5-chloro-2-methoxy-4-propylaminobenzoic acid | 174260-93-6

• 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: 5-chloro-2-methoxy-4-propylaminobenzoic acid
• 英文别名: 5-Chloro-2-methoxy-4-(propylamino)benzoic acid
• CAS: 174260-93-6
• 化学式: C₁₁H₁₄ClNO₃
• 分子量: 243.69
• InChiKey: AUNBDHUFGWVSRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-2-methoxy-4-propylaminobenzoic acid 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 N-(1-Benzyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-propylamino-benzamide
  参考文献：
  名称：

  Synthesis and neuroleptic activity of benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds

  摘要：

  Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.

  DOI：

  10.1021/jm00142a019

文献信息

• N-(3-PYRROLIDINYL)BENZAMIDE DERIVATIVE
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0757985A1

  公开（公告）日：1997-02-12

  N-(3-Pyrrodinyl)benzamide derivatives represented by the following general formula (I) which have potent and selective antagonism against dopamine D3 and/or D4 receptor and are useful as a psychotropic, a schizophrenia-treating agent and the like, or a pharmaceutically acceptable salt thereof or a pharmaceutical preparation thereof. (wherein each symbol in the formula has the following meaning, R1: hydrogen, lower alkyl, aralkyl, or cycloalkyl or cycloalkyl-lower alkyl having 3 to 8 ring atoms, R2: bicyclic or tricyclic bridged hydrocarbon ring of 4 to 16 ring atoms which may have lower alkyl, R3: lower alkoxy, amino or mono- or di-lower alkylamino, R4: hydrogen, halogen, lower alkyl which may have hydroxyl, lower alkoxy, cyano, nitro, amino, mono- or di-lower alkylamino, acyl or a group represented by -S(O)m-R5, R5: lower alkyl, amino or mono- or di-lower alkylamino, m: 0, 1 or 2, X: a bond or a group represented by -O-, -S(O)n-, -NH- or -CONH-, and n: 0, 1 or 2, with the proviso that, when R1 is cycloalky, the cases wherein X is -CONH-, R3 is lower alkoxy and R4 is halogen are excluded.)

  N-(3-吡咯烷基)苯甲酰胺衍生物，由以下通式(I)代表，对多巴胺 D3 和/或 D4 受体具有强效和选择性拮抗作用，可用作精神药物、精神分裂症治疗剂等，或其药学上可接受的盐或其药物制剂。 (式中各符号含义如下、 R1：氢、低级烷基、芳烷基、环烷基或具有 3 至 8 个环原子的环烷基-低级烷基、 R2：具有 4 至 16 个环原子的双环或三环桥式烃环，其中可能有低级烷基、 R3：低级烷氧基、氨基或单或双低级烷基氨基、 R4：氢、卤素、可能具有羟基的低级烷基、低级烷氧基、氰基、硝基、氨基、单或双低级烷基氨基、酰基或由 -S(O)m-R5 所代表的基团、 R5：低级烷基、氨基或单或双低级烷基氨基、 m：0、1 或 2、 X：键或由-O-、-S(O)n-、-NH-或-CONH-代表的基团，以及 n:0、1 或 2、 但当 R1 为环烷基时，不包括 X 为-CONH-、R3 为低级烷氧基和 R4 为卤素的情况）。
• IWANAMI, SUMIO;TAKASHIMA, MUTSUO;HIRATA, YASUFUMI;HASEGAWA, OSAMU;USUDA, +, J. MED. CHEM., 1981, 24, N 10, 1224-1230
  作者：IWANAMI, SUMIO、TAKASHIMA, MUTSUO、HIRATA, YASUFUMI、HASEGAWA, OSAMU、USUDA, +

  DOI：——

  日期：——
• US5686482A
  申请人：——

  公开号：US5686482A

  公开（公告）日：1997-11-11
• Synthesis and neuroleptic activity of benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide and related compounds
  作者：Sumio Iwanami、Mutsuo Takashima、Yasufumi Hirata、Osamu Hasegawa、Shinji Usuda

  DOI：10.1021/jm00142a019

  日期：1981.10

  Three series of benzamides of N,N-disubstituted ethylenediamines (linear alkane-1,2-diamines), 1-substituted 2-(aminomethyl)pyrrolidines, and 1-substituted 3-aminopyrrolidines (cyclic alkane-1,2-diamines) were designed and synthesized as potential neuroleptics. All target compounds were evaluated for their inhibitory effects on apomorphine-induced stereotyped behavior in rats, and a good correlation between structure and activity was found throughout the series. In the linear series (analogues of metoclopramide), introduction of a benzyl group on the terminal nitrogen, rather than an ethyl group, and a methyl group on the p-amino group of metoclopramide both enhanced the activity. The resulting N-[2-(N-benzyl-N-methylamino)ethyl]-5-chloro-2-methoxy-4-(methylamino) benzamide(23) was about 15 times more active than metoclopramide. In the cyclic series, particularly among the benzamides of 1-benzyl-3-aminopyrrolidine, most of the compounds tested were more active than the corresponding linear benzamides. cis-N-(1-Benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino) benzamide (YM-09151-2, 55) was the most active among all of the compounds tested, being 13 and 408 times more potent than haloperidol and metoclopramide, respectively. Moreover, compound 55 exhibited a fairly high ratio of antistereotypic activity to cataleptogenicity compared with haloperidol and metoclopramide. It is expected that compound 55 may be used as a potent drug with few side effects in the treatment of psychosis.