<<1-(phenylmethyl)-4-piperidinyl>oxy>acetyl chloride

• 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: <<1-(phenylmethyl)-4-piperidinyl>oxy>acetyl chloride
• 英文别名: 2-(1-Benzylpiperidin-4-yl)oxyacetyl chloride；2-(1-benzylpiperidin-4-yl)oxyacetyl chloride
• 化学式: C₁₄H₁₈ClNO₂
• 分子量: 267.755
• InChiKey: XDUHGOWOLBVNCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  <<1-(phenylmethyl)-4-piperidinyl>oxy>acetyl chloride 、 正丁胺 以 氯仿 为溶剂， 反应 4.0h， 生成 N-butyl<<1-(phenylmethyl)-4-piperidinyl>oxy>acetamide
  参考文献：
  名称：

  2,4-Diamino-6,7-dimethoxyquinazolines. 2. 2-(4-Carbamoylpiperidino) derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents

  摘要：

  A series of 4-amino-2-(4-carbamoylpiperidino)-6,7-dimethoxyquinazolines (2) were synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. These compounds displayed high binding affinity (Ki, 10(-9)-10(-10) M) and selectivity for alpha 1-adrenoceptors in vitro, and 12, 14, 21-26, and 29 showed similar potency to prazosin. Compounds 26 and 28 were also shown to be competitive antagonists of the postjunctional, vasoconstrictor action of norepinephrine with no significant activity at prejunctional alpha 2-sites. The high binding affinity for series 2 is rationalized in terms of enhanced basicity of the quinazoline nucleus (pKa's: 12, 7.38; 26, 7.53; prazosin, 6.8) and hydrophobic interactions of the carbamoyl substituents. Molecular mechanics calculations and computer-assisted superimposition suggest that the quinazoline 2-substituents in prazosin and 2 occupy the alpha 1-adrenoceptor site in different manners. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and 11, 15, 21, 22, and 26 displayed sustained prazosin-like efficacy at the 6-h time point. The high alpha 1-adrenoceptor affinity demonstrated by series 2 in vitro suggests that these marked, and prolonged, falls in blood pressure result from selective blockade of the alpha 1-mediated vasoconstrictor effects of norepinephrine.

  DOI：

  10.1021/jm00389a007
• 作为产物：
  描述：

  <<1-(phenylmethyl)-4-piperidinyl>oxy>acetic acid hydrochloride 在 氯化亚砜 作用下， 生成 <<1-(phenylmethyl)-4-piperidinyl>oxy>acetyl chloride
  参考文献：
  名称：

  2,4-Diamino-6,7-dimethoxyquinazolines. 2. 2-(4-Carbamoylpiperidino) derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents

  摘要：

  A series of 4-amino-2-(4-carbamoylpiperidino)-6,7-dimethoxyquinazolines (2) were synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. These compounds displayed high binding affinity (Ki, 10(-9)-10(-10) M) and selectivity for alpha 1-adrenoceptors in vitro, and 12, 14, 21-26, and 29 showed similar potency to prazosin. Compounds 26 and 28 were also shown to be competitive antagonists of the postjunctional, vasoconstrictor action of norepinephrine with no significant activity at prejunctional alpha 2-sites. The high binding affinity for series 2 is rationalized in terms of enhanced basicity of the quinazoline nucleus (pKa's: 12, 7.38; 26, 7.53; prazosin, 6.8) and hydrophobic interactions of the carbamoyl substituents. Molecular mechanics calculations and computer-assisted superimposition suggest that the quinazoline 2-substituents in prazosin and 2 occupy the alpha 1-adrenoceptor site in different manners. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and 11, 15, 21, 22, and 26 displayed sustained prazosin-like efficacy at the 6-h time point. The high alpha 1-adrenoceptor affinity demonstrated by series 2 in vitro suggests that these marked, and prolonged, falls in blood pressure result from selective blockade of the alpha 1-mediated vasoconstrictor effects of norepinephrine.

  DOI：

  10.1021/jm00389a007

文献信息

• [EN] QUINOLINE DERIVATIVE HAVING TLR INHIBITORY ACTIVITY<br/>[FR] DÉRIVÉ DE QUINOLINE POSSÉDANT UNE ACTIVITÉ INHIBITRICE DE TLR
  申请人：KOWA CO

  公开号：WO2014034719A1

  公开（公告）日：2014-03-06

  TLR3,7 及び/又は9 を阻害し、自己免疫疾患、炎症、ｱﾚﾙｷﾞｰ、喘息、移植片拒絶、GvHD 又は敗血症による心筋症の予防及び/又は治療効果に優れた、次の一般式(1)で示される化合物若しくはその塩又はそれらの溶媒和物。 A: (置換)5-6 員飽和含窒素ヘテロ環 Y: 結合,ﾌｪﾆﾚﾝ Z: 結合,C1-6 ｱﾙｷﾚﾝ,N-R7,O R1,R3,R5-R8: H,C1-3 ｱﾙｷﾙ等 R7: H,C1-6 ｱﾙｷﾙ,2-ﾆﾄﾛﾍﾞﾝｾﾞﾝｽﾙﾎﾆﾙ R2,R4：片方はR8,他方は式(2) (B:(置換)炭素環/複素環; W:C2-6 ｱﾙｹﾆﾚﾝ等; X,V:結合,C(O)NH,NHC(O)等; U:結合,C1-6 ｱﾙｷﾚﾝ 但し、X,V,U 全てが結合の場合は除く)
• 2,4-Diamino-6,7-dimethoxyquinazolines. 2. 2-(4-Carbamoylpiperidino) derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents
  作者：Valerie A. Alabaster、Simon F. Campbell、John C. Danilewicz、Colin W. Greengrass、Rhona M. Plews

  DOI：10.1021/jm00389a007

  日期：1987.6

  A series of 4-amino-2-(4-carbamoylpiperidino)-6,7-dimethoxyquinazolines (2) were synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. These compounds displayed high binding affinity (Ki, 10(-9)-10(-10) M) and selectivity for alpha 1-adrenoceptors in vitro, and 12, 14, 21-26, and 29 showed similar potency to prazosin. Compounds 26 and 28 were also shown to be competitive antagonists of the postjunctional, vasoconstrictor action of norepinephrine with no significant activity at prejunctional alpha 2-sites. The high binding affinity for series 2 is rationalized in terms of enhanced basicity of the quinazoline nucleus (pKa's: 12, 7.38; 26, 7.53; prazosin, 6.8) and hydrophobic interactions of the carbamoyl substituents. Molecular mechanics calculations and computer-assisted superimposition suggest that the quinazoline 2-substituents in prazosin and 2 occupy the alpha 1-adrenoceptor site in different manners. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and 11, 15, 21, 22, and 26 displayed sustained prazosin-like efficacy at the 6-h time point. The high alpha 1-adrenoceptor affinity demonstrated by series 2 in vitro suggests that these marked, and prolonged, falls in blood pressure result from selective blockade of the alpha 1-mediated vasoconstrictor effects of norepinephrine.