.sup.2 is acetoxy; andR.sup.3 is a hydrogen atom or a carboxyl protecting group (wherein when R.sup.2 contains quaternary ammonium, r.sup.2 and R.sup.3 may form a zwitter ion).The present invention also relates to the non-toxic and pharmaceutically acceptable salts of the cephalosporin compounds of the formula (I). Also described are compositions containing the antibiotics according to the present invention.

摘要翻译： 本发明涉及具有高抗微生物活性的新型头孢菌素化合物，其由式（I）表示，及其制备方法其中R 1为氢原子或氨基保护基; R2是乙酰氧基; 并且R 3是氢原子或羧基保护基（其中当R 2含有季铵时，r 2和R 3可以形成一个两性离子）。 本发明还涉及式（I）的头孢菌素化合物的无毒和药学上可接受的盐。 还描述了含有根据本发明的抗生素的组合物。

公开(公告)号：US5292733A

公开(公告)日：1994-03-08

申请号：US866156

申请日：1992-04-09

申请人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang ,  Hyeon J. Yim

发明人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang ,  Hyeon J. Yim

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/00 ,  C07D501/04 ,  C07D501/36

CPC分类号： C07D501/00

摘要： The present invention relates to a cephalosporin compound including the pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates thereof of the formula(I) and its isomers: ##STR1## wherein: R.sup.1 is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-4 alkynyl or --C(R.sup.3)(R.sup.4)COOH wherein R.sup.3 and R.sup.4, which may be the same or different, are hydrogen, C.sub.1-4 alkyl group, or constitute a C.sub.3-7 cycloalkyl group with the carbon atoms to which R.sup.3 and R.sup.4 are attached;R.sup.2, which may be attached to N.sup.a or N.sup.b, is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-7 cycloalkyl, aryl or amino group; andQ.sub.1 and Q.sub.2, which may be the same or different, are CH or N.

摘要翻译： 本发明涉及一种头孢菌素化合物，其包括式（I）的药学上可接受的无毒盐，生理上可水解的酯，水合物和溶剂化物及其异构体：（*化学结构*）（I）（*化学结构*） 其中：R 1是C 1-4烷基，C 3-4烯基，C 3-4炔基或-C（R 3）（R 4）COOH，其中R 3和R 4可以相同或不同，是氢，C 1-4烷基 或者构成与R3和R4相连的碳原子的C3-7环烷基; 可以连接到Na或Nb的R2是C1-4烷基，C3-4烯基，C3-7环烷基，芳基或氨基; 和可以相同或不同的Q1和Q2是CH或N.

公开(公告)号：US5462935A

公开(公告)日：1995-10-31

申请号：US971986

申请日：1993-02-10

申请人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Chan S. Bang ,  Won S. Kim ,  Hyeon J. Yim

发明人： Yong Z. Kim ,  Hun S. Oh ,  Jae H. Yeo ,  Jong C. Lim ,  Chan S. Bang ,  Won S. Kim ,  Hyeon J. Yim

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D20060101 ,  C07D501/00 ,  C07D501/04 ,  C07D501/36 ,  C07D501/56 ,  C07D50/36

CPC分类号： C07D501/00

摘要： The present invention provides a cephalosporin compound represented by formulas (I-S) and (I-R) ##STR1## wherein: R.sup.1 is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-4 cycloalkyl, amino optionally substituted with a C.sub.1-4 alkyl radical, phenyl, or 2-,4- or 6- substituted phenyl group with two or fewer substitutents chosen from C.sub.1-4 alkyl, C.sub.1-3 alkoxy, halogen and hydroxy radicals;R.sup.2 is hydrogen or a C.sub.1-4 alkyl group;R.sup.a and R.sup.b, which should be different from each other, are hydrogen or a C.sub.1-4 alkyl group; andQ is N or CH,and the pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates thereof, which possess potent and broad antibacterial activities. The invention also provides processes for preparing these compounds and to pharmaceutical compositions containing them as active ingredients.

