1-[1,1-dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropylamino)-2-pyridinyl)amino]piperidine | 179556-73-1

• 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-[1,1-dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropylamino)-2-pyridinyl)amino]piperidine
• 英文别名: 1-[1,1-Dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropyl amino)-2-pyridinyl)amino]piperidine；tert-butyl 4-[methyl-[3-(2-methylbutan-2-ylamino)pyridin-2-yl]amino]piperidine-1-carboxylate
• CAS: 179556-73-1
• 化学式: C₂₁H₃₆N₄O₂
• 分子量: 376.542
• InChiKey: CDIUWUXTDOKHLT-UHFFFAOYSA-N

物化性质

• 沸点：
  492.6±45.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[1,1-dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropylamino)-2-pyridinyl)amino]piperidine 在 palladium on activated charcoal 吡啶 、 氢气 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 1-[5-methanesulfonamidoindole-2-carbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropylamino)-2-pyridinyl)amino]piperidine
  参考文献：
  名称：

  Targeting Delavirdine/Atevirdine Resistant HIV-1:  Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHPSs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.

  DOI：

  10.1021/jm960158n
• 作为产物：
  描述：

  1-(1,1-dimethylethoxycarbonyl)-4-[N-methyl-N-(3-amino-2-pyridinyl)amino]piperidine 在 镍 氢气 、 铜 、 copper(l) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、275.79 kPa 条件下， 反应 23.0h， 生成 1-[1,1-dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(1,1-dimethylpropylamino)-2-pyridinyl)amino]piperidine
  参考文献：
  名称：

  Targeting Delavirdine/Atevirdine Resistant HIV-1:  Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHPSs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.

  DOI：

  10.1021/jm960158n

文献信息

• Substituted indoles as anti-AIDS pharmaceuticals
  申请人：The Upjohn Company

  公开号：US05599930A1

  公开（公告）日：1997-02-04

  Substituted indoles of formula (I) ##STR1## are useful anti-AIDS pharmaceuticals.

  式(I)的取代吲哚化合物是有用的抗艾滋病药物。
• Alkyl substituted piperadinyl and piperazinyl anti-AIDS compounds
  申请人：Pharmacia & Upjohn Company

  公开号：US05866589A1

  公开（公告）日：1999-02-02

  Anti-AIDS compounds of formula (I) ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are as defined in the specification and R.sub.8 is alkyl of substituted alkyl.

  化合物的抗艾滋病公式（I）##STR1##其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5、R.sub.6和R.sub.7如规范中定义，R.sub.8是取代烷基的烷基。
• [EN] ALKYL SUBSTITUTED PIPERADINYL AND PIPERAZINYL ANTI-AIDS COMPOUNDS<br/>[FR] COMPOSES DE PIPERADINYLE ET PIPERAZINYLE ANTI-SIDA A SUBSTITUTION ALKYLE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1996018628A1

  公开（公告）日：1996-06-20

  (EN) Anti-AIDS compounds of formula (I), where the aromatic/heteroaromatic ring is bonded to a carbon atom of the R8 substituent are disclosed as well as specific Anti-AIDS pyridines (V).(FR) L'invention se rapporte à des composés anti-SIDA de la formule (I) dans laquelle le noyau aromatique/hétéroaromatique est lié à un atome de carbone du substituant de R8, ainsi qu'à des pyridines (V) spécifiques anti-SIDA.

  抗艾滋病化合物的公式（I）被揭示，其中芳香/杂环芳香环与R8取代基的一个碳原子结合，以及特定的抗艾滋病吡啶（V）。
• INDOLE DERIVATIVE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0485636A1

  公开（公告）日：1992-05-20

  An indole derivative represented by general formula (1), a pharmacologically acceptable salt thereof, and an immunosuppressant containing the same as an active ingredient, wherein R₁ represents CV₁ to C₅ alkyl, C₄ to C₇ cycloalkylalkyl, C₅ to C₇ cycloalkenylalkyl, C₇ to C₁₄ aralkyl, C₄ or C₅ trans-alkenyl, alkyl, C₁ to C₅ furanyl-2-ylalkyl, C₁ to C₅ thienyl-2-ylalkyl, vinyloxycarbonyl, trichloroethoxycarbonyl, benzyloxycarbonyl, C₁ to C₅ alkanoyl, C₇ to C₁₄ aralkylcarbonyl, 2-furoyl, thiophene-2-carbonyl, C₄ to C₇ cycloalkylcarbonyl, C₃ to C₈ alkenylcarbonyl or anisoyl; R₂ represents hydrogen, C₁ to C₃ alkyl, benzyl or C₁ to C₅ alkanoyl; R₃ represents hydrogen, fluorine, chlorine, bromine, nitro or C₁ to C₅ alkyl; R₄ represents hydrogen, C₁ to C₅ alkyl, benzyl or phenyl; R₅ represents hydrogen, hydroxy or C₁ to C₅ alkanoyloxy; and the general formula includes all of the (+), (-) and (±) forms.

