1-<(4,5,6,7-tetrahydrofuro<3,2-c>pyridin-4-yl)methyl>-3-pyrrolidinol | 129823-10-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-<(4,5,6,7-tetrahydrofuro<3,2-c>pyridin-4-yl)methyl>-3-pyrrolidinol
• 英文别名: 1-[(4,5,6,7-Tetrahydrofuro[3,2-c]pyridin-4-yl)methyl]-3-pyrrolidinol；1-(4,5,6,7-Tetrahydrofuro[3,2-c]pyridin-4-ylmethyl)pyrrolidin-3-ol
• CAS: 129823-10-5
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: ITZOFHUSEXDPGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  48.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-<(4,5,6,7-tetrahydrofuro<3,2-c>pyridin-4-yl)methyl>-3-pyrrolidinol 在 草酰氯 、 二甲基亚砜 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 5-[(3,4-Dichlorophenyl)acetyl]-4,5,6,7-tetrahydro-4-[(3-oxo-1-pyrrolidinyl)methyl]furo[3,2-c]pyridine
  参考文献：
  名称：

  4-[(Alkylamino)methyl]furo[3,2-c]pyridines: A New Series of Selective .kappa.-Receptor Agonists

  摘要：

  The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c]pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-pyrrolidinol analogue 17 (IC50 = 2.7 nM) was found to be approximately 5-fold more potent than the corresponding pyrrolidine analogue 16 (IC50 15 nM). In the rat and hamster vasa deferentia (mu-specific and delta-specific tissues, respectively), 17 showed only weak antagonist activity (PKB > 5.5), underlining its selectivity for the kappa-opioid receptor. The major activity for 17 is resident in the 4S,3'S-isomer 26 (rabbit vas deferens IC50 = 1.1 nM). Compound 26 displays excellent antinociceptive activity, as determined in the mouse acetylcholine-induced abdominal constriction test (ED(50) = 0.001 mg/kg, sc).

  DOI：

  10.1021/jm00040a004
• 作为产物：
  描述：

  1-<(4,5,6,7-tetrahydrofuro<3,2-c>pyridin-4-yl)carbonyl>-3-pyrrolidinol 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以97%的产率得到1-<(4,5,6,7-tetrahydrofuro<3,2-c>pyridin-4-yl)methyl>-3-pyrrolidinol
  参考文献：
  名称：

  4-[(Alkylamino)methyl]furo[3,2-c]pyridines: A New Series of Selective .kappa.-Receptor Agonists

  摘要：

  The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c]pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-pyrrolidinol analogue 17 (IC50 = 2.7 nM) was found to be approximately 5-fold more potent than the corresponding pyrrolidine analogue 16 (IC50 15 nM). In the rat and hamster vasa deferentia (mu-specific and delta-specific tissues, respectively), 17 showed only weak antagonist activity (PKB > 5.5), underlining its selectivity for the kappa-opioid receptor. The major activity for 17 is resident in the 4S,3'S-isomer 26 (rabbit vas deferens IC50 = 1.1 nM). Compound 26 displays excellent antinociceptive activity, as determined in the mouse acetylcholine-induced abdominal constriction test (ED(50) = 0.001 mg/kg, sc).

  DOI：

  10.1021/jm00040a004

文献信息

• Pharmaceutically useful furo[3,2-c]pyridines
  申请人：Glaxo Group Limited

  公开号：US05109008A1

  公开（公告）日：1992-04-28

  Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents hydrogen, unsubstituted or substituted C.sub.1-6 alkyl, halogen, --COR.sub.4 or --CO.sub.2 R.sub.4 (where R.sub.4 represents hydrogen or unsubstituted or substituted C.sub.1-6 alkyl); 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, C.sub.1-6 acyloxy, oxo, optionally substituted methylidene, --COR.sub.5 (where R.sub.5 represents C.sub.1-6 alkyl, OR.sub.6 or --NHR.sub.6, and R.sub.6 represents hydrogen, C.sub.1-6 alkyl, aryl or ar(C.sub.1-6)alkyl) or said ring is substituted by .dbd.NOR.sub.7 (where R.sub.7 represents C.sub.1-6 alkyl); Z represents --O-- or --S--; X represents a direct bond, --CH.sub.2 -- or --CH.sub.2 O--; Ar represents a substituted phenyl moiety; and pharmaceutically acceptable salts thereof. The compounds are indicated as useful in 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##STR1##，其中R1代表氢，未取代或取代的C1-6烷基，卤素，--COR4或--CO2R4（其中R4代表氢或未取代或取代的C1-6烷基）；R2和R3相同或不同，为C1-6烷基或C3-6烯基；或--NR2R3形成一个5元环（可选地含有与氮原子相邻的一个氧原子）或一个6元环，该环可选地含有一个不饱和单元，并且该环未取代或取代有羟基，C1-6酰氧基，氧亚基，可选地取代的亚甲基，--COR5（其中R5代表C1-6烷基，OR6或--NHR6，R6代表氢，C1-6烷基，芳基或芳(C1-6)烷基）或该环被.dbd.NOR7取代（其中R7代表C1-6烷基）；Z代表--O--或--S--；X代表直接键，--CH2--或--CH2O--;Ar代表取代的苯基部分；以及它们的药物可接受的盐。这些化合物被指示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。
• Furo- and thieno[3,2-c]pyridines and pharmaceutical compositions containing them
  申请人：GLAXO GROUP LIMITED

