公开(公告)号：US07524952B2

公开(公告)日：2009-04-28

申请号：US10533183

申请日：2003-11-13

申请人： Keita Nishino ,  Teruyoshi Koga

发明人： Keita Nishino ,  Teruyoshi Koga

IPC分类号： C07D477/06 ,  C07D477/20 ,  C07D477/04

CPC分类号： C07D477/06 ,  C07F7/1892 ,  Y02P20/55

摘要： The present invention provides a process for efficiently producing a 1β-methylcarbapenem compound for oral administration. The process, which is for producing a 1β-methylcarbapenem compound represented by general formula (2), is characterized by reacting a β-lactam compound represented by general formula (1) as a starting material with a thiol compound (R3—SH) in the presence of a base and optionally eliminating the protective group R1. In the formulae (1) and (2), R1 denotes a hydrogen atom, a trimethylsilyl group or a triethylsilyl group; R2 denotes an alkyl group having 1 to 10 carbon atoms or a cycloalkyl group having 3 to 10 carbon atoms; R3 denotes an organic group; and R4 denotes hydrogen, a trimethylsilyl group or a triethylsilyl group.

摘要翻译： 本发明提供一种有效地制备口服给药的1β-甲基碳青霉烯化合物的方法。 用于制备由通式（2）表示的1β-甲基碳青霉烯化合物的方法的特征在于使由通式（1）表示的β-内酰胺化合物作为起始原料与硫醇化合物（R3-SH）在 碱的存在和任选地除去保护基团R1。 在式（1）和（2）中，R 1表示氢原子，三甲基甲硅烷基或三乙基甲硅烷基; R2表示碳原子数1〜10的烷基或碳原子数3〜10的环烷基。 R3表示有机基团; R4代表氢，三甲基甲硅烷基或三乙基甲硅烷基。

公开(公告)号：US5750735A

公开(公告)日：1998-05-12

申请号：US445388

申请日：1995-05-19

申请人： Yang-I Lin ,  Panayota Bitha ,  Subas Sakya ,  Timothy W. Strohmeyer ,  Karen Bush ,  Carl Bernard Ziegler ,  Gregg Brian Feigelson

发明人： Yang-I Lin ,  Panayota Bitha ,  Subas Sakya ,  Timothy W. Strohmeyer ,  Karen Bush ,  Carl Bernard Ziegler ,  Gregg Brian Feigelson

IPC分类号： A61K31/40 ,  A61K31/397 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/42 ,  A61K31/425 ,  A61K31/44 ,  A61K31/495 ,  A61K31/535 ,  A61P31/00 ,  A61P31/04 ,  C07D307/18 ,  C07D333/34 ,  C07D333/48 ,  C07D477/00 ,  C07D477/04 ,  C07D477/06 ,  C07D477/12 ,  C07D477/14 ,  C07D477/20 ,  C07F9/6561 ,  C07H11/00 ,  C07H19/01 ,  C07D307/02

CPC分类号： C07D307/18 ,  C07D333/34 ,  C07D477/14 ,  C07F9/65611 ,  C07H11/00 ,  C07H19/01 ,  Y02P20/582

摘要： Carbapenem antibiotic compounds of the general formula: ##STR1## wherein the moiety ##STR2## is a 4, 5 or 6 membered mono, di- or tri-substituted oxygen or sulfur containing ring; wherein Z is oxygen, sulfur, sulfoxide and sulfone, pharmaceutical compositions thereof useful for the treatment of bacterial infections, processes for preparing the compounds and new intermediates useful in the process.

摘要翻译： 具有以下通式的卡巴培南抗生素化合物：其中部分“IMAGE”是4,5或6元单，二或三取代的含氧或含硫环; 其中Z是氧，硫，亚砜和砜，其用于治疗细菌感染的药物组合物，用于制备化合物的方法和可用于该方法的新中间体。

公开(公告)号：US20200281894A1

公开(公告)日：2020-09-10

申请号：US16879892

申请日：2020-05-21

申请人： Southern Methodist University ,  University of Central Florida Research Foundation, Inc.

