methyl 2-(1-pyrrolidinylmethyl)pyridine-5-carboxylate | 125104-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 2-(1-pyrrolidinylmethyl)pyridine-5-carboxylate
• 英文别名: methyl 6-(pyrrolidine-1-ylmethyl)nicotinate；methyl 6-(pyrrolidin-1-ylmethyl)nicotinate；methyl 6-(1-pyrrolidinylmethyl)pyridine-3-carboxylate；methyl 6-(pyrrolidin-1-ylmethyl)pyridine-3-carboxylate
• CAS: 125104-82-7
• 化学式: C₁₂H₁₆N₂O₂
• 分子量: 220.271
• InChiKey: HFHCLCQANASYDF-UHFFFAOYSA-N

物化性质

• 沸点：
  309.7±32.0 °C(Predicted)
• 密度：
  1.164±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  methyl 2-(1-pyrrolidinylmethyl)pyridine-5-carboxylate 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 22.0 ℃ 、101.32 kPa 条件下， 以62%的产率得到methyl 2-(1-pyrrolidinylmethyl)piperidine-5-carboxylate
  参考文献：
  名称：

  New .kappa.-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus

  摘要：

  The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]2-[(alkylamino)methyl]peperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]2-[[1-(3-oxopyrrolidinyl)methyl]?? piperidine (10) possesses high activity in the rabbit vas deferens (LCD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antiociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg sc). The spirocyclic analogue 8-[3,4-dichlorophenyl)acetyl]7-(1-pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

  DOI：

  10.1021/jm00081a009
• 作为产物：
  描述：

  6-甲基烟酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 28.0h， 生成 methyl 2-(1-pyrrolidinylmethyl)pyridine-5-carboxylate
  参考文献：
  名称：

  PYRROLOPYRIMIDINE COMPOUNDS USED AS TLR7 AGONIST

  摘要：

  公开号：

  EP3190113B1

文献信息

• Spiropiperidine derivatives
  申请人：Glaxo Group Limited

  公开号：US05114945A1

  公开（公告）日：1992-05-19

  Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents hydroxy, C.sub.1-6 alkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 carboxyalkyl, phenyl, oxo, amino, carboxy, amido, --NR.sub.4 COR.sub.5 (where R.sub.4 and R.sub.5 both represent C.sub.1-6 alkyl), optionally substituted methylidene or, together with the carbon atom to which it is attached, R.sub.1 forms a 5 or 6-membered ring containing one or more heteroatoms; R.sub.2 and R.sub.3 are the same or different and are C.sub.1-6 alkyl or C.sub.3-6 alkenyl; or --NR.sub.2 R.sub.3 forms a 5-membered (optionally containing an oxygen atom adjacent to the nitrogen) or a 6-membered ring, which ring optionally contains one unit of unsaturation and which is unsubstituted or substituted by hydroxy, oxo, optionally substituted methylidene, --COR.sub.6 (where R.sub.6 represents C.sub.1-6 alkyl, OR, or --NHR, and R represents hydrogen, C.sub.1-6 alkyl, aryl, ar(C.sub.1-6)alkyl) or .dbd.NOR.sub.8 (where R.sub.8 represents C.sub.1-6 alkyl); X represents a direct bond, --CH.sub.2 -- or --CH.sub.2 0--; Ar represents a substituted phenyl moiety; and physiologically acceptable salts thereof. The compounds are indicated as useful for the treatment of pain and cerebral ischemia. Proccesses and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.

  披露了公式(I)的化合物##STR1##，其中R1代表羟基，C1-6烷基，C1-6羟烷基，C1-6羧烷基，苯基，氧代，氨基，羧基，酰胺基，--NR4COR5（其中R4和R5都代表C1-6烷基），可选地取代亚甲基，或者与它连接的碳原子一起，R1形成一个含有一个或多个杂原子的5或6元环；R2和R3相同或不同，是C1-6烷基或C3-6烯基；或者--NR2R3形成一个5元环（可选地含有一个靠近氮原子的氧原子）或6元环，该环可选地含有一个不饱和单元，并且该环未取代或被羟基，氧代，可选地取代亚甲基，--COR6（其中R6代表C1-6烷基，OR或--NHR，R代表氢，C1-6烷基，芳基，芳(C1-6)烷基）或.dbd.NOR8（其中R8代表C1-6烷基）取代；X代表直接键，--CH2--或--CH2O--; Ar代表一个取代的苯基部分；以及它们的生理学可接受盐。这些化合物被指出用于治疗疼痛和脑缺血。还披露了它们的制备过程和中间体以及含有它们的药物组合物。
• Piperidine derivatives
  申请人：GLAXO GROUP LIMITED

