N-[2-(3,4-dichlorophenyl)-4-[(methylsulfonyl)oxy]butyl]-N-methyl benzamide | 142001-87-4

• 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: N-[2-(3,4-dichlorophenyl)-4-[(methylsulfonyl)oxy]butyl]-N-methyl benzamide
• 英文别名: N-[4-Methanesulphonyloxy-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide；N-[2-(3,4-Dichlorophenyl)-4-(methanesulphonyloxy)butyl]-N-methylbenzamide；1-N-Methylbenzoylamino-2-(3,4-dichlorophenyl)-4-mesyloxybutane；(-)-N-[4-Methanesulphonyloxy-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide；[4-[benzoyl(methyl)amino]-3-(3,4-dichlorophenyl)butyl] methanesulfonate
• CAS: 142001-87-4；142001-91-0
• 化学式: C₁₉H₂₁Cl₂NO₄S
• 分子量: 430.352
• InChiKey: XQCYMBCLCQRQJF-UHFFFAOYSA-N

物化性质

• 沸点：
  617.1±55.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-(3,4-dichlorophenyl)-4-[(methylsulfonyl)oxy]butyl]-N-methyl benzamide 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 50.0h， 生成
  参考文献：
  名称：

  Parallel-compound synthesis: Methodology for accelerating drug discovery

  摘要：

  Parallel compound synthesis enables large numbers of individual compounds to be prepared simultaneously using semiautomated techniques. This fast and efficient methodology has an important role to play in accelerating lead optimisation and hence the whole drug discovery process. The potential of this strategy to rapidly optimise chemical leads and provide structure-activity relationship (SAR) information was demonstrated in two therapeutic areas, antiviral agents (herpes simplex virus), and neurokinin-2 receptor antagonists. Copyright (C) 1996 Elsevier Science Ltd.

  DOI：

  10.1016/0968-0896(96)00058-2
• 作为产物：
  描述：

  1-氨基-2-(3,4-二氯苯基)-4-(四氢吡喃-2-氧基)丁烷 在 N-甲基吗啉 、 sodium hydride 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 43.0h， 生成 N-[2-(3,4-dichlorophenyl)-4-[(methylsulfonyl)oxy]butyl]-N-methyl benzamide
  参考文献：
  名称：

  CARBOXY SUBSTITUTED CARBOXAMIDE DERIVATIVES AS TACHYKININ RECEPTOR ANTAGONISTS

  摘要：

  公开号：

  EP1077942B1

文献信息

• Substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl)
  申请人：Hoechst Marion Roussel, Inc.

  公开号：US05932571A1

  公开（公告）日：1999-08-03

  The present invention relates to novel N-methyl-N-(4-(4-(1H-benzimidazol-2-yl)\x9b1,4!diazepan-1-yl)-2-(aryl)butyl)b enzamide derivatives of the formula: ##STR1## stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

  本发明涉及新型N-甲基-N-(4-(4-(1H-苯并咪唑-2-基)\x9b1,4!二氮杂环己烷-1-基)-2-(芳基)丁基)苯酰胺衍生物的公式：##STR1## 其立体异构体，以及其药学上可接受的盐，可用作组胺受体拮抗剂和速激肽受体拮抗剂。这类拮抗剂在过敏性鼻炎的治疗中很有用，包括季节性鼻炎和鼻窦炎；炎症性肠病，包括克罗恩病和溃疡性结肠炎；哮喘；支气管炎；以及呕吐。
• Carboxy substituted acylic carboxamide derivatives
  申请人：Aventis Pharmaceuticals Inc.

  公开号：US06316445B1

  公开（公告）日：2001-11-13

  The present invention relates to novel carboxy substituted acyclic carboxamide derivatives of formula (1)): and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.

  本发明涉及新型的带有羧基取代的无环羧酰胺衍生物（化学式（1））及其立体异构体和药学上可接受的盐，以及它们作为速激肽受体拮抗剂的用途。这类拮抗剂在治疗包括哮喘、咳嗽和支气管炎在内的速激肽介导的疾病和症状中很有用。
• Arylalkylamines, process for preparing them and pharmaceutical
  申请人：Sanofi

  公开号：US05236921A1

  公开（公告）日：1993-08-17

  The invention relates to compounds of formula: ##STR1## in which Y represents--either a group Cy--N in which Cy represents a phenyl, optionally substituted; a C.sub.3 -C.sub.7 cycloalkyl group; a pyrimidinyl group or a pyridyl group; or a group ##STR2## in which Ar represents a phenyl, optionally substituted, a pyridyl group; a thienyl group; x is zero or one; X represents a hydroxyl, a C.sub.1 -C.sub.4 alkoxy; a hydroxyalkyl; a C.sub.1 -C.sub.4 acyloxy; a phenacyloxy; a carboxyl; a C.sub.1 -C.sub.4 carbalkoxy; a cyano; an aminoalkylene; a group --N--(X.sub.1).sub.2 in which the groups X.sub.1 independently represent hydrogen, a C.sub.1 -C.sub.4 alkyl; a group ##STR3## in which Alk represents a C.sub.1 -C.sub.6 alkyl; a group ##STR4## in which the Alk.sub.1 is a C.sub.1 -C.sub.3 alkylene and Alk'.sub.1 is a C.sub.1 -C.sub.3 alkyl; a C.sub.1 -C.sub.4 acyl; a group --S--X.sub.2 in which X.sub.2 represents hydrogen or a C.sub.1 -C.sub.4 alkyl group; or alternatively X forms a double bond with the carbon atom to which it is linked and with the adjacent carbon atom in the heterocycle; m is 2 or 3; Ar' represents a phenyl, optionally substituted; a thienyl; a benzothienyl; a naphthyl; an indolyl; an indolyl N-substituted with a C.sub.1 -C.sub.3 alkyl; R represents hydrogen, a C.sub.1 -C.sub.4 alkyl; T represents a group selected from --C(O)-- and --C(W)--NH-- W being an oxygen or sulphur atom, and Z represents either hydrogen, or M or OM when T represents a --C(O)-- group, or M when T represents a group--C(W)--NH; M represents a C.sub.1 -C.sub.6 alkyl; a phenylalkyl, a pyridyl alkyl; a naphthylalkyl; a pyridylthioalkyl; a styryl; or one of its salts with inorganic or organic acids.

