O-(3,5-dichlorobenzyl)hydroxylamine | 755740-10-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O-(3,5-dichlorobenzyl)hydroxylamine
• 英文别名: O-[(3,5-dichlorophenyl)methyl]hydroxylamine
• CAS: 755740-10-4
• 化学式: C₇H₇Cl₂NO
• 分子量: 192.045
• InChiKey: JDDDGXOQVRPABR-UHFFFAOYSA-N

物化性质

• 沸点：
  306.1±32.0 °C(Predicted)
• 密度：
  1.374±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  O-(3,5-dichlorobenzyl)hydroxylamine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 O-(3,5-dichlorobenzyl)hydroxylamine hydrochloride
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028
• 作为产物：
  描述：

  3,5-二氯苯甲醇 在 偶氮二甲酸二异丙酯 、 一水合肼 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 O-(3,5-dichlorobenzyl)hydroxylamine
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028

文献信息

• [EN] PRODRUG INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE 1 (IDO1)<br/>[FR] INHIBITEURS DE PROMÉDICAMENTS D'INDOLÉAMINE 2,3-DIOXYGÉNASE-1 (JDO1)
  申请人：LANKENAU INST MEDICAL RES

  公开号：WO2019051198A1

  公开（公告）日：2019-03-14

  Indoleamine 2,3-dioxygenase-1 prodrugs and methods of use thereof are disclosed.

  揭示了吲哚胺2,3-二氧化酶-1前药及其使用方法。
• 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。
• METHOD FOR PREPARING 3'-O-AMINO-2'-DEOXYRIBONUCLEOSIDE-5'-TRIPHOSPHATES
  申请人：DNA Script

  公开号：US20210300961A1

  公开（公告）日：2021-09-30

  Methods for preparing 3′-O-amino-2′-deoxyribonucleoside-5′-triphosphates with reduced 3′-hydroxy-2′-deoxyribonucleoside-5′-triphosphate contamination by converting 3′-(N-acetone-oxime)-2′-deoxynucleoside triphosphate to 3′-O-amine-2′-deoxynucleoside triphosphate by treatment with an aryl-oxyamine and compositions produced therefrom.

  制备方法，用于制备含有较少3'-羟基-2'-脱氧核苷酸-5'-三磷酸污染的3'-O-氨基-2'-脱氧核苷酸-5'-三磷酸，通过将3'-(N-丙酮肟)-2'-脱氧核苷酸三磷酸转化为3'-O-氨基-2'-脱氧核苷酸三磷酸，并由此产生的组合物。
• IDO INHIBITORS
  申请人：Newlink Genetics

  公开号：EP2227233A2

  公开（公告）日：2010-09-15
• [EN] IDO INHIBITORS<br/>[FR] INHIBITEURS DE L'IDO
  申请人：NEWLINK GENETICS

  公开号：WO2009073620A2

  公开（公告）日：2009-06-11

  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.