发明人： John D. Buynak ,  Noora M. S. A. Al-Kharji ,  Weirui Chai ,  Thu Q. Nguyen ,  Maha Alqurafi ,  Kyle Rohde ,  Rashmi Gupta

IPC分类号： A61K31/407 ,  C07D477/06 ,  C07D477/00 ,  A61K45/06 ,  C07D477/04 ,  C07D477/20

摘要： The present invention includes a composition, method of making and method of using a novel C5-substituted carbapenem antibiotic of formula 1: R1 is H or CH3 R2 is not H, and is CH3, or C1-C6 straight chain, or branched alkyl, or C3-C6 cycloalkyl group, or unsaturated alkenyl, including C═CH2; R3 is H, CH3, or a C1-C6 alkyl or cycloalkyl group, a heteroatom-substituted alkyl; and R4 is a C1 to C6 alkyl, or substituted alkyl group, especially including substituents which possess positive charge, or a hydroxyl group; or R4 is an SRa, where Ra is an unsubstituted C1 to C6 alkyl group, a substituted C1 to C6 alkyl group, or a functional group that is positively charged, or which bears a positive charge when in aqueous solution at pH 7; or R4 is a CH2ORb, where Rb=C1 to C6 alkyl or substituted alkyl groups, substituted or unsubstituted aryl, or a heteroaryl groups.

公开(公告)号：US09169258B2

公开(公告)日：2015-10-27

申请号：US14387829

申请日：2012-09-26

申请人： SHENZHEN HAIBIN PHARMACEUTICAL CO., LTD.

发明人： Lisong Long ,  Zhaoqiang Lu ,  Cheng Ding ,  Guangcheng Li ,  Zhili Lv ,  Congquan Wu ,  Yanjun Zhang ,  Peng Ren

IPC分类号： C07D477/20 ,  C07D477/06 ,  C07D477/08

CPC分类号： C07D477/20 ,  C07D477/06 ,  C07D477/08 ,  Y02P20/55

摘要： The present invention provides a doripenem intermediate compound shown by formula (XIV), wherein PNB is p-nitrobenzyl, and HX is an acid; and when HX is a monobasic acid, n=1; and when HX is a polybasic acid, n=2. The present invention also provides a process for preparing the doripenem intermediate compound (XIV). In addition, the present invention provides a process for preparing doripenem (I) from the doripenem intermediate compound (XIV) in a simple manner, with a high yield and low production costs. The new mono-protected doripenem intermediate compound provided in the present invention contains only one protecting group, reducing the difficulty and complexity in the subsequent de-protection step by catalytic hydrogenation, increasing the yield of the catalytic hydrogenation reaction, and thus reducing the production cost of the final product. The process is easy to operate and suitable for industrialized production.

摘要翻译： 本发明提供式（XIV）所示的多巴培南中间体化合物，其中PNB为对硝基苄基，HX为酸; 当HX是一元酸时，n = 1; 当HX为多元酸时，n = 2。 本发明还提供了制备多巴培南中间体化合物（XIV）的方法。 此外，本发明提供了以简单的方式从多巴培南中间体化合物（XIV）制备多巴培南（I）的方法，产率高，生产成本低。 本发明提供的新的单保护多代替巴中间体化合物仅含有一个保护基，通过催化氢化降低后续脱保护步骤的难度和复杂性，提高催化氢化反应的产率，从而降低生产成本 的最终产品。 该工艺易于操作，适用于工业化生产。

公开(公告)号：US20110118229A1

公开(公告)日：2011-05-19

申请号：US12742966

申请日：2008-11-18

申请人： Young-Ro Choi ,  Bong-Jin Kim ,  Bok-Ju Song ,  Bum-Soo Lee ,  Dong-Woo Lee ,  Dong-Geun Seo ,  Young-Cheol Jeong ,  Si-Min Kim ,  Jee-Woong Kwon ,  Jae-Yang Kong ,  Heeyeong Cho

发明人： Young-Ro Choi ,  Bong-Jin Kim ,  Bok-Ju Song ,  Bum-Soo Lee ,  Dong-Woo Lee ,  Dong-Geun Seo ,  Young-Cheol Jeong ,  Si-Min Kim ,  Jee-Woong Kwon ,  Jae-Yang Kong ,  Heeyeong Cho

IPC分类号： A61K31/407 ,  C07D477/20 ,  C07D477/08 ,  C07D477/06 ,  A61P31/04

CPC分类号： C07D477/20

摘要： The present invention provides a 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, and a pharmaceutical composition comprising the same. The 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives or their pharmaceutically acceptable salts show high oral absorption rate, and thus can be orally administered. The active metabolites thereof have a broad spectrum of antibacterial activities against Gram-positive and Gram-negative bacteria and excellent antibacterial activities against methicillin-resistant Staphylococcus aurus (MRSA) and quinolone-resistant strains (QRS). In particular, the acid addition salts of the 2-arylmethylazetidine-carbapenem-3-carboxylic acid ester derivatives are obtained in crystalline forms having excellent stability.

