(3S,5S)-3-acetylthio-1-allyloxycarbonylpyrrolidin-5-carboxylic acid | 145352-54-1

• 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-1-allyloxycarbonylpyrrolidin-5-carboxylic acid
• 英文别名: (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-carboxypyrrolidine；(2S,4S),4-acetylsulfanyl-pyrrolidine-1,2-dicarboxylic acid 1-allyl ester；(2S,4S)-1-allyloxycarbonyl-2-carboxy-pyrrolidin-4-yl thioacetate；(2S,4S)-4-acetylsulfanyl-1-prop-2-enoxycarbonylpyrrolidine-2-carboxylic acid
• CAS: 145352-54-1
• 化学式: C₁₁H₁₅NO₅S
• 分子量: 273.31
• InChiKey: QVXPNOIZWSKQHC-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,5S)-3-acetylthio-1-allyloxycarbonylpyrrolidin-5-carboxylic acid 在 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 4.0h， 生成 (2S,4S)-4-Mercapto-2-{3-[(Z)-methoxyimino]-pyrrolidine-1-carbonyl}-pyrrolidine-1-carboxylic acid allyl ester
  参考文献：
  名称：

  Synthesis and biological activity of novel 1β-Methylcarbapenems with oxyiminopyrrolidinylamide moiety

  摘要：

  The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.039
• 作为产物：
  描述：

  (2S,4R)-N-(allyloxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 、 苯甲醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 11.5h， 生成 (3S,5S)-3-acetylthio-1-allyloxycarbonylpyrrolidin-5-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological activity of novel 1β-Methylcarbapenems with oxyiminopyrrolidinylamide moiety

  摘要：

  The synthesis and antibacterial activity of novel 1beta-methylcarbapenems 1a-f bearing oxyiminopyrrolidinylamide moiety at C-5 position of pyrrolidine are described. Most compounds exhibited comparable antibacterial activity to meropenem against a wide range of Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa isolates. Of these carbapenems, 1a showed potent and broad spectrum of antibacterial activity and similar stability to DHP-I to meropenem. Against clinical isolates of 40 Gram-negative bacterial species including MDR and ESBL-producing strains, the selected carbapenem 1a possessed excellent in vitro activity except for MDR P. aeruginosa, and was comparable in potency to meropenem. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.039
• 作为试剂：
  描述：

  (3S,5S)-3-acetylthio-1-allyloxycarbonylpyrrolidin-5-carboxylic acid 、 3-氨基-苯甲酸烯丙酯 在 (3S,5S)-3-acetylthio-1-allyloxycarbonylpyrrolidin-5-carboxylic acid 作用下， 生成 (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(3-allyloxycarbonylphenylcarbamoyl)pyrrolidine
  参考文献：
  名称：

  [EN] CARBAPENEMS CONTAINING A CARBOXY SUBSTITUTED PHENYL GROUP, PROCESSES FOR THEIR PREPARATION, INTERMEDIATES AND USE AS ANTIBIOTICS

  摘要：

  本发明涉及碳青霉烯，并提供化合物(I)或其药学上可接受的盐或$ i（in vivo）$可水解酯，其中：R1为1-羟基乙基，1-氟乙基或羟甲基; R2为氢或C1-4烷基; R3为氢或C1-4烷基; R4和R5相同或不同，选择自氢，卤素，氰基，C1-4烷基，硝基，羟基，羧基，C1-4烷氧基，C1-4烷氧基羰基，氨基磺酰基，C1-4烷基氨基磺酰基，双C1-4烷基氨基磺酰基，氨基甲酰基，C1-4烷基氨基甲酰基，双C1-4烷基氨基甲酰基，三氟甲基，磺酸，氨基，C1-4烷基氨基，双C1-4烷基氨基，C1-4酰胺基，C1-4酰基（$i（N）$-C1-4烷基）氨基，C1-4烷基磺酰胺和C1-4烷基S（O）n-，其中n为零，一或二; 前提是在连接到-NR3-的位置$ i（ortho）$上没有羟基或羧基取代基。本发明还涉及制备这些化合物的过程，制备中间体，它们作为治疗剂的用途以及包含它们的药物组合物。

  公开号：

  WO1993015078A1

文献信息

• Carbapenem antibiotic compounds
  申请人：Zeneca Limited

  公开号：US05541178A1

  公开（公告）日：1996-07-30

  A carbapenem 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; R.sup.4 is hydroxy or carboxy; and the phenyl ring is optionally further substituted 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, carbamoyl, C.sub.1-4 alkylcarbamoyl, di-C.sub.1-4 alkylcarbamoyl, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino sulphonic acid, C.sub.1-4 alkylS(O).sub.n --(wherein n is 0-2), N-C.sub.1-4 alkanesulphonamido, C.sub.1-4 alkanoylamino and C.sub.1-4 alkanoyl(N-C.sub.1-4 alkyl)amino: provided that the phenyl ring is substituted by at least one carboxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof.