摘要翻译： 本发明提供由式（IS）和（1R）表示的头孢菌素化合物。其中：R1是C1-4烷基，C3-4链烯基，C3-4环烷基，氨基 任选被C1-4烷基，苯基或2-，4-或6-取代的苯基取代，具有两个或更少个选自C 1-4烷基，C 1-3烷氧基，卤素和羟基的取代基; R2是氢或C1-4烷基; 应该彼此不同的R a和R b是氢或C 1-4烷基; 和Q是N或CH，以及其药学上可接受的无毒盐，生理上可水解的酯，水合物和溶剂合物，其具有有效和广泛的抗菌活性。 本发明还提供了制备这些化合物的方法和含有它们作为活性成分的药物组合物。

公开(公告)号：US5142041A

公开(公告)日：1992-08-25

申请号：US673673

申请日：1991-03-22

申请人： Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang

发明人： Yong Z. Kim ,  Jae H. Yeo ,  Jong C. Lim ,  Won S. Kim ,  Chan S. Bang

IPC分类号： A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/00 ,  C07D501/06 ,  C07D501/18 ,  C07D501/36

CPC分类号： C07D501/00

摘要： The present invention provides certain novel cephalosporin derivatives represented by following formula(I), which are especially useful as intermediates for the preparation of cephalosporin compounds possessed with potent and broad antibacterial activities. ##STR1## wherein: R.sup.1 is a C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.3-4 cycloalkyl, amino optionally substituted with a C.sub.1-4 alkyl radical, or phenyl group optionally substituted on its 2-, 4-and/or 6-position with a halogen, C.sub.1-4 alkyl, C.sub.1-3 alkoxy or hydroxy radical;R.sup.2 is hydrogen or a C.sub.1-4 alkyl group; andn is either 0 or 1.The invention also relates to processes for preparing these intermediates and their pharmacologically active cephalosporin antibiotics.

摘要翻译： 本发明提供一些由下式（I）表示的新型头孢菌素衍生物，其特别可用作制备具有强效和广泛抗菌活性的头孢菌素化合物的中间体。 （I）其中：R1是C1-4烷基，C3-4链烯基，C3-4环烷基，任选被C 1-4烷基取代的氨基或在其2-，4-和/或6上任意取代的苯基 - 卤素，C 1-4烷基，C 1-3烷氧基或羟基; R2是氢或C1-4烷基; 并且n为0或1.本发明还涉及制备这些中间体及其药理学活性头孢菌素抗生素的方法。

公开(公告)号：US06682759B2

公开(公告)日：2004-01-27

申请号：US10066146

申请日：2002-02-01

申请人： Jong C. Lim ,  John N. Shell

发明人： Jong C. Lim ,  John N. Shell

IPC分类号： A61K922

CPC分类号： A61K9/209 ,  A61K31/155 ,  A61K2300/00

摘要： A method is disclosed for manufacturing a pharmaceutical tablet for oral administration, the tablet combining both immediate-release and prolonged-release modes of drug delivery and using an immediate-release drug that is either insoluble in water or only sparingly soluble and is present in a very small amount compared to the prolonged-release drug. The method involves the use of particles of the immediate-release drug that are equal to or less than 10 microns in diameter, applied as a layer or coating over a core of the prolonged-release drug, the layer or coating being either the drug particles themselves, applied as an aqueous suspension, or a solid mixture containing the drug in admixture with a material that disintegrates rapidly in gastric fluid. The result in both cases is a high degree of uniformity in the proportions of the immediate-release and prolonged-release drugs, uniformity that is otherwise difficult to achieve in view of the insolubility of the immediate-release drug and its relatively small amount compared to the prolonged-released drug.

摘要翻译： 公开了用于制造用于口服给药的药物片剂的方法，所述药片结合药物递送的立即释放和延长释放模式并且使用不溶于水或仅溶于微溶并且存在于 与延长释放药物相比非常少量。 该方法包括使用直径为等于或小于10微米的速释药物的颗粒，作为延长释放药物的核心上的层或涂层施用，该层或涂层是药物颗粒 或者含有药物的固体混合物与在胃液中快速分解的物质混合。 两种情况的结果是立即释放和延长释放药物的比例高度均匀，鉴于立即释放药物的不溶性而难以实现的均匀性，并且相对于 延长释放的药物。