4-(3-tert-Butoxy-propyl)-piperidine | 184042-88-4

• 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-(3-tert-Butoxy-propyl)-piperidine
• 英文别名: 4-[3-[(2-Methylpropan-2-yl)oxy]propyl]piperidine
• CAS: 184042-88-4
• 化学式: C₁₂H₂₅NO
• 分子量: 199.337
• InChiKey: RMQYXBGJWZKNMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-tert-Butoxy-propyl)-piperidine 在 N-甲基吗啉 、 盐酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency

  摘要：

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

  DOI：

  10.1021/jm9811209
• 作为产物：
  描述：

  3-(4-哌啶基)-1-丙醇 、 异丁烯 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 4-(3-tert-Butoxy-propyl)-piperidine
  参考文献：
  名称：

  Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency

  摘要：

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

  DOI：

  10.1021/jm9811209

文献信息

• [EN] TRYPSIN AND THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE TRYPSINE ET DE THROMBINE
  申请人：NOVARTIS AG

  公开号：WO1996029327A1

  公开（公告）日：1996-09-26

  (EN) The present invention provides a compound of general formula (I), in which Ar is a substituted or unsubstituted aryl or heterocyclic residue; Aa is an amino acid residue usually of L configuration and (a) is a residue of formula (IV) or formula (V), wherein X is hydrogen or a C1-C5 alkyl group; Y is a) an SO3H, PO(OR14)2, OH, SH, NR15R16, or halogen group or is b) a residue -(CqH2q)-Q wherein Q is H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 or Hal wherein R14, R15 and R16 are hydrogen, C1-C5 alkyl, C5-C8 cycloalkyl or C7-C11 aralkyl or R15 and R16 together with the nitrogen atom to which they are bound form a 5 or 6 membered azacycloalkyl or oxazacycloalkyl, q is 0 or an integer from 1 to 8 and the residue CqH2q may be optionally substituted by OH or interrupted by oxygen, sulfur, oxycarbonyl O.CO, carbonyloxy CO.O, aminocarbonyl NHCO, sulfonamido, NHSO2 or carboxamido CONH; or is c) a residue (CwH2w+1-y-z)FyOHz in which w is an integer from 1 to 8, y is an integer from 1 to 17 and z is 0 or 1, or X and Y together are = O, Z is a direct bond, oxygen or nitrogen optionally substituted by X or Y, m = 2 to 4, n = 2 to 4 and m + n = 4 to 6, j = 0 to 2, k = 0 to 2 and j + k = 2 or 3, wherein X has its previous significance and Y is a residue (CqH2q)-Q, wherein q and Q have their previous significance, and salts thereof, provided that when As is arginine, X and Y are not alkyl and when Q is COR14, q is an integer from 1 to 8.(FR) La présente invention concerne un composé de la formule générale (I). Dans cette formule, Ar est un reste aryle ou hétérocyclique, substitué ou non; Aa est un reste d'acide aminé ayant généralement la configuration L et (a) est un reste ayant la formule (IV) ou (V). Dans ces formules, X est un hydrogène ou un groupe alkyle C1-C5, Y est a) un SO3H, PO(OR14)2, OH, SH, NR15R16 ou un groupe halogène, ou b) un reste -(CqH2q)-Q où Q est H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 ou Hal où R14, R15 et R16 représentent hydrogène, alkyle C1-C5, cycloalkyle C5-C8 ou aralkyle C7-C11 ou R15 et R16 forment ensemble avec l'atome d'azote auquel ils sont fixés un azacycloalkyle ou un oxazacycloalkyle à 5 - 6 éléments, q est égal à 0 ou à un nombre entier compris entre 1 et 8 et le reste CqH2q peut être, à titre facultatif, substitué par un OH ou interrrompu par un oxygène, un soufre, un oxycarbonyle O.CO, un carbonyloxy CO.O, un aminocarbonyle NHCO, un sulfonamido NHSO2 ou un carboxamido CONH; ou c), un reste (CwH2w+1-y-z)FyOHz dans lequel w est un nombre entier entre 1 et 8, y est un nombre entier entre 1 et 17 et z est égal à 0 ou 1, ou X et Y ensemble = 0, Z est une liaison directe, un oxygène ou un azote substitué éventuellement par X ou Y, m = 2 à 4, et m + n = 4 à 6, j = 0 à 2, k = 0 à 2 et j + k = 2 ou 3, où X a la signification précédente et Y représente un reste (CqH2q)-Q où q et Q ont la signification précédente. L'invention concerne également les sels de ces composés, à condition que, quand Aa représente l'arginine, X et Y ne représentent pas alkyle et quand Q représente COR14, q représente un nombre entier entre 1 et 8.

