4-(2,4-二氟苯甲基)哌啶 | 203860-02-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(2,4-二氟苯甲基)哌啶
• 中文别名: 4-(2,4-二氟苄基)哌啶
• 英文名称: 4-(2,4-difluoro-benzyl)-piperidine
• 英文别名: 4-(2,4-Difluorobenzyl)piperidine；4-[(2,4-difluorophenyl)methyl]piperidine
• CAS: 203860-02-0
• 化学式: C₁₂H₁₅F₂N
• 分子量: 211.255
• InChiKey: VXQMAHFHVBQZHC-UHFFFAOYSA-N

物化性质

• 沸点：
  280.2±30.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 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：
  12
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2,4-二氟苯甲基)哌啶 、 N-(2-oxo-2,3-dihydro-benzoxazol-6-yl)-oxalamic acid 生成 2-[4-(2,4-Difluoro-benzyl)-piperidin-1-yl]-2-oxo-N-(2-oxo-2,3-dihydro-benzoxazol-6-yl)-acetamide
  参考文献：
  名称：

  Piperdine derivatives as NMDA receptor antagonists

  摘要：

  本发明涉及化合物式（I）：1其中：V和U为氢、卤素、C1-C4烷基氨基或一起形成一个含有一个或多个杂原子的基团，且与一个或多个：（a）氢原子；（b）碳原子；（c）—CH═基团；（d）—CH2—基团；或（e）同一种或不同种类的其他杂原子；或任意组合，形成一个4-7环的同环或异环环，其中同环或异环环可以与苯基结合形成双环环，且同环或异环环或双环环可以含有一个或多个氧代、硫代、氨基、巯基、三氟甲基、C1-C4烷基、═S或—SH基团；W：为—CO—、—CH2—或—CH2—（C1-C4烷基）-；X：为—CO—；Y：为—O—、C1-C4亚烷基、C1-C4炔基、环烷基、氨基甲酰、—NH—、—N（C1-C4烷基）-、—C1-C4烷基-N（C1-C4烷基）-、—CH2O—、—CH（OH）—或—OCH2—；Z：为氢、卤素、硝基、氨基、C1-C4烷基、C1-C4烷氧基、氰基、三氟甲基、羟基或羧基；R1和R2：为氢，或一起形成一个C1-C3桥；n和m：独立地为0-3，其中n和m不能同时为0；或其光学对映体、外消旋体或药学上可接受的盐。化合物式（I）的羧酸酰衍生物是NMDA受体高效、选择性的拮抗剂。

  公开号：

  US20040157886A1
• 作为产物：
  描述：

  4-(2,4-difluoro-benzyl)-piperidin-1-carboxylic acid tert-butyl ester 以 diethyl ether ethyl acetate 为溶剂， 生成 4-(2,4-二氟苯甲基)哌啶
  参考文献：
  名称：

  Benzoyl Urea Derivatives

  摘要：

  公式（I）中的新苯甲酰脲衍生物，其中X和Y的含义独立地为氢原子，羟基，苄氧基，氨基，硝基，C1-C4烷基磺酰胺，可选地被卤素原子或卤素原子取代，C1-C4酰胺基，可选地被卤素原子或卤素原子取代，C1-C4烷氧基，芳酰基脲，可选地被卤素原子或C1-C4烷基或C1-C4烷氧羰基基团取代，或相邻的X和Y基团可选地与一个或多个相同或不同的额外杂原子和-CH═和/或-CH2-基团一起形成可选地取代的4-7成员同源或异源环，优选为吗啉，吡咯，吡咪啉，氧-或硫代-吡咪啉，吡唑，吡唑啉，咪唑，咪唑啉，氧-或硫代-咪唑或咪唑啉，1,4-噁唑啉，噁唑，噁唑啉，三唑，氧-或硫代-噁唑啉，或3-氧代-1,4-噁唑环，V和Z独立地为氢或卤素原子，氰基，C1-C4烷基，C1-C4烷氧基，三氟甲基，羟基或可选的酯化羧基，W为氧原子，以及C1-C4烷基，C2-C4烯基，氨基羰基，-NH-，-N（烷基）-，-CH2O-，-CH2S-，-CH（OH）-，-OCH2-基团，其中烷基的含义是C1-C4烷基，当点状键（）表示简单的C-C键时，U为羟基或氢原子，或当W为C1-C4烷基或C2-C4烯基时，点状键（）中的一个可以表示进一步的双重C-C键，在这种情况下，U表示参与双键的电子对和光学对映体，外消旋体和其盐是高效和选择性的NMDA受体拮抗剂，此外，大多数化合物是NMDA受体NR2B亚型的选择性拮抗剂。此外，本发明的目标是含有公式（I）的新苯甲酰脲衍生物、光学对映体或外消旋体或其盐作为活性成分的药物组合物，以及制备这些化合物和药物组合物的过程。