  公开号：EP0366327A1

  公开（公告）日：1990-05-02

  Compounds are disclosed of formula (I) wherein R₁ represents hydrogen, unsubstituted or substituted C₁₋₆alkyl, halogen, -COR₄ or -CO₂R₄ (where R₄ represents hydrogen or unsubstituted or substituted (C₁₋₆alkyl); R₂ and R₃ are the same or different and are C₁₋₆alkyl or C₃₋₆alkenyl 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, C₁₋₆acyloxy, oxo, optionally substituted methylidene, -COR₅ (where R₅ represents C₁₋₆alkyl, OR₆ or -NHR₆, and R₆ represents hydrogen, C₁₋₆alkyl, aryl, ar(C₁₋₆)alkyl) or =NOR₇ (where R₇ represents C₁₋₆alkyl); Z represents -O- or -S-; X represents a direct bond, -CH₂- or -CH₂O-; Ar represents a substituted phenyl moiety; and pharmaceutically acceptable salts thereof. The compounds are indicated as useful in the treatment of pain and cerebral ischaemia. Processes and intermediates for their preparation and pharmaceutical compositions containing them are also disclosed.

  公开了式(I)化合物 其中 R₁ 代表氢、未取代或取代的 C₁₋₆烷基、卤素、-COR₄ 或 -CO₂R₄（其中 R₄ 代表氢或未取代或取代的 C₁₋₆烷基）； R₂ 和 R₃ 相同或不同，并且是 C₁₋₆ 烷基或 C₃₋₆ 烯基或-NR₂R₃ 形成一个 5 元环（可选含有一个与氮相邻的氧原子）或一个 6 元环，该环可选含有一个不饱和度单位，且该环未被羟基取代或被羟基取代、C₁₋₆乙氧基、氧代、任选取代的亚甲基、-COR₅（其中 R₅ 代表 C₁₋₆烷基、OR₆或 -NHR₆、和 R₆ 代表氢、C₁₋₆、芳基、ar(C₁₋₆)烷基)或 =NOR₇ (其中 R₇ 代表 C₁₋₆烷基)； Z 代表-O-或-S-； X 代表直接键、-CH₂- 或 -CH₂O-； Ar 代表取代的苯基； 及其药学上可接受的盐类。 这些化合物可用于治疗疼痛和脑缺血。 此外，还公开了制备这些化合物的工艺和中间体以及含有这些化合物的药物组合物。
• Naylor Alan, Judd Duncan B., Scopes David I. C., Hayes Ann G., Birch Phil+, J. Med. Chem, 37 (1994) N 14, S 2138-2144
  作者：Naylor Alan, Judd Duncan B., Scopes David I. C., Hayes Ann G., Birch Phil+

  DOI：——

  日期：——
• US5109008A
  申请人：——

  公开号：US5109008A

  公开（公告）日：1992-04-28
• 4-[(Alkylamino)methyl]furo[3,2-c]pyridines: A New Series of Selective .kappa.-Receptor Agonists
  作者：Alan Naylor、Duncan B. Judd、David I. C. Scopes、Ann G. Hayes、Philip J. Birch

  DOI：10.1021/jm00040a004

  日期：1994.7

  The synthesis of 5-(arylacetyl)-4-[(alkylamino)methyl]furo[3,2-c]pyridines (16-23, 26, 27) and their activities as kappa-opioid receptor agonists are described. kappa-Agonist potency was particularly sensitive to the nature of the basic moiety. In particular, in the rabbit vas deferens (kappa-specific tissue), the 3-pyrrolidinol analogue 17 (IC50 = 2.7 nM) was found to be approximately 5-fold more potent than the corresponding pyrrolidine analogue 16 (IC50 15 nM). In the rat and hamster vasa deferentia (mu-specific and delta-specific tissues, respectively), 17 showed only weak antagonist activity (PKB > 5.5), underlining its selectivity for the kappa-opioid receptor. The major activity for 17 is resident in the 4S,3'S-isomer 26 (rabbit vas deferens IC50 = 1.1 nM). Compound 26 displays excellent antinociceptive activity, as determined in the mouse acetylcholine-induced abdominal constriction test (ED(50) = 0.001 mg/kg, sc).