(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3hydroxypropene | 143321-95-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3hydroxypropene
• 英文别名: (R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-hydroxypropene；benzyl (2R)-2-(3-hydroxyprop-1-enyl)pyrrolidine-1-carboxylate
• CAS: 143321-95-3
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: XRVPHGWCSXRKAY-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-Benzyl-1,3-thiazol-2-yl)-2-bromo-1-trifluoroacetylaminobenzene 、 (R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3hydroxypropene 在 二氯甲烷 作用下， 以afforded the title compound (97%) as a white foam的产率得到(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3-(N-(2-bromo-4-(4-benzyl-1.3-thiazol-2-yl)phenyl)-N-trifluoroacetylamino)propene
  参考文献：
  名称：

  Indole derivatives as 5-HT1 agonists

  摘要：

  式子为##STR1##的化合物，其中A代表直接键，C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4烯基；n为0，1或2；R.sub.1为氢，C.sub.1-C.sub.6烷基，芳基，C.sub.1-C.sub.3烷基芳基，C.sub.1-C.sub.3烷基杂芳基或--(CH.sub.2).sub.m R.sub.6；W、X、Y和Z分别独立地为氧、硫、氮或碳，但至少一个为氮；R.sub.2、R.sub.3、R.sub.4和R.sub.5分别独立地为氢，C.sub.1-C.sub.6烷基，芳基，C.sub.1-C.sub.3烷基芳基，C.sub.1-C.sub.3烷基杂芳基，卤素，氰基，三氟甲基，硝基，--OR.sub.7，--NR.sub.7 R.sub.8，--(CH.sub.2).sub.s OR.sub.7，--SR.sub.7，--SO.sub.2 NR.sub.7 R.sub.8，--NR.sub.7 SO.sub.2 R.sub.8，--NR.sub.7 CO.sub.2 R.sub.8，--CONR.sub.7 R.sub.8或--CO.sub.2 R.sub.7；R.sub.2和R.sub.3、R.sub.3和R.sub.4或R.sub.4和R.sub.5中的一个可以结合形成五到七元的烷基环、六元的芳基环、具有1个N、O或S杂原子的五到七元的杂烷基环或具有1或2个N、O或S杂原子的五到六元的杂芳基环；R.sub.6为氰基，三氟甲基或--OR.sub.9；R.sub.7、R.sub.8和R.sub.9分别独立地为氢，C.sub.1到C.sub.6烷基，--(CH.sub.2).sub.m R.sub.10，C.sub.1到C.sub.3烷基芳基或芳基；R.sub.7和R.sub.8可以结合形成C.sub.4-C.sub.7烷基环；R.sub.10为氰基，三氟甲基或C.sub.1-C.sub.4烷氧基；R.sub.11为氢，--OR.sub.12或--NHCOR.sub.12；R.sub.12为C.sub.1到C.sub.6烷基，芳基或C.sub.1到C.sub.3烷基-芳基；m为1、2或3；s为0、1、2或3；上述芳基和上述烷基芳基中的芳基基团是独立选择自苯基和取代苯基，其中所述取代苯基可以被1到3个C.sub.1-C.sub.4烷基，卤素，羟基，氰基，羧酰胺基，硝基和C.sub.1-C.sub.4烷氧基中的一个取代。这些化合物是有用的心理治疗药物，是有效的5-羟色胺（5-HT.sub.1）激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛和慢性阵发性半侧头痛以及与缺乏5-羟色胺能神经递质有关的其他疾病。这些化合物还可以用作中枢作用的降压剂和血管扩张剂。

  公开号：

  US05717102A1
• 作为产物：
  描述：

  (R)-ethyl 3-(N-benzyloxycarbonylpyrrolidin-2-yl)-2-propenoate 、 trifluoroborane diethyl ether 、 diisobutylaluminum hydride 在 柠檬酸 、 乙酸乙酯 、 magnesium sulfate 、 silica gel 、 ethyl acetate n-hexane 作用下， 以 四氢呋喃 为溶剂， 反应 5.67h， 以to give the-title compound as an oil (260 g)的产率得到(R)-1-(N-Benzyloxycarbonylpyrrolidin-2-yl)-3hydroxypropene
  参考文献：
  名称：

  Indole derivatives

  摘要：

  化合物的公式为##STR1##其中n为0、1或2；X为氢、氯、溴或碘；R.sub.1为氢；R.sub.3选择自氢和C.sub.1到C.sub.6线性或支链烷基；而R.sub.2如规范中所定义，其药学上可接受的盐是有用的心理治疗剂，并且是有效的血清素（5-HT.sub.1）激动剂，可以用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛、慢性阵发性半头痛和与血管障碍有关的头痛，以及由于血清素能神经递质不足引起的其他疾病。这些化合物也可用作中枢作用的降压剂和血管扩张剂。还公开了通过过渡金属催化的双卤代中间体环化形成吲哚的方法。

  公开号：

  US05545644A1

文献信息

• Indole derivative for the treatment of migraine
  申请人：Pfizer Inc

  公开号：US05945118A1

  公开（公告）日：1999-08-31

  This invention relates to (R)-5-(aminosulphonylmethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole and its pharmaceutically acceptable salts. This compound is particularly useful in treating disorders arising from deficient serotonergic neurotransmission, especially migraine.

