1-hydroxy-3-(1H-indol-3-yl)propan-2-one | 4568-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-hydroxy-3-(1H-indol-3-yl)propan-2-one
• CAS: 4568-87-0
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: HDTKTUMIYBSLSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-hydroxy-3-(1H-indol-3-yl)propan-2-one 在 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成
  参考文献：
  名称：

  发现一种有效，高度选择性和口服有效的胰岛素受体小分子活化剂。

  摘要：

  合成了一系列3,6-二芳基-2,5-二羟基苯醌，并评估了其选择性激活人胰岛素受体酪氨酸激酶（IRTK）的能力。2、5-二羟基-6-（1-甲基吲哚-3-基）-3-苯基-1,4-苯醌（2h）被确定为有效，高选择性和口服活性的小分子胰岛素受体活化剂。它以300 nM的EC（50）激活IRTK，并且在浓度高达30,000 nM的情况下不诱导紧密相关的受体（IGFIR，EGFR和PDGFR）的激活。向高血糖db / db小鼠（0.1-10 mg / kg /天）口服给予该化合物可引起剂量依赖性完全或几乎完全纠正高血糖。在ob / ob小鼠中，该化合物（10 mg / kg）导致高胰岛素血症明显减少。在IRTK分析中不起作用的结构相关化合物2c，在相同的暴露水平下未能影响db / db小鼠的血糖水平。化合物2h的其他研究结果旨在评估经典的醌相关现象，为进行更广泛的毒理学评估提供了足够的乐观理由。

  DOI：

  10.1021/jm000285q
• 作为产物：
  描述：

  L-色氨醇 在 recombinant phenylalanine dehydrogenase from Quasibacillus thermotolerans 、 聚甘氨酸 、 还原型辅酶Ⅰ 、 sodium hydroxide 作用下， 生成 1-hydroxy-3-(1H-indol-3-yl)propan-2-one
  参考文献：
  名称：

  一种新型热稳定性苯丙氨酸脱氢酶，用于有效合成大体积芳香氨基酸及其衍生物

  摘要：

  苯丙氨酸脱氢酶（PDH）由于能够通过不对称还原胺化产生伯胺，因此在制药和精细化工行业中发挥着重要作用。然而，PDH 的工业应用往往因其稳定性差、底物特异性窄（尤其是对于非天然底物）而受到限制。在这里，使用来自芽孢杆菌的Bb PDH作为探针，通过基因挖掘鉴定了来自耐热准芽孢杆菌( Qt PDH)的新型 PDH 。Qt PDH 表现出出色的热稳定性，特别是在 30 °C、pH 8.5 下的半衰期为 23 天，比Bb PDH 长约 300 倍。Qt PDH可以催化各种苯基丙酮酸类似物，包括2-氧代-4-苯基丁酸乙酯和l-苯基甘氨醇，以及大体积的3-(萘-1-基)-2-氧代丙酸，还原胺化比活性为1.90 U·毫克–1。在Qt PDH与Bm GDH 的共同催化下，在 1.0 M 3-(2-氯苯基)-2-氧代丙酸下实现了2-氯-l-苯丙氨酸的高效生产，转化率 > 99 %， ee 99 % ，空间-一次收率30

  DOI：

  10.1016/j.mcat.2023.113713

文献信息

• IDO Inhibitors
  申请人：Mautino Mario

  公开号：US20110053941A1

  公开（公告）日：2011-03-03

  Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.

