4-[(S)-2-methylsulfinylphenyl]piperidine | 171426-58-7

• 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-methylsulfinylphenyl]piperidine
• 英文别名: 4-{2-[(S)-Methanesulfinyl]phenyl}piperidine；4-[2-[(S)-methylsulfinyl]phenyl]piperidine
• CAS: 171426-58-7
• 化学式: C₁₂H₁₇NOS
• 分子量: 223.339
• InChiKey: GETHXZBPJVUSBH-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 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：
  3

反应信息

• 作为反应物：
  描述：

  4-[(S)-2-methylsulfinylphenyl]piperidine 、 2-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-1-oxo-1,3,4,6-tetrahydro-2H-naphtho[1,2-f][1,4]oxazocine-7-carbonitrile 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 2.5h， 以69%的产率得到2-((2S)-2-(3,4-dichlorophenyl)-4-{4-[2-(methylsulfinyl)phenyl]piperidin-1-yl}butyl)-1-oxo-1,3,4,6-tetrahydro-2H-naphtho[1,2-f][1,4]oxazocine-7-carbonitrile
  参考文献：
  名称：

  Naphtho[2,1-b][1,5] and [1,2-f][1,4]oxazocines as selective NK1 antagonists

  摘要：

  Previously we reported on the synthesis and properties of a series of highly potent piperidinyl 2-subsituted-3-cyano-1-naphthamide NK1 antagonists that includes 3 and 4. Here we report our efforts to alleviate a troublesome atropisomeric property of those derivatives by introduction of a tethering bridge that, in addition, could be used to lock the resulting cyclic derivatives in a purported NK1 pharmacophore conformation. Using 3 as a starting point, the naphtho[2, 1-b][1,5]oxazocine, 17, was found to contain the optimal ring tether size (8) for retaining NK1 activity, was more NK1 versus NK2 selective, and reduced the number of atropisomers from four to two. Cyclic derivatives 29 and 32, which exist as essentially single atropisomers in the purported pharmacophore conformation. were prepared in the closely related naphtho[1,2-f][1,4]oxazocine series as part of an effort to use mono methyl substitution of the tethering bridge as a conformation stabilizing factor. Both 29 and 32 were found to be less active as NK1 antogonists than the non-methylated parent 28 possibly due to methyl group destabilization of receptor interaction. We discuss the above findings in the context of a previously proposed NK1 pharmacophore model and present a further refinement of that model. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.015

文献信息

• Neurokinin antagonists for use as medicaments
  申请人：——

  公开号：US20030158170A1

  公开（公告）日：2003-08-21

  A compound having the general formula (I) and methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.

  一种具有通式(I)的化合物，以及使用此类化合物治疗疾病的方法和包含此类化合物的制药组合物。
• [EN] NAPHTHALENECARBOXAMIDES AS TACHYKININ RECEPTOR ANTAGONISTS<br/>[FR] NAPHTALENE-CARBOXAMIDES UTILISES EN TANT QU'ANTAGONISTES DES RECEPTEURS DES TACHYKININES
  申请人：ZENECA LTD

  公开号：WO2000020389A1

  公开（公告）日：2000-04-13

  A compound having formula (I) wherein R1 is oxo, -ORa, -OC(=O)Rb; or (A); R2 is H; or R?1 is -ORc and R2 is -ORd; or R1 and R2¿ together form -O(CH¿2?)mO-; 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.

  化合物式(I)的化合物，其中R1是氧代、-ORa、-OC（=O）Rb；或（A）；R2是H；或者R1是-ORc且R2是-ORd；或者R1和R2在一起形成-O（CH2）mO-；以及其任何药学上可接受的盐，用于治疗抑郁症、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、胃肠过度运动、焦虑症、呕吐、亨廷顿病、包括抑郁症、高血压、偏头痛、膀胱过度运动或荨麻疹的方法，以及制备这些化合物和含有这些化合物的制药组合物。
• [EN] N-SUBSTITUTED NAPHTHALENE CARBOXAMIDES AS NEUROKININ-RECEPTOR ANTAGONISTS<br/>[FR] NAPHTALENE CARBOXAMIDES N-SUBSTITUES EN TANT QU'ANTAGONISTES DE RECEPTEURS DES NEUROKININES
  申请人：ZENECA LTD

