公开(公告)号：US4302580A

公开(公告)日：1981-11-24

申请号：US185594

申请日：1980-09-09

申请人： Katsuyoshi Iwamatsu ,  Jiro Itoh ,  Shoji Omoto ,  Takashi Tsuruoka ,  Shigeharu Inouye

发明人： Katsuyoshi Iwamatsu ,  Jiro Itoh ,  Shoji Omoto ,  Takashi Tsuruoka ,  Shigeharu Inouye

IPC分类号： C07D501/04 ,  C07D501/36 ,  C07D501/57 ,  C12P35/08

CPC分类号： C12P35/08

摘要： A chemotherapeutic, antibacterial agent, 7.beta.-[(2D-2-amino-2-carboxy)ethylthioacetamido]-7.alpha.-methoxy-3-[(1-methyl-1H-tetrazole-5-yl)thiomethyl]-3-cephem-4-carboxylic acid is produced economically and efficiently starting from cephamycin A and/or B by a "new route" process comprising the consecutive steps of reaction of cephamycin with 5-mercapto-1-methyl-1H-tetrazole; protection of the terminal amino group thereof by acylation; protection of the two carboxyl groups thereof by esterification; replacement of the acyl group initially having attached to the 7-amino group by a halogenoacetyl group; deprotection of the blocked 4-carboxyl group; and condensation of D-cysteine with the halogenoacetyl group attaching to the 7-amino group.

摘要翻译： 7β-[（2D-2-氨基-2-羧基）乙硫基乙酰氨基]-7α-甲氧基-3 - [（1-甲基-1H-四唑-5-基）硫代甲基] -3- 头孢霉素-4-羧酸从头孢霉素A和/或B开始通过包含头孢霉素与5-巯基-1-甲基-1H-四唑的连续步骤的“新途径”方法经济有效地产生; 通过酰化保护其末端氨基; 通过酯化保护其两个羧基; 用卤代乙酰基取代最初连接在7-氨基上的酰基; 封闭的4-羧基脱保护; 和D-半胱氨酸与连接于7-氨基的卤代乙酰基缩合。

公开(公告)号：US3959256A

公开(公告)日：1976-05-25

申请号：US505310

申请日：1974-09-12

申请人： Shigeharu Inouye ,  Shoji Omoto ,  Katsuyoshi Iwamatsu ,  Taro Niida ,  Toyoaki Kawasaki ,  Takashi Tsuruoka

发明人： Shigeharu Inouye ,  Shoji Omoto ,  Katsuyoshi Iwamatsu ,  Taro Niida ,  Toyoaki Kawasaki ,  Takashi Tsuruoka

IPC分类号： C07H17/08

CPC分类号： C07H17/08

摘要： A 9-O-alkanoyl-3"-O-alkanoyloxymethyl-SF-837 substance is now synthetized, which is a new compound useful in that this new 9-O-alkanoyl-3"-O-alkanoyloxymethyl derivative of the SF-837 substance exhibits an antibacterial activity comparable to that of the parent SF-837 substance but is advantageously free from the unpleasant bitter taste inherent to the SF-837 substance and is hence adapted for oral administration. A process of producing the 9-O-alkanoyl-3"-O-alkanoyloxymethyl-SF-837 substance is also provided, which comprises hydrolysing partially and selectively a 9,2'-di-O-alkanoyl-3"-O-alkanoyloxymethyl-SF-837 substance in an aqueous alkanol or aqueous acetone. The 9,2'-di-O-alkanoyl-3"-O-alkanopyloxymethyl-SF-837 substance may be prepared by reacting a 9,2'-di-alkanoyl- or O-mono-O-alkanoyl-3"-O-thiomethoxymethyl-SF-837 substance with an alkanoic anhydride which is exemplified by acetic anhydride or propionic anhydride in the specification.

