3-(chloromethyl)-N,1-bis(methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine | 1034474-25-3

• 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: 3-(chloromethyl)-N,1-bis(methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine
• 英文别名: 3-(chloromethyl)-N,1-bis(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine；3-(chloromethyl)-N,1-bis[(4-methoxyphenyl)methyl]pyrazolo[3,4-b]pyridin-6-amine
• CAS: 1034474-25-3
• 化学式: C₂₃H₂₃ClN₄O₂
• 分子量: 422.914
• InChiKey: FRZAMQDRFXLCKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(chloromethyl)-N,1-bis(methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine 在 三氟乙酸 、 lithium tert-butoxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-({1-[(6-amino-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-5-chloro-1H-indazol-4-yl}oxy)-5-chlorobenzonitrile
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase

  摘要：

  Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired immunodeficiency syndrome (AIDS) related mortality. Despite this success, there remains a critical need for new HIV therapies to address the emergence of drug resistant viral strains. Next generation NNRTIs are sought that are effective against these mutant forms of the HIV virus. The bound conformations of our lead inhibitors, MK-1107 (1) and MK-4965 (2), were divergent about the oxymethylene linker, and each of these conformations was rigidified using two isomeric cyclic constraints. The constraint derived from the bioactive conformation of 2 provided novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Systematic SAR led to the identification of indazole as the optimal conformational constraint to provide MK-6186 (3) and MK-7445 (6). Despite their reduced flexibility, these compounds had potency comparable to that of the corresponding acyclic ethers in both recombinant enzyme and cell based assays against both the wild-type and the clinically relevant mutant strains.

  DOI：

  10.1021/jm2010173
• 作为产物：
  描述：

  6-氟-1H-吡唑并[3,4-b]吡啶-3-羧酸叔丁酯 在 lithium aluminium tetrahydride 、 氯化亚砜 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 氯仿 为溶剂， 反应 2.0h， 生成 3-(chloromethyl)-N,1-bis(methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-6-amine
  参考文献：
  名称：

  Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase

  摘要：

  Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired immunodeficiency syndrome (AIDS) related mortality. Despite this success, there remains a critical need for new HIV therapies to address the emergence of drug resistant viral strains. Next generation NNRTIs are sought that are effective against these mutant forms of the HIV virus. The bound conformations of our lead inhibitors, MK-1107 (1) and MK-4965 (2), were divergent about the oxymethylene linker, and each of these conformations was rigidified using two isomeric cyclic constraints. The constraint derived from the bioactive conformation of 2 provided novel, highly potent NNRTIs that possess broad spectrum antiviral activity and good pharmacokinetic profiles. Systematic SAR led to the identification of indazole as the optimal conformational constraint to provide MK-6186 (3) and MK-7445 (6). Despite their reduced flexibility, these compounds had potency comparable to that of the corresponding acyclic ethers in both recombinant enzyme and cell based assays against both the wild-type and the clinically relevant mutant strains.

  DOI：

  10.1021/jm2010173

文献信息

• Non-nucleoside reverse transcriptase inhibitors
  申请人：Anthony Neville J.

  公开号：US20080275097A1

  公开（公告）日：2008-11-06

  Compounds of Formula I: are HIV reverse transcriptase inhibitors, wherein V, W, X, Y, Z, R 1 , R 2 , R 4 , R 5 , R 6 , ring A, ring B, j and k are defined herein. The compounds of Formula I, and the pharmaceutically acceptable salts and prodrugs thereof, are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  化合物I的公式是HIV反转录酶抑制剂，其中V、W、X、Y、Z、R1、R2、R4、R5、R6、环A、环B、j和k在此定义。化合物I及其医药上可接受的盐和前药在抑制HIV反转录酶、预防和治疗HIV感染以及预防、延迟发病或进展和治疗艾滋病方面具有用途。这些化合物及其盐可以与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用作为药物组成部分。
• NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  申请人：Tucker Thomas J.

  公开号：US20100256181A1

  公开（公告）日：2010-10-07

  Heteroaromatic compounds of Formula (I) are HIV reverse transcriptase inhibitors, wherein ring A is: (ii-a), (ii-b), (ii-c), (ii-d), or (ii-e); and wherein n, L, M, U, X, Y, Z, R E , R F , R 1 , R 2A , R 2B , R 2C , R 3 , R 8 , R 9 and R 10 are defined herein. The compounds of Formula I and their pharmaceutically acceptable salts and prodrugs are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts and prodrugs can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  公式（I）的杂环芳香化合物是HIV反转录酶抑制剂，其中环A为：（ii-a）、（ii-b）、（ii-c）、（ii-d）或（ii-e）；其中n、L、M、U、X、Y、Z、RE、RF、R1、R2A、R2B、R2C、R3、R8、R9和R10的定义见本文。公式I的化合物及其药学上可接受的盐和前药在抑制HIV反转录酶、预防和治疗HIV感染以及预防、延迟发病或进展和治疗艾滋病方面有用。这些化合物及其盐和前药可作为药物组成部分，可与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。
• WO2008/76223
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase
  作者：Robert Gomez、Samson Jolly、Theresa Williams、Thomas Tucker、Robert Tynebor、Joe Vacca、Georgia McGaughey、Ming-Tain Lai、Peter Felock、Vandna Munshi、Daniel DeStefano、Sinoeun Touch、Mike Miller、Youwei Yan、Rosa Sanchez、Yuexia Liang、Brenda Paton、Bang-Lin Wan、Neville Anthony

  DOI：10.1016/j.bmcl.2011.10.027

  日期：2011.12

  Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI's. (C) 2011 Elsevier Ltd. All rights reserved.
• US7781454B2
  申请人：——

  公开号：US7781454B2

  公开（公告）日：2010-08-24