(1-苄基哌啶-4-基)脲 | 61220-35-7

• 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: (1-苄基哌啶-4-基)脲
• 英文名称: 1-Benzyl-4-ureido-piperidin
• 英文别名: (1-Benzylpiperidin-4-yl)urea
• CAS: 61220-35-7
• 化学式: C₁₃H₁₉N₃O
• mdl: MFCD09803352
• 分子量: 233.313
• InChiKey: OGDDDXCCTAQTJC-UHFFFAOYSA-N

物化性质

• 沸点：
  362.0±42.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1-苄基哌啶-4-基)脲 在 1-氯乙基氯甲酸酯 、 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 18.0h， 生成 1,3-二氢-5-甲基-4-苯基-1-(4-哌啶基)-2H-咪唑-2-酮
  参考文献：
  名称：

  1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1,3-dihydroimidazol-2-one:  A Selective High-Affinity Antagonist for the Human Dopamine D₄ Receptor with Excellent Selectivity over Ion Channels

  摘要：

  After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1,3-dihydroimidazol-2-yl)piperidine . Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot'' procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1,3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or B-position of the 1,3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater Selectivity( > 1000-foId) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has > 1000-fold selectivity over-all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D-4 receptor.

  DOI：

  10.1021/jm991029k
• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 50.0h， 生成 (1-苄基哌啶-4-基)脲
  参考文献：
  名称：

  1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1,3-dihydroimidazol-2-one:  A Selective High-Affinity Antagonist for the Human Dopamine D₄ Receptor with Excellent Selectivity over Ion Channels

  摘要：

  After the requirement of pseudocycle formation in the ureas 3 and 7 for hD(4) binding and selectivity was confirmed, structural hybridization with the known hD(4) ligand 2 led to the design and identification of the lead 4-(2-oxo-1,3-dihydroimidazol-2-yl)piperidine . Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD(4) over all other receptors while retaining the good pharmacokinetic properties of the lead. After initial preparation of 8 as a minor component in a low-yielding reaction, a novel and regioselective "four-step/one-pot'' procedure was developed which proved to be applicable to rapid investigation of the SAR of the 1,3-dihydroimidazol-2-one ring. Various changes to substituents attached to the 3-, 4-, or B-position of the 1,3-dihydroimidazol-2-one core of 8 did not significantly improve selectivity for hD(4) over hD(2) and hD(3). Greater Selectivity( > 1000-foId) was ultimately achieved by meta substitution of the benzyl group of 8 with various substituents. Compounds 28, 31, and 32 all possess the required selectivity for hD(4) over the other dopamine subtypes, but only 32 has > 1000-fold selectivity over-all the key counterscreens we tested against. Compound 32 is an antagonist at hD(4) and has a good pharmacokinetic profile in the rat, with excellent estimated in vivo receptor occupancy, thus making it a potentially useful pharmacological tool to investigate the role of the D-4 receptor.

  DOI：

  10.1021/jm991029k

文献信息

• [EN] 3-FURANYL ANALOGS OF TOXOFLAVINE AS KINASE INHIBITORS<br/>[FR] ANALOGUES DE 3-FURANYLE DE TOXOFLAVINE EN TANT QU'INHIBITEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004007499A1

  公开（公告）日：2004-01-22

  The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents an integer being 0 or 1; n represents an integer being 0, 1 or 2; R1 represents C1-4alkyl, C1-4alkyl substituted with pyridinyl, phenyl, piperidinyl or piperidinyl substituted with C1-4-alkyloxycarbonyl; R2 represents hydrogen or C1-4 alkyl; R3 represents hydrogen or C1-4alkyl; or R2 and R3 taken together with the carbon atom to which they are attached form cyclopentyl or piperidinyl wherein said cyclopentyl or piperidinyl each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from C1-4alkyloxycarbonyl, phenylcarbonyl or -C(=NH)-NH2; R4 represents halo or C1-4alkyloxy; R5 represents Het2, C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy, halo, Het3 or NR6R7, or C1-4alkyloxy substituted with one or where possible more substituents being selected from Het4 or -C(=O)-Het4; R6 and R7 are each independently selected from hydrogen, C1-4alkyl, Het5 or C1-4alkyl substituted with one or where possible more substituents being selected from hydroxy or Het5; Het2 represents piperazinyl; Het3 represents a heterocycle selected from morpholinyl, pyrrolidinyl, piperidinyl, or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C1-4alkyl preferably methyl, aminosulfonyl, mono- or di(C1-4alkyl)aminosulfonyl, hydroxyC1 -4alkyloxyC1-4alkyl, C1-4alkyloxyC1-4alkyl or C1-4alkyloxy; Het4 represents a heterocycle selected from morpholinyl or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three C1-4alkyl substituents, preferably methyl; Het5 represents a heterocycle selected from pyridinyl, pyrrolidinyl or piperidinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from aminosulfonyl, C1-4alkyloxycarbonyl or mono- or di(C1-4alkyl)aminosulfonyl.

