cis-1-isobutyl-3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline | 107494-23-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: cis-1-isobutyl-3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline
• 英文别名: methyl (1S,3S)-1-isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；(1S,3S)-methyl 1-isobutyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；methyl (1S,3S)-1-(2-methylpropyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 107494-23-5
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: LFBDUYMSBJXRJJ-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-1-isobutyl-3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline 在 palladium on activated charcoal 甲酸铵 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (5aS,12S,14aS)-12-isobutyl-1,2,3,5a,6,11,12,14a-octahydro-5H,14H-pyrrolo[1'',2'':4',5']pyrazino[2',1':6,1]pyrido[3,4-b]indole-5,14-dione
  参考文献：
  名称：

  萤火虫全合成的合成方法II旋光五环中间体的合成及其脱氢

  摘要：

  由L和D色氨酸合成了旋光性五环（13-18），其中两个（13和15）被烷基化并脱氢成21和22。

  DOI：

  10.1016/s0040-4039(00)84762-0
• 作为产物：
  描述：

  L-色氨酸甲酯 在 三氟乙酸 、 原甲酸三甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 26.5h， 生成 cis-1-isobutyl-3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline
  参考文献：
  名称：

  Synthesis and Evaluation of Tryprostatin B and Demethoxyfumitremorgin C Analogues

  摘要：

  Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G(2)/M transition. N-Alkyl derivatives of the L-TrP-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these were more active than the natural product. A second series of cis- and trans-tetrahydro-beta-carbolines annulated to a diketopiperazine were prepared as analogues of demethoxyfumitremorgin C. The nature of the alkyl substituent, as well as its cis or trans relationship in the tetrahydro-beta-carboline ring, was found to have a significant effect on cytotoxic activity. Small cis-alkyl substituents fall into the demethoxyfumitremorgin C family, whereas bulky benzyl trans compounds appear to act via a different mechanism of action.

  DOI：

  10.1021/jm9905662

文献信息

• Exploration of TRPM8 Binding Sites by β-Carboline-Based Antagonists and Their In Vitro Characterization and In Vivo Analgesic Activities
  作者：Alessia Bertamino、Carmine Ostacolo、Alicia Medina、Veronica Di Sarno、Gianluigi Lauro、Tania Ciaglia、Vincenzo Vestuto、Giacomo Pepe、Manuela Giovanna Basilicata、Simona Musella、Gerardina Smaldone、Claudia Cristiano、Sara Gonzalez-Rodriguez、Asia Fernandez-Carvajal、Giuseppe Bifulco、Pietro Campiglia、Isabel Gomez-Monterrey、Roberto Russo

  DOI：10.1021/acs.jmedchem.0c00816

  日期：2020.9.10

  Transient receptor potential melastatin 8 (TRPM8) ion channel represents a valuable pharmacological option for several therapeutic areas. Here, a series of conformationally restricted derivatives of the previously described TRPM8 antagonist N,N′-dibenzyl tryptophan 4 were prepared and characterized in vitro by Ca2+-imaging and patch-clamp electrophysiology assays. Molecular modeling studies led to

  瞬时受体电位褪黑素8（TRPM8）离子通道代表了几个治疗领域的宝贵药理学选择。在此，制备了先前描述的TRPM8拮抗剂N，N′-二苄基色氨酸4的一系列构象受限的衍生物，并通过Ca 2+成像和膜片钳电生理测定体外表征。分子建模研究导致在TRPM8结合位点内确定了这些衍生物的广泛且明确定义的相互作用网络，这是其拮抗剂活性的基础。（5 R，11a S）-5-（4-氯苯基）-2-（4-氟苄基）-5,6,11,11a-四氢-1 H-咪唑[1'，5'：1,6]吡啶[3,4-b ]吲哚-1,3（2 H）-二酮（31a）以有效的（IC 50 = 4.10±1.2 nM），选择性且代谢稳定的TRPM8拮抗剂出现。在体内，31a在icilin诱导的WDS（11.5 mg / kg ip），奥沙利铂诱导的冷异常性疼痛（10-30μgsc）和CCI诱导的热痛觉过敏（11.5 mg / kg）中显示出显着的靶标覆盖范围。
• Model studies related to the total synthesis of the fumitremorgins; the Pictet-Spengler cyclisation and the formation and intramolecular acylation of a 1,2-dihydro-β-carboline derivative
  作者：David M. Harrison、Ram Bilas Sharma

