acetoacetic acid N-[3-(4,4-diphenylpiperidin-1-yl)propyl]amide | 157066-75-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: acetoacetic acid N-[3-(4,4-diphenylpiperidin-1-yl)propyl]amide
• 英文别名: N-(3-(4,4-diphenylpiperidin-1-yl)propyl)acetoacetamide；N-[3-(4,4-Diphenyl-piperidin-1-yl)-propyl]-3-oxo-butyramide；N-[3-(4,4-diphenylpiperidin-1-yl)propyl]-3-oxobutanamide
• CAS: 157066-75-6
• 化学式: C₂₄H₃₀N₂O₂
• 分子量: 378.514
• InChiKey: MZEHCTSKFFQDIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  574.2±50.0 °C(predicted)
• 密度：
  1.089±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对甲基苯甲醛 、 methyl (E)-3-aminocrotonate 、 acetoacetic acid N-[3-(4,4-diphenylpiperidin-1-yl)propyl]amide 以 异丙醇 为溶剂， 以33%的产率得到Methyl 5-[3-(4,4-diphenylpiperidin-1-yl)propylcarbamoyl]-2,6-dimethyl-4-(4-methylphenyl)-1,4-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  Identification of a Dihydropyridine as a Potent α_1a Adrenoceptor-Selective Antagonist That Inhibits Phenylephrine-Induced Contraction of the Human Prostate

  摘要：

  A number of novel dihydropyridine derivatives based upon 1,4-dihydro-3-(methoxycarbonyl)-2,6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, diphenylpiperdin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human a adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2,6-dimethyl-4-(4-nitrophenyl)- 3-((3-(4,4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha(1a) adrenoceptor (pK(i) = 8.73) and potently inhibited (pA(2) = 9.23) phenylephrine-induced contraction of the human prostate.

  DOI：

  10.1021/jm980077m
• 作为产物：
  描述：

  3-(4,4-Diphenylpiperidin-1-yl)propionitrile 在 硼烷四氢呋喃络合物 作用下， 以 甲苯 为溶剂， 生成 acetoacetic acid N-[3-(4,4-diphenylpiperidin-1-yl)propyl]amide
  参考文献：
  名称：

  基于L型Ca2 +通道拮抗剂niguldipine的alpha 1a-肾上腺素受体拮抗剂的发现。

  摘要：

  DOI：

  10.1021/jm00010a001

文献信息

• Aromatic amine derivatives
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05508306A1

  公开（公告）日：1996-04-16

  This invention relates to novel aromatic amine compounds having the structure: ##STR1## where each W, Z.sup.1 and Z.sup.2 is independently H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, OH, F, Cl, Br, I, NO.sub.2, CN, SO.sub.2 NHR.sup.3, NR.sup.4.sub.2, CONR.sup.3.sub.2, COR.sup.5 ; where each R.sup.1 and R.sup.2 is independently H, C.sub.1 -C.sub.6 straight or branched chain alkyl or phenyl; where each X and Y is independently CH.sub.2, NR.sup.4, S, S.dbd.O, SO.sub.2 ; where n is 0, 1 or 2; where each p and q is independently 1 or 2; where R.sup.3 is H, C.sub.1 -C.sub.6 straight or branched chain alkyl or phenyl; where R.sup.4 is H, C.sub.1 -C.sub.6 straight or branched chain alkyl or COR.sup.3 ; and where R.sup.5 is H, C.sub.1 -C.sub.6 straight or branched chain alkyl or phenyl, C.sub.1 -C.sub.6 straight or branched chain alkoxy or OH. In addition the invention includes using such compounds for the treatment of benign prostatic hyperplasia, lowering intraocular pressure and inhibiting cholesterol synthesis.

  这项发明涉及具有以下结构的新型芳香胺化合物：其中每个W，Z.sup.1和Z.sup.2独立地为H，C.sub.1 -C.sub.6烷基，C.sub.1 -C.sub.6烷氧基，OH，F，Cl，Br，I，NO.sub.2，CN，SO.sub.2NHR.sup.3，NR.sup.4.sub.2，CONR.sup.3.sub.2，COR.sup.5；其中每个R.sup.1和R.sup.2独立地为H，C.sub.1 -C.sub.6直链或支链烷基或苯基；其中每个X和Y独立地为CH.sub.2，NR.sup.4，S，S.dbd.O，SO.sub.2；其中n为0、1或2；其中每个p和q独立地为1或2；其中R.sup.3为H，C.sub.1 -C.sub.6直链或支链烷基或苯基；其中R.sup.4为H，C.sub.1 -C.sub.6直链或支链烷基或COR.sup.3；其中R.sup.5为H，C.sub.1 -C.sub.6直链或支链烷基或苯基，C.sub.1 -C.sub.6直链或支链烷氧基或OH。此外，该发明还包括使用这些化合物治疗良性前列腺增生、降低眼内压和抑制胆固醇合成。
• Use of .alpha.-1C specific compounds to treat benign prostatic
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05578611A1

  公开（公告）日：1996-11-26

  The subject invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human .alpha..sub.1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human .alpha..sub.1A adrenergic receptor, a human .alpha..sub.1B adrenergic receptor, a human histamine H.sub.1 receptor and .alpha..sub.2 adrenergic receptor. The subject invention also provides a method of inhibiting contraction of prostate tissue which comprises contacting the prostate tissue with an effective contraction-inhibiting amount of such compound.

