2-[(4-苄基-2-吗啉基)甲基]-1H-异吲哚-1,3(2H)-二酮 | 110859-48-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 2-[(4-苄基-2-吗啉基)甲基]-1H-异吲哚-1,3(2H)-二酮
• 英文名称: N-[(4-benzyl-2-morpholinyl)methyl]phthalimide
• 英文别名: N-<(4-benzyl-2-morpholinyl)methyl>phthalimide；4-benzyl-2-(phthalimidomethyl)morpholine；2-phthalimidomethyl-4-benzylmorpholine；4-benzyl-2-phthalimidomethylmorpholine；2-{[(2R,S)-4-(phenylmethyl)-2-morpholinyl]methyl}-1H-isoindole-1,3(2H)-dione；2-(4-benzylmorpholine-2-yl)methylphthalimide；2-[(4-Benzylmorpholin-2-yl)methyl]isoindoline-1,3-dione；2-[(4-benzylmorpholin-2-yl)methyl]isoindole-1,3-dione
• CAS: 110859-48-8
• 化学式: C₂₀H₂₀N₂O₃
• mdl: MFCD11101104
• 分子量: 336.39
• InChiKey: YAQSVEHQDFSDCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-[(4-苄基-2-吗啉基)甲基]-1H-异吲哚-1,3(2H)-二酮 在 palladium on activated charcoal 一水合肼 、 三乙胺 作用下， 以 乙醇 、 异丙醇 、 甲苯 、 乙腈 为溶剂， 反应 17.0h， 生成
  参考文献：
  名称：

  Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships

  摘要：

  A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro- 1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.

  DOI：

  10.1021/jm00062a007
• 作为产物：
  描述：

  N-苄基乙醇胺 在 硫酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2-[(4-苄基-2-吗啉基)甲基]-1H-异吲哚-1,3(2H)-二酮
  参考文献：
  名称：

  新型苯甲酰胺作为选择性和有效的胃动力剂。1. N-[（2-吗啉基）烷基]苯甲酰胺的合成及其构效关系。

  摘要：

  为了获得比甲氧氯普胺（1）更有效和选择性的胃动力，合成了一系列新的N-[（2-吗啉基）烷基]苯甲酰胺（17-52），并通过测定对胃泌素的作用来评估其胃动力。大鼠和小鼠胃中酚红半固体粉和树脂颗粒固体粉的胃排空。考虑到西沙必利（2）的侧链结构后，新设计了吗啉基部分，并与甲氧氯普胺和西沙必利的4-氨基-5-氯-2-甲氧基苯甲酰基偶联时产生了所需的活性。苯甲酰基的取代基的改性显着影响了活性。特别是，

  DOI：

  10.1021/jm00167a020

文献信息

• Pyrimidine derivatives
  申请人：Nisshin Flour Milling Co., Ltd.

  公开号：US05736550A1

  公开（公告）日：1998-04-07

  Pyrimidine derivatives useful as a gastrointestinal prokinetic agent, represented by formula ##STR1## wherein X is O or NR.sup.5, Y is O, S or NR.sup.5 wherein R.sup.5 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.1 and R.sup.2 may be the same or different and each is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.3 is CN, or COOR.sup.6 wherein R.sup.6 is a C.sub.1 -C.sub.6 alkyl group, a C.sub.3 -C.sub.6 cycloalkyl group, an aryl group or the like; R.sup.4 is --SR.sup.7 or --NR.sup.8 R.sup.9 wherein R.sup.7 is a C.sub.1 -C.sub.6 alkyl group; R.sup.8 is a C.sub.1 -C.sub.6 alkyl group or the like; R.sup.9 is a hydrogen atom, a C.sub.1 -C.sub.6 alkyl group or the like, or R.sup.8 and R.sup.9 may represent, together with the nitrogen atom to which they are attached, an N-substituted piperazine ring of formula (X) ##STR2## wherein R.sup.10 represents a C.sub.1 -C.sub.6 alkyl group or the like or a pharmacologically acceptable salt thereof. The above-mentioned compounds are useful as a gastrointestinal prokinetic agent used for the therapy of digestive tract diseases.

  嘧啶衍生物可用作胃肠促动力药物，其化学式表示为##STR1##其中X为O或NR.sup.5，Y为O、S或NR.sup.5，其中R.sup.5为氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.1和R.sup.2可以相同也可以不同，每个都是氢原子、C.sub.1 -C.sub.6烷基或类似物；R.sup.3为CN，或COOR.sup.6，其中R.sup.6为C.sub.1 -C.sub.6烷基、C.sub.3 -C.sub.6环烷基、芳基或类似物；R.sup.4为--SR.sup.7或--NR.sup.8 R.sup.9，其中R.sup.7为C.sub.1 -C.sub.6烷基；R.sup.8为C.sub.1 -C.sub.6烷基或类似物；R.sup.9为氢原子、C.sub.1 -C.sub.6烷基或类似物，或R.sup.8和R.sup.9可以与它们连接的氮原子一起表示为化学式(X)的N-取代哌嗪环，其中R.sup.10代表C.sub.1 -C.sub.6烷基或类似物，或其药理学上可接受的盐。上述化合物可用作治疗消化道疾病的胃肠促动力药物。
• Substituted benzamide derivatives, for enhancing gastrointestinal
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04870074A1