  该发明涉及以下结构的化合物：##STR1##其中Y代表--一个基团Cy--N，其中Cy代表一个苯基，可选择性地取代；一个C.sub.3 -C.sub.7环烷基基团；一个嘧啶基团或吡啶基团；或一个基团##STR2##其中Ar代表一个苯基，可选择性取代，一个吡啶基团；一个噻吩基团；x为零或一；X代表一个羟基，一个C.sub.1 -C.sub.4烷氧基；一个羟基烷基；一个C.sub.1 -C.sub.4酰氧基；一个苯乙酰氧基；一个羧基；一个C.sub.1 -C.sub.4羰基氧基；一个氰基；一个氨基烷基；一个基团--N--(X.sub.1).sub.2，其中基团X.sub.1独立地代表氢，一个C.sub.1 -C.sub.4烷基；一个基团##STR3##其中Alk代表一个C.sub.1 -C.sub.6烷基；一个基团##STR4##其中Alk.sub.1是一个C.sub.1 -C.sub.3烷基烯和Alk'.sub.1是一个C.sub.1 -C.sub.3烷基；一个C.sub.1 -C.sub.4酰基；一个基团--S--X.sub.2，其中X.sub.2代表氢或一个C.sub.1 -C.sub.4烷基基团；或者X形成与其连接的碳原子和杂环中相邻碳原子的双键；m为2或3；Ar'代表一个苯基，可选择性取代；一个噻吩基；一个苯并噻吩基；一个萘基；一个吲哚基；一个N-烷基取代的吲哚基；R代表氢，一个C.sub.1 -C.sub.4烷基；T代表从--C(O)--和--C(W)--NH--中选择的一个基团，其中W是氧或硫原子，Z代表氢，或当T代表一个--C(O)--基团时为M或OM，或当T代表一个基团--C(W)--NH时为M；M代表一个C.sub.1 -C.sub.6烷基；一个苯基烷基，一个吡啶基烷基；一个萘基烷基；一个吡啶硫基烷基；一个苯乙烯基；或其与无机或有机酸的盐之一。
• Spiro-Substituted Piperidines as Neurokinin Receptor Antagonists. II. Syntheses and NK2 Receptor-Antagonistic Activities of N-(2-Aryl-4-(spiro-substituted piperidin-1'-yl)butyl)carboxamides.
  作者：Hirokazu KUBOTA、Akio KAKEFUDA、Hitoshi NAGAOKA、Osamu YAMAMOTO、Ken IKEDA、Makoto TAKEUCHI、Tadao SHIBANUMA、Yasuo ISOMURA

  DOI：10.1248/cpb.46.242

  日期：——

  In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-(spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10-9M. Among these compounds, (±)-1'-[4-(N-benzoyl-N-methylamino)-3-(3, 4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2-oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84nM, respectively). It showed more potent inhibitory activity (ID50 20μg/kg (i.v.)) against [β-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41μg/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41μg/kg.

  在我们对作为神经激肽受体拮抗剂的螺旋化合物的研究中，基于YM-35375 (3)作为先导化合物，设计了N-[2-芳基-4-(螺旋取代吡啶-1'-基)丁基]羧酰胺，并评估了其对NK2受体的拮抗活性。一些衍生物以IC50值在10^-9M水平上抑制了放射性标记的神经激肽A与NK2受体结合。在这些化合物中，(±)-1'-[4-(N-苯甲酰-N-甲基氨基)-3-(3, 4-二氯苯基)丁基]螺[苯并[c]噻吩-1(3H), 4'-吡啶] 2-氧化物 (58，YM-38336) 的NK2受体结合亲和力比化合物3强10倍 (IC50值分别为8.9和84nM)。该化合物对由[β-Ala8]-NKA(4-10)诱导的豚鼠支气管收缩表现出更强的抑制活性 (ID50 20μg/kg (静脉注射))，相比之下化合物3的ID50为41μg/kg (静脉注射)。在同一模型中，该化合物在十二指肠给药时也显示出有效性，ID50值为0.41μg/kg。
• Substituted N-methyl-N-(4-(4-(1H-Benzimidazol-2-YL-amino)
  申请人：Hoechst Marion Roussel, Inc.

  公开号：US05922737A1

  公开（公告）日：1999-07-13

  The present invention relates to novel substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)-2-(aryl)butyl )benzamide derivatives of the formula: ##STR1## stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

  本发明涉及一种新型的取代N-甲基-N-(4-(4-(1H-苯并咪唑-2-基氨基)哌啶-1-基)-2-(芳基)丁基)苯甲酰衍生物，其化学式为：##STR1## 其立体异构体，以及其药学上可接受的盐，可用作组胺受体拮抗剂和催吐受体拮抗剂。这些拮抗剂在过敏性鼻炎的治疗中有用，包括季节性鼻炎和鼻窦炎；炎症性肠道疾病，包括克罗恩病和溃疡性结肠炎；哮喘；支气管炎；以及呕吐。