acetylamino-(3,4-dichloro-benzyl)-malonic acid diethyl ester | 114872-55-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: acetylamino-(3,4-dichloro-benzyl)-malonic acid diethyl ester
• 英文别名: Acetylamino-(3,4-dichlor-benzyl)-malonsaeure-diaethylester；Ethyl-2-acetamido-2-carbethoxy-3-(3,4-dichlorophenyl)propionate；diethyl (3,4-Dichlorobenzyl)acetamidomalonate；diethyl 2-acetamido-2-[(3,4-dichlorophenyl)methyl]propanedioate
• CAS: 114872-55-8
• 化学式: C₁₆H₁₉Cl₂NO₅
• 分子量: 376.237
• InChiKey: PVAUVBQOBQVDSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  acetylamino-(3,4-dichloro-benzyl)-malonic acid diethyl ester 在 氢溴酸 作用下， 生成 3,4-二氯苯丙氨酸
  参考文献：
  名称：

  Synthesis of Phenylalanine Analogs as Antimetabolites

  摘要：

  DOI：

  10.1021/ja01145a022
• 作为产物：
  描述：

  2-氯-4-甲基苯胺 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 亚硝酸特丁酯 、 硫酸 、 硝酸 、 乙酸酐 、 铁粉 、 sodium hydride 、 copper dichloride 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 24.92h， 生成 acetylamino-(3,4-dichloro-benzyl)-malonic acid diethyl ester
  参考文献：
  名称：

  3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

  摘要：

  On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.021

文献信息

• Aromatic compounds, pharmaceutical compositions containing them and
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US05472978A1

  公开（公告）日：1995-12-05

  Compounds of formula (I), and salts and prodrugs thereof, wherein Q represents optionally substituted phenyl, naphthyl, indolyl, benzothiophenyl, benzofuranyl, benzyl or indazolyl; Z represents O, S or NR.sup.8 ; X and Y are H or are together .dbd.O; R.sup.1 and R.sup.2 are H; optionally substituted C.sub.1-6 alkyl; optionally substituted phenyl(C.sub.1-4 alkyl); COR.sup.c ; CO.sub.2 R.sup.c ; CONR.sup.c R.sup.d ; CONR.sup.c COOR.sup.d ; or SO.sub.2 R.sup.c ; R.sup.3 is H or C.sub.1-6 alkyl, R.sup.4 is H , C.sub.1-6 alkyl or optionally substituted phenyl; and R.sup.5 represents optionally substituted phenyl; are tachykinin antagonists. They and compositions thereof are useful in therapy.

  式(I)的化合物，以及其盐和前药，其中Q代表可选择地取代的苯基、萘基、吲哚基、苯并噻吩基、苯并呋喃基、苄基或吲唑基；Z代表O、S或NR.sup.8；X和Y为H或一起.dbd.O；R.sup.1和R.sup.2为H；可选择地取代的C.sub.1-6烷基；可选择地取代的苯基(C.sub.1-4烷基)；COR.sup.c；CO.sub.2R.sup.c；CONR.sup.cR.sup.d；CONR.sup.cCOOR.sup.d；或SO.sub.2R.sup.c；R.sup.3为H或C.sub.1-6烷基，R.sup.4为H，C.sub.1-6烷基或可选择地取代的苯基；R.sup.5代表可选择地取代的苯基；它们是缓激肽拮抗剂。它们及其组合物在治疗中是有用的。
• Hetercyclic compounds, processes for their preparation and
  申请人：Merck Sharpe & Dohme, Ltd.