摘要翻译： 现在合成了9-O-烷酰基-3“-O-烷酰氧基甲基-SF-837物质，这是一种新的化合物，有用的是这种新型的9-O-烷酰基-3'-O-烷酰氧基甲基衍生物 -837物质表现出与母体SF-837物质相当的抗菌活性，但有利地没有SF-837物质固有的不愉快的苦味，因此适于口服给药。 还提供了制备9-O-烷酰基-3“-O-烷酰氧基甲基-SF-837物质的方法，其包括部分和选择性地水解9,2'-二-O-烷酰基-3'-O - 烷酰氧基甲基-SF-837物质在链烷醇水溶液或丙酮水溶液中。 9,2'-二-O-烷酰基-3“-O-烷酰氧基甲基-SF-837物质可以通过使9,2'-二烷酰基或O-单-O-烷酰基-3' 具有链烷酸酐的“-O-硫代甲氧基甲基-SF-837”物质，其例示在说明书中的乙酸酐或丙酸酐。

公开(公告)号：US4325951A

公开(公告)日：1982-04-20

申请号：US200410

申请日：1980-10-24

申请人： Shigeharu Inouye ,  Takashi Tsuruoka ,  Katsuyoshi Iwamatsu

发明人： Shigeharu Inouye ,  Takashi Tsuruoka ,  Katsuyoshi Iwamatsu

IPC分类号： A61K31/535 ,  A61P31/04 ,  C07D505/00 ,  C07D498/04

CPC分类号： C07D505/00 ,  Y02P20/55

摘要： New antibacterial 1-oxadethiacephalosporin derivatives of the general formula ##STR1## wherein R is a heterocyclic group or a group --S--Het where Het denotes a heterocyclic group, Y is a hydrogen atom or a methoxy group; x and y are each an integer of 1 to 3 is produced by a process comprising condensing a 1-oxacephem compound of the formula ##STR2## wherein R, Y, y are as defined above; R' is a hydrogen atom or a carboxyl-protecting group; and Z is a halo group, with a sulfur-containing amino acid of the formula ##STR3## wherein x is as defined above, in a solvent and removing, if necessary, the residual protective group from the resultant condensation product. The new 1-oxadethiacephalosporin derivatives and the pharmaceutically acceptable salts and esters thereof exhibit high and broad "in vitro" and "in vivo" antibacterial activity, particularly against .beta.-lactamase-producing strains of gram-negative bacteria.

摘要翻译： 其中R是杂环基的新型抗菌1-恶二硫醚类衍生物或其中Het表示杂环基的基团-S-Het，Y是氢原子或甲氧基; x和y各自为1〜3的整数，是通过下列方法制备的：其中R 1，Y，y如上所定义的式 R'是氢原子或羧基保护基; Z为卤素基，其中x如上定义，其中x如上所定义，并且如有必要，从所得缩合产物中除去残留的保护基团，其中含有式“IMAGE”的含硫氨基酸。 新的1-羟基乙硫菌醚衍生物及其药学上可接受的盐和酯在革兰氏阴性菌的β-内酰胺酶生产菌株中表现出高且广泛的“体外”和“体内”抗菌活性。

公开(公告)号：US4324891A

公开(公告)日：1982-04-13

申请号：US178604

申请日：1980-08-15

申请人： Katsuyoshi Iwamatsu ,  Takashi Tsuruoka ,  Kazuko Mizutani ,  Katsumi Kawaharajyo ,  Tadahiro Watanabe ,  Shigeharu Inouye

发明人： Katsuyoshi Iwamatsu ,  Takashi Tsuruoka ,  Kazuko Mizutani ,  Katsumi Kawaharajyo ,  Tadahiro Watanabe ,  Shigeharu Inouye

IPC分类号： C07D501/04 ,  C07D501/57

CPC分类号： C07D501/57 ,  Y02P20/55

摘要： A new, efficient process is provided for the production of 7.beta.-[(2D-2-amino-2-carboxy)-ethylthio-acetamido]-7.alpha.-methoxy-3-[(1-methyl-1H-tetrazole-5-yl) thiomethyl]-3-cephem-4-carboxylic acid useful as new antibacterial agent. This process is economic in using as the starting material the inexpensive, corresponding cephem compound containing no 7.alpha.-methoxy group on the cephem nucleus and comprises 7.alpha.-methoxylation of a protected derivative of the starting cephem compound with t-butyl hypochlorite and lithium methoxide, followed by inactivation of the excessive methoxylation reagents with a trialkyl phosphite and acetic acid to prevent undesired side-reactions such as oxidation of the alkylthioacetyl group of the product, and further by conventional removal of the protecting groups.

