N-(1-Aminooxalyl-pentyl)-2-[(E)-2-(4-dimethylaminomethyl-phenyl)-vinyl]-benzamide | 709608-70-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-(1-Aminooxalyl-pentyl)-2-[(E)-2-(4-dimethylaminomethyl-phenyl)-vinyl]-benzamide
• 英文别名: A-705239 free base；N-(1-amino-1,2-dioxoheptan-3-yl)-2-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]benzamide
• CAS: 709608-70-8
• 化学式: C₂₅H₃₁N₃O₃
• 分子量: 421.539
• InChiKey: IQBMKJFMQJTTKQ-FOCLMDBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-硝基戊烷 在 palladium on activated charcoal 盐酸 、 二氯乙酸 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 65.0h， 生成 N-(1-Aminooxalyl-pentyl)-2-[(E)-2-(4-dimethylaminomethyl-phenyl)-vinyl]-benzamide
  参考文献：
  名称：

  Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability

  摘要：

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.

  DOI：

  10.1021/jm0210717

文献信息

• Novel substituted amides, their preparation and use
  申请人：Abbott GmbH & Co., KG

  公开号：US20040082569A1

  公开（公告）日：2004-04-29

  An amide of the formula I 1 and its tautomeric forms, possible enantiomeric and diastereomeric forms, E and Z forms, and possible physiologically tolerated salts, in which the variables have the following meanings: A —(CH 2 ) p —R 1 , where R 1 can be pyrrolidine [sic], morpholine [sic], piperidine [sic], —NR 5 R 6 and 2 and R 5 , R 6 and R 7 can, independently of one another, be hydrogen, C 1 -C 4 -alkyl, CH 2 Ph, Ph, CH 2 CH 2 Ph, it also being possible for the phenyl rings to be substituted by R 6 , and p can be 1 and 2, and B can be phenyl [sic], pyridyl [sic], pyrimidyl [sic] and pyridazyl [sic], it also being possible for the rings to be substituted by up to 2 R 8 radicals, and D can be a bond, —(CH 2 ) m —, —CH═CH—, —C≡C—, and R 2 is chlorine, bromine, fluorine, C 1 -C 6 -alkyl, NHCO—C 1 -C 4 -alkyl, NHSO 2 —C 1 -C 4 -alkyl, NO 2 , —O—C 1 -C 4 -alkyl and NH 2 , and R 3 is —C 1 -C 6 -alkyl, branched or unbranched, and which may also carry a phenyl ring, indolyl ring or cyclohexyl ring which is in turn substituted by by [sic] a maximum of two R 8 radicals, where R 8 is hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, I, CF 3 , NO 2 , NH 2 , CN, COOH, COO—C 1 -C 4 -alkyl, NHCO—C 1 -C 4 -alkyl, —NHSO 2 -C 1 C 4 -alkyl and —SO 2 —C 1 -C 4 -alkyl; and Y is phenyl [sic], pyridine, pyrimidine and pyrazine and R 4 is hydrogen, COOR 9 and CO-Z in which Z is NR 10 R 11 and 3 R 9 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and R 10 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which itself may also be substituted by one or two R 12 radicals, and 4 R 11 is hydrogen, C 1 -C 6 -alkyl, branched or unbranched, which may also be and [sic] substituted by a phenyl ring which may also carry an R 9 radical, and R 12 can be hydrogen, C 1 -C 4 -alkyl, branched or unbranched, —O—C 1 -C 4 -alkyl, OH, Cl, F, Br, I, CF 3 , NO 2 , NH 2 , CN, COOH, COO—C 1 -C 4 -alkyl, —NHCO—C 1 -C 4 -alkyl, —NHCO-phenyl, —NHSO 2 —C 1 -C 4 -alkyl, NHSO 2 -phenyl, —SO 2 —C 1 -C 4 -alkyl and —SO 2 -phenyl, R 13 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and R 14 is hydrogen, C 1 -C 6 -alkyl, linear or branched, and which may [lacuna] substituted by a phenyl ring which may itself also be substituted by one or two R 12 radicals, and n is a number 0, 1 or 2, and m,q are, independently of one another, a number 0, 1, 2, 3 or 4.

