(3S,5S)-3-acetylthio-5-carboxy-1-p-nitrobenzyloxycarbonylpyrrolidine | 96034-60-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,5S)-3-acetylthio-5-carboxy-1-p-nitrobenzyloxycarbonylpyrrolidine
• 英文别名: (2S,4S)-4-Acetylthio-1-(4-nitrobenzyloxycarbonyl)-2-carboxypyrrolidine；(2S,4S)-4-acetylthio-2-carboxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine；(2S,4S)-1-(4-Nitrobenzyloxycarbonyl)-4-acetylthiocarboxypyrrolidine；(2S,4S)-1-(4-nitrobenzyloxycarbonyl)-4-acetylthio-2-carboxypyrrolidine；(2S,4S)-N-(4-Nitrobenzyloxycarbonyl)-2-carboxy-4-acetylthio pyrrolidine；(2S,4S)-1-(4-Nitrobenzyloxycarbonyl)-4-acetylthio-2carboxypyrrolidin；(2S,4S)-4-acetylsulfanyl-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 96034-60-5
• 化学式: C₁₅H₁₆N₂O₇S
• 分子量: 368.367
• InChiKey: MYFIPSUFYFSAPD-STQMWFEESA-N

物化性质

• 沸点：
  598.1±50.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S,5S)-3-acetylthio-5-carboxy-1-p-nitrobenzyloxycarbonylpyrrolidine 在 N-甲基吗啉 、 叠氮磷酸二苯酯 、 三氟乙酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 23.0h， 生成 (4-nitrophenyl)methyl (2S,4S)-4-acetylsulfanyl-2-aminopyrrolidine-1-carboxylate
  参考文献：
  名称：

  C-2位具有脯氨酸反向酰胺部分的新型碳青霉烯类的合成及抗菌活性

  摘要：

  描述了在 C-2 位具有脯氨酸反向酰胺部分的新型 1β-甲基碳青霉烯 (1a-l) 的合成及其体外抗菌活性。通过Mueller-Hinton琼脂稀释法评估化合物，并与作为对照的美罗培南进行比较。发现脂肪族酰胺 (1a – h) 比芳香族酰胺 (1i – l) 显示出更大的抗菌活性。此外，C-2 游离氨基化合物 (1m) 显示出比任何其他酰胺化合物 (1a-l) 更高的活性。

  DOI：

  10.1002/(sici)1521-4184(199804)331:4<139::aid-ardp139>3.0.co;2-u
• 作为产物：
  描述：

  2-O-[(4-methoxyphenyl)methyl] 1-O-[(4-nitrophenyl)methyl] (2S,4S)-4-acetylsulfanylpyrrolidine-1,2-dicarboxylate 生成 (3S,5S)-3-acetylthio-5-carboxy-1-p-nitrobenzyloxycarbonylpyrrolidine
  参考文献：
  名称：

  CYHAKABA, DZYUN;MATSUMURA, XARUKI;INOUEH, TAKAAKI;FUKADZAVA, MANSATOMO;KA+

  摘要：

  DOI：

文献信息

• Synthesis and biological evaluation of novel 1β-methylcarbapenems having a new moiety at C-2
  作者：Yong Koo Kang、Kye Jung Shin、Kyung Ho Yoo、Kyung Jae Seo、Seung Yong Park、Dong Jin Kim、Sang Woo Park

  DOI：10.1016/s0960-894x(99)00407-2

  日期：1999.8

  The synthesis and biological activity of the novel series of 1 beta-methylcarbapenems 1a-f, bearing a variety of 3",4"-disubstituted pyrrolidinamides as substituents at C-2, are described. Of these carbapenems, diol 1a showed the most potent and well balanced antibacterial activity against Gram-positive and Gram-negative. 1a was also evaluated for pharmacokinetics and in vivo therapeutic efficacy in