  本发明涉及(R)-5-(氨基磺酰甲基)-3-(N-甲基吡咯烷-2-甲基)-1H-吲哚及其药学上可接受的盐。该化合物在治疗由于缺乏5-羟色胺能神经递质引起的疾病中特别有用，尤其是偏头痛。
• Indole derivatives as 5-HT1 agonists
  申请人：Pfizer Inc

  公开号：US06380233B1

  公开（公告）日：2002-04-30

  Compounds of the formula where W is n is 0, 1, or 2; m is 0, 1, 2, or 3: Y and G are each independently oxygen or sulfur; Z is —O—, —S—, —NH, or —CH2; R1 is hydrogen, C1 to C8 alkyl, substituted C1 to C8 alkyl substituted with one hydroxy, C3 to C8 alkenyl, C3 to C8 alkynyl, aryl, C1 to C3 alkylaryl, C1 to C3 alkylheteroaryl, or —Q—R4; R2 and R3 are each independently hydrogen, C1 to C6 alkyl, aryl, C1 to C3 alkylaryl, or C1 to C3 alkylheteroaryl; R4 is cyano, trifluoromethyl, —COR8, —CO2R8, —CONR8R10, —OR9, —SO2NR9R10, or —S(O)4R8; R8 and R10 are each independently hydrogen, C1 to C8 alkyl, C1 to C3 alkylaryl, aryl, or R9 and R10 may together be taken to form a three- to seven-membered alkyl ring or a three- to seven-membered heteroalkyl ring having 1 heteroatom of O; Q is C1 to C3 alkyl; R11 is hydrogen, —OR12, or —NHCOR12; R12 is hydrogen, C1 to C6 alkyl, aryl, or C1 to C3 alkyl-aryl; q is 0, 1, or 2; a first chiral carbon is designated by an asterisk; a second chiral carbon is designated by #; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are independently selected from phenyl and substituted phenyl, wherein said substituted phenyl may be substituted with one to three groups selected from C1 to C4 alkyl, halogen, hydroxy, cyano, carboxamido, nitro, and C1 to C4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

  该化合物的公式为：其中W为n，为0、1或2；m为0、1、2或3；Y和G各自独立地为氧或硫；Z为—O—、—S—、—NH或—CH2；R1为氢、C1至C8烷基、取代的C1至C8烷基，取代基为一个羟基、C3至C8烯基、C3至C8炔基、芳基、C1至C3烷基芳基、C1至C3烷基杂环芳基或—Q—R4；R2和R3各自独立地为氢、C1至C6烷基、芳基、C1至C3烷基芳基或C1至C3烷基杂环芳基；R4为氰基、三氟甲基、—COR8、—CO2R8、—CONR8R10、—OR9、—SO2NR9R10或—S（O）4R8；R8和R10各自独立地为氢、C1至C8烷基、C1至C3烷基芳基或芳基，或R9和R10可一起形成一个具有1个O杂原子的三至七元烷基环或三至七元杂烷基环；Q为C1至C3烷基；R11为氢、—OR12或—NHCOR12；R12为氢、C1至C6烷基、芳基或C1至C3烷基芳基；q为0、1或2；第一个手性碳由星号指定；第二个手性碳由#指定；上述芳基和上述烷基-芳基基团的芳基部分分别选择自苯基和取代苯基，其中所述取代苯基可用1至3个C1至C4烷基、卤素、羟基、氰基、羧酰胺基、硝基和C1至C4烷氧基中的一个或多个基团取代，并且其药物可接受的盐。这些化合物在治疗偏头痛和其他疾病方面具有新的用途。这些化合物是有用的心理治疗药物，是有效的5-羟色胺（5-HT1）激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛、慢性阵发性半头痛和与血管障碍相关的头痛以及其他由5-羟色胺能神经传递不足引起的疾病。这些化合物也可用作中枢作用的降压剂和扩血管剂。
• Indole derivatives
  申请人：Pfizer Inc

  公开号：US05559129A1

  公开（公告）日：1996-09-24

  Compounds of the formula ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, X and n are as defined in the claims and the pharmaceutically acceptable salts thereof are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting hypertensives and vasodilators. A process for forming indoles by transition metal catalyzed cyclization of dihalogenated intermediate is also disclosed.

  该公式化合物 ##STR1## 中，其中R.sub.1、R.sub.2、R.sub.3、X和n如权利要求中所定义，以及其药用可接受盐是新的。这些化合物是有用的精神治疗药物，是有效的血清素(5-HT.sub.1)激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集簇头痛、偏头痛、疼痛、慢性阵发性半头痛和与血管疾病相关的头痛，以及其他由血清素神经递质缺乏引起的疾病。这些化合物还可用作中枢作用降压药和扩血管剂。还公开了通过过渡金属催化的二卤代中间体环化形成吲哚的方法。
• Indole derivatives as 5-HT1 agonists
  申请人：Pfizer Inc

  公开号：US05594014A1

  公开（公告）日：1997-01-14

  Compounds of the formula (I) where A represents a direct bond, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl; n is 0, 1, or 2; W, X, Y, and Z are each independently oxygen, sulfur, nitrogen or carbon, provided that at least one of W, X, Y, or Z is nitrogen. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

  化合物的公式（I），其中A代表直接键，C.sub.1-C.sub.4烷基或C.sub.1-C.sub.4烯基; n为0、1或2; W、X、Y和Z各自独立地表示氧、硫、氮或碳，但至少其中一个是氮。这些化合物是有用的心理治疗药物，是有效的5-羟色胺（5-HT.sub.1）激动剂，可用于治疗抑郁症、焦虑症、饮食失调、肥胖症、药物滥用、集群性头痛、偏头痛、疼痛和慢性阵发性半边头痛以及与血管障碍相关的头痛和其他因缺乏5-羟色胺能神经递质而引起的疾病。这些化合物也可以用作中枢作用的降压剂和扩血管剂。