  目前提供以下方法：(a) 通过接触本文中描述的化合物的调节有效量与吲哚胺2,3-二氧化酶相互作用，从而调节吲哚胺2,3-二氧化酶的活性；(b) 治疗需要吲哚胺2,3-二氧化酶(IDO)介导的免疫抑制的患者，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(c) 治疗需要抑制吲哚胺-2,3-二氧化酶酶活性的医疗状况，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(d) 增强抗癌治疗的有效性，包括给予抗癌剂和本文中描述的化合物；(e) 治疗与癌症相关的肿瘤特异性免疫抑制，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量；(f) 治疗与传染病相关的免疫抑制，例如HIV-1感染，包括给予本文中描述的化合物的有效吲哚胺2,3-二氧化酶抑制剂量。
• NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE 1
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20140288119A1

  公开（公告）日：2014-09-25

  This invention provides a compound having the structure: wherein R 1 is H, halogen, —NR 5 R 6 , —NR 5 —C(═O)—R 6 , —NH—C(═O)—OR 7 , —OR 7 , —NO 2 , —CN, —SR 7 , —SO 2 R 7 , —CO 2 R 7 , CF 3 , —SOR 7 , —POR 7 , —C(═S)R 7 , —C(═O)—NR 5 R 6 , —CH 2 —C(═O)—NR 5 R 6 , —C(═NR 5 )R 6 , —P(═O)(OR 5 )(OR 6 ), —P(OR 5 )(OR 6 ), —C(═S)R 7 , C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R 5 , R 6 , and R 7 and are each, independently, H, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R 2 and R 3 are each, independently, H, halogen, —NH 2 , —CX 3 , —C(═O)OR 8 , C(═O)R 8 , —C(═O)NR 9 R 10 , C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R 8 , R 9 and R 10 are each, independently, H, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar 1 —Z— or —Z—Ar 1 —Z—, wherein Ar 1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is —O—, —S—, —CH 2 —, —C(O)— —NH—, —NH—NH—, —NHC(═O)—, —C(═O)NH—, —NHC(═O)CH 2 NH—, —NHC(═O)CH 2 C(═O)—, —N(OH)—, —CH 2 CH 2 — or —NHC(═O)CH═CH—; and R 4 is alkyl, —OR 11 or —NH—OR 11 , wherein R 11 is H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is —Ar 1 —Z—, Z is absent, Ar 1 is phenyl, R 2 and R 3 are H, n=1, and R 4 is —NHOH, then R 1 is other than carbazole, tetrahydro-β-carboline, tetrahydro-γ-carboline, —C(═O)—NR 5 R 6 and —NR 5 —C(═O)—R 6 , wherein one of R 5 or R 6 is quinoline and the other of R 5 or R 6 is H; or a pharmaceutically acceptable salt thereof.

  该发明提供了一种具有以下结构的化合物：其中，R1为H、卤素、—NR5R6、—NR5—C(═O)—R6、—NH—C(═O)—OR7、—OR7、—NO2、—CN、—SR7、—SO2R7、—CO2R7、CF3、—SOR7、—POR7、—C(═S)R7、—C(═O)—NR5R6、—CH2—C(═O)—NR5R6、—C(═NR5)R6、—P(═O)(OR5)(OR6)、—P(OR5)(OR6)、—C(═S)R7、C1-5烷基、C2-5烯基、C2-5炔基、芳基、杂芳基或杂环烷基，其中，R5、R6和R7各自独立地为H、C1-5烷基、C2-5烯基、C2-5炔基、杂基、环烷基、杂环烷基、芳基或杂芳基；m为0到2的整数；R2和R3各自独立地为H、卤素、—NH2、—CX3、—C(═O)OR8、C(═O)R8、—C(═O)NR9R10、C1-10烷基、C2-10烯基、C2-10炔基、杂基、芳基、杂芳基或杂环烷基，其中，X为Cl、Br或F；R8、R9和R10各自独立地为H、C1-5烷基、C2-5烯基、C2-5炔基、杂基、环烷基、杂环烷基、芳基或杂芳基；Q为—Ar1—Z—或—Z—Ar1—Z—，其中，Ar1为芳基或杂芳基；Z的每次出现都是独立存在或缺失的，当存在时为—O—、—S—、—CH2—、—C(O)——NH—、—NH—NH—、—NHC(═O)—、—C(═O)NH—、—NHC(═O)CH2NH—、—NHC(═O)CH2C(═O)—、—N(OH)—、—CH2CH2—或—NHC(═O)CH═CH—；R4为烷基、—OR11或—NH—OR11，其中，R11为H、C1-10烷基、C2-10烯基、C2-10炔基、芳基、杂芳基或杂环烷基，当Q为—Ar1—Z—，Z不存在，Ar1为苯基，R2和R3为H，n=1，且R4为—NHOH时，R1不是咔唑、四氢-β-咔啉、四氢-γ-咔啉、—C(═O)—NR5R6和—NR5—C(═O)—R6，其中R5或R6之一为喹啉，另一个为H；或其药学上可接受的盐。
• Biocatalysts and methods for synthesizing derivatives of tryptamine and tryptamine analogs
  申请人：Codexis, Inc.