  公开号：US05328927A1

  公开（公告）日：1994-07-12

  Compounds of formula (I), and salts and prodrugs thereof ##STR1## wherein Q.sup.1 is halo substituted phenyl; naphthyl; indolyl; benzthiophenyl; benzofuranyl; benzyl; or fluorenyl; . . is an optional covalent bond; one of X and Y is H and the other is hydroxy or C.sub.1-6 alkoxy, or X and Y are together .dbd.0 or .dbd.NOR.sup.5 ; R.sup.1 and R.sup.2 are H; C.sub.1-6 alkyl optionally substituted by hydroxy, cyano, COR.sup.c, CO.sub.2 R.sup.c, CONR.sup.c R.sup.d, or NR.sup.c R.sup.d (where R.sup.c and R.sup.d are H, C.sub.1-6 alkyl or phenyl(C.sub.0-4 alkyl) optionally substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo and trifluoromethyl); phenyl(C.sub.1-4 alkyl) (optionally substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo or trifluoromethyl); COR.sup.c ; CO.sub.2 R.sup.c ; CONR.sup.c R.sup.d ; COC.sub.1-6 alkylNR.sup.c R.sup.d ; CONR.sup.c COOR.sup.d ; or SO.sub.2 R.sup.c ; R.sup.3 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; and R.sup.4 is phenyl optionally substituted by C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, OR.sup.a, SR.sup.a, SOR.sup.a, NR.sup.a R.sup.b, NR.sup.a COR.sup.b, NR.sup.a CO.sub.2 R.sup.b, CO.sub.2 R.sup.a or CONR.sup.a R.sup.b, where R.sup.a and R.sup.b are H, C.sub.1-6 alkyl, phenyl or trifluoromethyl; are tachykinin antagonists.

  化合物的公式（I），以及其盐和前药，其中Q.sup.1是卤代苯基；萘基；吲哚基；苯并噻吩基；苯并呋喃基；苄基；或芴基；. . 是一个可选的共价键；X和Y中的一个是H，另一个是羟基或C.sub.1-6烷氧基，或X和Y在一起.dbd.0或.dbd.NOR.sup.5；R.sup.1和R.sup.2是H；C.sub.1-6烷基，可选择地被羟基，氰基，COR.sup.c，CO.sub.2 R.sup.c，CONR.sup.c R.sup.d，或NR.sup.c R.sup.d（其中R.sup.c和R.sup.d是H，C.sub.1-6烷基或苯基（C.sub.0-4烷基）可选择地被C.sub.1-6烷基，C.sub.1-6烷氧基，卤素和三氟甲基取代）；苯基（C.sub.1-4烷基）（可选择地被C.sub.1-6烷基，C.sub.1-6烷氧基，卤素或三氟甲基取代）；COR.sup.c；CO.sub.2 R.sup.c；CONR.sup.c R.sup.d；COC.sub.1-6烷基NR.sup.c R.sup.d；CONR.sup.c COOR.sup.d；或SO.sub.2 R.sup.c；R.sup.3是H，C.sub.1-6烷基或C.sub.2-6烯基；R.sup.4是苯基，可选择地被C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，卤素，氰基，硝基，三氟甲基，三甲基硅基，OR.sup.a，SR.sup.a，SOR.sup.a，NR.sup.a R.sup.b，NR.sup.a COR.sup.b，NR.sup.a CO.sub.2 R.sup.b，CO.sub.2 R.sup.a或CONR.sup.a R.sup.b，其中R.sup.a和R.sup.b是H，C.sub.1-6烷基，苯基或三氟甲基；是催吐肽拮抗剂。
• PORTER, JOHN;DYKERT, JOHN;RIVIER, JEAN, INT. J. PEPTIDE AND PROTEIN RES., 30,(1987) N 1, 13-21
  作者：PORTER, JOHN、DYKERT, JOHN、RIVIER, JEAN

  DOI：——

  日期：——
• TAYLOR, DAVID C.;WIGHTMAN, R. H.;WIGHTMAN, F.;WAND, A. J., BIOORG. CHEM., 15,(1987) N 4, 335-345
  作者：TAYLOR, DAVID C.、WIGHTMAN, R. H.、WIGHTMAN, F.、WAND, A. J.

  DOI：——

  日期：——
• US5472978A
  申请人：——

  公开号：US5472978A

  公开（公告）日：1995-12-05