摘要翻译： 提供了一种新的，有效的方法，用于生产7β - [（2D-2-氨基-2-羧基） - 乙硫基 - 乙酰氨基]-7α-甲氧基-3 - [（1-甲基-1H-四唑-5 - 基）硫代甲基] -3-头孢烯-4-羧酸，可用作新的抗菌剂。 该方法在起始物质中是经济的，其是在头孢烯核上不含有7个α-甲氧基的廉价相应的头孢烯化合物，并且包括起始头孢烯化合物与叔丁基次氯酸盐和甲醇锂的保护的衍生物的7α-甲氧基化 然后用亚磷酸三烷基酯和乙酸使过量的甲氧基化试剂失活，以防止不期望的副反应如产物的烷基硫代乙酰基氧化，并进一步通过常规除去保护基。

公开(公告)号：US5061702A

公开(公告)日：1991-10-29

申请号：US402814

申请日：1989-09-05

申请人： Kunio Atsumi ,  Katsuyoshi Iwamatsu ,  Kenji Sakagami ,  Takashi Yoshida ,  Haruo Yamamoto ,  Seiji Shibahara ,  Shigeharu Inouye

发明人： Kunio Atsumi ,  Katsuyoshi Iwamatsu ,  Kenji Sakagami ,  Takashi Yoshida ,  Haruo Yamamoto ,  Seiji Shibahara ,  Shigeharu Inouye

IPC分类号： C07D501/22 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  C07D501/04 ,  C07D501/06 ,  C07D501/24

CPC分类号： C07D501/24 ,  Y02P20/55

摘要： A novel cephem compound which has antimicrobial activity is disclosed. The cephem compound is represented by the formula: ##STR1## wherein R.sup.1 represents a hydrogen atom or a carboxyl group; R.sup.2 and R.sup.3, which may be the same or different, each represent a hydrogen atom or a lower alkyl group of 1-3 carbon atoms; and R.sup.4 and R.sup.5, which may be the same or different, each represent a hydrogen atom or an acyl group; and pharmaceutically acceptable salts thereof.

公开(公告)号：US5028601A

公开(公告)日：1991-07-02

申请号：US184323

申请日：1988-04-21

申请人： Shinichi Kondo ,  Takashi Tsuruoka ,  Katsuyoshi Iwamatsu ,  Kiyoaki Katano ,  Satoru Nakabayashi ,  Hiroko Ogino ,  Takashi Yoshida ,  Masaji Sezaki

发明人： Shinichi Kondo ,  Takashi Tsuruoka ,  Katsuyoshi Iwamatsu ,  Kiyoaki Katano ,  Satoru Nakabayashi ,  Hiroko Ogino ,  Takashi Yoshida ,  Masaji Sezaki

IPC分类号： C07D501/00 ,  C07D501/20

CPC分类号： C07D501/00

摘要： Cephalosporin compounds of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 may be the same or different and are a hydrogen atom or a lower alkyl group of 1-5 carbon atoms and A is a hydrogen atom or a nucleophilic compound residue or pharmacologically acceptable salts thereof have excellent antibacterial activity against Gram positive and Gram negative microorganisms.

