3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yl]oxy}benzonitrile | 1034474-19-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yl]oxy}benzonitrile
• 英文别名: 3-chloro-5-[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yloxy]benzonitrile；MK-6186；3-chloro-5-[5-chloro-1-(2H-pyrazolo[3,4-b]pyridin-3-ylmethyl)indazol-4-yl]oxybenzonitrile
• CAS: 1034474-19-5
• 化学式: C₂₁H₁₂Cl₂N₆O
• 分子量: 435.272
• InChiKey: FZBAOOQVQXATRL-UHFFFAOYSA-N

物化性质

• 沸点：
  656.4±55.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yl]oxy}benzonitrile 、 间氯过氧苯甲酸 在 acetonitrile-water 、 三氟乙酸 作用下， 反应 18.0h， 生成
  参考文献：
  名称：

  Non-nucleoside reverse transcriptase inhibitors

  摘要：

  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。

  公开号：

  US20080275097A1
• 作为产物：
  描述：

  3-甲基-1H-吡唑并[3,4-b]吡啶 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 水 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.33h， 生成 3-chloro-5-{[5-chloro-1-(1H-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1H-indazol-4-yl]oxy}benzonitrile
  参考文献：
  名称：

  WO2008/76223

  摘要：

  公开号：

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。
• Design and Synthesis of Conformationally Constrained Inhibitors of Non-Nucleoside Reverse Transcriptase
  作者：Robert Gomez、Samson J. Jolly、Theresa Williams、Joseph P. Vacca、Maricel Torrent、Georgia McGaughey、Ming-Tain Lai、Peter Felock、Vandna Munshi、Daniel DiStefano、Jessica Flynn、Mike Miller、Youwei Yan、John Reid、Rosa Sanchez、Yuexia Liang、Brenda Paton、Bang-Lin Wan、Neville Anthony

  DOI：10.1021/jm2010173

  日期：2011.11.24

  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.
• Process Development and Large-Scale Synthesis of MK-6186, a Non-Nucleoside Reverse Transcriptase Inhibitor for the Treatment of HIV
  作者：Adrian Goodyear、Xin Linghu、Brian Bishop、Cheng Chen、Ed Cleator、Mark McLaughlin、Faye J. Sheen、Gavin W. Stewart、Yingju Xu、Jingjun Yin.

  DOI：10.1021/op200334x

  日期：2012.4.20

  A new synthetic route has been developed to drug candidate 1, a second-generation NNRTI being developed as a potential treatment of HIV. Regiocontrol in a key alkylation step was achieved by selective N-alkylation of hydrazone 13. After a deprotection and cyclisation sequence, 1 was isolated in six steps in 35% overall yield from readily available starting materials.
• USE OF INORGANIC MATRIX AND ORGANIC POLYMER COMBINATIONS FOR PREPARING STABLE AMORPHOUS DISPERSIONS
  申请人：Higgins John

  公开号：US20140206717A1

  公开（公告）日：2014-07-24

  The present invention relates to methods for processing pharmaceutically active substances having poor water solubility in the presence of an inorganic matrix, e.g., magnesium aluminometasilicate, and a secondary polymer as a means of converting the crystalline API to substantially amorphous and stable form, i.e., the crystallinity is less than 5%. The methods of the invention result in more complete amorphization, increased solubility, drug loading and stability as compared to typical amorphization or literature methods.
• US7781454B2
  申请人：——

  公开号：US7781454B2

  公开（公告）日：2010-08-24