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    Nitric Oxide Enhancing Antimicrobial Compounds, Compositions and Methods of Use
    1.
    发明申请
    Nitric Oxide Enhancing Antimicrobial Compounds, Compositions and Methods of Use 审中-公开
    一氧化氮增强抗菌化合物，组合物和使用方法

    公开(公告)号：US20090018091A1

    公开(公告)日：2009-01-15

    申请号：US11997536

    申请日：2006-08-02

    申请人： James L. Ellis ,  David S. Garvey

    发明人： James L. Ellis ,  David S. Garvey

    IPC分类号： A61K31/7036 ,  C07H15/234 ,  C07D417/12 ,  A61K31/397 ,  A61K31/4375 ,  C07D471/04 ,  A61K31/407 ,  C07D487/04 ,  A61P31/04 ,  A61P31/10 ,  A61P31/12

    CPC分类号： C07D417/12 ,  C07D215/56 ,  C07D401/04 ,  C07D417/14 ,  C07D471/04 ,  C07D477/26

    摘要： The invention describes compositions and kits comprising at least one nitric oxide enhancing group antimicrobial compound, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitric oxide enhancing antimicrobial compound, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating bacterial infections; (b) treating viral infections; (c) treating fungal infections; and (d) treating lesions. The antimicrobial compounds of the invention are preferably tobramycin, aztreonam, ciprofloxacin and doripenam. The nitric oxide enhancing antimicrobial compounds are substituted with at least one heterocyclic nitric oxide donor group and/or at least one nitroxide group. The nitric oxide enhancing groups are nitroxides and/or heterocyclic nitric oxide donors. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines. In one embodiment the methods of the invention are for the treatment of bacterial infections associated with pulmonary diseases such as cystic fibrosis and for treating Bacillus anthracis infections.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强组抗微生物化合物或其药学上可接受的盐的组合物和试剂盒，以及包含至少一种一氧化氮增强抗微生物化合物和任选的至少一种一氧化氮增强化合物和/或 至少一种治疗剂。 本发明还提供了（a）治疗细菌感染的方法; （b）治疗病毒感染; （c）治疗真菌感染; 和（d）治疗病变。 本发明的抗微生物化合物优选为妥布霉素，氨曲南，环丙沙星和多瑞培南。 一氧化氮增强抗微生物化合物被至少一个杂环一氧化氮供体基团和/或至少一个氮氧化物基团取代。 一氧化氮增强基团是氮氧化物和/或杂环一氧化氮供体。 杂环一氧化氮供体是呋喃糖，苏氨酸，氧杂三唑-5-酮和/或氧杂三唑-5-亚胺。 在一个实施方案中，本发明的方法用于治疗与肺部疾病如囊性纤维化相关的细菌感染和用于治疗炭疽芽孢杆菌感染。

    6- and 1-Substituted-1-carbadethiapen-2-em-3-carboxylic acid
    4.
    发明授权
    6- and 1-Substituted-1-carbadethiapen-2-em-3-carboxylic acid 失效
    6-和1-取代的1-碳代萘二烯-2-烯-3-羧酸

    公开(公告)号：US4206219A

    公开(公告)日：1980-06-03

    申请号：US954274

    申请日：1978-10-24

    申请人： Burton G. Christensen ,  David H. Shih

    发明人： Burton G. Christensen ,  David H. Shih

    IPC分类号： C07C205/42 ,  C07D205/08 ,  C07D477/20 ,  C07D477/26 ,  C07D498/04 ,  C07F7/18 ,  C07F9/568 ,  C07D487/04 ,  A61K31/40

    CPC分类号： C07D477/20 ,  C07C205/42 ,  C07D205/08 ,  C07D477/26 ,  C07F7/1804 ,  C07F9/5683

    摘要： Disclosed are 6- and 1-substituted-1-carbadethiapen-2-em-3-carboxylic acids of the following structure: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl. Such compounds as well as their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotics effect is indicated.

    摘要翻译： 公开了以下结构的6-和1-取代-1-碳氮杂萘-2-烯-3-羧酸：其中R 1，R 2和R 3特别地独立地选自氢，烷基 ，芳基和芳烷基。 这些化合物及其药学上可接受的盐，酯和酰胺衍生物可用作抗生素。 还公开了制备这些化合物的方法，包含这些化合物的药物组合物和治疗方法，包括当指出抗生素效应时施用这些化合物和组合物。

    Photocatalyzed process for producing carbapenams and carbapen-2-ems
    6.
    发明授权
    Photocatalyzed process for producing carbapenams and carbapen-2-ems 失效
    用于生产碳青霉烯和碳青霉素2-em的光催化过程

