(S)-(+)-2-(tritylamino)butan-1-ol | 176315-10-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (S)-(+)-2-(tritylamino)butan-1-ol
• 英文别名: (S)-2-(trityl-amino)-butan-1-ol；(S)-2-(tritylamino)butan-1-ol；(2S)-2-(tritylamino)butan-1-ol
• CAS: 176315-10-9
• 化学式: C₂₃H₂₅NO
• 分子量: 331.458
• InChiKey: CSJUGIJIZSGDQL-QFIPXVFZSA-N

物化性质

• 沸点：
  481.8±40.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-(+)-2-(tritylamino)butan-1-ol 在 草酰氯 、 copper(I) bromide dimethylsulfide complex 、 二甲基亚砜 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 (3RS,4S)-2-methyl-4-(tritylamino)hexan-3-ol
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitors

  摘要：

  The cyclin-dependent kinase (CDK) inhibitor seliciclib (1, CYC202) is in phase II clinical development for the treatment of cancer. Here we describe the synthesis of novel purines with greater solubility, lower metabolic clearance, and enhanced potency versus CDKs. These compounds exhibit novel selectivity profiles versus CDK isoforms. Compound alpha SbR-21 inhibits CDK2/cyclin E with IC(50) = 30 nM, CDK7-cyclin H with IC(50) = 1.3 mu M, and CDK9-cyclinT with IC(50) = 0.11 mu M; it (CCT68127) inhibits growth of HCT116 colon cancer cells in vitro with GI(50) = 0.7 mu M; and shows antitumour activity when dosed p.o. at 50 mg/kg to mice bearing HCT116 solid human tumour xenografts. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.051
• 作为产物：
  描述：

  (S)-(+)-2-氨基-1-丁醇 、 三苯基氯甲烷 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 24.0h， 生成 (S)-(+)-2-(tritylamino)butan-1-ol
  参考文献：
  名称：

  探测酶的立体特异性。手性胺和氨基醇衍生物对α-胰凝乳蛋白酶和枯草杆菌蛋白酶Carlsberg的抑制作用

  摘要：

  已经评估了各种对映体胺和氨基醇酰胺以及α-酮酰胺衍生物作为代表性丝氨酸蛋白酶α-胰凝乳蛋白酶（CT）和枯草杆菌蛋白酶Carlsberg（SC）的竞争性抑制剂。研究的每种化合物都是两种酶的有效竞争抑制剂。然而，仅对于最佳抑制剂，N-丙酮酰-1-（1-萘基）乙胺（对于CT的S-对映异构体，K 1 27μM）是值得注意的对映异构体区别，其中S-对映异构体明显更有效CT和SC的抑制剂比R-分别对应12.6和73倍的因子。通过分子模型分析揭示了负责这种强结合和对映异构的酶-抑制剂相互作用。

  DOI：

  10.1016/0040-4020(96)00078-6

文献信息

• [EN] PROCESS FOR THE PREPARATION OF PURINE DERIVATIVES EXHIBITING CDK INHIBITORY ACTIVITY<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE PURINE PRÉSENTANT UNE ACTIVITÉ INHIBITRICE DE CDK
  申请人：CYCLACEL LTD

  公开号：WO2021148793A1

  公开（公告）日：2021-07-29

  The present invention relates to a process for preparing a compound of formula [I], or a pharmaceutically acceptable salt thereof, said process comprising the steps of: (i) forming a reaction mixture comprising a compound of formula [II] and a compound of formula [III]; (ii) heating said reaction mixture to a temperature of at least about 130°C to form a compound of formula [I]; (iii) isolating said compound of formula [I] from the mixture and optionally recovering unreacted compound of formula [III]; and (iv) optionally converting said compound of formula [I] into salt form; wherein: R1 and R2 are each independently H, alkyl or haloalkyl; R3 and R4 are each independently H, alkyl, haloalkyl or aryl; R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups; R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and where one of X, Y and Z is N and the remainder are CR9; R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H. Further aspects of the invention relate to a process for preparing intermediates of formula [II], and other intermediates useful in the synthesis of compounds of formula [I].