  公开号：EP0330461A3

  公开（公告）日：1990-10-17

  Compounds are disclosed of formula (I) wherein R₁ represents hydroxy, C₁₋₆ alkyl, C₁₋₆ hydroxyalkyl, C₁₋₆ carboxyalkyl, phenyl, oxo, amino, carboxy, amido, -NR₄COR₅ (where R₄ and R₅ both represent C₁₋₆ alkyl), optionally substituted methylidene or, together with the carbon atom to which it is attached, R₁ forms a 5 or 6-membered ring containing one or more heteroatoms; R₂ and R₃ are the same or different and are C₁₋₆ alkyl or C₃₋₆ alkenyl; or -NR₂R₃ forms a 5-membered (optionally containing an oxygen atom adjacent to the nitrogen) or a 6-membered ring, which ring optionally contains one unit of unsaturation and which is unsubstituted or substituted by hydroxy, oxo, optionally substituted methylidene, -COR₆ (where R₆ represents C₁₋₆ alkyl, OR₇ or -NHR₇, and R₇ represents hydrogen, C₁₋₆ alkyl, aryl, ar(C₁₋₆)alkyl) or =NOR₈ (where R₈ represents C₁₋₆ alkyl); X represents a direct bond, -CH₂- or -CH₂O-; Ar represents a substituted phenyl moiety; and physiologically acceptable salts thereof.The compounds are indicated as useful for the treatment of pain and cerebral ischaemia.Processes and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.

  披露了公式(I)的化合物，其中 R₁代表羟基，C₁₋₆烷基，C₁₋₆羟烷基，C₁₋₆羧烷基，苯基，氧代，氨基，羧基，酰胺，-NR₄COR₅（其中R₄和R₅都代表C₁₋₆烷基），可选地取代的亚甲基，或者与它连接的碳原子一起，R₁形成一个含有一个或多个杂原子的5或6元环； R₂和R₃相同或不同，是C₁₋₆烷基或C₃₋₆烯丙基；或者-NR₂R₃形成一个5元环（可选地含有与氮原子相邻的氧原子）或6元环，该环可选地含有一个不饱和单元，并且该环未取代或被羟基，氧代，可选地取代的亚甲基，-COR₆（其中R₆代表C₁₋₆烷基，OR₇或-NHR₇，R₇代表氢，C₁₋₆烷基，芳基，芳(C₁₋₆)烷基）或=NOR₈（其中R₈代表C₁₋₆烷基）取代； X代表直接键，-CH₂-或-CH₂O-； Ar代表取代的苯基部分； 以及它们的生理可接受盐。 这些化合物被指出用于治疗疼痛和脑缺血。还披露了它们的制备过程和中间体以及含有它们的药物组合物。
• Pyrrolopyrimidine compounds used as TLR7 agonist
  申请人：CHIA TAI TIANQING PHARMACEUTICAL GROUP CO., LTD.

  公开号：US10555949B2

  公开（公告）日：2020-02-11

  The present invention relates to a pyrrolopyrimidine compound as TLR7 agonist, and particularly relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof, a preparation process thereof, a pharmaceutical composition containing such compounds and use thereof for manufacturing a medicament against viral infection.

  本发明涉及一种作为 TLR7 激动剂的吡咯并嘧啶化合物，特别是涉及一种式（I）化合物或其药学上可接受的盐、其制备工艺、含有这种化合物的药物组合物及其用于制造抗病毒感染药物的用途。
• [EN] PYRROLOPYRIMIDINE COMPOUNDS USED AS TLR7 AGONIST<br/>[FR] COMPOSÉS PYRROLOPYRIMIDINE UTILISÉS EN TANT QU'AGONISTES DU TLR7<br/>[ZH] 作为TLR7激动剂的吡咯并嘧啶化合物
  申请人：CHIA TAI TIANQING PHARMACEUTICAL GROUP CO LTD

  公开号：WO2016023511A1

  公开（公告）日：2016-02-18

  提供了作为TLR7激动剂的吡咯并嘧啶化合物，具体涉及式（I）化合物或其药学上可接受的盐、其制备方法、含有该类化合物的药物组合物、及其用于制备抗病毒药物的用途。
• [EN] FIVE-MEMBERED HETEROCYCLO-PYRIMIDINE COMPOUND, PHARMACEUTICAL COMPOSITION AND USE THEREOF<br/>[FR] COMPOSÉ D'HÉTÉROCYCLO-PYRIMIDINE À CINQ CHAÎNONS, COMPOSITION PHARMACEUTIQUE ET UTILISATION ASSOCIÉE<br/>[ZH] 五元杂环并嘧啶类化合物、药物组合物及用途
  申请人：LUOXIN PHARMACEUTICAL SHANGHAI CO LTD

  公开号：WO2019196918A1

  公开（公告）日：2019-10-17

  本发明公开了一种五元杂环并嘧啶类化合物、含有这类化合物的药物组合物、以及使用这类化合物和药物组合物用于提高TLR 7的活性的用途。所述化合物的结构如下式（I）所示，其中R1、R2、R3、R4、R5、R6、R7、R9、X、Y、Z、A和B如本文说明书所定义。本发明的所述化合物或药物组合物作为TLR7激动剂可用于治疗疾病如肝脏相关疾病、肿瘤或艾滋病。