    公开(公告)号：US4348264A

    公开(公告)日：1982-09-07

    申请号：US232156

    申请日：1981-02-09

    申请人： Robert L. Rosati

    发明人： Robert L. Rosati

    IPC分类号： C07D487/04 ,  C07D477/26 ,  C07D499/00 ,  B01J19/12

    CPC分类号： C07D477/26 ,  C07D499/00 ,  Y02P20/55

    摘要： Carbapenam-3-carboxylic acids and carbapen-2-em-3-carboxylic acids substituted at the 1-position with an oxo, a hydroxy or an acetoxy group, variously substituted at the 2-position with such groups as methyl, acetoxymethyl, methanesulfonyloxy, alkoxy, alkylthio, aminoalkylthio or amidinoalkylthio and optionally substituted at the 6-position with a hydroxyalkyl group, an acetoxyalkyl group or a conventional penicillin side-chain, pharmaceutically-acceptable salts thereof and various esters thereof wherein the esterifying group is selectively removed in the laboratory, or hydrolyzed under physiological conditions.These compounds are useful either systemically or topically in the treatment of diseases caused by susceptible microorganisms, as animal feed additives for promotion of growth, or in the preservation of biodegradable materials, or as intermediates to compounds having such antibacterial activity.Key to the synthesis of these compounds is the light catalyzed rearrangement of 2-diazo-1-oxoceph-3-em-4-carboxylates to 1-oxocarbapen-2-em-3-carboxylates, a newly discovered reaction determined to be of general applicability.

    摘要翻译： 在1-位被氧代，羟基或乙酰氧基取代的碳青霉烯-3-羧酸和在2-位上被甲基，乙酰氧基甲基，甲磺酰氧基等基团取代的碳代萘-2-羧酸 ，烷氧基，烷硫基，氨基烷硫基或脒基烷硫基，并且任选在6-位被羟烷基，乙酰氧基烷基或常规青霉素侧链取代，其药学上可接受的盐及其各种酯，其中酯化基团在 实验室，或在生理条件下水解。 这些化合物可以全身或局部用于治疗由易感微生物引起的疾病，作为用于促进生长的动物饲料添加剂，或用于生物降解材料的保存，或作为具有这种抗菌活性的化合物的中间体。 合成这些化合物的关键是2-重氮-1-氧代头孢-3-烯-4-羧酸酯轻链催化重排1-氧代羧基-2-em-3-羧酸酯，新发现的反应确定为一般 适用性。

    3 -Substituted-6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxyl ic acid
    7.
    发明授权
    3 -Substituted-6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxyl ic acid 失效
    3-取代的6-取代-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸

    公开(公告)号：US4347368A

    公开(公告)日：1982-08-31

    申请号：US207042

    申请日：1980-11-14

    申请人： Burton G. Christensen ,  David B. R. Johnston ,  Susan M. Schmitt

    发明人： Burton G. Christensen ,  David B. R. Johnston ,  Susan M. Schmitt

    IPC分类号： C07D205/08 ,  C07D477/20 ,  C07D477/26 ,  C07D498/04 ,  C07F7/10 ,  C07D487/04

    CPC分类号： C07D477/26 ,  C07D205/08 ,  C07D477/20 ,  C07F7/10

    摘要： Disclosed are 3- and 6-substituted 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acids having the structure: ##STR1## wherein R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds as well as their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

    摘要翻译： 公开了具有以下结构的3-和6-取代的7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸：其中R6，R7和R8特别独立地选自 由氢，烷基，烯基，芳基和芳烷基组成的组。 这些化合物及其药学上可接受的盐，酯和酰胺衍生物可用作抗生素。 还公开了制备这些化合物的方法，包含这些化合物的药物组合物和治疗方法，包括当指出抗生素作用时施用这些化合物和组合物。

    LYOPHILIZED PREPARATION OF 1-METHYLCARBAPENEM
    8.
    发明申请
    LYOPHILIZED PREPARATION OF 1-METHYLCARBAPENEM 审中-公开
    L-甲基胆碱酯的制备

    公开(公告)号：US20100010214A1

    公开(公告)日：2010-01-14

    申请号：US12439046

    申请日：2007-08-28

    申请人： Takayuki Kikuchi ,  Fumihiro Kihara ,  Masahiko Suzuki

    发明人： Takayuki Kikuchi ,  Fumihiro Kihara ,  Masahiko Suzuki

    IPC分类号： C07D487/04

    CPC分类号： A61K9/19 ,  C07D477/00 ,  C07D477/26

    摘要： A lyophilized preparation comprising (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-[(2S,4S)-2-[(3S)-3-(2-guanidinoacetylamino)pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylic acid or a pharmacologically acceptable salt thereof as a carbapenem compound, which has a 1-alkylpyrrolidine structure and possesses a superior antimicrobial activity, and sodium chloride.