  公开（公告）日：1989-09-26

  Compounds of the formula: ##STR1## wherein R is hydrogen, alkoxycarbonyl, benzyloxycarbonyl, heteroarylalkyl, phenylalkenyl, or --T--(Y).sub.p --R.sub.6 (wherein T is single bond or alkylene, Y is oxygen, sulfur or carbonyl, R.sub.6 is phenyl, substituted phenyl, naphthyl, or diphenylmethyl, and p is 0 or 1, provided that when T is single bond, p is 0); R.sub.1 is halogen, hydroxy, alkoxy, cycloalkyloxy, alkenyloxy, alkynyloxy, alkoxy interrupted by oxygen or carbonyl, alkylthio, amino, monosubstituted amino, or a substituted alkoxy; R.sub.2 is hydrogen; R.sub.3 is hydrogen, halogen, amino, alkylamino, dialkylamino, alkanoylamino, or nitro; R.sub.4 is hydrogen, halogen, nitro, sulfamoyl, alkylsulfamoyl, or dialkylsulfamoyl; or any two adjacent groups of the R.sub.1, R.sub.2, R.sub.3 and R.sub.4 may combine to form alkylenedioxy, and the remaining two groups are each hydrogen; R.sub.5 is hydrogen or alkyl; X is alkylene; m and n are each 1 or 2; provided that at least one of the groups R.sub.2, R.sub.3 and R.sub.4 is other than hydrogen, and acid addition salts, quaternary ammonium salts and N-oxide derivatives thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds, salts and N-oxide derivatives thereof show excellent gastrointestinal motility enhancing activity.

  式中R为氢、烷氧羰基、苄氧羰基、杂环烷基、苯基烯基，或--T--(Y).sub.p --R.sub.6（其中T为单键或烷基，Y为氧、硫或羰基，R.sub.6为苯基、取代苯基、萘基或二苯甲基，p为0或1，但当T为单键时，p为0）；R.sub.1为卤素、羟基、烷氧基、环烷氧基、烯基氧基、炔基氧基、被氧或羰基中断的烷氧基、烷基硫醚、氨基、单取代氨基，或取代烷氧基；R.sub.2为氢；R.sub.3为氢、卤素、氨基、烷基氨基、二烷基氨基、烷酰氨基，或硝基；R.sub.4为氢、卤素、硝基、磺酰胺基、烷基磺酰胺基，或二烷基磺酰胺基；或R.sub.1、R.sub.2、R.sub.3和R.sub.4中的任意两个相邻基团可结合形成亚烷二氧基，其余两个基团各为氢；R.sub.5为氢或烷基；X为烷基；m和n各为1或2；但R.sub.2、R.sub.3和R.sub.4中至少有一个基团不是氢，以及其酸盐、季铵盐和N-氧化物衍生物，其制备方法，以及含有它们的药物组合物。所述化合物、盐及其N-氧化物衍生物表现出优异的胃肠动力增强活性。
• AMIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：Kato Shiro

  公开号：US20100249399A1

  公开（公告）日：2010-09-30

  Disclosed is a compound having a strong affinity to serotonin-4 receptors, which is useful as an enterokinesis-promoting agent or a digestive tract function-improving agent. Specifically, disclosed is a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof. Also specifically disclosed is a pharmaceutical composition containing a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof. [In Formula (1), Ar represents a group represented by Formula (Ar-1) or Formula (Ar-2).]

  揭示了一种具有强烈亲和力的化合物，对5-羟色胺-4受体具有亲和力，可用作促进肠动力或改善消化道功能的药剂。具体地，揭示了一种由化学式（1）表示的化合物或其药学上可接受的盐。还具体揭示了一种含有由化学式（1）表示的化合物或其药学上可接受的盐的药物组合物。【在化学式（1）中，Ar代表由化学式（Ar-1）或化学式（Ar-2）表示的基团。】
• Quinolonecarboxylic acid compounds and pharmaceutical use thereof
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US04889857A1

  公开（公告）日：1989-12-26

  A quinolonecarboxylic acid compound of the formula: ##STR1## wherein R.sup.1 is an alkyl group, a cycloalkyl group, a haloalkyl group, an alkenyl group, mono- or di-alkylamino groups, a phenyl group or a phenyl group substituted by one to three substituents selected from the group consisting of a halogen atom, an alkyl group, an alkoxy group, a hydroxy group, a nitro group or an amino group, R.sup.2 is a hydrogen atom, an alkyl group, a cycloalkyl group, an acyl group or an alkoxycarbonyl group, R.sup.3 is a hydrogen atom, an alkyl group or an aralkyl group, or R.sup.2 and R.sup.3 together with the adjacent nitrogen atom form a heterocyclic ring, R.sup.4 is a hydrogen atom or an alkyl group, R.sup.5 is a hydrogen atom, an alkyl group, an aralkyl group or an ester residue which is readily hydrolyzable in vivo, X is a hydrogen atom, a halogen atom or an alkyl group, n is interger of 1 to 3, and a salt thereof, and pharmaceutical use thereof. The compounds exhibit antibacterial activites and are useful for the treatment of various infectious diseases.

