N-tert-butyloxycarbonyl-N-methyl-4-chlorophenylalanine methyl ester | 182492-20-2

• 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: N-tert-butyloxycarbonyl-N-methyl-4-chlorophenylalanine methyl ester
• 英文别名: Methyl 3-(4-chlorophenyl)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoate
• CAS: 182492-20-2
• 化学式: C₁₆H₂₂ClNO₄
• 分子量: 327.808
• InChiKey: RYNHYNKJKGJKPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-tert-butyloxycarbonyl-N-methyl-4-chlorophenylalanine methyl ester 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 生成 2-(N-tert-butyloxycarbonyl-N-methyl)-amino-3-(4-chlorophenyl)-propionaldehyde
  参考文献：
  名称：

  Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

  摘要：

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00631-x
• 作为产物：
  描述：

  2-氨基-3-(4-氯苯基)丙酸甲酯 在 三乙胺 、 silver carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-tert-butyloxycarbonyl-N-methyl-4-chlorophenylalanine methyl ester
  参考文献：
  名称：

  Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

  摘要：

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00631-x

文献信息

• 1-aryl-2-acylamino-ethane compounds and their use as neurokinin
  申请人：Novartis AG

  公开号：US05929067A1

  公开（公告）日：1999-07-27

  1-Aryl-2-acylaminoethane compounds of formula I ##STR1## wherein R.sub.1 -R.sub.4, X and Am are as defined in the description, have valuable pharmaceutical properties and are especially effective as NK-1 antagonists.

  式I的1-芳基-2-酰氨基乙烷化合物具有有价值的药理特性，特别是作为NK-1拮抗剂特别有效，其中R.sub.1 -R.sub.4、X和Am如描述中定义。
• [EN] 1-ARYL-2-ACYLAMINO-ETHANE COMPOUNDS AND THEIR USE AS NEUROKININ ESPECIALLY NEUROKININ 1 ANTAGONISTS<br/>[FR] COMPOSES 1-ARYL-2-ACYLAMINO-ETHANE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DES NEUROKININES ET NOTAMMENT DES NEUROKININES 1
  申请人：NOVARTIS AG

  公开号：WO1996026183A1

  公开（公告）日：1996-08-29

  (EN) 1-Aryl-2-acylamino-ethane compounds of formula (I), wherein R1 is aryl or heteroaryl; R2 is hydrogen, lower alkyl or aryl-lower alkyl; R3 is hydrogen, lower alkyl, aryl or heteroaryl; R4 is aryl or heteroaryl; X is C1-C7alkylene, C2-C7 alkenyline or C4-C7 alkanedienylene, and Am is an unsubstituted or mono- or di-substituted amino group, a disubstituted amino group being understood as including also an amino group in which the amino nitrogen is bonded into a ring, or a salt thereof, have valuable pharmaceutical properties and are especially effective as NK1 antagonists. They are prepared in a manner known $i(per se).(FR) Composés 1-aryl-2-acylamino-éthane de la formule (I), ou un sel de ceux-ci, dans laquelle R1 représente aryle ou hétéroaryle; R2 représente hydrogène, alkyle inférieur ou aryle-alkyle inférieur; R3 représente hydrogène, alkyle inférieur, aryle ou hétéroaryle; R4 représente aryle ou hétéroaryle; X représente alkylène C1-C7, alcénylène C2-C7 ou alcanediénylène C4-C7, et Am représente un groupe amino non substitué ou mono ou disubstitué, un groupe amino disubstitué s'entendant comme comprenant également un groupe amino dans lequel l'amino azote est lié dans un noyau. Ces composés possèdent des propriétés pharmacologiques précieuses et ils sont notamment efficaces en tant qu'antagonistes des neurokinines 1 (NK1). On les prépare d'une manière connue en soi.

  1-基团后的有机化学化合物合成方法已知。这种化合物的分子式为(I)，其中，R1代表芳香基或杂芳香基；R2代表氢、低级碳饱和烃基或芳香基-低级碳饱和烃基；R3代表氢、低级碳饱和烃基、芳香基或杂芳香基；R4代表芳香基或杂芳香基；X代表C1-C7烯基、C2-C7 cis-烯基或C4-C7二烯烯基；Am代表未取代、单取代或双取代的氨基团，侧链氨基或环状结构氨基亦可被含环氨基取代，或作为相应的盐类。它们具有重要的医药性质，并且特别有效作为NK1受体拮抗剂（NK1 antagonist）。以已知的方法合成这些化合物。
• 1-ARYL-2-ACYLAMINO-ETHANE COMPOUNDS AND THEIR USE AS NEUROKININ ESPECIALLY NEUROKININ 1 ANTAGONISTS
  申请人：Novartis AG

  公开号：EP0810991A1

  公开（公告）日：1997-12-10
• US5929067A
  申请人：——

  公开号：US5929067A

  公开（公告）日：1999-07-27
• Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides
  作者：Marc Gerspacher、Luigi La Vecchia、Robert Mah、Andreas von Sprecher、Gary P. Anderson、Natarajan Subramanian、Kathleen Hauser、Heinrich Bammerlin、Sabine Kimmel、Viviane Pawelzik、Karin Ryffel、Howard A. Ball

  DOI：10.1016/s0960-894x(01)00631-x

  日期：2001.12

  Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)- 3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK2 affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3- yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK2 receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK1/NK2 antagonist. (C) 2001 Elsevier Science Ltd. All rights reserved.