    摘要翻译： 包含（1R，5S，6S）-6 - [（1R）-1-羟乙基] -1-甲基-2 - [（2S，4S）-2 - [（3S）-3-（2-胍基乙酰氨基 ）吡咯烷-1-基羰基] -1-甲基吡咯烷-4-基硫代] -1-碳代青霉-2-烯-3-羧酸或其药理学上可接受的盐作为碳青霉烯化合物，其具有1-烷基吡咯烷结构并具有 优良的抗菌活性和氯化钠。

    Carbapenams and carbapen-2-ems and process therefor
    9.
    发明授权
    Carbapenams and carbapen-2-ems and process therefor 失效
    碳青霉烯和碳青霉烯2-ems及其加工方法

    公开(公告)号：US4429128A

    公开(公告)日：1984-01-31

    申请号：US347853

    申请日：1982-02-11

    申请人： Robert L. Rosati

    发明人： Robert L. Rosati

    IPC分类号： C07D477/26 ,  C07D499/00 ,  C07D487/04

    CPC分类号： C07D477/26 ,  C07D499/00

    摘要： Carbapenam-3-carboxylic acids and carbapen-2-em-3-carboxylic acids substituted at the 1-position with an oxo, a hydroxy or an acetoxy group, variously substituted at the 2-position with such groups as methyl, acetoxymethyl, methanesulfonyloxy, alkoxy, alkylthio, aminoalkylthio or amidinoalkylthio and optionally substituted at the 6-position with a hydroxyalkyl group, an acetoxyalkyl group or a conventional penicillin side-chain, pharmaceutically-acceptable salts thereof and various esters thereof wherein the esterifying group is selectively removed in the laboratory, or hydrolyzed under physiological conditions.These compounds are useful either systemically or topically in the treatment of diseases caused by susceptible microorganisms, as animal feed additives for promotion of growth, or in the preservation of biodegradable materials, or as intermediates to compounds having such antibacterial activity.Key to the synthesis of these compounds is the light catalyzed rearrangement of 2-diazo-1-oxoceph-3-em-4-carboxylates to 1-oxocarbapen-2-em-3-carboxylates, a newly discovered reaction determined to be of general applicability.

    摘要翻译： 在1-位被氧代，羟基或乙酰氧基取代的碳青霉烯-3-羧酸和在2-位上被甲基，乙酰氧基甲基，甲磺酰氧基等基团取代的碳代萘-2-羧酸 ，烷氧基，烷硫基，氨基烷硫基或脒基烷硫基，并且任选在6-位被羟烷基，乙酰氧基烷基或常规青霉素侧链取代，其药学上可接受的盐和其各种酯，其中酯化基团在 实验室，或在生理条件下水解。 这些化合物可以全身或局部用于治疗由易感微生物引起的疾病，作为用于促进生长的动物饲料添加剂，或用于生物降解材料的保存，或作为具有这种抗菌活性的化合物的中间体。 合成这些化合物的关键是2-重氮-1-氧代头孢-3-烯-4-羧酸酯轻链催化重排1-氧代羧基-2-em-3-羧酸酯，新发现的反应确定为一般 适用性。

    6-, 1- and 2-Substituted-1-carbadethiapen-2-em-3-carboxylic acids
    10.
    发明授权
    6-, 1- and 2-Substituted-1-carbadethiapen-2-em-3-carboxylic acids 失效
    6-，1-和2-取代的1-碳代二烯-2-烯-3-羧酸

    公开(公告)号：US4232036A

    公开(公告)日：1980-11-04

    申请号：US954272

    申请日：1978-10-24

    申请人： Burton G. Christensen ,  David H. Shih

    发明人： Burton G. Christensen ,  David H. Shih

    IPC分类号： C07C205/42 ,  C07D205/08 ,  C07D477/20 ,  C07D477/26 ,  C07D498/04 ,  C07F7/18 ,  C07F9/568 ,  A61K31/40 ,  C07D487/04

    CPC分类号： C07D477/26 ,  C07C205/42 ,  C07D205/08 ,  C07D477/20 ,  C07F7/1804 ,  C07F9/5683

    摘要： Disclosed are 6-, 1- and 2-substituted-1-carbadethiapen-2-em-3-carboxylic acids having the structure: ##STR1## wherein: R.sup.1, R.sup.6, R.sup.7 and R.sup.8 are, inter alia, independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl and aralkyl. Such compounds as well as their pharmaceutically acceptable salt, ester and amide derivatives are useful as antibiotics. Also disclosed are processes for the preparation of such compounds, pharmaceutical compositions comprising such compounds and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.

    摘要翻译： 公开了具有以下结构的6-，1-和2-取代-1-碳代二脱氧-2-烯-3-羧酸：其中：R 1，R 6，R 7和R 8特别地独立地选自 由氢，烷基，烯基，芳基和芳烷基组成。 这些化合物及其药学上可接受的盐，酯和酰胺衍生物可用作抗生素。 还公开了制备这些化合物的方法，包含这些化合物的药物组合物和治疗方法，包括当指出抗生素作用时施用这些化合物和组合物。