1-丁基哌啶-4-甲酰胺 | 66073-48-1

• 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-丁基哌啶-4-甲酰胺
• 英文名称: 4-carboxamide-1-butylpiperidine
• 英文别名: 1-butyl-iso-nipecotamide；1-Butyl-4-carbamoylpiperidin；4-Piperidinecarboxamide, 1-butyl-；1-butylpiperidine-4-carboxamide
• CAS: 66073-48-1
• 化学式: C₁₀H₂₀N₂O
• mdl: MFCD20542445
• 分子量: 184.282
• InChiKey: PWVIGOPEAZKAPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-丁基哌啶-4-甲酰胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 4-氨甲基-1-(正丁基)哌啶
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of carboxamide derivatives as selective serotoninergic 5-HT4 receptor agonists

  摘要：

  A number of new carboxamide derivatives were synthesized. The affinity of these compounds for the serotoninergic 5-HT4 receptor was evaluated by use of radioligand-binding techniques. The agonistic activity was evaluated as the contractile effect of the ascending colon isolated from guinea-pigs. Among these compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4-piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT4 receptor (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT4 receptors than the other receptors, including, 5-HT3 and dopamine D-2 receptors. In addition, compound 24 was confirmed to be a potent 5-HT4 receptor agonist (ED50 - 7.0 nM). An interaction model between compound 24 and 5-HT4 receptor was proposed. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80083-x
• 作为产物：
  描述：

  正溴丁烷 、 哌啶-4-甲酰胺 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 1-丁基哌啶-4-甲酰胺
  参考文献：
  名称：

  （1-丁基-4-哌啶基）甲基8-氨基-7-氯-1,4-苯并二恶烷-5-羧酸盐酸盐：一种高效且选择性的从甲氧氯普胺衍生的5-HT4受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00077a018

文献信息

• [EN] 1H-INDAZOLE-3-CARBOXAMIDE COMPOUNDS AS CYCLIN DEPENDENT KINASES (CDK) INHIBITORS<br/>[FR] COMPOSES 1H-INDAZOLE-3-CARBOXAMIDE UTILISES EN TANT QU'INHIBITEURS DE KINASES CYCLINE-DEPENDANTES (CDK)
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2004014864A1

  公开（公告）日：2004-02-19

  The invention provides a compound of the formula (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase: wherein A is a group R2 or CH2-R2 where R2 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; B is a bond or an acyclic linker group having a linking chain length of up to 3 atoms selected from C, N, S and O; R1 is hydrogen or a group selected from SO2Rb,SO2NR7R8,CONR7R8,NR7R9 and carbocyclic and heterocyclic groups having from 3 to 7 ring members; R3, to R9 are defined in the description but excluding the compounds N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide and N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide.

  本发明提供了一种式(I)化合物，用于预防或治疗由细胞周期蛋白依赖性激酶介导的疾病状态或条件：其中A是R2基团或CH2-R2，其中R2是具有3至12个环成员的碳环或杂环基团；B是键或具有最多3个原子（选自C、N、S和O）的链长的不饱和链连接基团；R1是氢或选自SO2Rb、SO2NR7R8、CONR7R8、NR7R9以及具有3至7个环成员的碳环和杂环基团；R3至R9在说明书中定义，但不包括化合物N-[(吗啉-4-基)苯基-1H-吲唑-3-甲酰胺]和N-[4-(乙酰氨基磺酰基)苯基-1H-吲唑-3-甲酰胺]。
• [EN] 1H-INDAZOLE-3-CARBOXAMIDE COMPOUNDS AS MAPKAP KINASE MODULATORS<br/>[FR] COMPOSES 1H-INDAZOLE-3-CARBOXAMIDE UTILISES COMME MODULATEURS DE LA MAPKAP KINASE
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2005014554A1

  公开（公告）日：2005-02-17

  The invention provides compounds of the formula: (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a MAPKAP kinase: wherein A is a bond or a group CH2; R1 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; R3, R4, R5 and R6 are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra -Rb wherein Ra is a bond, 0, CO, X1C(X2), C(X2)Xl, X1C(X2)X1, S, SO, S02, NRc, SO2NRc or NRcS02; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; Rc is hydrogen or C1-4 hydrocarbyl; and X1 is O, S or NRc and X2 is =O, =S or =NRc.

  该发明提供了化合物的公式：（I），用于预防或治疗由MAPKAP激酶介导的疾病状态或病情：其中A是键或CH2基团; R1是具有3到12个环成员的碳环或杂环基团; R3，R4，R5和R6相同或不同，每个都选择自氢，卤素，羟基，三氟甲基，氰基，硝基，羧基，氨基，碳环和具有3到12个环成员的杂环基团中的一个; Ra-Rb基团，其中Ra是键，0，CO，X1C（X2），C（X2）Xl，X1C（X2）X1，S，SO，S02，NRc，SO2NRc或NRcS02; Rb选择自具有3到12个环成员的氢，碳环和杂环基团，以及C1-8烃基，可选地被一个或多个选择自羟基，氧化物，卤素，氰基，硝基，单或双C1-4烃基胺基，具有3到12个环成员的碳环和杂环基团的取代基取代，并且C1-8烃基的一个或多个碳原子可以选择性地被0，S，SO，SO2，NRc，X1C（X2），C（X2）X1或X1C（X2）X1取代; Rc是氢或C1-4烃基; X1是O，S或NRc，X2是=O，=S或=NRc。
• 1h-Indazole-3-carboxamide compounds as cyclin dependent kinase (cdk) inhibitors
  申请人：Berdino Valerio