  本发明涉及具有式（I）的化合物，其N-氧化物形式，药用可接受的加合物盐及其立体化异构体形式，其中m代表为0或1的整数；n代表为0，1或2的整数；R1代表C1-4烷基，带有吡啶基，苯基，哌啶基或带有C1-4-烷氧羰基的C1-4烷基；R2代表氢或C1-4烷基；R3代表氢或C1-4烷基；或R2和R3与它们连接的碳原子一起形成环戊烷基或哌啶基，其中所述的环戊烷基或哌啶基各自可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自C1-4烷氧羰基，苯甲酰基或-C（=NH）-NH2；R4代表卤素或C1-4烷氧基；R5代表Het2，带有一个或在可能的情况下更多取代基的C1-4烷基，所选取的取代基包括羟基，卤素，Het3或NR6R7，或带有一个或在可能的情况下更多取代基的C1-4烷氧基，所选取的取代基包括Het4或-C（=O）-Het4；R6和R7各自独立选择自氢，C1-4烷基，Het5或带有羟基或Het5的C1-4烷基取代基；Het2代表哌嗪基；Het3代表从吗啉基，吡咯啉基，哌啶基或哌嗪基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自C1-4烷基（最好是甲基），氨基磺酰基，单烷基或双烷基氨基磺酰基，羟基C1-4烷氧基C1-4烷基，C1-4烷氧基C1-4烷基或C1-4烷氧基；Het4代表从吗啉基或哌嗪基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个C1-4烷基取代基取代，最好是甲基；Het5代表从吡啶基，吡咯啉基或哌啶基中选择的杂环，其中所述的单环杂环可以选择性地被一个，或在可能的情况下，两个或三个取代基取代，每个取代基独立地选择自氨基磺酰基，C1-4烷氧羰基或单烷基或双烷基氨基磺酰基。
• Imidazolone and oxazolone derivatives as dopamine antagonists
  申请人：Merck, Sharp & Dohme, Ltd.

  公开号：US05698573A1

  公开（公告）日：1997-12-16

  A class of imidazolone and oxazolone derivatives of Structure I, ##STR1## wherein X represents oxygen or N--R.sup.1 ; Q represents a substituted five-, six- or seven-membered monocyclic heteroaliphatic ring which contains one nitrogen atom as the sole heteroatom and is linked to the imidazolone or oxazolone ring via a carbon atom; R.sup.1 represents hydrogen or C.sub.1-6 alkyl; and one of R.sup.2 and R.sup.3 represents hydrogen or C.sub.1-6 alkyl and the other of R.sup.2 and R.sup.3 represents cycloalkyl or a group of formula (i), (ii) or (iii): ##STR2## in which Z represents oxygen, sulphur or NH; R.sup.4, R.sup.5 and R.sup.6 independently represent hydrogen, a hydrocarbon group or a heterocyclic group wherein the hydrocarbon group and heterocyclic group are as defined in the specification; or a pharmaceutically acceptable salt or prodrug thereof, which are ligands for dopamine receptor subtypes within the brain and are therefore of use in the treatment and/or prevention of disorders of the dopamine system, such as schizophrenia.

  I. 结构的咪唑酮和噁唑酮衍生物类，其中X代表氧或N--R.sup.1；Q代表一种取代的五、六或七元杂环脂肪环，其中含有一个氮原子作为唯一杂原子，并通过一个碳原子连接到咪唑酮或噁唑酮环上；R.sup.1代表氢或C.sub.1-6烷基；R.sup.2和R.sup.3中的一个代表氢或C.sub.1-6烷基，另一个代表环烷基或式(i)、(ii)或(iii)的基团：##STR2## 其中Z代表氧、硫或NH；R.sup.4、R.sup.5和R.sup.6独立地代表氢、烃基或杂环基，其中烃基和杂环基如规范中定义；或其药学上可接受的盐或前药，它们是大脑内多巴胺受体亚型的配体，因此可用于治疗和/或预防多巴胺系统紊乱，如精神分裂症。
• [EN] IMIDAZOLONE AND OXAZOLONE DERIVATIVES AS DOPAMINE ANTAGONISTS<br/>[FR] DERIVES D'IMIDAZOLONE ET D'OXAZOLONE UTILISES COMME ANTAGONISTES DE LA DOPAMINE
  申请人：MERCK SHARP & DOHME LIMITED

  公开号：WO1995007904A1

  公开（公告）日：1995-03-23

  (EN) A class of imidazolone and oxazolone derivatives are ligands for dopamine receptor subtypes within the brain and are therefore of use in the treatment and/or prevention of disorders of the dopamine system, such as schizophrenia.(FR) Une classe de dérivés d'imidazolone et d'oxazolone constituent des ligands pour les sous-types de récepteurs de la dopamine dans le cerveau et s'avèrent donc utiles pour le traitement et/ou la prévention des troubles du système dopaminergique, et en particulier pour le traitement de la schizophrénie.