  化合物的结构式（I）如下：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；R.sup.4为羟基或羧基；苯环可选择进一步由卤素、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、C.sub.1-4烷基S(O).sub.n--（其中n为0-2）、N-C.sub.1-4烷磺酰胺基、C.sub.1-4烷酰胺基和C.sub.1-4烷酰（N-C.sub.1-4烷基）氨基等取代基取代；前提是苯环至少被一个羧基取代；或其药学上可接受的盐或体内可水解的酯。
• 2-Aza-substituted 1-carbadethiapen-2-EM-3-carboxylic acids
  申请人：Merck & Co., Inc.

  公开号：EP0208889A1

  公开（公告）日：1987-01-21

  Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids 1, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, triazolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: wherein R" is H or CH,, preferably beta-methyl; R6, and R7 are independently hydrogen, linear, branched or cyclic C1-C5alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R' and R' taken together can also be C2-C4 alkylidene, similarly substituted; with the proviso that both R6 and R7 are not unsubstituted alkyl, R' and R2 are, inter alia, hydrogen, alkyl, acyl, and can be joined to form a ring comprising 3 to 7 atoms; Ra is hydrogen, a salt cation, a removable protecting group, or a pharmaceutically acceptable ester moiety. Also disclosed are pharmaceutical compositions comprising such compounds.

  本发明涉及2-aza取代的1-卡巴德噻吩-2-乙烯-3-羧酸1，其中通用的2-aza基团包括偶氮基、酰胺基、氨基、烷基氨基、二烷基氨基、三唑基、三唑啉基、环氧丙基和它们的药学上可接受的盐、酯、无水物和酰胺衍生物，其作为抗生素有用。还公开了从已知的适当取代的双环酮酯II通过2-偶氮中间体III制备I的过程：其中R"为H或CH，优选为β-甲基；R6和R7独立地为氢、线性、支链或环状C1-C5烷基，可被氟、羟基、保护羟基、磺酰氧基、氨基、保护氨基取代，其中R'和R'在一起也可以是C2-C4烷基亚甲基，同样被取代；条件是R6和R7都不是未取代的烷基，R'和R2是氢、烷基、酰基等，可以连接形成包含3到7个原子的环；Ra是氢、盐阳离子、可移除的保护基或药学上可接受的酯基。还公开了包含这些化合物的制药组合物。
• Antibiotic compounds
  申请人：Betts John Michael

  公开号：US20050209212A1

  公开（公告）日：2005-09-22

  The present invention relates to carbapenems and provides a compound of the formula (I): or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof wherein: R 1 is 1 -hydroxyethyl, 1 -fluoroethyl or hydroxymethyl; R 2 is hydrogen or C 1-4 alkyl; R 3 is hydrogen or C 1-4 alkyl; R 4 and R 5 are the same or different and are selected from hydrogen, halo, cyano, C 1-4 alkyl, nitro, hydroxy, carboxy, C 1-4 alkoxy, C 1-4 alkoxycarbonyl, aminosulphonyl, C 1-4 alkylaminosulphonyl, di-C 1-4 -alkylaminosulphonyl, carbamoyl, C 1-4 alkylcarbamoyl, di-C 1-4 alkylcarbamoyl, trifluoromethyl, sulphonic acid, amino, C 1-4 alkylamino, di-C 1-4 alkylamino, C 1-4 alkanoylamino, C 1-4 alkanoyl( N —C 1-4 alkyl)amino, C 1-4 alkanesulphonamido and C 1-4 alkylS(O) n — wherein n is zero; one or two: with the proviso that there is no hydroxy or carboxy substituent in a position ortho to the link to —NR 3 —. 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化合物，并提供以下式子（I）的化合物或其药学上可接受的盐或体内水解酯： 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；R4和R5相同或不同，选自氢，卤素，氰基，C1-4烷基，硝基，羟基，羧基，C1-4烷氧基，C1-4烷氧羰基，氨基磺酰基，C1-4烷基氨基磺酰基，二C1-4烷基氨基磺酰基，氨基甲酰基，C1-4烷基甲酰基，二C1-4烷基甲酰基，三氟甲基，磺酸基，氨基，C1-4烷基氨基，二C1-4烷基氨基，C1-4酰胺基，C1-4酰基（N-C1-4烷基）氨基，C1-4烷基磺酰胺基和C1-4烷基S（O）n-，其中n为零；但是，在连接到—NR3—的位置上，不存在羟基或羧基取代基。本发明还提供了其制备过程，制备中间体，作为治疗剂的使用以及包含它们的制药组合物。
• Antibiotic carbapenem derivatives
  申请人：ZENECA LIMITED