  公开号：

  US20090170901A1

文献信息

• [EN] NEW BENZOYL UREA DERIVATIVES<br/>[FR] NOUVEAUX DERIVES D'UREE BENZOYLE
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2006010966A1

  公开（公告）日：2006-02-02

  The new benzoyl urea derivatives of formula (I) wherein the meaning of X and Y independently are hydrogen atom, hydroxy, benzyloxy, amino, nitro, C1-C4 alkylsulfonamido optionally substituted with a halogen atom or halogen atoms, C1-C4 alkanoylamido optionally substituted with a halogen atom or halogen atoms, C1-C4 alkoxy, aroyl-carbamoyl optionally substituted with halogen atom or C1-C4 alkyl or C1-C4 alkoxycarbonyl group, or the neighboring X and Y groups optionally form together with one or more identical or different additional hetero atom and -CH= and/or -CH2- groups an optionally substituted 4-7 membered homo- or heterocyclic ring, preferably morpholine, pyrrole, pyrrolidine, oxo- or thioxo-pyrrolidine, pyrazole, pyrazolidine, imidazole, imidazolidine, oxo- or thioxo-imidazole or imidazolidine, 1,4-oxazine, oxazole, oxazolidine, triazole, oxo- or thioxo-oxazolidine, or 3-oxo-l,4-oxazine ring, V and Z independently are hydrogen or halogen atom, cyano, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, hydroxy or optionally esterized carboxyl group, W is oxygen atom, as well as C1-C4 alkylene, C2-C4 alkenylene, aminocarbonyl, -NH-, -N(alkyl)-, -CH2O-, -CH2S-, -CH(OH)-, -OCH2- group, wherein the meaning of alkyl is a C1-C4 alkyl group -, when the dotted bonds ( --- ) represent simple C-C bonds then U is hydroxy group or hydrogen atom or when W is C1-C4 alkylene or C2-C4 alkenylene group, then one of the dotted bonds ( --- ) can represent a further double C-C bond and in this case U means an electron pair, which participate in the double bond and optical antipodes, racemates and the salts thereof are highly effective and selective antagonists of NMDA receptor, and moreover most of the compounds are selective antagonist of NR2B subtype of NMDA receptor. Furthermore objects of the present invention are the pharmaceutical compositions containing new benzoyl urea derivatives of formula (I) or optical antipodes or racemates or the salts thereof as active ingredients and processes for producing these compounds and pharmaceutical compositions.