  公式I1的酰胺及其互变异构体、可能的对映异构体和顺反异构体、E和Z形式，以及可能的生理耐受盐，其中变量具有以下含义：A -（CH2）p-R1，其中R1可以是吡咯烷、吗啉、哌啶、-NR5R6和2，而R5、R6和R7可以独立地是氢、C1-C4-烷基、CH2Ph、Ph、CH2CH2Ph，苯环也可以被R6取代，p可以是1和2，B可以是苯、吡啶、嘧啶和吡嗪，环也可以被最多2个R8基团取代，D可以是键、（CH2）m、CH=CH、C≡C，R2是氯、溴、氟、C1-C6-烷基、NHCO-C1-C4-烷基、NHSO2-C1-C4-烷基、NO2、O-C1-C4-烷基和NH2，R3是C1-C6-烷基、支链或非支链，也可以携带苯环、吲哚环或环己烷环，该环可以被最多两个R8基团取代，其中R8是氢、C1-C4-烷基、支链或非支链、O-C1-C4-烷基、OH、Cl、F、Br、I、CF3、NO2、NH2、CN、COOH、COO-C1-C4-烷基、NHCO-C1-C4-烷基、NHSO2-C1C4-烷基和-SO2-C1-C4-烷基；Y是苯、吡啶、嘧啶和吡嗪，R4是氢、COOR9和CO-Z，其中Z是NR10R11和3，R9是氢、C1-C6-烷基、线性或支链，也可以被一个苯环取代，该苯环本身也可以被一个或两个R12基团取代，R10是氢、C1-C6-烷基、线性或支链，也可以被一个苯环取代，该苯环本身也可以被一个或两个R12基团取代，4R11是氢、C1-C6-烷基、支链或非支链，也可以被一个苯环取代，该苯环也可以携带一个R9基团，R12可以是氢、C1-C4-烷基、支链或非支链、O-C1-C4-烷基、OH、Cl、F、Br、I、CF3、NO2、NH2、CN、COOH、COO-C1-C4-烷基、NHCO-C1-C4-烷基、NHCO-苯基、NHSO2-C1-C4-烷基、NHSO2-苯基、SO2-C1-C4-烷基和SO2-苯基，R13是氢、C1-C6-烷基、线性或支链，也可以被一个苯环取代，该苯环本身也可以被一个或两个R12基团取代，R14是氢、C1-C6-烷基、线性或支链，也可以被一个苯环取代，该苯环本身也可以被一个或两个R12基团取代，n是0、1或2，m、q独立地是0、1、2、3或4的数字。
• NEUE SUBSTITUIERTE AMIDE, DEREN HERSTELLUNG UND ANWENDUNG
  申请人：Abbott GmbH & Co. KG

  公开号：EP1073641B1

  公开（公告）日：2004-04-14
• US7276500B2
  申请人：——

  公开号：US7276500B2

  公开（公告）日：2007-10-02
• US7956093B2
  申请人：——

  公开号：US7956093B2

  公开（公告）日：2011-06-07
• [DE] VERWENDUNG VON CYSTEINPROTEASE-INHIBITOREN ZUR BEHANDLUNG VON ERKRANKUNGEN<br/>[EN] USE OF CYSTEINE PROTEASE-INHIBITORS FOR TREATING ILLNESSES<br/>[FR] UTILISATION D'INHIBITEURS DE LA CYSTEINE PROTEASE POUR LE TRAITEMENT DE MALADIES PULMONAIRES
  申请人：ABBOTT GMBH & CO KG

  公开号：WO2003080182A1

  公开（公告）日：2003-10-02

  Die vorliegende Erfindung betrifft die Verwendung von Cysteinprotease-Inhibitoren, insbesondere Calpain-Inhibitoren zur Herstellung eines pharmazeutischen Mittels zur Behandlung von Erkrankungen der Lunge, insbesondere Adult Respiratory Distress Syndrome (ARDS).