  公开号：EP0508682A1

  公开（公告）日：1992-10-14

  A carbapenem compound of the formula (I) wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C₁₋₄alkyl; R3 is hydrogen or C₁₋₄alkyl; R4 is hydroxy or carboxy; and the phenyl ring is optionally further substituted by one or two substitutents selected from halo, cyano, C₁₋₄alkyl, nitro, hydroxy, carboxy, C₁₋₄alkoxy, trifluoromethyl, C₁₋₄alkoxycarbonyl, carbamoyl, C₁₋₄alkylcarbamoyl, di-C₁₋₄alkylcarbamoyl, amino, C₁₋₄alkylamino, di-C₁₋₄alkylamino, sulphonic acid, C₁₋₄alkylS(O)n- (wherein n is 0-2), N-C₁₋₄alkanesulphonamido, C₁₋₄alkanoylamino and C₁₋₄alkanoyl(N-C₁₋₄alkyl)amino: provided that the phenyl ring is substituted by at least one carboxy; or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof.

  式 (I) 的碳青霉烯类化合物 其中 R1 是 1-羟乙基、1-氟乙基或羟甲基； R2 是氢或 C₁₋₄ 烷基； R3 是氢或₁₋₄烷基； R4 是羟基或羧基； 苯基环可任选地被选自卤代、氰基、C₁₋₄烷基的一个或两个取代基进一步取代、硝基、羟基、羧基、C₁₋₄烷氧基、三氟甲基、C₁₋₄烷氧基羰基、氨基甲酰基、C₁₋₄烷基氨基甲酰基、二-C₁₋₄烷基氨基甲酰基、氨基、C₁₋₄烷基氨基、二-C₁₋₄烷基氨基、磺酸、C₁₋₄烷基S(O)n- (其中n为0-2)、N-C₁₋₄烷磺酰胺基、C₁₋₄烷基氨基和C₁₋₄烷基(N-C₁₋₄烷基)氨基： 条件是苯基环至少被一个羧基取代； 或其药学上可接受的盐或体内可水解的酯。
• Antibiotic carbapenem compounds
  申请人：ZENECA LIMITED

  公开号：EP0581500A1

  公开（公告）日：1994-02-02

  The present invention relates to carbapenems and provides a compound of the formula (I) wherein : R1 is i-hydroxyethyl, 1-fluoroethyl or hydroxymethyl ; R2 is hydrogen or C1-4alkyl ; R3 is hydrogen or C1-4alkyl ; P' is of the formula : and one or two of A,B,C,D,E,F,G and H, are nitrogen and the remainder are CH ; and P is bonded to the nitrogen of the linking carbamoyl group by a carbon atom, in either ring, is substituted by the carboxy group on a carbon atom, in either ring, and is optionally further substituted, by up to three substitutents, on a carbon atom, in either 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，提供了一种式 (I) 的化合物 其中： R1 是 i-羟乙基、1-氟乙基或羟甲基； R2 是氢或 C1-4 烷基； R3 是氢或 C1-4 烷基； P' 为式： A、B、C、D、E、F、G 和 H 中的一个或两个为氮，其余为 CH；且 P 在任一环中通过一个碳原子与连接氨基甲酰基的氮键合，在任一环中的一个碳原子上被羧基取代，并在任一环中的一个碳原子上任选被最多三个取代基进一步取代；或其药学上可接受的盐或体内可水解的酯。此外，还介绍了它们的制备工艺、制备过程中的中间体、它们作为治疗剂的用途以及含有它们的药物组合物。