  公开号：US10544402B2

  公开（公告）日：2020-01-28

  The present disclosure provides engineered transaminase polypeptides for the production of amines, polynucleotides encoding the engineered transaminases, host cells capable of expressing the engineered transaminases, and methods of using the engineered transaminases to prepare compounds useful in the production of active pharmaceutical agents.

  本公开提供了用于生产胺的工程化转氨酶多肽、编码工程化转氨酶的多核苷酸、能够表达工程化转氨酶的宿主细胞，以及使用工程化转氨酶制备用于生产活性药剂的化合物的方法。
• BIOCATALYSTS AND METHODS FOR SYNTHESIZING DERIVATIVES OF TRYPTAMINE AND TRYPTAMINE ANALOGS
  申请人：Codexis, Inc.

  公开号：EP2828385B1

  公开（公告）日：2018-02-07
• NOVEL MOLECULES THAT SELECTIVELY INHIBIT HISTONE DEACETYLASE 6 RELATIVE TO HISTONE DEACETYLASE
  申请人：Breslow Ronald

  公开号：US20170066712A1

  公开（公告）日：2017-03-09

  This invention provides a compound having the structure: wherein R 1 is H, halogen, —NR 5 R 6 , —NR 5 —C(═0)-R 6 , —NH—C(═O)—OR 7 , —OR 7 , —NO 2 , —CN, —SR 7 , —SO 2 R 7 , —CO 2 R 7 , CF 3 , —SOR 7 , —POR 7 , —C(═S)R 7 , —C(═O)—NR 5 R 6 , —CH 2 —C(═O)—NR 5 R 6 , —C(═NR 5 )R 6 , —P(═O)(OR 5 )(OR 6 ), —P(OR 5 )(OR 6 ), —C(═S)R 7 , C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R 5 , R 6 , and R 7 and are each, independently, H, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R 2 and R 3 are each, independently, H, halogen, —NH 2 , —CX 3 , —C(═O)OR 8 , C(═O)R 8 , —C(═O)NR 9 R 10 , C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R 8 , R 9 and R 10 are each, independently, H, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is —Ar 1 —Z— or —Z—Ar 1 —Z—, wherein Ar 1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is —O—, —S—, —CH 2 —, —C(O)—, —NH—, —NH—NH—, —NHC(═O)—, —C(═O)NH—, —NHC(═O)CH 2 NH—, —NHC(═O)CH 2 C(═O)—, —N(OH)—, —CH 2 CH 2 — or —NHC(═O)CH═CH—; and R 4 is alkyl, —OR 11 or —NH—OR 11 , wherein R 11 is H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is —Ar 1 —Z—, Z is absent, Ar 1 is phenyl, R 2 and R 3 are H, n=1, and R 4 is —NHOH, then R 1 is other than carbazole, tetrahydro-β-carboline, tetrahydro-γ-carboline, —C(═O)—NR 5 R 6 and —NR 5 —C(═0)-R 6 , wherein one of R 5 or R 6 is quinline and the other of R 5 or R 6 is H; or a pharmaceutically acceptable salt thereof.