  DOI：10.1016/s0040-4020(01)89899-9

  日期：1993.4

  tetrahydro-β-carbolines 8, 9b, and 9d are described. The Pictet-Spengler reaction of L-tryptophyl-L-proline methyl ester with 3-methylbutanal gave the tetrahydro-β-carbolines 20 and 21; subsequent acid-catalysed cyclisation afforded the fumitremorgin analogues 22 and 23. The 2-(p-toluenesulphonyl)tetrahydro-β-carboline 27a furnished the unsaturated pentacycle 28a upon treatment with alkali.

  的四氢β咔啉的制剂8，图9B，和图9d中描述。L-色氨酸-L-脯氨酸甲酯与3-甲基丁醛的Pictet-Spengler反应得到四氢-β-咔啉20和21。随后的酸催化环化提供了fumitremorgin类似物22和23。在用碱处理后，2-（对甲苯磺酰基）四氢-β-咔啉27a提供了不饱和五环28a。
• Total Synthesis of (+)-Elacomine and (?)-Isoelacomine, Two Hitherto Unnamed Oxindole Alkaloids fromElaeagnus commutata
  作者：Claudio Pellegrini、Michael Weber、Hans-J�rg Borschberg

  DOI：10.1002/hlca.19960790116

  日期：1996.2.7

  Racemic elacomine ((±)-2), a hemiterpene spiro oxindole alkaloid from Elaeagnus commutata, was synthesized in five steps from 6-methoxytryptamine (19) in 16% overall yield (Scheme 3). The final oxidative rearrangement of the corresponding β-carboline precursor (±)-21 furnished isoelacomine ((±)-22) as a by-product (6% overall yield). A more elaborate route that started from L-tryptophan furnished (+)-2

  外消旋可卡因（（±）-2）是一种从Elaeagnus commutata合成的半萜烯螺形羟吲哚生物碱，由6个甲氧基色胺（19）分五步合成，总收率为16％（方案3）。相应的β-咔啉前体（±）-21的最终氧化重排提供了副产物异丁香碱（（±）-22）（6％的总收率）。从L-色氨酸提供的（+）- 2和（-）- 22的光学纯度为76％（方案4）开始，这是一条更精细的路线，并确定了这些化合物的绝对构型。的根的生物碱含量的重新调查E. commutata 结果表明，可卡因和异可卡因均以外消旋形式自然存在。
• Synthetic approach to the total synthesis of fumitremorgins II synthesis of optically active pentacyclic intermediates and their dehydrogenation
  作者：Masako Nakagawa、Hiroshi Fukushima、Tomohiko Kawate、Mitsuya Hongu、Shin-ichi Kodato、Teruaki Une、Mikio Taniguchi、Tohru Hino

  DOI：10.1016/s0040-4039(00)84762-0

  日期：1986.1

  Optically active pentacycles ( 13–18 ) were synthesized from L- and D-tryptophans, two of which ( 13 and 15 ) were alkylated and dehydrogenated to 21 and 22, respectively.

  由L和D色氨酸合成了旋光性五环（13-18），其中两个（13和15）被烷基化并脱氢成21和22。
• Synthesis of a new inhibitor of breast cancer resistance protein with significantly improved pharmacokinetic profiles
  作者：Yuexian Li、Jiyeon Woo、Jessica Chmielecki、Cindy Q. Xia、Mingxiang Liao、Bei-Ching Chuang、Johnny J. Yang、Miao Y. Guan、Mihaela Plesescu、Shimoga R. Prakash

  DOI：10.1016/j.bmcl.2015.11.077

  日期：2016.1

  The design, synthesis, in vitro inhibitory potency, and pharmacokinetic (PK) profiles of Ko143 analogs are described. Compared to commonly used Ko143, the new breast cancer resistance protein (BCRP) inhibitor (compound A) showed the same potency and a significantly improved PK profile in rats (lower clearance [1.54 L/h/kg] and higher bioavailability [123%]). Ko143 on the other hand suffers from poor bioavailability. Compared to Ko143, compound A would be a useful probe for delineating the role of BCRP during in vivo studies in animals. (C) 2015 Elsevier Ltd. All rights reserved.