摘要翻译： 本发明提供2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐，其制备方法和包含其的药物组合物。 2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物或其药学上可接受的盐显示出高的口服吸收率，因此可以口服给药。 其活性代谢物对革兰氏阳性和革兰氏阴性菌具有广谱的抗菌活性，对耐甲氧西林金黄色葡萄球菌（MRSA）和喹诺酮耐药菌株（QRS）具有优异的抗菌活性。 特别地，2-芳基甲基氮杂环丁烷 - 碳青霉烯-3-羧酸酯衍生物的酸加成盐以稳定性优异的结晶形式得到。

公开(公告)号：US5885981A

公开(公告)日：1999-03-23

申请号：US470944

申请日：1995-06-06

申请人： Hiromitsu Iwata ,  Takashi Nakatsuka ,  Rie Tanaka ,  Masaji Ishiguro

发明人： Hiromitsu Iwata ,  Takashi Nakatsuka ,  Rie Tanaka ,  Masaji Ishiguro

IPC分类号： C07D499/897 ,  A61K31/43 ,  A61K31/431 ,  A61P31/04 ,  C07D499/04 ,  C07D499/88 ,  C07D499/887 ,  C07D499/893 ,  C07D477/06

CPC分类号： C07D499/88

摘要： Antibiotic penem compounds are represented by the following formula: ##STR1## wherein R represents a group of the general formula: ##STR2## in which R.sub.1 is a hydrogen atom or linear or branched C.sub.1 --C.sub.6 alkyl group, R.sub.2 is a particular substituted or unsubstituted alkyl, aryl or aralkyl group, n is an integer of 1-6, Y is a 5- or 6-membered heterocyclic aliphatic group having 1 or 2 oxygen atoms in the ring thereof, and Z is a specific 5-substituted 2-oxo-1,3-dioxolen-4-yl group. Antibiotic compositions for oral administration are also described.

摘要翻译： 抗生素penem化合物由下式表示：其中R表示下列通式的基团：其中R 1为氢原子或直链或支链C 1 -C 6烷基，R 2为特定的取代或未取代的 烷基，芳基或芳烷基，n为1-6的整数，Y为其环中具有1或2个氧原子的5或6元杂环脂族基团，Z为特定的5-取代的2-氧代 -1,3-二氧杂环戊烯-4-基。 还描述了用于口服给药的抗生素组合物。

公开(公告)号：US5646139A

公开(公告)日：1997-07-08

申请号：US477968

申请日：1995-06-07

申请人： Ronald Eugene White ,  Thomas Prosser Demuth, Jr.

发明人： Ronald Eugene White ,  Thomas Prosser Demuth, Jr.

IPC分类号： C07D499/897 ,  A61K31/431 ,  A61K31/47 ,  A61K31/535 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04 ,  A61P43/00 ,  C07D215/56 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D417/12 ,  C07D417/14 ,  C07D455/04 ,  C07D463/00 ,  C07D463/16 ,  C07D471/04 ,  C07D477/10 ,  C07D477/14 ,  C07D477/20 ,  C07D487/04 ,  C07D498/04 ,  C07D498/06 ,  C07D499/00 ,  C07D499/04 ,  C07D499/86 ,  C07D499/87 ,  C07D499/88 ,  C07D501/00 ,  C07D501/18 ,  C07D501/20 ,  C07D501/34 ,  C07D503/00 ,  C07D505/00 ,  C07D513/04 ,  C07D513/06 ,  C07D513/16 ,  C07D519/00 ,  C07D519/06 ,  C07D521/00 ,  C07F9/6561 ,  C07D477/06 ,  A61K31/40 ,  A61K31/435

CPC分类号： C07D401/04 ,  C07D215/56 ,  C07D401/12 ,  C07D401/14 ,  C07D417/14 ,  C07D455/04 ,  C07D463/18 ,  C07D463/22 ,  C07D471/04 ,  C07D477/10 ,  C07D487/04 ,  C07D499/00 ,  C07D501/00 ,  C07D503/00 ,  C07D505/00 ,  C07D513/04

摘要： Compounds of Structure: ##STR1## as well as their pharmaceutically-acceptable salts and biohydrolyzable esters, and hydrates thereof, are effective antiinfective agents, useful in treating and preventing infection.