  该发明提供了一种治疗良性前列腺增生的方法，包括向受试者施用一种与人类α1C肾上腺素受体结合的化合物的治疗有效量，其结合亲和力比化合物与人类α1A肾上腺素受体、人类α1B肾上腺素受体、人类组胺H1受体和α2肾上腺素受体结合的亲和力高出十倍以上。该发明还提供了一种抑制前列腺组织收缩的方法，包括用该化合物接触前列腺组织，使其受到有效的抑制收缩作用的量。
• Use of .alpha..sub.1C specific compounds to treat benign prostatic
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05403847A1

  公开（公告）日：1995-04-04

  A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human .alpha..sub.1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human .alpha..sub.1A adrenergic receptor, a human .alpha..sub.1B adrenergic receptor, and a human histamine H.sub.1 receptor, and, binds to a human .alpha..sub.2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such .alpha..sub.1C adrenergic receptor. Compounds meeting these criteria are provided.

  一种治疗良性前列腺增生的方法，包括向患者投与一种与人类α1C肾上腺素受体结合的化合物的治疗有效量，其结合亲和力比其与人类α1A肾上腺素受体、人类α1B肾上腺素受体和人类组胺H1受体结合的亲和力高出十倍以上，并且与人类α2肾上腺素受体结合的亲和力比其与该α1C肾上腺素受体结合的亲和力低出十倍以上。提供符合这些标准的化合物。
• Use of alpha-1C specific compounds to treat benign prostatic hyperplasia
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US06015819A1

  公开（公告）日：2000-01-18

  A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human .alpha..sub.1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human .alpha..sub.1A adrenergic receptor, a human .alpha..sub.1B adrenergic receptor, and a human histamine H.sub.1 receptor, and, binds to a human .alpha..sub.2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such .alpha..sub.1C adrenergic receptor. Compounds meeting these criteria are provided.

  一种治疗良性前列腺增生的方法，包括向受试者投予与人类α1C肾上腺素受体结合的化合物的治疗有效量，其结合亲和力比其与人类α1A肾上腺素受体、人类α1B肾上腺素受体和人类组胺H1受体结合的亲和力高出十倍以上，并且与人类α2肾上腺素受体结合的亲和力比其与该α1C肾上腺素受体结合的亲和力低出十倍以上。提供符合这些标准的化合物。
• Dihydropyridines and new uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US20020193599A1

  公开（公告）日：2002-12-19

  The invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound having the structure: 1 wherein Y is —(CH 2 ) n —, where n is 1, 2, 3, 4 or 5; —(CH 2 ) b —O—(CH 2 ) k —, where h and k are independently the same or different and are 2, 3 or 4; —(CH 2 ) b —CH═CH—(CH 2 ) k —; or —(CH 2 ) h —C═C—(CH 2 ) k —, where h and k are independently the same or different and are 1, 2, 3 or 4; wherein Z is O, NH, or CH 2 ; wherein R 1 is a linear or branched chain alkyl, alkoxyalkyl or arylalkyl group; wherein R 2 and R 4 are independently the same or different and are H, or a linear or branched chain alkyl group; wherein R 3 is H, a linear or branched chain alkyl, alkoxy, alkoxyalkyl or acyl group; and wherein R 5 and R 6 are independently the same or different and are H, OH, Cl, Br, F, NO 2 , CN, CF 3 , or NH 2 , or a linear or branched chain alkyl, alkoxy, alkoxycarbonyl, acyl, alkylsulfoxide, alkylsulfone, or mono- or dialkylamino group. Other active compounds containing one, two or three rings are also disclosed as well as pharmaceutical compositions prepared therefrom and methods of use in the treatment of BPH, inhibition of cholesterol synthesis, and reduction of intraocular pressure.

  本发明提供了一种治疗良性前列腺增生症的方法，该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：1其中，Y为—(CH2)n—，其中n为1、2、3、4或5；—(CH2)b—O—(CH2)k—，其中h和k独立且相同或不同，为2、3或4；—(CH2)b—CH═CH—(CH2)k—；或—(CH2)h—C═C—(CH2)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CH2；R1为线性或支链烷基、烷氧基烷基或芳基烷基；R2和R4独立且相同或不同，为H或线性或支链烷基；R3为H、线性或支链烷基、烷氧基、烷氧基烷基或酰基；R5和R6独立且相同或不同，为H、OH、Cl、Br、F、NO2、CN、CF3或NH2，或线性或支链烷基、烷氧基、烷氧基羰基、酰基、烷基亚砜、烷基磺酸、或单烷基或双烷基氨基。还公开了其他含有一个、两个或三个环的活性化合物，以及由此制备的药物组成物和用于治疗BPH、抑制胆固醇合成和降低眼压的使用方法。