  一种由通式(1)代表的吲哚衍生物、其药理学上可接受的盐，以及一种以其为活性成分的免疫抑制剂，其中R₁代表CV₁至C₅烷基、C₄至C₇环烷基烷基、C₅至C₇环烯基烷基、C₇至C₁₄芳基、C₄ 或 C₅ 反式烯基、烷基、C₁ 至 C₅ 呋喃-2-基烷基、C₁ 至 C₅ 噻吩-2-基烷基、乙烯氧基羰基、三氯乙烷氧基羰基、苄氧基羰基、C₁ 至 C₅ 烷酰基、C₇ 至 C₁ ₄ 芳烷基羰基、2-糠基、噻吩-2-羰基、C₄ 至 C₇ 环烷基羰基、C₃ 至 C₈ 烯基羰基或苯甲酰基；R₂ 代表氢、C₁ 至 C₃ 烷基、苄基或 C₁ 至 C₅ 烷酰基；R₃ 代表氢、氟、氯、溴、硝基或 C₁ 至 C₅ 烷基；R₄ 代表氢、C₁ 至 C₅ 烷基、苄基或苯基； R₅ 代表氢、羟基或 C₁ 至 C₅ 烷酰氧基；通式包括所有 (+)、(-) 和 (±) 形式。
• Method for the production of isoquinoline derivatives and their use as intermediates in the preparation of indole derivatives
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0735026A1

  公开（公告）日：1996-10-02

  An isoquinoline derivative represented by the general formula (101): wherein R101 is a hydrogen atom or a C1-5 alkyl, C4-7 cycloalkylalkyl, C6-8 cycloalkenylalkyl, C7-14 aralkyl, C4-5 transalkenyl, allyl, furanyl-2-ylalkyl, thienyl-2-ylalkyl or R107OCO group (wherein R107 is a 2,2,2-trichloroethyl or benzyl group) or is a R108CO group (wherein R108 is a C1-5 alkyl, C3-6 cycloalkyl, C5-7 cycloalkenyl, phenyl, C7-13 aralkyl, C4-5 trans-alkenyl, vinyl, 2-furanyl or 2-thienyl group), R102, R103, R104 and R105 are each independently a hydrogen atom or a hydroxy, alkanoyloxy having up to 5 carbon atoms or C1-5 alkoxy group or wherein R102 and R103 jointly or R104 and R105 jointly may form oxo or R103 and R104 jointly may form a 1,3-dioxolan ring, R106 is a hydrogen atom or a hydroxy, C1-5 alkoxy or alkanoyloxy group having up to 5 carbon atoms and wherein the general formula (101) embraces a (+) form, a (-) form, and a (±) form, or a pharmacologically acceptable salt thereof; is prepared by oxidizing the carbamate form of an enamine represented by the general formula (103): wherein R102, R103, R104, R105, R106 and R107 are as defined above, thereby forming an oxide represented by the general formula (101a): wherein R102, R103, R104, R105, R106 and R107 are as defined above, and wherein the formula (101a) embraces a (+) form, a (-) form, and a (±) form; and optionally converting the group to any of the other values of the group R101. The compounds are intermediates for the production of pharmaceutically useful indole derivatives.

  由通式(101)代表的异喹啉衍生物： 其中 R101 是氢原子或 C1-5 烷基、C4-7 环烷基、C6-8 环烯基、C7-14 芳基、C4-5 反烯基、烯丙基、呋喃基-2-烷基、噻吩基-2-烷基或 R107OCO 基团（其中 R107 是 2,2、2-三氯乙基或苄基）或 R108CO 基团（其中 R108 是 C1-5 烷基、C3-6 环烷基、C5-7 环烯基、苯基、C7-13 芳基、C4-5 反式烯基、乙烯基、2-呋喃基或 2-噻吩基），R102、R103、R102、R103、R104 和 R105 各自独立地为氢原子或羟基、最多 5 个碳原子的烷酰氧基或 C1-5 烷氧基，或其中 R102 和 R103 共同或 R104 和 R105 共同可形成氧代或 R103 和 R104 共同可形成 1、3-二氧戊环，R106 是氢原子或具有最多 5 个碳原子的羟基、C1-5 烷氧基或烷酰氧基，其中通式 (101) 包含 (+) 形式、(-) 形式和 (±) 形式，或其药理上可接受的盐；通过氧化通式（103）代表的烯胺的氨基甲酸酯形式制备： 其中 R102、R103、R104、R105、R106 和 R107 如上定义，从而形成通式 (101a) 所代表的氧化物： 其中 R102、R103、R104、R105、R106 和 R107 如上所定义，式 (101a) 包含 (+) 形式、(-) 形式和 (±) 形式；并可选择地将基团转化为 转化为基团 R101 的任何其他值。这些化合物是生产药用吲哚衍生物的中间体。