(3R,4R)-1-benzyl-N-cyclopropyl-4-methylpyrrolidine-3-carboxamide | 604798-21-2

• 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: (3R,4R)-1-benzyl-N-cyclopropyl-4-methylpyrrolidine-3-carboxamide
• 英文别名: trans-1-benzyl-N-cyclopropyl-4-methyl-3-pyrrolidinecarboxamide；(3R,4R)-1-benzyl-N-cyclopropyl-4-methyl-3-pyrrolidine carboxamide；(3R,4R)-1-benzyl-N-cyclopropyl-4-methyl-3-pyrrolidinecarboxamide
• CAS: 604798-21-2
• 化学式: C₁₆H₂₂N₂O
• 分子量: 258.363
• InChiKey: UUPRZHFECHMJNI-WFASDCNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4R)-1-benzyl-N-cyclopropyl-4-methylpyrrolidine-3-carboxamide 在 dimethyl sulfide borane 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以94%的产率得到(3S,4R)-1-benzyl-3-cyclopropylaminomethyl-4-methylpyrrolidine
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel Pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic Acid Derivatives Carrying the 3-Cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl Group as a C-10 Substituent

  摘要：

  Novel pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid derivatives 5-9 carrying a 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl moiety at the C-10 position were synthesized and their in vitro antibacterial activity, intravenous single-dose toxicity, convulsion inductive ability, and phototoxicity were evaluated. It appeared evident that compounds 5a, 6a, 8a, and 9a, which have a cis-oriented 4-methyl or 4-fluoro-3-cyclopropylaminomethyl-1-pyrrolidinyl moiety at the C-10 position, exhibited 2- to 16-fold more potent in vitro antibacterial activity than clinafloxacin against quinolone-resistant Gram-positive clinical isolates. Furthermore, it was obvious that introduction of a fluorine atom to the C-4 position of the 3-cyclopropylaminomethyl-1-pyrrolidinyl moiety reduced intraveneous single-dose acute toxicity and the convulsion inductive ability, and introduction of a fluorine atom to the C-3 methyl group of the pyridobenzoxazine nucleus eliminated the phototoxicity.

  DOI：

  10.1021/jm701428b
• 作为产物：
  描述：

  1-benzyl-4-(R)-methyl-3-(R)-[(4-(S)-phenyl-2-oxazolidinone-3-yl)carbonyl]pyrrolidine 在 异丙醚 、 二氯甲烷 、 盐酸 、 ice water 、 sodium hydroxide 、 水 作用下， 以 环丙胺 为溶剂， 反应 24.17h， 以to give (3R,4R)-1-benzyl-N-cyclopropyl-4-methyl-3-pyrrolidinecarboxamide as white crystals (52.2 g)的产率得到(3R,4R)-1-benzyl-N-cyclopropyl-4-methylpyrrolidine-3-carboxamide
  参考文献：
  名称：

  7- (4-substituted-3-cyclopropylaminomethyl-1-pyrrolidinyl) quinolonecarboxylic acid derivative technical field

  摘要：

  目标 提供新型喹诺酸类化合物，作为安全、强效的抗菌剂，对耐药菌有良好的抗菌效果，对传统抗菌剂不敏感。 解决方法 提供7-(4-取代-3-环丙氨甲基吡咯烷基)喹诺酸衍生物（如1-环丙基-7-[(3S,4S)-3-环丙氨甲基-4-氟-1-吡咯烷基]-6-氟-1,4-二氢-8-甲氧基-4-氧代-3-喹啉羧酸），对革兰阳性菌有强效的抗菌活性，如MRSA、PRSP和VRE，同时具有安全性。这些化合物的一般式如下（I）：

  公开号：

  US20090176824A1

文献信息

• 10-(3-cyclopropylaminomethyl-1-pyrrolidinyl)pyridobenzoxazinecarboxylic acid derivative effective against resistant bacterium
  申请人：Asahina Yoshikazu

  公开号：US20050182052A1

  公开（公告）日：2005-08-18

  A compound as represented by the general formula (I) shown below exhibits high antibacterial activity against gram-positive bacteria, in particular, such drug-resistant bacteria as mRNA, PRSP and VRE: wherein R1 is a methyl group, a fluoromethyl group, a methoxymethyl group, an acetoxymethyl group, a hydroxymethyl group or a methylene; R2 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, or a pharmaceutically acceptable cation and an ester of a prodrug; R3 is a hydrogen atom or a halogen atom; R4 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, a fluoromethyl group, a trifluoromethyl group or a fluorine atom; and R5 is a hydrogen atom or a fluorine atom, with exceptions where R1 is a methyl group, R4 and R5 are at the same time a hydrogen atom, and R3 is a fluorine atom.