  公开号：WO2000002859A1

  公开（公告）日：2000-01-20

  A compound of formula (I) wherein: R is alkyl; R1 is optionally substituted phenyl, 2-oxo-tetrahydro-1(2H)-pyrimidinyl, or 2-oxo-1-piperidinyl; R2 is hydrogen, alkoxy, alkanoyloxy, alkoxycarbonyl, alkanoylamino, acyl, alkyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl where the alkyl groups are the same or different, hydroxy, thioacyl, thiocarbamoyl, N-alkylthiocarbamoyl, or N,N-dialkylthiocarbamoyl where the alkyl groups are the same or different. X¿1? and X2 are independently hydrogen or halo, provided that at least one of X1 or X2 is halo; and R?3, R4, R5, and R6¿ are independently hydrogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, or alkylsulfonyl are antagonists of at least one tachykinin receptor and are useful in the treatment of depression, anxiety, asthma, pain, inflammation, urinary incontinence and other disease conditions. Processes for their preparation are described, as are compositions containing them and their use.

  化合物的化学式(I)，其中：R为烷基; R1为可选取代的苯基，2-氧代-四氢-1(2H)-嘧啶基或2-氧代-1-哌啶基; R2为氢、烷氧基、烷酰氧基、烷氧羰基、烷酰胺、烷基、氨基甲酰、N-烷基氨基甲酰、N,N-二烷基氨基甲酰，其中烷基团相同或不同，羟基、硫代酰基、硫代氨基、N-烷基硫代氨基、N,N-二烷基硫代氨基，其中烷基团相同或不同。X1和X2独立地为氢或卤素，但至少其中之一为卤素; R3、R4、R5和R6独立地为氢、氰基、硝基、三氟甲氧基、三氟甲基或烷基磺酰基，是至少一种快速激动肽受体的拮抗剂，可用于治疗抑郁症、焦虑症、哮喘、疼痛、炎症、尿失禁和其他疾病。描述了它们的制备过程，以及包含它们和它们的使用的组合物。
• New neurokinin antagonists for use as medicaments
  申请人：Albert Scott Jeffrey

  公开号：US20070021406A1

  公开（公告）日：2007-01-25

  The present application relates to internally cyclized naphthamide compounds of the formula Ia (wherein R 1a , R 1b , R 1c , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X 1 , X 2 , Y, Z, and n are as defined herein), which are useful, for example, for antagonizing the pharmacological actions of the neurokinin 1 (NK 1 ) receptor. In particular, these compounds are useful in the treatment of diseases in which Substance P is involved such as, for example, major depressive disorder, severe anxiety disorders, stress disorders, major depressive disorder with anxiety, eating disorders, bipolar disorder, substance use disorder, schizophrenic disorders, psychotic disorders, movement disorders, cognitive disorders, depression and/or anxiety, mania or hypomania, aggressive behaviour, obesity, rheumatoid arthritis, Alzheimer's disease, cancer, oedema, allergic rhinitis, inflammation, pain, gastrointestinal-hypermotility, Huntington's disease, chronic obstructive pulmonary disorder (COPD), hypertension, migraine, bladder hypermotility, and urticaria.

  本申请涉及公式Ia的内环化萘酰胺化合物（其中R1a，R1b，R1c，R2，R3，R4，R5，R6，R7，R8，X1，X2，Y，Z和n的定义如本文所述），这些化合物可用于拮抗神经激肽1（NK1）受体的药理作用。特别地，这些化合物可用于治疗与物质P有关的疾病，例如重度抑郁障碍、严重焦虑障碍、应激障碍、伴有焦虑的重度抑郁障碍、进食障碍、躁狂障碍、物质使用障碍、精神分裂障碍、精神病性障碍、运动障碍、认知障碍、抑郁和/或焦虑、狂躁或亢进行为、肥胖症、类风湿性关节炎、阿尔茨海默病、癌症、水肿、过敏性鼻炎、炎症、疼痛、胃肠道高动力性、亨廷顿病、慢性阻塞性肺疾病（COPD）、高血压、偏头痛、膀胱高动力性和荨麻疹。
• 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 -O O- 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。