  描述了一系列新型的1β-甲基卡巴木烯1a-f的合成和生物活性，这些化合物在C-2处带有多个3“，4”-二取代的吡咯烷基酰胺作为取代基。在这些碳青霉烯类中，二醇1a对革兰氏阳性和革兰氏阴性显示出最有效和最均衡的抗菌活性。还评估了1a在全身感染中的药代动力学和体内治疗功效。
• Preparation and Antimicrobial Assessment of 2-Thioether-linked Quinolonyl-carbapenems.
  作者：PAUL M. HERSHBERGER、A. GREG SWITZER、KENNETH E. YELM、MILT C. COLEMAN、CAROL A. DEVRIES、F. JAMES ROURKE、BARB W. DAVIS、WILLIAM G. KRAFT、TRACY L. TWINEM、PAULA M. KOENIGS、SUZANNE M. PAULE、RICHARD J. SIEHNEL、PAUL H. ZOUTENDAM、REBECCA IMBUS、THOMAS P. Jr. DEMUTH

  DOI：10.7164/antibiotics.51.857

  日期：——

  This reports the synthesis and in vitro antimicrobial properties of a series of 2-thioether-linked quinolonyl-carbapenems. Although the title compounds exhibited broad spectrum activity, the MICs were generally higher than those observed for selected benchmark carbapenems, quinolonyl-penems, and quinolones. Enzyme assays suggested that the title compounds are potent inhibitors of penicillin binding proteins and inefficient inhibitors of bacterial DNA-gyrase. Uptake studies indicated that the new compounds are not substrates for the norA encoded quinolone efflux pump.

  本报告介绍了系列2-硫醚连接的喹诺酮-碳青霉烯的合成及其体外抗菌活性。尽管标题化合物显示出广谱活性，但其最低抑菌浓度（MICs）通常高于所选的基准碳青霉烯、喹诺酮-青霉烯及喹诺酮。酶试验表明，标题化合物是青霉素结合蛋白的强效抑制剂，但对细菌DNA旋转酶的抑制效果不佳。吸收研究显示，新化合物并非norA编码的喹诺酮外排泵的底物。
• Antibiotic compounds
  申请人：Zeneca Limited

  公开号：US05571805A1

  公开（公告）日：1996-11-05

  The present invention relates to carbapenems and provides a compound of the formula (I) ##STR1## wherein: R.sup.1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxyethyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; R.sup.3 is hydrogen or C.sub.1-4 alkyl; P is of the formula (IA), (IB) or (IC) ##STR2## and in the formula (IB) the naphthyl group may be bonded to the nitrogen of the linking carbamoyl group at either ring; Z is carboxy, sulfonic acid, sulfinic acid, C.sub.1-4 alkanamidosulfonyl (--SO.sub.2 NHCOC.sub.1-3 alkyl), benzamidosulfonyl, C.sub.1-4 alkylsulfonylcarbamoyl (--CONHSO.sub.2 C.sub.1-4 alkyl), phenylsulfonylcarbamoyl, C.sub.1-4 alkoxy carbamoyl, hydroxycarbamoyl, sulfoamino, N--C.sub.1-4 alkanesulfonamido, cyanocarbamoyl, cyanosulfamoyl, tetrazol-5-yl, 3-hydroxyisoxazol-4-yl and 3-hydroxyisoxazol-5-yl; and P is optionally further substituted provided that when P is of the formula (IA) or (IC), Z is not carboxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them are also described.

  本发明涉及碳青霉烯类药物，并提供了一种具有以下结构的化合物（I）： 其中：R.sup.1为1-羟基乙基、1-氟乙基或羟基乙基；R.sup.2为氢或C.sub.1-4烷基；R.sup.3为氢或C.sub.1-4烷基；P为以下结构之一（IA）、（IB）或（IC）： 在结构（IB）中，萘基可以与连接的碳酰胺基团的氮原子结合在任一环上；Z为羧基、磺酸、亚磺酸、C.sub.1-4烷基氨基磺酰（-SO.sub.2 NHCOC.sub.1-3烷基）、苯甲酰磺酰、C.sub.1-4烷基磺酰基碳酰胺（-CONHSO.sub.2 C.sub.1-4烷基）、苯基磺酰基碳酰胺、C.sub.1-4烷氧基碳酰胺、羟基碳酰胺、磺酰氨基、N-烷基磺酰氨基、氰基碳酰胺、氰基磺酰胺、四唑-5-基、3-羟基异噁唑-4-基和3-羟基异噁唑-5-基；P可进一步取代，但当P为结构（IA）或（IC）时，Z不为羧基；或其药学上可接受的盐或体内可水解的酯。还描述了其制备方法、制备中间体、作为治疗剂的用途以及含有它们的药物组合物。
• Carbapenem antibiotic compounds
  申请人：Zeneca Limited

