3-aminomethylpyrrolidin-4-one O-methyloxime dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-aminomethylpyrrolidin-4-one O-methyloxime dihydrochloride
• 英文别名: 4-aminomethyl-3-methoxyiminopyrrolidinium dihydrochloride；4-(aminomethyl)pyrrolidin-3-one O-methyloxime dihydrochloride；[(4Z)-4-methoxyiminopyrrolidin-3-yl]methanamine;hydrochloride
• 化学式: C₆H₁₃N₃O*2ClH
• 分子量: 216.111
• InChiKey: JUUHKTUGPCDVIF-MLBSPLJJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.41
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  59.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-aminomethylpyrrolidin-4-one O-methyloxime dihydrochloride 在 硼酸 、 乙酸酐 、 溶剂黄146 、 三乙胺 作用下， 以 甲苯 、 乙酸酐 、 溶剂黄146 、 乙腈 为溶剂， 反应 11.0h， 生成 7-[(4Z)-3-aminomethyl-4-methoxyimino-pyrrolidin-1-yl]-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-b]quinoline-3,4-dione hydrochloride
  参考文献：
  名称：

  8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents

  摘要：

  该发明提供了化合物和盐的公式I和公式II：具有抗微生物活性。该发明还提供了在制备公式I和公式II化合物中有用的新型合成中间体。这里定义了变量n、m、p、RA、RB、A1、R2、R3、R5、R6、R7、A8和R9。本文披露的公式I和公式II的某些化合物是细菌DNA合成和细菌复制的有效和/或选择性抑制剂。该发明还提供了抗微生物组合物，包括含有一个或多个公式I或公式II化合物和一个或多个载体、赋形剂或稀释剂的制药组合物。这些组合物可能仅含有公式I或公式II化合物作为唯一活性剂，也可能含有公式I或公式II化合物与一个或多个其他活性剂的组合。该发明还提供了治疗真核生物微生物感染的方法。

  公开号：

  US20060100215A1
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-2-(2-cyanoethyl)aminoacetic acid ethyl ester 在 甲醇 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 乙醇 、 盐酸羟胺 、 sodium ethanolate 、 三氧化硫吡啶 、 碳酸氢钠 、 二甲基亚砜 、 三乙胺 、 乙酰氯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 7.33h， 生成 3-aminomethylpyrrolidin-4-one O-methyloxime dihydrochloride
  参考文献：
  名称：

  Novel Fluoroquinolone Antibacterial Agents Containing Oxime-Substituted (Aminomethyl)pyrrolidines:  Synthesis and Antibacterial Activity of 7-(4-(Aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro- 4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic Acid (LB20304)^,1

  摘要：

  New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C-5-NH2) > F (C-5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C-5-NH2) > naphthyridine = F (C-5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (mu g/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Acinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

  DOI：

  10.1021/jm970202e

文献信息

• Process for preparing a protected 4-aminomethyl-pyrrolidi-3-one
  申请人：LG Chemical, LTD

  公开号：US06307059B1

  公开（公告）日：2001-10-23

  A process for preparing a compound of formula (1) in which P1 and P2 are protecting groups; comprising a) reaction of a compound of formula (5) wherein P1 is as defined for formula (1); with a Raney-nickel catalyst in a solvent under hydrogen to produce a compound of formula (6) wherein P1 is as defined for formula (1); b) protecting the amino group to produce a compound of formula (7) wherein P1 and P2 are as defined for formula (1); and c) selective reduction of the double bond to produce the compound of formula (1).

  一种制备式（1）化合物的过程，其中P1和P2是保护基；包括a）将式（5）化合物与Raney镍催化剂在氢气溶剂下反应，其中P1如式（1）所定义，产生式（6）化合物；b）保护氨基以产生式（7）化合物，其中P1和P2如式（1）所定义；以及c）选择性还原双键以产生式（1）化合物。
• PROCESS FOR THE PREPARATION OF GEMIFLOXACIN
  申请人：Ramasubbu Chandrasekaran

  公开号：US20100076193A1

  公开（公告）日：2010-03-25

  The present invention relates to an improved process for the preparation of Gemifloxacin mesylate of formula (V). The present invention further provides novel intermediates of formula (II) and (IV), which are useful intermediates for the preparation of Gemifloxacin mesylate of formula (V). wherein R 1 is linear or branched chain alkyl group having 1-3 carbon atoms.

  本发明涉及一种改进的制备公式（V）的Gemifloxacin甲磺酸盐的过程。本发明还提供了公式（II）和（IV）的新型中间体，它们是制备公式（V）的Gemifloxacin甲磺酸盐的有用中间体。其中R1是具有1-3个碳原子的线性或支链烷基。
• Discovery of gemifloxacin (Factive, LB20304a): a quinolone of new a generation
  作者：Chang Yong Hong

  DOI：10.1016/s0014-827x(01)01017-5

  日期：2001.3

  Novel quinolone antibacterials, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been designed and synthesized. These fluoroquinolones were found to possess extremely potent antimicrobial activity against Gram-positive organisms including resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds our development candidate, Gemifloxacin (Factive, LB20304a), showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good safety pharmacological properties. Gemifloxacin was found to be especially effective against respiratory tract infections that account for over 70% of all infections. With once-a-day dosage, potency against respiratory tract infections such as chronic bronchitis and pneumonia was ensured without any significant side effect. In December 1999, Gemifloxacin filed a NDA for marketing approval to the US Food and Drug Administration. (C) 2001 Elsevier Science S.A. All rights reserved.
• WO2008/53324
  申请人：——

  公开号：——

  公开（公告）日：——
• PROCESS FOR PRODUCTION OF NAPHTHYRIDINE-3-CARBOXYLIC ACID DERIVATIVES
  申请人：LG Life Sciences, Ltd.

  公开号：EP1214321B1

  公开（公告）日：2004-07-14