摘要翻译： 结构化合物：或及其药学上可接受的盐和可生物水解的酯及其水合物是有效的抗感染剂，可用于治疗和预防感染。

公开(公告)号：US5623081A

公开(公告)日：1997-04-22

申请号：US448052

申请日：1995-05-23

申请人： Yang-I Lin ,  Panayota Bitha ,  Subas Sakya ,  Timothy W. Strohmeyer ,  Karen Bush ,  Carl B. Ziegler ,  Gregg B. Feigelson

发明人： Yang-I Lin ,  Panayota Bitha ,  Subas Sakya ,  Timothy W. Strohmeyer ,  Karen Bush ,  Carl B. Ziegler ,  Gregg B. Feigelson

IPC分类号： A61K31/40 ,  A61K31/397 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/42 ,  A61K31/425 ,  A61K31/44 ,  A61K31/495 ,  A61K31/535 ,  A61P31/00 ,  A61P31/04 ,  C07D307/18 ,  C07D333/34 ,  C07D333/48 ,  C07D477/00 ,  C07D477/04 ,  C07D477/06 ,  C07D477/12 ,  C07D477/14 ,  C07D477/20 ,  C07F9/6561 ,  C07H11/00 ,  C07H19/01 ,  C07D307/02

CPC分类号： C07D307/18 ,  C07D333/34 ,  C07D477/14 ,  C07F9/65611 ,  C07H11/00 ,  C07H19/01 ,  Y02P20/582

摘要： Tetrahydrofuanyl compounds of the following formulae: ##STR1## are disclosed.

摘要翻译： 公开了下式的四氢芳烃基化合物：。

公开(公告)号：US11234966B2

公开(公告)日：2022-02-01

申请号：US16879892

申请日：2020-05-21

申请人： Southern Methodist University ,  University of Central Florida Research Foundation, Inc.

发明人： John D. Buynak ,  Noora M. S. A. Al-Kharji ,  Weirui Chai ,  Thu Q. Nguyen ,  Maha Alqurafi ,  Kyle Rohde ,  Rashmi Gupta

IPC分类号： C07D477/06 ,  A61K31/407 ,  C07D477/00 ,  A61K45/06 ,  C07D477/04 ,  C07D477/20

摘要： The present invention includes a composition, method of making and method of using a novel C5-substituted carbapenem antibiotic of formula 1: R1 is H or CH3 R2 is not H, and is CH3, or C1-C6 straight chain, or branched alkyl, or C3-C6 cycloalkyl group, or unsaturated alkenyl, including C═CH2; R3 is H, CH3, or a C1-C6 alkyl or cycloalkyl group, a heteroatom-substituted alkyl; and R4 is a C1 to C6 alkyl, or substituted alkyl group, especially including substituents which possess positive charge, or a hydroxyl group; or R4 is an SRa, where Ra is an unsubstituted C1 to C6 alkyl group, a substituted C1 to C6 alkyl group, or a functional group that is positively charged, or which bears a positive charge when in aqueous solution at pH 7; or R4 is a CH2ORb, where Rb=C1 to C6 alkyl or substituted alkyl groups, substituted or unsubstituted aryl, or a heteroaryl groups.

公开(公告)号：US20180353476A1

公开(公告)日：2018-12-13

申请号：US16006374

申请日：2018-06-12

申请人： Southern Methodist University ,  University of Central Florida Research Foundation, Inc.

发明人： John D. Buynak ,  Noora M. S. A. Al-Kharji ,  Weirui Chai ,  Thu Q. Nguyen ,  Maha Alqurafi ,  Kyle Rohde ,  Rashmi Gupta

IPC分类号： A61K31/407 ,  A61K45/06 ,  C07D477/00 ,  C07D477/06

摘要： The present invention includes a composition, method of making and method of using a novel C5-substituted carbapenem antibiotic of formula 1: R1 is H or CH3 R2 is not H, and is CH3, or C1-C6 straight chain, or branched alkyl, or C3-C6 cycloalkyl group, or unsaturated alkenyl, including C═CH2; R3 is H, CH3, or a C1-C6 alkyl or cycloalkyl group, a heteroatom-substituted alkyl; and R4 is a C1 to C6 alkyl, or substituted alkyl group, especially including substituents which possess positive charge, or a hydroxyl group; or R4 is an SRa, where Ra is an unsubstituted C1 to C6 alkyl group, a substituted C1 to C6 alkyl group, or a functional group that is positively charged, or which bears a positive charge when in aqueous solution at pH 7; or R4 is a CH2ORb, where Rb=C1 to C6 alkyl or substituted alkyl groups, substituted or unsubstituted aryl, or a heteroaryl groups.