公开(公告)号：US4758557A

公开(公告)日：1988-07-19

申请号：US872316

申请日：1986-06-09

申请人： Takashi Tsuruoka ,  Katsuyoshi Iwamatsu ,  Kiyoaki Katano ,  Hiroko Ogino ,  Ryoichi Okamoto ,  Takashi Yoshida ,  Masaji Sezaki ,  Fumio Kai ,  Shigeharu Inoue ,  Shinichi Kondo

发明人： Takashi Tsuruoka ,  Katsuyoshi Iwamatsu ,  Kiyoaki Katano ,  Hiroko Ogino ,  Ryoichi Okamoto ,  Takashi Yoshida ,  Masaji Sezaki ,  Fumio Kai ,  Shigeharu Inoue ,  Shinichi Kondo

IPC分类号： A61K31/545 ,  C07D501/24 ,  C07D501/36 ,  C07D501/46

CPC分类号： C07D501/24

摘要： Cephalosporin compounds represented by the following formula (I) and pharmaceutically acceptable salts thereof have a broad bactericidal spectrum against various pathogenic bacteria including Psuedomonas aeruginosa and are useful as bactericidal remedies for pathogenic diseases of human and animals: ##STR1## wherein A represents an unsubstituted or substituted pyridylthio group of a formula (I-1); ##STR2## or an unsubstituted or substituted pyridiniumthio group of a formula (I-2): ##STR3## or an unsubstituted or substituted pyridinium group of a formula (I-3); ##STR4## or a 5- or 6-membered heterocyclicthio or bicycloheterocyclicthio group of a formula (I-4):--S--Het (I-4).

摘要翻译： 由下式（I）表示的头孢菌素化合物及其药学上可接受的盐对各种致病细菌（包括铜绿假单胞菌）具有广泛的杀菌谱，并且可用作人和动物的致病性疾病的杀菌剂：其中A代表 式（I-1）的未取代或取代的吡啶硫基; （I-1）或式（I-2）的未取代或取代的吡啶硫基：式（I-2）或未取代或取代的式（I-3）吡啶鎓基; （I-3）或式（I-4）的5-或6-元杂环硫或二环杂环硫基：-S-Het（I-4）。

公开(公告)号：US4785090A

公开(公告)日：1988-11-15

申请号：US704077

申请日：1985-02-21

申请人： Takashi Tsuruoka ,  Seiji Shibahara ,  Katsuyoshi Iwamatsu ,  Tsuneo Okonogi ,  Satoru Nakabayashi ,  Yasushi Murai ,  Hiroko Ogino ,  Kiyoaki Katano ,  Takashi Yoshida ,  Shigeharu Inoue ,  Shunzo Fukatsu ,  Shinichi Kondo

发明人： Takashi Tsuruoka ,  Seiji Shibahara ,  Katsuyoshi Iwamatsu ,  Tsuneo Okonogi ,  Satoru Nakabayashi ,  Yasushi Murai ,  Hiroko Ogino ,  Kiyoaki Katano ,  Takashi Yoshida ,  Shigeharu Inoue ,  Shunzo Fukatsu ,  Shinichi Kondo