  一类咪唑酮和噁唑酮衍生物是大脑内多巴胺受体亚型的配体，因此可用于治疗和/或预防多巴胺系统的疾病，如精神分裂症。
• 3-Furanyl analogs of toxoflavine as kinase inhibitors
  申请人：LaCrampe Armand Jean Fernand

  公开号：US20060040943A1

  公开（公告）日：2006-02-23

  The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents an integer being 0 or 1; n represents an integer being 0, 1 or 2; R 1 represents C 1-4 alkyl, C 1-4 alkyl substituted with pyridinyl, phenyl, piperidinyl or piperidinyl substituted with C 1-4 alkyloxycarbonyl; R 2 represents hydrogen or C 1-4 alkyl; R 3 represents hydrogen or C 1-4 alkyl; or R 2 and R 3 taken together with the carbon atom to which they are attached form cyclopentyl or piperidinyl wherein said cyclopentyl or piperidinyl each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from C 1-4 alkyloxycarbonyl, phenylcarbonyl or —C(═NH)—NH 2 ; R 4 represents halo or C 1-4 alkyloxy; R5 represents Het 2 , C 1-4 alkyl substituted with one or where possible more substituents being selected from hydroxy, halo, Het 3 or NR 6 R 7 , or C 1-4 alkyloxy substituted with one or where possible more substituents being selected from Het 4 or —C(═O)-Het 4 ; R 6 and R 7 are each independently selected from hydrogen, C 1-4 alkyl, Het 5 or C 1-4 alkyl substituted with one or where possible more substituents being selected from hydroxy or Het 5 ; Het 2 represents piperazinyl; Het 3 represents a heterocycle selected from morpholinyl, pyrrolidinyl, piperidinyl, or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C 1-4 alkyl preferably methyl, aminosulfonyl, mono- or di(C 1-4 alkyl)aminosulfonyl, hydroxyC 1-4 alkyloxyC 1-4 alkyl, C 1-4 alkyloxyC 1-4 alkyl or C 1-4 alkyloxy; Het 4 represents a heterocycle selected from morpholinyl or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three C 1-4 alkyl substituents, preferably methyl; Het 5 represents a heterocycle selected from pyridinyl, pyrrolidinyl or piperidinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from aminosulfonyl, C 1-4 alkyloxycarbonyl or mono- or di(C 1-4 alkyl)aminosulfonyl.

  本发明涉及式化合物 其 N-氧化物形式、药学上可接受的加成盐及其立体化学异构形式，其中 m 代表 0 或 1 的整数；n 代表 0、1 或 2 的整数；R 1 代表 C 1-4 烷基、C 1-4 烷基、被吡啶基、苯基、哌啶基或被 C 1-4 烷氧羰基取代的 C 1-4 烷基 2 代表氢或 C 1-4 烷基；R 3 代表氢或 C 1-4 烷基；或 R 2 和 R 3 与它们所连接的碳原子一起形成环戊基或哌啶基，其中所述环戊基或哌啶基可分别独立地被一个或两个或三个取代基所取代，这些取代基分别独立地选自 C 1-4 烷氧羰基、苯基羰基或-C(═NH)-NH 2 ; R 4 代表卤代烃或 C 1-4 烷氧基；R5 代表 Het 2 , C 1-4 被一个或可能有多个取代基取代的烷基，这些取代基选自羟基、卤代、 Het 3 或 NR 6 R 7 或 C 1-4 被一个或可能有多个取代基取代的烷氧基，这些取代基选自 Het 4 或-C(═O)-Het 4 ; R 6 和 R 7 各自独立选自氢、C 1-4 烷基、Het 5 或 C 1-4 被选自羟基或 Het 5 的一个或多个取代基取代的 C 1-4 烷基 5 ；Het 2 代表哌嗪基；Het 3 代表选自吗啉基、吡咯烷基、哌啶基或哌嗪基的杂环，其中所述单环杂环各自独立地可任选被一个或在可能的情况下被两个或三个各自独立地选自 C 1-4 烷基（优选甲基）、氨基磺酰基、单-或二(C-1-4-烷基) 1-4 烷基）氨基磺酰基、羟基 C 1-4 烷氧基 C 1-4 烷基、C 1-4 烷氧基C 1-4 烷基或 C 1-4 烷氧基 4 代表选自吗啉基或哌嗪基的杂环，其中所述单环杂环可各自独立地被一个或两个或三个 C 1-4 烷基取代基，最好是甲基； Het 5 代表选自吡啶基、吡咯烷基或哌啶基的杂环，其中所述单环杂环可分别独立地被一个或两个或三个取代基取代，这些取代基分别独立地选自氨基磺酰基、C 1-4 烷氧羰基或单个或二个（C 1-4 烷基）氨基磺酰基。
• HUEBNER, C. F.
  作者：HUEBNER, C. F.

  DOI：——

  日期：——