  下列通式（I）所代表的化合物对革兰氏阳性细菌表现出高度的抗菌活性，特别是对那些耐药菌如mRNA、PRSP和VRE： 其中，R1是甲基、氟甲基、甲氧甲基、乙酰氧甲基、羟甲基或亚甲基；R2是氢原子、具有1至3个碳原子的低烷基或药学上可接受的阳离子和前药的酯；R3是氢原子或卤素原子；R4是氢原子、具有1至3个碳原子的低烷基、氟甲基、三氟甲基或氟原子；R5是氢原子或氟原子，除非R1是甲基、R4和R5同时为氢原子，且R3是氟原子的情况。
• 7-(4-Substituted-3-cyclopropylaminomethyl-1 pyrrolidinyl) quinolonecarboxylic acid derivative
  申请人：Asahina Yoshikazu

  公开号：US20060281779A1

  公开（公告）日：2006-12-14

  OBJECT To provide novel quinolonecarboxylic acid compounds serving as safe, strong antibacterial agents that are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. SOLVING MEANS There are provided 7-(4-substituted-3-cyclopropylaminomethylpyrrolidinyl)quinolonecarboxylic acid derivatives (such as 1-cyclopropyl-7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid) that exhibit strong antibacterial activity against gram-positive bacteria, such as MRSA, PRSP and VRE, while being safe. The compounds are shown by the following general formula (I):

  目的：提供新型喹诺酮羧酸化合物，作为安全、强效的抗菌剂，对耐药菌有良好的抗菌效果，而且对传统抗菌剂的抗性较低。 解决方法：提供7-(4-取代的3-环丙氨甲基吡咯烷基)喹诺酮羧酸衍生物（例如1-环丙基-7-[(3S,4S)-3-环丙氨甲基-4-氟-1-吡咯烷基]-6-氟-1,4-二氢-8-甲氧基-4-氧代-3-喹啉羧酸），对革兰氏阳性菌（如MRSA、PRSP和VRE）表现出强效的抗菌活性，同时具有安全性。这些化合物的通用式如下（I）：
• 7- (4-substituted-3-cyclopropylaminomethyl-1-pyrrolidinyl) quinolonecarboxylic acid derivative
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US08106072B2

  公开（公告）日：2012-01-31

  Object To provide novel quinolinecarboxylic acid compounds serving as safe, strong antibacterial agents that are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. Solving Means There are provided 7-(4-substituted-3-cyclopropylaminomethylpyrrolidinyl)quinolonecarboxylic acid derivatives (such as 1-cyclopropyl-7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid) that exhibit strong antibacterial activity against gram-positive bacteria, such as MRSA, PRSP and VRE, while being safe. The compounds are shown by the following general formula (I):

  目标：提供新型喹诺酸类化合物，作为安全、强效的抗菌剂，对耐药细菌具有有效作用，且对常规抗菌剂的敏感性较低。 解决方法：提供7-(4-取代的3-环丙氨甲基吡咯啉基)喹诺酸衍生物（例如1-环丙基-7-[(3S,4S)-3-环丙氨甲基-4-氟-1-吡咯啉基]-6-氟-1,4-二氢-8-甲氧基-4-氧代-3-喹诺酸），对革兰氏阳性菌（如MRSA、PRSP和VRE）表现出强效的抗菌活性，同时具有安全性。这些化合物由以下通式（I）表示：
• 10-(3-CYCLOPROPYLAMINOMETHYL-1-PYRROLIDINYL)PYRIDOBENZOXAZINECARBOXYLIC ACID DERIVATIVE EFFECTIVE AGAINST RESISTANT BACTERIUM
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP1486500A1

  公开（公告）日：2004-12-15

  A compound as represented by the general formula (I) shown below exhibits high antibacterial activity against gram-positive bacteria, in particular, such drug-resistant bacteria as MRNA, PRSP and VRE: wherein R1 is a methyl group, a fluoromethyl group, a methoxymethyl group, an acetoxymethyl group, a hydroxymethyl group or a methylene; R2 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, or a pharmaceutically acceptable cation and an ester of a prodrug; R3 is a hydrogen atom or a halogen atom; R4 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, a fluoromethyl group, a trifluoromethyl group or a fluorine atom; and R5 is a hydrogen atom or a fluorine atom, with exceptions where R1 is a methyl group, R4 and R5 are at the same time a hydrogen atom, and R3 is a fluorine atom.

  下图所示通式(I)代表的化合物对革兰氏阳性菌，特别是 MRNA、PRSP 和 VRE 等耐药菌具有很强的抗菌活性： 其中 R1 是甲基、氟甲基、甲氧基甲基、乙酰氧甲基、羟甲基或亚甲基；R2 是氢原子、具有 1 至 3 个碳原子的低级烷基或药学上可接受的阳离子和原药的酯类；R3 是氢原子或卤素原子；R4 是氢原子、1-3 个碳原子的低级烷基、氟甲基、三氟甲基或氟原子；R5 是氢原子或氟原子，但 R1 是甲基、R4 和 R5 同时是氢原子和 R3 是氟原子的情况除外。
• 10-(3-CYCLOPROPYLAMINOMETHYL-1-PYRROLIDINYL)PYRIDOBENZOXAZINECARBOXYLIC ACID DERIVATIVE EFFECTIVE AGAINST RESISTANT BACTERIA
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP1486500B1

  公开（公告）日：2009-09-16