4-acetyl-1-(3-aminopropyl)-4-phenylpiperidine | 166809-67-2

• 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-acetyl-1-(3-aminopropyl)-4-phenylpiperidine
• 英文别名: 1-[1-(3-aminopropyl)-4-phenylpiperidin-4-yl]ethanone
• CAS: 166809-67-2
• 化学式: C₁₆H₂₄N₂O
• 分子量: 260.379
• InChiKey: NTQVHBVWXDUWGU-UHFFFAOYSA-N

物化性质

• 沸点：
  397.6±42.0 °C(Predicted)
• 密度：
  1.045±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-carboxamido-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)pyridine-3-carboxylic acid 、 4-acetyl-1-(3-aminopropyl)-4-phenylpiperidine 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 2,6-Dimethyl-4-(4-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-{[3-(4-acetyl-4-phenyl-piperidin-1-yl)-propyl]-amide} 5-amide
  参考文献：
  名称：

  Design and Synthesis of Novel α_1a Adrenoceptor-Selective Dihydropyridine Antagonists for the Treatment of Benign Prostatic Hyperplasia

  摘要：

  We report the synthesis and evaluation of novel alpha(1a) adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha(1a), antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a K-i of 2.8 nM, in agreement with the cloned human receptor binding data (K-i = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a K-i of 3.6 nM and confirmed it to be a potent antagonist (K-b = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP K-b/IUP K-b ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha(1a) adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha(1) antagonists such as prazosin and terazosin, with fewer side effects.

  DOI：

  10.1021/jm980506g
• 作为产物：
  描述：

  1-(4-苯基哌啶-4-基)乙酮 、 3-溴丙胺氢溴酸盐 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以40%的产率得到4-acetyl-1-(3-aminopropyl)-4-phenylpiperidine
  参考文献：
  名称：

  Dihydropyridines and new uses thereof

  摘要：

  该发明提供了一种治疗良性前列腺增生的方法，包括向受试者施用具有以下结构的化合物的治疗有效量： 其中Y为--(CH.sub.2).sub.n --，其中n为1、2、3、4或5；--(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为2、3或4；--(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --；或--(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为1、2、3或4；其中Z为O、NH或CH.sub.2；其中R.sup.1为线性或支链烷基、烷氧基烷基或芳基烷基；其中R.sup.2和R.sup.4独立且相同或不同，为H，或线性或支链烷基；其中R.sup.3为H、线性或支链烷基、烷氧基、烷氧基烷基或酰基；其中R.sup.5和R.sup.6独立且相同或不同，为H、OH、Cl、Br、F、NO.sub.2、CN、CF.sub.3或NH.sub.2，或线性或支链烷基、烷氧基、烷氧羰基、酰基、烷基亚砜、烷基砜、或单烷基或二烷基氨基基团。还公开了含有一、两个或三个环的其他活性化合物，以及由此制备的药物组合物和在治疗BPH、抑制胆固醇合成和降低眼压中的使用方法。

  公开号：

  US05767131A1

文献信息

• DNA encoding a human melanin concentrating hormone receptor (MCH1) and uses thereof
  申请人：——

  公开号：US20030082623A1

  公开（公告）日：2003-05-01

  This invention provides an isolated nucleic acid encoding a human MCH1 receptor, a purified human MCH1 receptor, vectors comprising isolated nucleic acid encoding a human MCH1 receptor, cells comprising such vectors, antibodies directed to a human MCH1 receptor, nucleic acid probes useful for detecting nucleic acid encoding human MCH1 receptors, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding human MCH1 receptors, transgenic, nonhuman animals which express DNA encoding a normal or mutant human MCH1 receptor, methods of isolating a human MCH1 receptor, methods of treating an abnormality that is linked to the activity of a human MCH1 receptor, as well as methods of determining binding of compounds to mammalian MCH1 receptors. This invention provides a method of modifying the feeding behavior of a subject which comprises administering to the subject an amount of an MCH1 antagonist effective to decrease the body mass of the subject and/or decrease the consumption of food by the subject. This invention further provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of an MCH1 antagonist effective to treat the subject's depression and/or anxiety.