IPC分类号： C07D213/64 ,  C07D213/68 ,  C07D221/04 ,  C07D501/36 ,  C07D501/38 ,  A61K31/545

CPC分类号： C07D221/04 ,  C07D213/64 ,  C07D213/68

摘要： This is a class of antibacterial compounds of the formula: ##STR1## wherein Y is straight or branched alkyl or alkenyl chain, cycloalkanomethyl of 3-6 carbon atoms, each group being optionally substituted by halogen, or a group ##STR2## wherein n is 0 or an integer of 1-3, A is a group --COR.sup.3 wherein R.sup.3 is hydroxy, a group ##STR3## wherein R.sup.4 and R.sup.5, which may be the same or different, are hydrogen or alkyl of 1-5 carbon atoms, a group ##STR4## or a 5- or 6-membered heterocyclic group containing nitrogen and/or sulfur, and R.sup.1 and R.sup.2, which may be the same or different, are hydrogen, alkyl of 1-5 carbon atoms, or R.sup.1 and R.sup.2 may be combined together to form cycloalkylidene of 3-5 carbon atoms, and Z is a group of the formula: ##STR5## wherein m is 0 or an integer of 3-5, R.sup.6 is hydrogen or alkyl of 1-3 carbon atoms, and R.sup.7, when m is an integer of 3-5, is alkyl of 1-5 carbon atoms, alkenyl, cyclopropyl, a group --(CH.sub.2).sub.p B wherein p is 0 or an integer of 1-3 and B is amino, alkyl-substituted amino, hydroxy, carboxy, carbamoyl, trifluoromethyl, sulfonic acid, sulfonic acid amide, alkylthio or cyano or, when m is 0, is alkyl of 1-5 carbon atoms, which may optionally be substituted by halogen, alkenyl, a group ##STR6## wherein R.sup.8 is hydrogen, alkyl of 1-4 carbon atoms or phenyl, or cyclopropyl, and a salt thereof.

摘要翻译： 这是一类具有下式的抗菌化合物：其中Y是直链或支链烷基或烯基链，3-6个碳原子的环烷基甲基，每个基团任选被卤素取代，或基团< 其中n为0或1-3的整数，A为基团-COR 3，其中R 3为羟基，其中R 4和R 5可以相同或不同，为氢或1-5碳的烷基 原子，基团或含有氮和/或硫的5-或6-元杂环基，R 1和R 2可以相同或不同，为氢，1-5个碳原子的烷基或R1 并且R 2可以组合在一起形成3-5个碳原子的亚烷基，Z是下式的基团：其中m是0或3-5的整数，R6是氢或1-3个碳的烷基 原子和R 7，当m是3-5的整数时，是1-5个碳原子的烷基，烯基，环丙基，基团 - （CH 2）pB，其中p是0或1-3的整数，B是氨基 ，烷基取代的氨基 羟基，羧基，氨基甲酰基，三氟甲基，磺酸，磺酸酰胺，烷硫基或氰基，或当m为0时，其为1-5个碳原子的烷基，其可任选被卤素，链烯基，基团 其中R8是氢，1-4个碳原子的烷基或苯基，或环丙基及其盐。

公开(公告)号：US4017607A

公开(公告)日：1977-04-12

申请号：US597188

申请日：1975-07-18

申请人： Shigeharo Inouye ,  Shoji Omoto ,  Katsuyoshi Iwamatsu ,  Takashi Tsuruoka ,  Taro Niida ,  Toyoaki Kawasaki

发明人： Shigeharo Inouye ,  Shoji Omoto ,  Katsuyoshi Iwamatsu ,  Takashi Tsuruoka ,  Taro Niida ,  Toyoaki Kawasaki

IPC分类号： A61K31/70 ,  A61K31/7042 ,  A61K31/7048 ,  A61P31/04 ,  C07H17/08

CPC分类号： C07H17/08

摘要： As new compounds are provided 9,3",4"-trialkanoyl SF-837 M.sub.1 substances which have therapeutically useful antibacterial activity and do not show any objectionable long-lasting bitter taste upon its oral administration. These 9,3",4"-trialkanoyl SF-837 M.sub.1 substances may be prepared from SF-837 substance, 9,2',3"-tri-acetyl SF-837 M.sub.1 substance, 9,2'-di-acetyl SF-837 substance, 9-propionyl SF-837 substance or 9,2'-dipropionyl SF-837 substance by acylating the latter with an alkanoic acid anhydride at 50.degree.-120.degree. C to produce the corresponding 9,2',3",4"-tetra-alkanoyl SF-837 M.sub.1 substance and occasionally the 9,18,2',3",4"-penta-alkanoyl SF-837 M.sub.1 substance, with involving the shift of the 4"-alkanoyl group to the 3"-hydroxyl group. Partial and selective hydrolysis of the 9,2',3",4"-tetra-alkanoyl SF-837 M.sub.1 substance and/or the 9,18,2',3",4"-penta-alkanoyl SF-837 M.sub.1 substance so produced gives the desired 9,3",4"-tri-alkanoyl SF-837 M.sub.1 substance.

