4-[(S)-2-methylsulfinyl-4-fluorophenyl]piperidine | 263863-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[(S)-2-methylsulfinyl-4-fluorophenyl]piperidine
• 英文别名: 4-[4-fluoro-2-[(S)-methylsulfinyl]phenyl]piperidine
• CAS: 263863-22-5
• 化学式: C₁₂H₁₆FNOS
• 分子量: 241.33
• InChiKey: KKAQNNGAAUEDSX-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  48.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(S)-2-methylsulfinyl-4-fluorophenyl]piperidine 、 N-[2-(S)-(3,4-dichlorophenyl)-4-oxobutyl]-N-methyl-3-cyano-1-naphthamide 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以99%的产率得到N-[2-(S)-(3,4-dichlorophenyl)-4-[4-[4-fluoro-(S)-2-methylsulfinylphenyl]-1-piperidinyl]butyl]-N-methyl-3-cyano-1-naphthamide
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i
• 作为产物：
  描述：

  2-溴-5-氟苯酚 在 三乙烯二胺 、 titanium(IV) isopropylate 、 三乙基硅烷 、 叔丁基过氧化氢 、 氢氧化钾 、 正丁基锂 、 D-(-)-酒石酸二乙酯 、 potassium carbonate 、 三氟乙酸 、 N,N-二乙基苯胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[(S)-2-methylsulfinyl-4-fluorophenyl]piperidine
  参考文献：
  名称：

  Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity

  摘要：

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.

  DOI：

  10.1021/jm020094i

文献信息

• Naphthalenecarboxamides as tachykinin receptor antagonists
  申请人：AstraZeneca AB

  公开号：EP1433783A2

  公开（公告）日：2004-06-30

  A compound having the formula (I) wherein R1 is oxo, -ORa, -OC(=O)Rb; or (A); R2 is H; or R1 is -ORc and R2 is -ORd; or R1 and R2 together form -O(CH2)mO-; R3 is H or alkyl; R4, R5 and R6 are independently selected from hydroxy, cyano, nitro, trifluoromethoxy, trifluoromethyl, alkylsulfonyl, halo, alkoxy, alkyl, cyanoalkyl, alkenyl, alkynyl, carboxy, alkoxy-carbonyl, carbamoyl, alkylcarbamoyl, di-alkylcarbamoyl, alkanoyl, alkanoylamino, aminosulfonyl, and substituted alkyl; or R4 and R5 together form -OCH2O- or -OC(CH3)2O-; R6 may additionally be hydrogen; R7 is substituted phenyl; R8 is selected from hydrogen, hydroxy, alkoxy, alkanoyloxy, alkanoyl, alkoxycarbonyl, alkanoylamino, alkyl, carbamoyl, alkylcarbamoyl, and bis(alkyl)carbamoyl; Ra is hydrogen or alkyl; Rb is alkyl, aryl or arylalkyl; Rc and Rd are independently selected from alkyl; m is 2, 3, or 4; and X1 and X2 are independently H or halogen, wherein at least one of X1 and X2 are halogen; and any pharmaceutically-acceptable salt thereof along with their use in treating depression, anxiety, asthma, rheumatoid arthritis, Alzheimer's disease, cancer, schizophrenia, oedema, allergic rhinitis, inflammation, pain, gastrointestinal-hypermotility, anxiety, emesis, Huntington's disease, psychoses including depression, hypertension, migraine, bladder hypermotility, or urticaria, along with methods of making the compounds and pharmaceutical compositions containing the compounds.

  具有式 (I) 的化合物 其中 R1 是氧代、-ORa、-OC(=O)Rb；或 (A)； R2 是 H；或 R1 是-ORc，R2 是-ORd；或 R1 和 R2 共同形成-O(CH2)mO-； R3 是 H 或烷基；R4、R5 和 R6 独立选自羟基、氰基、硝基、三氟甲氧基、三氟甲基、烷基磺酰基、卤代、烷氧基、烷基、氰基烷基、烯基、炔基、羧基、烷氧基羰基、氨基甲酰基、烷基氨基甲酰基、二烷基氨基甲酰基、烷酰基、烷酰氨基、氨基磺酰基和取代烷基；或 R4 和 R5 共同形成 -OCH2O- 或 -OC(CH3)2O-；R6 还可以是氢；R7 是取代的苯基；R8 选自氢、羟基、烷氧基、烷酰氧基、烷酰基、烷氧羰基、烷酰氨基、烷基、氨基甲酰基、烷基氨基甲酰基和双(烷基)氨基甲酰基；Ra 是氢或烷基；Rb 是烷基、芳基或芳烷基；Rc 和 Rd 独立地选自烷基；m 是 2、3 或 4；以及 X1 和 X2 独立地是 H 或卤素，其中 X1 和 X2 中至少有一个是卤素；及其任何药学上可接受的盐，以及它们在治疗抑郁症、焦虑症、哮喘、类风湿性关节炎、阿尔茨海默病、癌症、精神分裂症、水肿、过敏性鼻炎、炎症、疼痛、胃肠道过度运动、焦虑症、呃逆、亨廷顿氏病、包括抑郁症在内的精神病、高血压、偏头痛、膀胱过度运动或荨麻疹中的用途，以及制造这些化合物和含有这些化合物的药物组合物的方法。
• NAPHTHALENECARBOXAMIDES AS TACHYKININ RECEPTOR ANTAGONISTS
  申请人：AstraZeneca AB

  公开号：EP1119551B1

  公开（公告）日：2004-12-29
• N-substituted amides as NK1 receptor antagonists
  申请人：AstraZeneca AB

  公开号：EP1345899B1

  公开（公告）日：2009-01-14
• Design, Synthesis, and SAR of Tachykinin Antagonists:  Modulation of Balance in NK₁/NK₂ Receptor Antagonist Activity
  作者：Jeffrey S. Albert、David Aharony、Donald Andisik、Herbert Barthlow、Peter R. Bernstein、Russell A. Bialecki、Robert Dedinas、Bruce T. Dembofsky、Daniel Hill、Karin Kirkland、Gerard M. Koether、Benedict J. Kosmider、Cyrus Ohnmacht、William Palmer、William Potts、William Rumsey、Lihong Shen、Ashok Shenvi、Scott Sherwood、Paul J. Warwick、Keith Russell

  DOI：10.1021/jm020094i

  日期：2002.8.1

  Through optimization of compounds based on the dual NK1/NK2 antagonist ZD6021, it was found that alteration of two key regions could modulate the balance of NK1 and NK2 potency. Substitution of the 2-naphthalene position in analogues of ZD6021 resulted in increased NK1 potency and thus afforded NK1 preferential antagonists. Alterations of the piperidine region could then increase NK2 potency to restore dual NK1/NK2 selectivity. Through these efforts, three novel receptor antagonists from a single chemically related series were identified; two are dual NK1/NK2 antagonists, and the third is an NK1 preferential antagonist. In this paper, the factors affecting the balance of NK1 and NK2 selectivity in this series are discussed and the in vitro and in vivo properties of the novel antagonists are described.