methyl 2-(chloromethyl)-4-pyridinecarboxylate hydrochloride | 125398-17-6

• 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-(chloromethyl)-4-pyridinecarboxylate hydrochloride
• 英文别名: Methyl 2-(chloromethyl)isonicotinate hydrochloride；methyl 2-(chloromethyl)pyridine-4-carboxylate;hydrochloride
• CAS: 125398-17-6
• 化学式: C₈H₈ClNO₂*ClH
• 分子量: 222.071
• InChiKey: ICQYKDMSIZPRPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.03
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P271,P280,P301+P330+P331,P303+P361+P353,P304+P340,P305+P351+P338,P310,P363,P403+P233,P405,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H302,H335,H314
• 包装等级：
  III

反应信息

• 作为反应物：
  描述：

  methyl 2-(chloromethyl)-4-pyridinecarboxylate hydrochloride 在 Rh on carbon 草酰氯 、 氢气 、 对甲苯磺酸 、 二甲基亚砜 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， -60.0~70.0 ℃ 、482.63 kPa 条件下， 反应 109.67h， 生成 7-<(3,4-dichlorophenyl)acetyl>-8-(1-pyrrolidinylmethyl)-7-aza-1,4-dioxaspiro<4.5>decane
  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：

  2-羟基甲基异烟酸甲酯 在 盐酸 、 氯化亚砜 作用下， 反应 4.0h， 以90%的产率得到methyl 2-(chloromethyl)-4-pyridinecarboxylate hydrochloride
  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

文献信息

• Tetrahydroisoquinolin-2-yl derivatives as thromboxane A2 antagonists
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0300725A1

  公开（公告）日：1989-01-25

  The invention provides compounds of the formula (I): and salts thereof; wherein A is a group NR³SO₂ or SO₂NR³; Ra is an acyclic hydrocarbon group having from 1 to 4 linear carbon atoms; Rb is a bond or an acyclic hydrocarbon group having from 1 to 3 linear carbon atoms, provided that the total number of linear carbon atoms in Ra and Rb taken together does not exceed four and that the carbon atom in Ra which is adjacent to the isoquinoline ring nitrogen atom is saturated; the group is a monocyclic group having between three and seven ring members and containing up to three heteroatoms; Y is CO₂H or a group hydrolysable to CO₂H; R¹ is phenyl optionally substituted by one or more substituents chosen from the group comprising halogen, C₁₋₄alkyl, C₁₋₆acyl, C₁₋₄alkoxy, nitro and trifluoromethyl; R² is hydrogen or one or more C₁₋₄alkyl substituents located at the 1, 3 and 4 positions of the isoquinoline ring; and R³ is hydrogen or C₁₋₆alkyl. Also provided are compositions containing the compounds of the formula (I), a process for their preparation and their use as thromboxane A₂ antagonists.

  本发明提供了式 (I) 的化合物： 及其盐类；其中 A 是基团 NR³SO₂ 或 SO₂NR³； Ra 是具有 1 至 4 个线性碳原子的无环烃基团； Rb 是键或具有 1 至 3 个直链碳原子的无环烃基，条件是 Ra 和 Rb 中的直链碳原子总数合计不超过 4 个，且 Ra 中与异喹啉环氮原子相邻的碳原子为饱和碳原子； 基团 是单环基团，具有 3 至 7 个环成员，并含有最多 3 个杂原子； Y 是 CO₂H 或可水解为 CO₂H 的基团； R¹ 是苯基，可任选被选自卤素、C₁₋₄烷基、C₁₋₆酰基、C₁₋₄烷氧基、硝基和三氟甲基中的一个或多个取代基取代； R² 是氢或位于异喹啉环 1、3 和 4 位的一个或多个 C₁₋₄烷基取代基；以及 R³ 是氢或 C₁₋₆烷基。 此外，还提供了含有式（I）化合物的组合物、其制备工艺及其作为血栓素 A₂拮抗剂的用途。
• US4866076A
  申请人：——

  公开号：US4866076A

  公开（公告）日：1989-09-12