  公式（I）的新苯甲酰脲衍生物，其中X和Y的含义独立地是氢原子、羟基、苄氧基、氨基、硝基、C1-C4烷基磺酰胺（可选择地与卤原子或卤原子取代）、C1-C4烷酰胺（可选择地与卤原子或卤原子取代）、C1-C4烷氧基、芳酰基-氨基（可选择地与卤原子或C1-C4烷基或C1-C4烷氧羰基团取代）或相邻的X和Y基团可选择地与一个或多个相同或不同的额外杂原子和-CH=和/或-CH2-基团一起形成一个可选择地取代的4-7成员同源或异源环，优选为吗啡啉、吡咯、吡咯烷、氧代或硫代吡咯烷、吡唑、吡唑烷、咪唑、咪唑烷、氧代或硫代咪唑或咪唑烷、1,4-氧杂噁啉、氧唑、氧杂噁啉、三唑、氧代或硫代氧杂噁啉或3-氧代-1,4-氧杂噁啉环，V和Z独立地是氢或卤原子、氰基、C1-C4烷基、C1-C4烷氧基、三氟甲基、羟基或可选择酯化的羧基，W是氧原子，以及C1-C4烷基、C2-C4烯基、氨基羰基、-NH-、-N(烷基)-、- O-、- S-、-CH(OH)-、-O -基团，其中烷基的含义是C1-C4烷基群-，当虚线键（---）代表简单的C-C键时，U是羟基或氢原子，或当W是C1-C4烷基或C2-C4烯基群时，那么虚线键（---）中的一个可以代表进一步的双键C-C键，在这种情况下，U表示参与双键和光学异构体、消旋体及其盐的电子对，这些化合物是NMDA受体的高效和选择性拮抗剂，而且大多数化合物是NMDA受体NR2B亚型的选择性拮抗剂。此外，本发明的目的是包含公式（I）的新苯甲酰脲衍生物、光学异构体或消旋体或其盐为活性成分的药物组合物，以及生产这些化合物和药物组合物的方法。
• [EN] PIPERIDINE DERIVATIVES AS NMDA RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PIPERIDINE UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR N-METHYL-D-ASPARTATE (NMDA)
  申请人：RICHTER GEDEON VEGYESZET

  公开号：WO2003010159A1

  公开（公告）日：2003-02-06

  The present invention relates to new carboxylic acid amide derivatives of formula (I), wherein U, V, W, X, Y, Z, n and m are as defined as in Claim 1. A further object of the invention are the processes for producing of carboxylic acid amide compounds of formula (I), and the pharmaceutical manufacture of medicaments containing these compounds, as well as the process of treatments with these compounds, which means administering to a mammal to be treated including human - effective amount/amounts of compounds of formula (I) of the present invention as such or as medicament. The new carboxylic acid amide derivatives of formula (I) of the present invention are highly effective and selective antagonists of NMDA receptor, and moreover most of the compounds are selective antagonist of NR2B subtype of NMDA receptor.

  本发明涉及公式（I）的新羧酸酰胺衍生物，其中U、V、W、X、Y、Z、n和m如权利要求书1中所定义。本发明的另一个目标是制备公式（I）的羧酸酰胺化合物的过程，以及包含这些化合物的药物制剂的制药制造，以及使用这些化合物进行治疗的过程，即向待治疗的哺乳动物（包括人类）施用本发明的公式（I）的化合物或药物的有效量/剂量。本发明的新羧酸酰胺衍生物是高效且选择性的NMDA受体拮抗剂，而且大多数化合物是NMDA受体NR2B亚型的选择性拮抗剂。
• [EN] CYCLIC AMINE COMPOUNDS AS CCR5 ANTAGONISTS<br/>[FR] COMPOSES D'AMINE CYCLIQUE UTILISES COMME ANTAGONISTES DE CCR5
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2001025200A1

