3-[3-(1H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate | 131012-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 3-[3-(1H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate
• 英文别名: 3-[3-(1 H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate；5-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1H-indazol-3-yl)-1,2,4-oxadiazole;oxalic acid
• CAS: 131012-83-4
• 化学式: C₂H₂O₄*C₁₆H₁₇N₅O
• 分子量: 385.379
• InChiKey: WODKAOHJHNLGIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-氮杂双环[2.2.2]辛烷-3-羧酸甲酯 、 [1H-Indazol-3-yl]amide oxime 生成 3-[3-(1H-Indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane hydrogen oxalate
  参考文献：
  名称：

  SWAIN, C. J.;BAKER, R.;KNEEN, C.;MOSELEY, J.;SAUNDERS, J.;SEWARD, E. M.;S+, J. MED. CHEM., 34,(1991) N, C. 140-151

  摘要：

  DOI：

文献信息

• Physiologically active 1,2,4,-oxa- and thiadiazoles
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US04952587A1

  公开（公告）日：1990-08-28

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl; V represents nitrogen, ##STR3## and W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: (a) a non-aromatic azacyclic or azabicyclic ring system; or (b) a group of formula --NR.sup.a R.sup.b, in which R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or aryl(C.sub.1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供一种式I的化合物或其盐或前药：##STR1## 其中虚线圆圈表示5元环中任何位置的一个或两个双键；X、Y和Z独立地表示氧、硫、氮或碳，但至少其中之一表示氧、硫或氮；A表示式II的基团：##STR2## 其中R.sup.1表示氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、--CONR.sup.6R.sup.7或--SO.sub.2NR.sup.6R.sup.7，其中R.sup.6和R.sup.7独立地表示氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2表示氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羰基；V表示氮、##STR3## 且W表示氧、硫或##STR4## 其中R.sup.8表示氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；E表示一条含有1至5个碳原子的直链或支链烷基链，可选地被羟基或苯基取代；F表示：(a)非芳香族的氮杂环或氮杂双环环系；或(b)式--NR.sup.aR.sup.b的基团，其中R.sup.a和R.sup.b独立地表示氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基或芳基(C.sub.1-6)烷基；这些化合物在治疗精神障碍（如精神分裂症和躁狂）、焦虑、酒精或药物戒断、疼痛、胃潴留、胃功能障碍（如消化不良、消化性溃疡、反流性食管炎和胃胀气）、偏头痛、恶心和呕吐以及老年性痴呆症方面具有用途。
• Pharmaceutically useful 3-(indol-3-yl)-1,2,4-oxa- and thiadiazoles
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05041456A1

  公开（公告）日：1991-08-20

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: ##STR2## in which: R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarobnyl; V represents nitrogen, ##STR3## W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: (a) a non-aromatic azacyclic or azabicyclic ring system; or (b) a group of formula --NR.sup.a R.sup.b, in which R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or aryl (C.sub.1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了公式I的化合物或其盐或前药：##STR1## 其中，虚线圆圈表示5元环中任何位置的一个或两个双键；X、Y和Z独立地表示氧、硫、氮或碳，但至少有一个X、Y和Z表示氧、硫或氮；A表示公式II的基团：##STR2## 其中：R.sup.1表示氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、--CONR.sup.6 R.sup.7或--SO.sub.2 NR.sup.6 R.sup.7，在其中R.sup.6和R.sup.7独立地表示氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2表示氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羧基；V表示氮、##STR3## W表示氧、硫或##STR4## 其中R.sup.8表示氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；E表示一条含有1至5个碳原子的直链或支链烷基链，可选地被羟基或苯基取代；F表示：(a)非芳香族氮杂环或氮杂双环系统；或(b)公式--NR.sup.a R.sup.b的基团，在其中R.sup.a和R.sup.b独立地表示氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基或芳基(C.sub.1-6)烷基；这些化合物在治疗精神障碍（如精神分裂症和躁狂症）；焦虑；酒精或药物戒断；疼痛；胃排空障碍；胃功能障碍（如消化不良、消化性溃疡、反流性食管炎和胀气）；偏头痛、恶心和呕吐；以及老年性痴呆症方面具有用途。
• Five-membered ring systems with bonded azacyclic ring substituents
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0328200A1

  公开（公告）日：1989-08-16

  The present invention provides a compound of formula I or a salt or prodrug thereof: wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: in which: R' represents hydrogen, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, hydroxy(C1-6)alkyl, halogen, amino, cyano, -CONR6R7 or -S02NR6R7, in which R6 and R7 independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; R2 represents hydrogen, halogen, C1 -6 alkyl, C1 -s alkoxy or C1 -6 alkylcarbonyl; V represents nitrogen, - CH or - C -; and W represents oxygen, sulphur or - NR8, in which R8 represents hydrogen, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: . a) a non-aromatic azacyclic or azabicyclic ring system; or b) a group of formula -NRaRb, in which Ra and Rb independently represent hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-s alkynyl or aryl(C1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了式 I 的化合物或其盐或原药： 其中圆点代表五元环任意位置上的一个或两个双键； X、Y和Z独立地代表氧、硫、氮或碳，条件是X、Y和Z中至少有一个代表氧、硫或氮； 其中 R'代表氢、羟基、C1-6 烷基、C2-6 烯基、C2-6 炔基、C1-6 烷氧基、羟基（C1-6）烷基、卤素、氨基、氰基、-CONR6R7 或 -S02NR6R7，其中 R6 和 R7 独立地代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； R2 代表氢、卤素、C1-6 烷基、C1-s 烷氧基或 C1-6 烷基羰基； V 代表氮、- CH 或 - C -；以及 W 代表氧、硫或- NR8，其中 R8 代表氢、C1-6 烷基、C2-6 烯基或 C2-6 烷炔基； E 代表键或含有 1 至 5 个碳原子的直链或支链亚烷基链，可选择被羟基或苯基取代； 以及 F 代表 a) 非芳氮杂环或氮杂环环系；或 b) 式-NRaRb 的基团，其中 Ra 和 Rb 独立代表氢、C1-6 烷基、C2-6 烯基、C2-s 烷炔基或芳基（C1-6）烷基。这些化合物可用于治疗精神病（如精神分裂症和躁狂症）、焦虑、戒酒或戒毒、疼痛、胃淤血、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心和呕吐以及先天性和老年性痴呆。
• US4952587A
  申请人：——

  公开号：US4952587A

  公开（公告）日：1990-08-28
• US5041456A
  申请人：——

  公开号：US5041456A

  公开（公告）日：1991-08-20