  一种喹诺酮羧酸化合物，其结构式如上：##STR1##其中，R1为烷基、环烷基、卤代烷基、烯基、单或双烷基氨基、苯基或被一个至三个选自卤素、烷基、烷氧基、羟基、硝基或氨基的取代基取代的苯基；R2为氢、烷基、环烷基、酰基或烷氧羰基；R3为氢、烷基或芳烷基，或者R2和R3与相邻的氮原子一起形成杂环；R4为氢或烷基；R5为氢、烷基、芳烷基或体内易水解的酯残基；X为氢、卤素或烷基；n为1至3的整数；及其盐，以及其在医药上的用途。这些化合物具有抗菌活性，可用于治疗各种感染性疾病。
• Pyrimido[5,4-B][1,4]oxazine derivatives and pharmaceutical compositions
  申请人：Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt

  公开号：US04748175A1

  公开（公告）日：1988-05-31

  The invention relates to novel pyrimido [5,4-b][1,4]oxazine derivatives of the formula (I), and the acid addition salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the formula (I) ##STR1## wherein R.sup.1 stands for a C.sub.1-4 alkyl group; R.sup.2 stands for hydrogen or halogen or an azido group or an --NR.sup.5 R.sup.6 group, wherein R.sup.5 represents hydrogen or a benzyl group, or a C.sub.1-4 alkyl group unsubstituted or substituted by a hydroxyl group, R.sup.6 stands for hydrogen, an amino group, a C.sub.3-6 cycloalkyl group, a straight or branched-chain C.sub.1-4 alkyl group optionally substituted by a hydroxyl, mercapto, aminocarbonyl, furyl, 2-benzo[1,4]dioxanyl, di(C.sub.1-4 alkyl)amino group or by a phenyl or phenoxy group optionally mono- or polysubstituted by halogen or C.sub.1-4 alkoxy group (s) or by a 6-membered, saturated nitrogen-containing heterocycle optionally containing an additional nitrogen or oxygen atom and optionally substituted by a C.sub.1-4 alkyl or benzyl group; further NR.sup.5 R.sup.6 may also represents a 6-membered, saturated, nitrogen-containing heterocycle optionally containing an additional nitrogen or oxygen atom and optionally substituted by a C.sub.2-4 alkoxycarbonyl or C.sub.1-4 hydroxyalkyl group; R.sup.3 and R.sup.4 are the same or different and stand for hydrogen or a C.sub.1-4 alkyl group; R.sup.9 stands for hydrogen or a C.sub.1-4 alkyl group unsubstituted or monosubstituted by an oxo, cyano, aminocarbonyl, C.sub.2-5 alkoxycarbonyl, pyridiyl, morpholinocarbonyl, or phenyl group or mono- or polysubstituted by OH group(s), with the proviso that R.sup.2 is different from chlorine, 4-morpholinyl and piperidyl group when R.sup.9 stands for hydrogen; or R.sup.2 is different from chlorine and 4-morpholinyl group when R.sup.9 stands for a methyl or benzyl group. The compounds of the formula (I) are capable to increase the myocardial contractile force (the performance of the failing heart) and the coronary blood flow, thus they can therapeutically be used for the treatment of the chronic heart failure and coronary disturbances.

  该发明涉及一种新型嘧啶并[5,4-b][1,4]噁嗪衍生物的公式(I)，以及其酸盐，含有它们的药物组合物和其制备方法。在公式(I)中，其中R^1代表一个C.sub.1-4烷基基团；R^2代表氢或卤素或偶氮基或--NR^5R^6基团，其中R^5代表氢或苄基团，或一个未取代或取代的C.sub.1-4烷基基团，R^6代表氢，氨基，C.sub.3-6环烷基基团，直链或支链的C.sub.1-4烷基基团，可选地取代羟基，巯基，氨基羰基，呋喃基，2-苯并[1,4]二氧杂基，二(C.sub.1-4烷基)氨基基团或由卤素或C.sub.1-4烷氧基基团单取代或多取代的苯基或苯氧基，或由含氮的饱和6-成员杂环取代的苯基或苯氧基；进一步NR^5R^6也可以表示含有额外氮或氧原子并可选地取代C.sub.1-4烷基或苄基的含氮饱和6-成员杂环；R^3和R^4相同或不同，代表氢或C.sub.1-4烷基基团；R^9代表氢或未取代或单取代的C.sub.1-4烷基基团，氧代脂肪酰基，氰基，氨基羰基，C.sub.2-5烷氧基羰基，吡啶基，吗啉基羰基或苯基或由OH基取代的单取代或多取代的羟基，条件是当R^9代表氢时，R^2与氯，4-吗啉基和哌啶基不同；或当R^9代表甲基或苄基时，R^2与氯和4-吗啉基不同。公式(I)化合物能够增加心肌收缩力（衰竭心脏的性能）和冠状血流，因此它们可以用于治疗慢性心力衰竭和冠状动脉障碍。