  公开号：US05519015A1

  公开（公告）日：1996-05-21

  The present invention relates to carbapenems and provides a compound of the formula (I) ##STR1## wherein: R.sup.1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; R.sup.3 is hydrogen or C.sub.1-4 alkyl; and the thienyl ring is optionally further substitued by one or two substituents selected from halo, cyano, C.sub.1-4 alkyl, nitro, hydroxy, carboxy, C.sub.1-4 alkoxy, trifluoromethyl, C.sub.1-4 alkoxycarbonyl, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino, sulfonic acid, C.sub.1-4 alkylS(O).sub.n -- (wherein n is 0-2), C.sub.1-4 alkanoylamino, C.sub.1-4 alkanoyl(N-C.sub.1-4 alkyl)amino, carbamoyl, C.sub.1-4 alkylcarbamoyl, di-C.sub.1-4 alkylcarbamoyl and N-C.sub.1-4 alkanesulfonamido; or by a tetramethylene group attached to adjacent carbon atoms on the thienyl ring; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them are also described.

  本发明涉及碳青霉烯类药物，并提供了化合物的结构式（I）##STR1##其中：R.sup.1为1-羟乙基、1-氟乙基或羟甲基；R.sup.2为氢或C.sub.1-4烷基；R.sup.3为氢或C.sub.1-4烷基；噻吩环可选择性地进一步被来自卤素、氰基、C.sub.1-4烷基、硝基、羟基、羧基、C.sub.1-4烷氧基、三氟甲基、C.sub.1-4烷氧羰基、氨基、C.sub.1-4烷基氨基、二-C.sub.1-4烷基氨基、磺酸基、C.sub.1-4烷基S(O).sub.n（其中n为0-2）、C.sub.1-4烷酰氨基、C.sub.1-4烷酰（N-C.sub.1-4烷基）氨基、羰酰基、C.sub.1-4烷基羰胺基、二-C.sub.1-4烷基羰胺基和N-C.sub.1-4烷基磺酰胺基等一种或两种取代基所取代；或者通过连接到噻吩环上相邻碳原子的四亚甲基基团；或其药物可接受的盐或体内可水解酯。还描述了其制备过程、制备中间体、作为治疗剂的用途以及含有它们的药物组合物。
• Carbapenem-antibiotic compounds
  申请人：Zeneca Limited

  公开号：US05444057A1

  公开（公告）日：1995-08-22

  The present invention relates to carbapenems and provides a compound of the formula (I) ##STR1## wherein: R.sup.1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R.sup.2 is hydrogen or C.sub.1-4 alkyl; R.sup.3 is hydrogen or C.sub.1-4 alkyl; and the pyridyl group is bonded to the nitrogen of the linking carbamoyl group by a carbon atom, is substituted with the carboxy group on a carbon atom and is optionally substituted on one or two pyridyl ring carbon atoms; or a pharmaceutically acceptable salt or in vivo hydrolyzable ester thereof. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.

  本发明涉及碳青霉烯类药物，并提供了式（I）的化合物。其中：R1为1-羟乙基、1-氟乙基或羟甲基；R2为氢或C1-4烷基；R3为氢或C1-4烷基；吡啶基通过碳原子与连接的氨基甲酰基团氮原子相结合，被羧基取代在一个碳原子上，并且在一个或两个吡啶环碳原子上选择性地被取代；或其药学上可接受的盐或体内水解酯。本发明还提供了它们的制备过程，制备中间体，以及它们作为治疗剂的用途和包含它们的制药组合物。