摘要翻译： 当新化合物被提供具有治疗上有用的抗菌活性的9,3“，4” - 三烷酰基SF-837M1物质，并且在其口服给药时不显示任何令人不快的持久苦味。 这些9,3“，4” - 三烷酰基SF-837 M1物质可以由SF-837物质，9,2'，3“ - 三乙酰基SF-837M1物质，9,2'-二 - 乙酰基SF-837物质，9-丙酰基SF-837物质或9,2'-二丙酰基SF-837物质，通过用烷基酸酐在50°-120℃下酰化后者，产生相应的9,2' 3“，4” - 四烷酰基SF-837 M1物质，偶尔有9,18,2'，3“，4” - 五烷酰基SF-837 M1物质，涉及4 “ - 烷酰基与3” - 羟基。 9,2'，3“，4” - 四烷酰基SF-837 M1物质和/或9,18,2'，3“，”4“ - 五烷酰基SF- 837如此生产的M1物质得到所需的9,3“，”4“ - 三烷酰基SF-837 M1物质。

公开(公告)号：US06867226B2

公开(公告)日：2005-03-15

申请号：US10219496

申请日：2002-08-16

申请人： Yasuo Sato ,  Megumi Yamada ,  Kazuko Kobayashi ,  Katsuyoshi Iwamatsu ,  Fukio Konno ,  Koichi Shudo

发明人： Yasuo Sato ,  Megumi Yamada ,  Kazuko Kobayashi ,  Katsuyoshi Iwamatsu ,  Fukio Konno ,  Koichi Shudo

IPC分类号： A61K31/42 ,  A61K31/423 ,  A61K31/44 ,  A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61K31/5513 ,  A61P1/00 ,  A61P1/08 ,  A61P1/12 ,  A61P1/14 ,  A61P25/04 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/26 ,  A61P43/00 ,  C07D263/30 ,  C07D263/58 ,  C07D263/60 ,  C07D413/04 ,  A61K31/50

CPC分类号： C07D263/58 ,  A61K31/496 ,  C07D263/30 ,  C07D413/04

摘要： This invention provides a serotonin 5-HT3 receptor partial activator which has a serotonin 5-HT3 receptor activating action, in addition to its serotonin 5-HT3 receptor antagonism, and does not cause constipation as a side effect.Particularly, based on the finding that newly synthesized benzoxazole derivatives typified by the compounds of the following formula (2) have strong serotonin 5-HT3 receptor antagonism and serotonin 5-HT3 receptor activating action, this invention provides these benzoxazole derivatives as serotonin 5-HT3 receptor partial activators. In the above formula, R1 to R4 may be the same or different from one another and each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group or a substituted or unsubstituted amino group, or two groups of R1 and R2 may be linked together to form a ring structure, namely benzene ring; R5 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group or a substituted or unsubstituted lower alkenyl group; and m is an integer of 1 to 4.

摘要翻译： 本发明提供除5-羟色胺5-HT 3受体拮抗作用之外还具有5-羟色胺5-HT 3受体激活作用的5-羟色胺5-HT 3受体部分活化剂，并且不引起便秘作为副作用。特别地，基于以下发现： 以下式（2）化合物为代表的新合成苯并恶唑衍生物具有强烈的5-羟色胺5-HT 3受体拮抗作用和5-羟色胺5-HT 3受体激活作用，本发明提供了这些苯并恶唑衍生物作为5-羟色胺5-HT 3受体部分活化剂。 式中，R 1〜R 4可以相同或不同，表示氢原子，卤素原子，取代或未取代的低级烷基，取代或未取代的低级烯基或取代或未取代的氨基，或二 R1和R2的基团可以连接在一起形成环结构，即苯环; R5表示氢原子，取代或未取代的低级烷基或取代或未取代的低级烯基; m为1〜4的整数。