  本发明提供了一种通式（I）的化合物，其中Ar是取代或未取代的芳基或杂环残基; Aa通常是L构型的氨基酸残基，而（a）是式（IV）或式（V）的残基，其中X是氢或C1-C5烷基基团; Y是a）SO3H、PO（OR14）2、OH、SH、NR15R16或卤素基团，或者b）残基-(CqH2q)-Q，其中Q是H、COR14、CO2R14、CONR15R16、SO3H、OR14、OCOR14、PO（OR14）2、NR15R16、SR14或Hal，其中R14、R15和R16是氢、C1-C5烷基、C5-C8环烷基或C7-C11芳基烷基，或者R15和R16与它们所连接的氮原子形成5或6元杂环烷基或氧杂环烷基，q是0或1-8的整数，而残基CqH2q可以选择性地被OH取代或被氧、硫、氧羰基O.CO、羰氧基CO.O、氨基羰基NHCO、磺酰胺基NHSO2或羧酰胺基CONH打断；或者c）残基（CwH2w+1-y-z）FyOHz，其中w是1-8的整数，y是1-17的整数，z是0或1，或者X和Y一起是=O，Z是直接键，氧或氮，可选地被X或Y取代，m=2-4，n=2-4，m+n=4-6，j=0-2，k=0-2，j+k=2或3，其中X具有其先前的意义，而Y是残基（CqH2q）-Q，其中q和Q具有其先前的意义，以及其盐，但当Aa为精氨酸时，X和Y不是烷基，而当Q为COR14时，q是1-8的整数。
• QUINOLINONE DERIVATIVES
  申请人：Renhowe A. Paul

  公开号：US20080070906A1

  公开（公告）日：2008-03-20

  Organic compounds having the formulas I and II are provided where the variables have the values described herein. Pharmaceutical formulations include the organic compounds or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier and may be prepared by mixing the organic compounds or pharmaceutically acceptable salts of the organic compounds with a carrier and water. A method of treating a patient includes administering a pharmaceutical formulation according to the invention to a patient in need thereof.

  提供了具有I和II公式的有机化合物，其中变量具有所述数值。制药配方包括有机化合物或其药学上可接受的盐以及药学上可接受的载体，并且可以通过将有机化合物或其药学上可接受的盐与载体和水混合来制备。治疗患者的方法包括向需要该药物的患者注射本发明的制药配方。
• Heterocyclic compounds
  申请人：Renhowe A. Paul

  公开号：US20070032528A1

  公开（公告）日：2007-02-08

  Organic compounds having the structural formula I are provided where the variables have the values described herein and R 1 and R 2 join together to form a 6 membered substituted or unsubstituted ring including at least one O, N, or S atom, and Z is an O, S, NH or NR group. Pharmaceutical formulations include the organic compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

  提供结构式I的有机化合物，其中变量具有此处描述的值，R1和R2结合形成一个6元取代或未取代环，其中包括至少一个O、N或S原子，Z是一个O、S、NH或NR基团。制药配方包括该有机化合物或其药学上可接受的盐和药学上可接受的载体。
• Benzimidazole quinolinones and uses thereof
  申请人：Barsanti Paul A.

  公开号：US20090281100A1

  公开（公告）日：2009-11-12

  Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

  提供了抑制各种酶和治疗各种疾病的方法，包括向受试者施用I或IB结构化合物，其药学上可接受的盐，其互变异构体或其药学上可接受的互变异构体盐。具有结构I和IB的化合物具有以下结构，并具有此处描述的变量。这些化合物可以用于制备药物，用于抑制各种酶的作用，并用于治疗由这些酶介导的疾病。
• METHODS FOR SYNTHESIZING HETEROCYCLIC COMPOUNDS.
  申请人：Galvin Gabriel

  公开号：US20110046376A1

  公开（公告）日：2011-02-24

  A method for synthesizing a heterocyclic compound includes: reacting 1-methylpiperazine with 5-chloro-2-nitroaniline at an internal temperature sufficient to provide a compound of Formula VIH The 1-methylpiperazine and the 5-chloro-2-nitroaniline are reacted in a solvent that comprises water in an amount greater than 50 percent by volume based on the amount of the solvent and/or are reacted in a solvent that comprises an organic solvent component that has a boiling point of greater than 100° C. at atmospheric pressure.

  一种合成杂环化合物的方法包括：在足够高的内部温度下反应1-甲基哌嗪和5-氯-2-硝基苯胺，以提供式VIH的化合物。1-甲基哌嗪和5-氯-2-硝基苯胺在溶剂中反应，该溶剂包含水，其体积占溶剂总量的50％以上，和/或在沸点大于100℃的有机溶剂组分中反应。