O-(2,3-dihydro-1H-inden-1-yl)hydroxylamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: O-(2,3-dihydro-1H-inden-1-yl)hydroxylamine
• 化学式: C₉H₁₁NO
• 分子量: 149.192
• InChiKey: WEDSHLSKMXCMHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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-(2,3-dihydro-1H-inden-1-yl)hydroxylamine 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 O-(2,3-dihydro-1H-inden-1-yl)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：

  2,3-二氢-1H-茚-1-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-(2,3-dihydro-1H-inden-1-yl)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] HIV PROTEASE INHIBITORS USEFUL FOR THE TREATMENT OF AIDS
  申请人：MERCK & CO., INC.

  公开号：WO1993009096A1

  公开（公告）日：1993-05-13

  (EN) Compounds of formula (I) where R1 and R2 are independently hydrogen or optionally-substituted C1-4alkyl or aryl, or R1 and R2 are joined together to form a monocyclic or bicyclic ring system, are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.(FR) L'invention décrit des composés ayant la formule (I) dans laquelle R1 et R2 représentent indépendamment l'hydrogène ou un groupe aryle ou alkyle de C1-4 éventuellement substitué, ou bien R1 et R2 forment ensemble un système d'anneau monocyclique ou bicyclique, ces composés étant des inhibiteurs de protéase du VIH efficace. Ces composés sont utiles dans la prévention ou le traitement de l'infection par le virus d'immunodéficience humaine et dans le traitement du SIDA, soit en tant que composés, en tant que sels pharmaceutiquement acceptables, ingrédients d'une composition pharmaceutique, combinés ou non à d'autres agents antiviraux, des immunomodulateurs, des antibiotiques ou des vaccins. Des procédés de traitement du SIDA et des procédés de prévention ou de traitement de l'infection par VIH sont également décrits.

  化合物的化学式为(I)，其中R1和R2独立地代表氢或可选取代的C1-4烷基或芳基，或R1和R2结合形成单环或双环环系统，是HIV蛋白酶抑制剂。这些化合物可用于预防或治疗HIV感染以及治疗艾滋病，无论是作为化合物、药学上可接受的盐、药物组成成分，还是与其他抗病毒、免疫调节剂、抗生素或疫苗组合使用。还描述了治疗艾滋病的方法和预防或治疗HIV感染的方法。
• [EN] HIV PROTEASE INHIBITORS USEFUL FOR THE TREATMENT OF AIDS<br/>[FR] INHIBITEURS DE LA PROTEASE CODEE PAR LE VIH UTILES DANS LE TRAITEMENT DU SIDA
  申请人：MERCK & CO., INC.

  公开号：WO1994026717A1

  公开（公告）日：1994-11-24

  (EN) Compounds of formula (I), where R1 and R2 are independently hydrogen or optionally-substituted C1-4alkyl or aryl, and R1 also forms a heterocycle or heterocycle-C1-4alkyl, are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.(FR) L'invention concerne des composés de la formule (I) dans laquelle R1 ainsi que R2 représentent indépendamment hydrogène ou aryle ou alkyle C1-4 facultativement subsitué, et R1 forme également un hétérocycle ou hétérocycle-alkyle C1-4, lesquels composés sont des inhibiteurs de la protéase codée par le VIH. Ces composés sont utiles dans la prévention ou dans le traitement d'infections par VIH, ainsi que dans le traitement du SIDA, soit comme composés, sels pharmaceutiquement acceptables, ingrédients de compositions pharmaceutiques, en combinaison ou non avec d'autres antiviraux, immunomodulateurs, antibiotiques soit comme vaccins. L'invention concerne également des procédés de traitements du SIDA ainsi que des procédés de prévention ou de traitement d'infections par VIH.

  化合物的化学式为(I)，其中R1和R2独立表示氢或可选取代的C1-4烷基或芳基，而R1还可以形成杂环或杂环-C1-4烷基，这些化合物是HIV蛋白酶抑制剂。这些化合物可用于预防或治疗HIV感染以及治疗艾滋病，无论是作为化合物、药学上可接受的盐、药物组成成分，还是与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。同时，还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。
• [EN] HIV PROTEASE INHIBITORS IN PHARMACEUTICAL COMBINATIONS FOR THE TREATMENT OF AIDS<br/>[FR] INHIBITEURS DE LA PROTEASE DU VIH ENTRANT DANS DES PREPARATIONS PHARMACEUTIQUES POUR LE TRAITEMENT DU SIDA
  申请人：MERCK & CO., INC.

  公开号：WO1994022480A1

  公开（公告）日：1994-10-13

  (EN) Compounds of formula (I) where R1 and R2 are independently hydrogen or optionally-substituted C1-4alkyl or aryl, or R1 and R2 are joined together to form a monocyclic or bycyclic ring system, are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.(FR) Composés de formule (I), inhibiteurs de la protéase du VIH, où R1 et R2 sont indépendamment un hydrogène ou des C1-4 alkyle ou aryle optionnellement substitués ou bien sont liés ensemble de façon à former un système mono ou bicyclique. Ces composés sont utilisés dans la prévention et le traitement d'infections dues au VIH et le traitment du SIDA, sous forme de composés, de sels pharmaco-compatibles et de préparations pharmaceutiques où ils sont ou non combinés à d'autres antiviraux, immunomodulateurs, antibiotiques et vaccins. Les méthodes de traitement du SIDA et les méthodes de prévention ou de traitement des infections dues au VIH sont également décrites.

  化合物的化学式为(I)，其中R1和R2分别为氢原子或选择性取代的C1-4烷基或芳基，或者R1和R2结合形成单环或双环环系统，是HIV蛋白酶抑制剂。这些化合物在预防或治疗HIV感染以及治疗艾滋病方面非常有用，无论是作为化合物、药学上可接受的盐、制药组成成分，还是与其他抗病毒药物、免疫调节剂、抗生素或疫苗联合使用。还描述了治疗艾滋病和预防或治疗HIV感染的方法。
• Allylamides useful in the treatment of alzheimer's disease
  申请人：Hom Roy

  公开号：US20050027007A1

  公开（公告）日：2005-02-03

  Disclosed are methods for treating Alzheimer's disease, and other diseases, and/or inhibiting beta-secretase enzyme, and/or inhibiting deposition of A beta peptide in a mammal, by use of compounds of formula (I) where R 1 , R 2 , R 3 , B, J 1 , J 2 , X and Z are as defined herein.

  本发明涉及使用式(I)的化合物治疗阿尔茨海默病和其他疾病，抑制β-分泌酶酶活性，以及抑制哺乳动物中A β肽沉积的方法，其中R1、R2、R3、B、J1、J2、X和Z的定义如本文所述。
• HIV protease inhibitors in pharmaceutical combinant for the treatment of AIDS
  申请人：MERCK & CO. INC.

  公开号：EP0617968A1

  公开（公告）日：1994-10-05

  Compounds of formula where R₁ and R₂ are independently hydrogen or optionally-substituted C₁₋₄alkyl or aryl, or R₁ and R₂ are joined together to form a monocyclic or bicyclic ring system, are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  式的化合物 其中 R₁ 和 R₂ 独立地为氢或任选取代的 C₁₋₄ 烷基或芳基，或 R₁ 和 R₂ 连接在一起形成单环或双环环状系统，是 HIV 蛋白酶抑制剂。这些化合物作为化合物、药学上可接受的盐、药物组合成分，无论是否与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用，都可用于预防或治疗艾滋病病毒感染和艾滋病的治疗。还描述了治疗艾滋病的方法和预防或治疗艾滋病毒感染的方法。