N-butyl-3-piperidinecarboxamide | 73415-66-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-butyl-3-piperidinecarboxamide
• 英文别名: N-butylpiperidine-3-carboxamide
• CAS: 73415-66-4
• 化学式: C₁₀H₂₀N₂O
• 分子量: 184.282
• InChiKey: YXJXOPXCTGLNEU-UHFFFAOYSA-N

物化性质

• 沸点：
  352.3±31.0 °C(Predicted)
• 密度：
  0.959±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 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：
  41.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-butyl-3-piperidinecarboxamide 、 2-氯-4-氨基-6,7-二甲氧基喹唑啉 在 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 24.0h， 生成 1-(4-amino-6,7-dimethoxy-quinazolin-2-yl)-piperidine-3-carboxylic acid butylamide
  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：

  烟酰氯 在 platinum(IV) oxide 氢气 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 30.0 ℃ 、344.73 kPa 条件下， 生成 N-butyl-3-piperidinecarboxamide
  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] INHIBITORS OF ARGININE GINGIPAIN<br/>[FR] INHIBITEURS D'ARGININE GINGIPAÏNE
  申请人：CORTEXYME INC

  公开号：WO2017083433A1

  公开（公告）日：2017-05-18

  The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its proteases arginine gingipain A/B (Rgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

  本发明通常涉及治疗靶向细菌 Porphyromonas gingivalis 的治疗药物，包括其蛋白酶精氨酸龈蛋白酶 A/B（Rgp），以及它们用于治疗与 P. gingivalis 感染相关的疾病，包括脑部疾病如阿尔茨海默病。在某些实施例中，本发明提供根据本文所述的 Formula I 的化合物及其药用盐。
• 4-Amino-2-piperidino-quinazolines
  申请人：Pfizer Inc.

  公开号：US04243666A1

  公开（公告）日：1981-01-06

  Regulators of the cardiovascular system and, in particular, in the treatment of hypertension having the formula ##STR1## wherein R is lower alkyl; X, is a 3- or 4-position substituent and is --(CH.sub.2).sub.n CONR.sup.1 R.sup.2, --O(CH.sub.2).sub.n CONR.sup.1 R.sup.2 or ##STR2## wherein n is 0, 1 or 2; R.sup.1 is hydrogen or lower alkyl, and R.sup.2 is lower alkyl; lower alkenyl, lower alkynyl, phenyl, substituted phenyl, C.sub.3 -C.sub.7 cycloalkyl; lower alkyl substituted by phenyl, substituted phenyl, C.sub.3 -C.sub.7 cycloalkyl, halogen, trifluoromethyl, hydroxy, lower alkoxy, lower alkoxycarbonyl, phenoxy, substituted phenoxy or --NR.sup.3 R.sup.4 wherein R.sup.3 and R.sup.4 each represent hydrogen, lower alkyl, lower alkanoyl or lower alkylsulfonyl; with the proviso that any O, N or halogen atom in R.sup.2 is separated by at least 2 carbon atoms from the nitrogen atom to which R.sup.2 is attached; or R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached form a morpholino group optionally substituted by one or two lower alkyl groups, or a 1,2,3,4-tetrahydroisoquinolyl group optionally substituted on the benzene ring portion by one or two lower alkoxy groups; the pharmaceutically acceptable bioprecursors therefor, and the pharmaceutically acceptable acid addition salts thereof.

  心血管系统的调节剂，尤其是治疗高血压的化合物，其化学式为##STR1##其中R为低碳基；X为3-或4-位置取代基，为--(CH.sub.2).sub.n CONR.sup.1 R.sup.2，--O(CH.sub.2).sub.n CONR.sup.1 R.sup.2或##STR2##其中n为0、1或2；R.sup.1为氢或低碳基，R.sup.2为低碳基；低碳烯基，低碳炔基，苯基，取代苯基，C.sub.3-C.sub.7环烷基；被苯基，取代苯基，C.sub.3-C.sub.7环烷基，卤素，三氟甲基，羟基，低碳基氧，低碳基氧羰基，苯氧基，取代苯氧基或--NR.sup.3 R.sup.4，其中R.sup.3和R.sup.4各代表氢，低碳基，低碳基酰基或低碳基磺酰基；但要求R.sup.2中的任何O、N或卤素原子与R.sup.2连接的氮原子之间至少相隔2个碳原子；或R.sup.1和R.sup.2与它们连接的氮原子一起形成一个吗啡啶基团，可选择地被一个或两个低碳基取代，或一个1,2,3,4-四氢异喹啉基团，可选择地在苯环部分上被一个或两个低碳基氧基取代；其药学上可接受的生物前体，以及其药学上可接受的酸加合物盐。
• INHIBITORS OF ARGININE GINGIPAIN
  申请人：Cortexyme, Inc.

  公开号：EP3374352A1

  公开（公告）日：2018-09-19
• US4243666A
  申请人：——

  公开号：US4243666A

  公开（公告）日：1981-01-06
• [EN] DERIVATIVES OF FLUORENE, ANTHRACENE, XANTHENE, DIBENZOSUBERONE AND ACRIDINE AND USES THEREOF<br/>[FR] DÉRIVÉS DU FLUORÈNE, DE L'ANTHRACÈNE, DU XANTHÈNE, DU DIBENZOSUBÉRONE ET DE L'ACRIDINE ET LEURS UTILISATIONS
  申请人：AVALON PHARMACEUTICALS

  公开号：WO2008140792A1

  公开（公告）日：2008-11-20

  [EN] Chemical agents, such as disulfonamide derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine, and similar heterocyclic ring structures, including salts thereof, that act as anti-cancer and anti-tumor agents, especially where such agents modulate the activity of the Wnt/ß-catenin signaling pathway, and serve to reduce ß-catenin levels present in cells, such as cancer cells, or where the agents modulate levels of gene expression in cellular systems, including cancer cells, are disclosed, along with methods for preparing such agents, as well as pharmaceutical compositions containing such agents as active ingredients and methods of using these as therapeutic agents.
  [FR] La présente invention concerne des agents chimiques, tels que les dérivés disulfonamide du fluorène, de l'anthracène, du xanthène, du dibenzosubérone et de l'acridine, et des structures en anneaux hétérocycliques similaires, y compris leurs sels, qui agissent comme agents anticancéreux et antitumoraux, en particulier lorsque ces agents régulent l'activité de la voie de signalisation de la Wnt/ß-caténine et servent à réduire les niveaux de ß-caténine présents dans les cellules, telles que les cellules cancéreuses, ou lorsque les agents régulent les niveaux d'expression des gènes dans les systèmes cellulaires, y compris les cellules cancéreuses. La présente invention concerne également les procédés de préparation de ces agents, ainsi que des compositions pharmaceutiques les contenant en tant qu'ingrédients actifs et les procédés de leur utilisation comme agents thérapeutiques.