  公开号：US20060135589A1

  公开（公告）日：2006-06-22

  The invention provides a compound of the formula (I) for use in the prophylaxis or treatment of a disease state or condition mediated by a cyclin dependent kinase: wherein A is a group R 2 or CH 2 —R 2 where R 2 is a carbocyclic or heterocyclic group having from 3 to 12 ring members; B is a bond or an acyclic linker group having a linking chain length of up to 3 atoms selected from C, N, S and O; R 1 is hydrogen or a group selected from SO 2 R b , SO 2 NR 7 R 8 , CONR 7 R 8 , NR 7 R 9 and carbocyclic and heterocyclic groups having from 3 to 7 ring members; R 3 , R 4 , R 5 and R 6 are the same or different and are each selected from hydrogen, halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group R a —R b wherein R a is a bond, O, CO, X 1 C(X 2 ), C(X 2 )X 1 , X 1 C(X 2 )X 1 , S, SO, SO 2 , NR c , SO 2 NR c or NR c SO 2 ; and R b is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 12 ring members, and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ; R c is hydrogen or C 1-4 hydrocarbyl; X 1 is O, S or NR c and X 2 is ═O, ═S or ═NR c ; R 7 is selected from hydrogen and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ; R 8 is selected from R 7 and carbocyclic and heterocyclic groups having from 3 to 12 ring members; R 9 is selected from R 8 , COR 8 and SO 2 R 8 ; or NR 7 R 8 or NR 7 R 9 may each form a heterocyclic group having from 5 to 12 ring members; but excluding the compounds N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide and N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide.

  该发明提供了化合物(I)的使用，用于预防或治疗由细胞周期依赖性激酶介导的疾病状态或病情：其中A是R2基团或CH2-R2基团，其中R2是具有3到12个环成员的碳环或杂环基团；B是键或具有链长高达3个C、N、S和O中选择的原子的非环状连接基团；R1是氢或从SO2Rb、SO2NR7R8、CONR7R8、NR7R9和具有3到7个环成员的碳环或杂环基团中选择的基团；R3、R4、R5和R6相同或不同，且每个都从氢、卤素、羟基、三氟甲基、氰基、硝基、羧基、氨基、具有3到12个环成员的碳环或杂环基团中选择；Ra-Rb基团其中Ra是键、O、CO、X1C(X2)、C(X2)X1、X1C(X2)X1、S、SO、SO2、NRc、SO2NRc或NRcSO2；Rb从具有3到12个环成员的碳环或杂环基团和C1-8烃基组中选择，可选地被一个或多个从羟基、氧代、卤素、氰基、硝基、氨基、单个或双个C1-4烃基氨基、具有3到12个环成员的碳环或杂环基团中选择的取代基所取代，其中C1-8烃基组的一个或多个碳原子可选择被O、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1所取代；Rc是氢或C1-4烃基；X1是O、S或NRc，X2是═O、═S或═NRc；R7从氢和可选地被一个或多个从羟基、氧代、卤素、氰基、硝基、氨基、单个或双个C1-4烃基氨基、具有3到12个环成员的碳环或杂环基团中选择的取代基所取代的C1-8烃基中选择，其中C1-8烃基的一个或多个碳原子可选择被O、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1所取代；R8从R7和具有3到12个环成员的碳环或杂环基团中选择；R9从R8、COR8和SO2R8中选择；或NR7R8或NR7R9各自可以形成具有5到12个环成员的杂环基团；但不包括化合物N-[(morpholin-4-yl)phenyl-1H-indazole-3-carboxamide和N-[4-(acetylaminosulphonyl)phenyl-1H-indazole-3-carboxamide]。
• An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
  作者：Marcela Vettorazzi、Emilio Angelina、Santiago Lima、Tomas Gonec、Jan Otevrel、Pavlina Marvanova、Tereza Padrtova、Petr Mokry、Pavel Bobal、Lina M. Acosta、Alirio Palma、Justo Cobo、Janette Bobalova、Jozef Csollei、Ivan Malik、Sergio Alvarez、Sarah Spiegel、Josef Jampilek、Ricardo D. Enriz

  DOI：10.1016/j.ejmech.2017.08.017

  日期：2017.10

  Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b] pyrimido[5,4-f]azepine and two alkyl3-/4-[-1-hydroxy-2-(4-arylpiperazin-1-yl)ethyliphenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands. (C) 2017 Elsevier Masson SAS. All rights reserved.
• BINIECKI S.; PROKOPCZYK B., ROCZ. CHEM. <ROCH-AC>, 1977, 51, NO 11, 2263-2265
  作者：BINIECKI S.、 PROKOPCZYK B.

  DOI：——

  日期：——