  公开（公告）日：2001-04-12

  A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R?1 and R2¿ may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N?+-R5 •Y-(R5¿ is a hydrocarbon group; Y- is a counter anion); R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1 is a bond, CO or SO¿2; G?2 is CO, SO¿2?, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G?1¿ is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  化合物式为（I）（其中R1是氢原子，可被取代的碳氢基团，可被取代的非芳香杂环基团，R2是可被取代的碳氢基团，可被取代的非芳香杂环基团，或R1和R2可以与A一起结合形成可被取代的杂环基团；A是N或N+ -R5 • Y-（R5是碳氢基团；Y-是反离子）；R3是可被取代的环烃基团或可被取代的杂环基团；n为0或1；R4是氢原子，可被取代的碳氢基团，可被取代的杂环基团，可被取代的烷氧基，可被取代的芳氧基，或可被取代的氨基，E是可被除氧基以外的基取代的二价脂肪烃基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是甲基或氮原子；Q和R中的每一个都是一个键或一个可被取代的二价C1-3脂肪基团；前提是当G2是OCO时，J是甲基，当另一个是键时，其中一个不是键，当G1是键时，Q和R中的每一个都没有被氧基团取代）或其盐具有强效的CCR5拮抗活性，并可用于人类各种HIV感染疾病（例如艾滋病）的治疗或预防。
• Substituted indoles
  申请人：Schadt Oliver

  公开号：US20050153980A1

  公开（公告）日：2005-07-14

  Substituted indoles of the formula (I) and physiologically acceptable derivatives and salts thereof, in which R 1 , D, E, R 12 , p, X 1 , E, G, X 2 and Z are as defined in claim 1, exhibit particular actions on the central nervous system, especially 5HT reuptake-inhibiting and 5 HTx-agonistic and/or -antagonistic actions and in particular serotonin-agonistic and -antagonistic properties and can be employed as antipsychotics, neuroleptics, antidepressants, anxiolytics and/or antihypertonics. They can furthermore be employed as excitatory amino acid antagonists for combating neurodegenerative diseases, including cerebrovascular diseases, epilepsy, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cerebral ischaemia, infarction or psychoses

  公式（I）及其生理可接受的衍生物和盐的取代吲哚在中枢神经系统上表现出特殊作用，尤其是5HT再摄取抑制和5HTx激动剂和/或拮抗剂作用，特别是血清素激动剂和拮抗剂特性，并可用作抗精神病药、神经元病药、抗抑郁药、抗焦虑药和/或降压药。它们还可用作兴奋性氨基酸拮抗剂，用于对抗神经退行性疾病，包括脑血管疾病、癫痫、精神分裂症、阿尔茨海默病、帕金森病、亨廷顿病、脑缺血、梗塞或精神病。
• Cyclic amine compounds as CCR5 antagonists
  申请人：——

  公开号：US20030114443A1

  公开（公告）日：2003-06-19

  A compound of formula (I) (wherein R 1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R 2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R 1 and R 2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N + —R 5 .Y − (R 5 is a hydrocarbon group; Y − is a counter anion); R 3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R 4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G 1 is a bond, CO or SO 2 ; G 2 is CO, SO 2 , NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C 1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G 2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G 1 is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  化合物的式子 (I) (其中R1是氢原子、可以被取代的碳氢基团、可以被取代的非芳香族杂环基团，R2是可以被取代的碳氢基团、可以被取代的非芳香族杂环基团，或R1和R2可以与A结合形成可以被取代的杂环基团；A是N或N+—R5.Y−(R5是碳氢基团；Y−是反离子)；R3是可以被取代的环烃基团或可以被取代的杂环基团；n为0或1；R4是氢原子、可以被取代的碳氢基团、可以被取代的杂环基团、可以被取代的烷氧基、可以被取代的芳氧基，或可以被取代的氨基团；E是可以被取代的二价脂肪烃基团，该基团可以被除氧基团外的其他基团取代；G1是键、CO或SO2；G2是CO、SO2、NHCO、CONH或OCO；J是甲基或氮原子；Q和R中的每一个都是键或可以被取代的二价C1-3脂肪基团；但是当G2是OCO时，J是甲基；当Q和R中的一个是键时，另一个不是键；当G1是键时，Q和R中的每一个都没有被氧基团取代)或其盐具有强效的CCR5拮抗活性，可以用于治疗或预防人类各种HIV感染性疾病（例如艾滋病）。