  这项发明提供了编码人类MCH1受体的孤立核酸，纯化的人类MCH1受体，包括编码人类MCH1受体的孤立核酸的载体，包含这种载体的细胞，针对人类MCH1受体的抗体，用于检测编码人类MCH1受体的核酸探针，互补于编码人类MCH1受体独特序列的反义寡核苷酸，表达编码正常或突变人类MCH1受体的转基因非人类动物，孤立人类MCH1受体的分离方法，治疗与人类MCH1受体活性相关的异常的方法，以及确定化合物与哺乳动物MCH1受体结合的方法。这项发明提供了一种修改受试者摄食行为的方法，包括向受试者投与足以减少受试者体重和/或减少受试者食物摄入量的MCH1拮抗剂的量。这项发明还提供了一种治疗患有抑郁和/或焦虑的受试者的方法，包括向受试者投与足以治疗受试者抑郁和/或焦虑的MCH1拮抗剂的量。
• Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof
  申请人：——

  公开号：US20030069261A1

  公开（公告）日：2003-04-10

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of modifying feeding behavior of a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. This invention further provides a method of treating a feeding disorder in a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. In an embodiment of the invention, the feeding disorder is bulimia, bulimia nervosa or obesity.

  这项发明涉及选择性拮抗黑素浓集激素-1（MCH1）受体的化合物。该发明提供了一种包括所述化合物的治疗有效量和药学可接受载体的药物组合物。该发明提供了一种通过结合本发明化合物的治疗有效量和药学可接受载体制备的药物组合物。该发明还提供了一种制备药物组合物的方法，包括结合本发明化合物的治疗有效量和药学可接受载体。该发明还提供了一种修改受试者进食行为的方法，包括向受试者投与本发明化合物的有效量以减少受试者的食物摄入量。该发明还提供了一种治疗受试者进食障碍的方法，包括向受试者投与本发明化合物的有效量以减少受试者的食物摄入量。在该发明实施方式中，进食障碍可以是暴食症、暴食症神经质或肥胖症。
• [EN] SELECTIVE MELANIN CONCENTRATING HORMONE-1 (MCH1) RECEPTOR ANTAGONISTS AND USES THEREOF<br/>[FR] ANTAGONISTES SELECTIFS DES RECEPTEURS (MCH1) D'HORMONE-1 DE CONCENTRATION DE LA MELANINE ET UTILISATION DE CEUX-CI
  申请人：SYNAPTIC PHARMARCEUTICAL CORP

  公开号：WO2002006245A1

  公开（公告）日：2002-01-24

  This invention is directed to compounds which are selective antagonists for melanin concentrating hormone-1 (MCH1) receptors. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention provides a pharmaceutical composition made by combining a therapeutically effective amount of the compound of this invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of modifying feeding behavior of a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. This invention further provides a method of treating a feeding disorder in a subject which comprises administering to the subject an amount of a compound of the invention effective to decrease the consumption of food by the subject. In an embodiment of the invention, the feeding disorder is bulimia, bulimia nervosa or obesity.

  本发明涉及选择性拮抗黑色素浓集激素-1（MCH1）受体的化合物。本发明提供一种制药组合物，包括本发明的化合物的治疗有效量和药学上可接受的载体。本发明提供了一种制药组合物，其由本发明的化合物的治疗有效量和药学上可接受的载体组合而成。本发明还提供一种制备制药组合物的方法，包括将本发明的化合物的治疗有效量和药学上可接受的载体组合。本发明还提供了一种修改受试者进食行为的方法，包括向受试者施用本发明的化合物的有效量，以减少受试者的食物摄入量。本发明还提供了一种治疗受试者进食障碍的方法，包括向受试者施用本发明的化合物的有效量，以减少受试者的食物摄入量。在本发明的实施方式中，进食障碍是贪食症、神经性贪食症或肥胖症。
• Morpholinone and morpholine derivatives and uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20030212062A1

  公开（公告）日：2003-11-13

  This invention is directed to morpholinone and morpholine derivatives which are selective antagonists for human &agr; 1a receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia, sympathetic mediated pain, migraine, and for the treatment of any disease where the antagonism of the &agr; 1a receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

  本发明涉及形式酰胺基吗啡和吗啡啶衍生物，其为人类α1a受体的选择性拮抗剂。本发明还涉及使用这些化合物降低眼压、抑制胆固醇合成、放松下尿道组织、治疗良性前列腺增生、阳痿、心律失常、交感介导的疼痛、偏头痛以及治疗任何可能有用的α1a受体拮抗剂的疾病。本发明还提供了一种药物组合物，包括上述定义的化合物的治疗有效量和药学上可接受的载体。
• MORPHOLINONE AND MORPHOLINE DERIVATIVES AND USES THEREOF
  申请人：SYNAPTIC PHARMACEUTICAL CORPORATION

  公开号：EP1140876A1

  公开（公告）日：2001-10-10