  本发明涉及一种制备化合物[I]或其药用可接受盐的方法，该方法包括以下步骤：(i)形成包含化合物[II]和化合物[III]的反应混合物；(ii)加热所述反应混合物至至少约130°C的温度以形成化合物[I]；(iii)从混合物中分离所述化合物[I]并可选择性地回收未反应的化合物[III]；以及(iv)可选择性地将所述化合物[I]转化为盐形式；其中：R1和R2分别独立地为H、烷基或卤代烷基；R3和R4分别独立地为H、烷基、卤代烷基或芳基；R5为烷基、烯基、环烷基或环烷基-烷基，其中每个可能可选择地被一个或多个羟基取代；R6从环丙基氨基、环丙基甲基氨基、环丁基氨基、环丁基甲基氨基中选择，其中X、Y和Z中的一个是N，其余为CR9；R7、R8和每个R9独立地为H、烷基或卤代烷基，其中至少一个R7、R8或R9不是H。该发明的进一步方面涉及一种制备中间体[II]和其他在合成化合物[I]过程中有用的中间体的方法。
• [EN] PROCESS FOR PREPARING PURINE DERIVATIVES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE DÉRIVÉS DE PURINE
  申请人：CYCLACEL LTD

  公开号：WO2018138500A1

  公开（公告）日：2018-08-02

  The present invention relates to a process for preparing a compound of formula [I], said process comprising the steps of: formula [II]+formula [III]−>formula [I] (i) forming a reaction mixture comprising (a) a compound of formula [II], (b) a compound of formula [III] and (c) 1,2-propanediol or polyethylene glycol, or a mixture thereof, and optionally (d) a base; (ii) heating said reaction mixture to a temperature of at least about 150°C to form a compound of formula [I]; (iii) isolating said compound of formula [I]; and (iv) optionally converting said compound of formula [I] into salt form; wherein: R1 and R2 are each independently H, alkyl or haloalkyl; R3 and R4 are each independently H, alkyl, haloalkyl or aryl; R5 is alkyl, alkenyl, cycloalkyl or cycloalkyl-alkyl, each of which may be optionally substituted with one or more OH groups; R6 is selected from cyclopropylamino, cyclopropylmethylamino, cyclobutylamino, cyclobutylmethylamino and formula (A) where one of X, Y and Z is N and the remainder are CR9; R7, R8 and each R9 are independently H, alkyl or haloalkyl, wherein at least one of R7, R8 and R9 is other than H. Further aspects of the invention relate to a highly diastereoselective process for the preparation of compounds of formula [III], a process for preparing intermediates of formula [II], and other intermediates useful in the synthesis of compounds of formula [I], and to a process for preparing the crystalline tartrate salt and free base of compounds of formula [I].

  本发明涉及一种制备式[I]化合物的过程，该过程包括以下步骤：式[II]+式[III]−＞式[I]（i）形成反应混合物，包括（a）式[II]化合物，（b）式[III]化合物和（c）1,2-丙二醇或聚乙二醇，或其混合物，以及可选的（d）碱；（ii）将反应混合物加热至至少约150°C的温度以形成式[I]化合物；（iii）分离所述式[I]化合物；（iv）可选地将所述式[I]化合物转化为盐形式；其中：R1和R2各自独立地为H，烷基或卤代烷基；R3和R4各自独立地为H，烷基，卤代烷基或芳基；R5为烷基，烯基，环烷基或环烷基-烷基，每个基团可以选择性地被一个或多个OH基团取代；R6选自环丙基氨基，环丙基甲基氨基，环丁基氨基，环丁基甲基氨基和式（A），其中X，Y和Z中的一个为N，其余为CR9；R7，R8和每个R9各自独立地为H，烷基或卤代烷基，其中至少一个R7，R8和R9不为H。本发明的其他方面涉及一种高度对映选择性的制备式[III]化合物的过程，一种制备式[II]中间体的过程，以及在合成式[I]化合物中有用的其他中间体，以及一种制备式[I]的结晶酒石酸盐和自由碱的过程。
• [EN] 2,6,9-SUBSTITUTED PURINE DERIVATIVES AND THEIR USE N THE TREATMENT OF PROLIFERATIVE DISORDERS<br/>[FR] DERIVES DE PURINE 2,6,9-SUBSTITUES ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES PROLIFERANTES
  申请人：CYCLACEL LTD

  公开号：WO2003002565A1

  公开（公告）日：2003-01-09

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R2 is 3-hydroxypiperidin-1-yl, or NHCH(R4)CH(R3) OH, wherein R3 is hydrogen or methyl and R4 is methyl, ethyl or isopropyl; R6 is 3-nitrophenylarnino, 3,4-dimethoxybenzylarnino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and/or viral disorders.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R2为3-羟基哌啶-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苄胺基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在另一个方面，本发明涉及包含所述化合物的药物组合物，以及它们在治疗抗增殖性疾病和/或病毒性疾病中的应用。
• New purine derivatives
  申请人：Fischer Martin Peter

  公开号：US20050256142A1

  公开（公告）日：2005-11-17

  The present invention relates to compounds of formula 1 or pharmaceutically acceptable salts thereof, wherein one of R 1 and R 2 is methyl, ethyl or isopropyl, and the other is H; R 3 and R 4 are each independently H, branched or unbranched C 1 -C 6 alkyl, or aryl, and wherein at least one of R 3 and R 4 is other than H; R 5 is a branched or unbranched C 1 -C 5 alkyl group or a C 1 -C 6 cycloalkyl group, each of which may be optionally substituted with one or more OH groups; R 6 , R 7 , R 8 and R 9 are each independently H, halogen, NO 2 , OH, OMe, CN, NH 2 , COOH, CONH 2 , or SO 2 NH 2 . A further aspect of the invention relates to pharmaceutical compositions comprising compounds of formula 1, and the use of said compounds in treating proliferative disorders, viral disorders, CNS disorders, diabetes, stroke, alopecia or neurodegenerative disorders.

  本发明涉及公式1的化合物或其药学上可接受的盐，其中R1和R2中的一个是甲基、乙基或异丙基，另一个是氢；R3和R4各自独立地是氢、支链或非支链的C1-C6烷基，或芳基，其中至少一个是非氢基；R5是支链或非支链的C1-C5烷基或C1-C6环烷基，每个基团可以选择性地被一个或多个羟基取代；R6、R7、R8和R9各自独立地是氢、卤素、NO2、羟基、OMe、CN、NH2、COOH、CONH2或SO2NH2。本发明的另一个方面涉及包括公式1化合物的药物组合物，以及使用该化合物治疗增生性疾病、病毒性疾病、中枢神经系统疾病、糖尿病、中风、脱发或神经退行性疾病的用途。
• 2,6,9-Substituted purine derivatives and their use in the treatment of proliferative disorders
  申请人：Fischer Martin Peter

  公开号：US20050009846A1

  公开（公告）日：2005-01-13

  The present invention relates to compounds of formula I or a pharmaceutically acceptable salt thereof wherein R 2 is 2-hydroxymethylpyrrolidin- 1 -yl, or NHCH(R 4 )CH(R 3 )OH, wherein R 3 is hydrogen or methyl and R 4 is methyl, ethyl or isopropyl; R 6 is 3-nitrophenylamino, 3,4-dimethoxybenzylamino, 3-iodobenzyl-amino, pyrid-2-yl-methylamino, pyrid-4-yl-methylamino or indan-5-amino; R 9 is isopropyl or cyclopentanyl. In a further aspect, the invention relates to pharmaceutical compositions comprising said compounds, and the use thereof in treating antiproliferative disorders and or viral disorders.

  本发明涉及式I的化合物或其药学上可接受的盐，其中R2为2-羟甲基吡咯烷-1-基或NHCH（R4）CH（R3）OH，其中R3为氢或甲基，R4为甲基、乙基或异丙基；R6为3-硝基苯胺基、3,4-二甲氧基苯甲基氨基、3-碘苯甲基氨基、吡啶-2-基甲基氨基、吡啶-4-基甲基氨基或茚-5-基氨基；R9为异丙基或环戊基。在进一步方面，本发明涉及包括所述化合物的制药组合物及其在治疗抗增殖性疾病和/或病毒性疾病中的用途。